tag:blogger.com,1999:blog-34921974691439637422024-03-05T13:10:57.115-05:00Infection LandscapesA consideration of the epidemiology, ecology, and physical and social landscapes of infectious diseasesMichael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.comBlogger57125tag:blogger.com,1999:blog-3492197469143963742.post-40755859188172034042013-08-27T11:47:00.002-04:002013-08-27T11:55:00.216-04:00Anthrax<div dir="ltr" style="text-align: left;" trbidi="on">
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This time on Infection Landscapes we will cover another zoonotic infection that has afflicted humans and their domestic livestock probably for thousands of years: anthrax. This discussion will focus only on zoonotic infections in humans, and to a lesser extent enzootic and epizootic transmission among animals. The use of anthrax as a biological weapon will <i>not</i> be covered here as this does not fall within the purview of Infection Landscapes.<br />
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<b>The Pathogen</b>: Anthrax is caused by the gram-positive bacterium, <i>Bacillus anthracis</i>. As indicated by the genus name, this is a bacillary, or rod-shaped, bacterium:<br />
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<span style="font-size: x-small;"><i>Bacillus anthracis rods </i></span></div>
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The organism is spore-forming and metabolically aerobic when active. The spores are extremely robust to environmental insult and, as such, can last for many years in the environment until favorable conditions emerge. <i>B. anthracis</i> initially targets macrophages in the host. <b>Pathogenicity and virulence are driven specifically by the presence the bacterium's capsule and its production of endotoxins</b>. The capsule prevents phagocytosis by macrophages and other phagocytic cells, and thus is able to evade an important arm of innate immunity in the host. The endotoxins are directly responsible for pathogenesis: <b>edema factor</b> mediates an increase in intracellular cAMP, which leads to severe edema in tissues, while <b>lethal factor</b> leads to tissue necrosis. Subsequently, the bacilli can be disseminated by way of the blood and lymph circulation.<br />
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<b>The Disease</b>. Anthrax typically falls into one of three distinct categories of clinical presentation: cutaneous, pulmonary, and gastrointestinal.<br />
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<b>Cutaneous anthrax is the most common presentation in humans</b>. Cutaneous anthrax typically presents with an abscess on the skin, which quickly progresses to a black eschar of necrotized tissue:<br />
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This kind of presentation generally follows transmission of the spores via open breaks or wounds in the skin following the handling or processing of infected animals. If treated effectively, cutaneous anthrax typically remains localized without generating a potentially life threatening toxemia. However, if cutaneous anthrax is not treated then the disease is subsequently associated with approximately 20% case fatality.<br />
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<b>Pulmonary anthrax is a much more severe form of disease</b>. Early presentation mimics an influenza-like illness, with fever, malaise, and cough. However, this can progress to fulminant disease and ultimate respiratory collapse, which is associated with a case fatality greater than 95%. If treated early, i.e. before fulminant disease ensues, this case fatality can be reduced by half. Pulmonary anthrax follows the inhalation of anthrax spores and is therefore known as "inhalation anthrax". However, the infective dose of pulmonary anthrax is much higher than for cutaneous anthrax (~10,000-20,000 spores).<br />
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<b>Gastrointestinal anthrax is the least common disease form, but is also quite severe</b>. Severe inflammation and lesions can present throughout the entire alimentary canal. Severe diarrhea and vomiting, both with or without blood, and anorexia are common early and persistent symptoms. The greatest threat from gastrointestinal anthrax results from the bacilli gaining the circulation from the gut tract, which can subsequently lead to a life threatening toxemia. Gastrointestinal anthrax typically follows the consumption of meat infected with <i>B. anthracis</i>. The case fatality associated with gastrointestinal anthrax can range from approximately 25% if treatment is initiated early to approximately 60% if treatment is significantly delayed.<br />
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<b>The Epidemiology and the Landscape</b>. There are three primary modes of transmission for <i>B. anthracis</i> infection in humans. Direct contact between breaks or wounds in the skin and spores in the environment or via infected animals is probably the most common route for human infection. Infection via this route is associated with cutaneous anthrax. Airborne transmission is possible when the spores are inhaled and subsequently initiate infection in the lungs, which has been associated with processing in certain kinds of animal industry. Infection via this route leads to pulmonary anthrax. Finally, food-borne transmission results from the consumption of contaminated meat. This mode of transmission is probably the least common in most endemic areas, however community outbreaks of gastrointestinal anthrax can be quite large particularly if infection is widespread among a herd of cattle slaughtered for food.<br />
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Global surveillance on anthrax incidence is quite poor, particularly in endemic areas. The map below, produced by the World Health Organization Collaborating Center for Remote Sensing and Geographic Information Systems for Public Health, depicts the general areas of endemicity by country across the world:<br />
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While the absolute numbers of incident cases are not likely to be high on an annual basis, large geographic areas of endemicity are apparent across much of the world including Central America, the Andean region of South America, sub-Saharan Africa, and Central, South, East, and Southeast Asia.<br />
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The landscape of anthrax is one delineated primarily by the spaces of interaction between humans and domestic livestock. More importantly, the specific kinds of animal processing in different kinds of industry define the types of interaction that can take place, and which may lead to transmission between infected animals, or their infectious products, and susceptible human hosts. The graphic below, prepared by the World Health Organization, demonstrates the primary routes of infection transmission (note: the route of vectored transmission by biting fly depicted by the dashed line is largely theoretical): <br />
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<b>Where anthrax remains endemic, it typically infects the grass-eating bovids, domestic or sylvan, which encounter spores in the environment as they graze. Individuals working in industries that process livestock animals, such as cattle, goats, and sheep, in these endemic areas are at greatest risk of infection</b>. More specifically, the direct handling of animal products in this setting is a common source of exposure. For example, the processing of animal hides for the production of clothing or other products that use these materials, such as drums, etc, can lead to contact transmission and subsequent cutaneous anthrax disease. Individuals involved with the processing of wool from sheep have historically experienced the highest risk of any occupation due to the significant potential for inhalation of the airborne spores in dust particles during the sheering of infected sheep as well as during the subsequent textile production. The latter route of transmission is quite uncommon today because most areas of the world where sheep husbandry is an important industry have eliminated anthrax in their animal populations. The two examples above illustrate how the landscape of infection can be comprised of intersecting physical and social spaces. In other words, risk of infection is not limited to those with direct contact with infected animals, but rather can extend to those who work with the products of those animals in occupational spaces potentially far removed from the original source of the pathogen.<br />
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Additionally, an outbreak of anthrax has been reported among injection drug users. Transmission in this scenario resulted from heroin contaminated with bone meal from infected animals. The bone meal is used to cut the drug prior to distribution.<br />
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<b>Control and Prevention</b>. Animal vaccines for livestock have been the cornerstone of anthrax prevention for more than one hundred years. Effective vaccination campaigns have reduced the burden of anthrax in livestock, and secondarily in people, in many parts of the world. The work of Louis Pasteur in the late 19th century, and then later Max Sterne in 1935, contributed to effective vaccination against anthrax in livestock animals. Louis Pasteur's anthrax vaccine was the first vaccine developed against a bacterium, and only the second vaccine produced up to that point in time (the first vaccine was developed by Edward Jenner against smallpox). Indeed, Louis Pasteur coined the term "vaccine". While Pasteur's vaccine was quite effective against infection with <i>B. anthracis</i>, it was also quite difficult to effect minimal virulence and maximal immunogenicity during the processing of this live-attenuated vaccine. Sterne was able to isolate a particular strain of <i>B. anthracis</i> that was much more amenable to efficient vaccine production and remains the current vaccine of choice for the protection of livestock in endemic areas of the world.<br />
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Human vaccines are also available in the United States, Europe, and China, but these are primarily used in military personnel among whom exposure to <i>B. anthracis</i> as a biological weapon may be anticipated. However, as described above, this form of anthrax transmission is beyond the scope of Infection Landscapes and so will not be discussed here.<br />
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Finally, the carcasses of animals killed by anthrax can be a significant public health threat if left unattended in the landscape. Specific measures to contain <i>B. anthracis</i> and prevent any further spread of the bacteria are critical interventions.<br />
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These carcasses must be removed to prevent contact with sylvan scavengers as well as to prevent contact with, and further dispersal within, the grazing lands of other domestic livestock. Burning or burying of infected dead animals are common methods that have been used for centuries. However, these are by no means fail proof. In particular, complete burning of an infected animal (which would be required to eliminate all pathogenic bacilli) can take days. Such a fuel-intensive process may not be feasible in many, or perhaps most, areas of the world where anthrax is endemic. Burying is also a difficult solution because this must be done at quite a substantial depth to prevent the re-emergence of spores due to subsequent weathering and/or other erosional forces. It is important to keep in mind that if the spores are not destroyed they can remain viable in the environment for many years.</div>
Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com49tag:blogger.com,1999:blog-3492197469143963742.post-88623844552338599562013-06-25T12:34:00.000-04:002013-06-25T12:37:06.170-04:00Leptospirosis<div dir="ltr" style="text-align: left;" trbidi="on">
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This time at Infection Landscapes we will explore one of the most widespread and prevalent zoonotic infections in the world: leptospirosis.<br />
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<b>The Pathogen</b>. Leptospirosis in humans is caused by one of five pathogenic bacteria species of the genus <i>Leptospira</i> in the the Leptospiraceae family. <i>Leptospira</i> spp. are spirochetes, displaying the characteristic spiraled cellular structure:<br />
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There are several species that are pathogenic to humans. These organisms have an outer membrane like gram negative bacteria, although the cell wall is not associated with this outer membrane but rather with the cytoplasmic membrane, which is structurally specific to spirochetes. <i>Leptospira</i> have two flagella used for motility.<br />
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<i>Leptospira</i> spp. bind to extracellular matrix, fibroblasts, endothelial cells, epithelial cells, and macrophages, ultimately making their way to the proximal renal tubules in the kidneys. The organisms are then shed in the urine of the infected host.<br />
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<b>The Disease</b>. <i>Leptospirosis can range from asymptomatic infection to severe life threatening illness</i>. Mild to moderate presentations may include fever, myalgia, headache, chills, diarrhea, vommiting, and petechial rash. Severe, complicated, leptospirosis, which is also referred to as Weil's disease, presents with multiple organ system involvement, most prominently the kidneys and liver. High concentrations of urea and creatinine in the blood, darkened and diminished urine output, and frank renal failure, and jaundice, abnormal liver enzymes, and frank liver failure characterized complicated leptospirosis in these two organ systems, respectively. Severe leptospirosis can also affect the lungs and heart, presenting with pulmonary hemorrhage, myocarditis, and pericarditis. Endothelial lesions and vascular injury are apparent in all involved organ systems. Depending on how extensive the vascular injury, complete cardiovascular collapse may follow. Finally, meningitis is another common complication in moderate to severe leptospirosis.<br />
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<b>The Epidemiology and the Landscape</b>. The spirochetes that cause leptospirosis are shed in the urine of infected mammals. The vast majority of human infections occur following contact with (most frequently) water or soil that has been contaminated by the urine containing the <i>Leptospira</i>. As such, <b>the primary route of transmission is through a common vehicle, although most infections do not occur as a result of ingestion but rather by way of water or soil contact with the conjunctiva, mucous membranes, or contact with wounds or abrasions in the skin</b>. Nevertheless, while this kind of common vehicle contact is typical, the more conventionally conceived mechanism for common vehicle transmission, i.e. the consumption of contaminated water (or food), can also play an important role in some epidemics. Indeed, consumption of a contaminated water source may be particularly relevant in some agricultural settings in the developing world where certain kinds of irrigation systems can combine with poor water and sanitation infrastructure to promote infection through the consumption of water.<br />
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Accurate estimates of the incidence of leptospirosis and associated morbidity and mortality are lacking in all areas of the world. This is in part due to the difficulty of diagnostic testing, and in part due to the lack of specific indicators of disease. As mentioned above, clinical leptospirosis can be quite similar to many infectious disease presentations, and there can be many asymptomatic cases as well. Nevertheless, <b>cautious estimates suggest that the incidence ranges from approximately less than 1 case per million persons per year in the developed world to 1 case per thousand persons per year in parts of the developing world</b>. The map below published by the International Livestock Research Institute displays the the distribution of leptospirosis in human and several other mammalian hosts in the geographic areas with the greatest burden of disease:<br />
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<b>An important feature of the landscape epidemiology of leptospirosis is the pathogen's ability to occupy two very distinct domains</b>. <b>First</b>, <i>Leptospira</i> can exist as free-living organisms in water and soil (provided the soils stays moist). <b>Second</b>, <i>Leptospira</i> can exist for extended periods of time in the kidneys of some sylvan and domestic hosts. <i>Rodents are the likely primary natural reservoir for these spirochetes</i>. However, other sylvan mammals including raccoons, rabbits, skunks, and deer also appear to be able to shed the organisms into the environment and transmit the infection to other mammals. Moreover, domestic livestock, such as cattle and sheep, and companion animals, such as dogs, are capable of shedding infectious <i>Leptospira</i> and passing infections on to human hosts. Indeed, domestic livestock can serve as the most significant source of infection to humans in many geographic settings.<br />
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<b>The particular importance of these two features lies distinctly within their spaces of intersection in the landscape</b>. Since the <i>Leptospira</i> can occupy both mammal hosts and water and soil environments, a cycle of pathogen movement from mammalian host to environment and back can be maintained efficiently in agricultural landscapes, which is aided by precipitation and the movement of water across such landscapes. In particular runoff from rainwater can directly spread the pathogen from one site of contamination to more distal sites, thus contaminating soil patches and bodies of water that may be distant from the original mammalian source of contamination. Indeed, in areas of both low and high endemicity, local outbreaks often follow periods of extensive rain. If such periods of rainfall follow seasonal patterns, then outbreaks of leptospirosis may follow seasonal patterns as well. Moreover, the use of canals and irrigation channels of varying size and integrity, which is very common in agricultural settings all over the world, can further enhance the transport of these pathogens across the landscape. Thus, the spatial range of this pathogen is a function of the presence and movement of water in specific landscapes:<br />
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<b>Control and Prevention</b>. Control and prevention of leptospirosis begins by following the usual guidelines: improving water infrastructure and sanitation in resource poor areas. In most settings in the world where leptospirosis constitutes a significant disease burden, improved infrastructure that can maintain adequate water resources is a first priority in its prevention. In addition, however, specific features of agricultural landscapes, particularly those that channel and pool water can be designed and constructed to reduce the potential contamination from livestock, or from other sylvan hosts. Unfortunately, in most places of the world that experience a significant burden of disease, specific engineering techniques or raw materials for expensive irrigation systems, or controlled placement and dispersal of livestock, are generally not available because of their high cost and resource demand. This is particularly true of subsistence farmers.<br />
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In addition, individuals should avoid recreational activities in specific high-risk contexts, for example swimming in bodies of water likely to be contaminated with urine from livestock. </div>
Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com38tag:blogger.com,1999:blog-3492197469143963742.post-28894737022064341892013-05-22T13:36:00.001-04:002013-05-22T13:36:38.783-04:00Rabies<div dir="ltr" style="text-align: left;" trbidi="on">
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This time at Infection Landscapes we cover the "madness" disease. Rabies is a zoonotic disease that causes encephalitis and, if no vaccine is administered, almost always results in death. While human rabies infection is not common in the developed world, it is a significant cause of death in the developing world where the vast majority of infections are acquired from dogs. The name "rabies" comes from the Latin word for madness. This is an ancient disease having been documented for almost four thousand years. It has always been associated with rage and violence in the afflicted.<br />
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<b>The Pathogen</b>: Rabies is caused by the rabies virus, which is the type species for the Lyssavirus genus in the Rhabdoviridae family. Rabies virus is an enveloped, single-stranded negative-sense RNA virus with a helical capsid. The virus is approximately 75 nm in diameter and 180 nm long.<br />
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The primary target host cells are neurons. Each stage of the rabies virus infection cycle in the host cell is illustrated in the graphic below (<i style="font-size: small;">published in Lancet Infectious Diseases Volume 2, Issue 6, June 2002, Pages 327–343</i>).<br />
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The virus first gains the peripheral nervous system where it passes along axons in the periphery until it eventually gains the central nervous system, which is the primary site of pathogenesis. The graphic below depicts the pathogenic cycle in animal rabies (<i style="font-size: small;">published in Lancet Infectious Diseases Volume 2, Issue 6, June 2002, Pages 327–343</i>):<br />
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<b>The Disease</b>. Rabies is an extremely serious disease, which almost always results in death if infected individuals do not receive post-exposure prophylaxis before symtpoms begin to appear. The incubation period is highly varied and can range from several days to several years, however for most human infections symptoms typically appear between 2 and 12 weeks following infection. Initial symptoms are often vague and may be comprised of only fever and general flu-like illness. However, this progresses rapidly to include neurologic sequelae.<br />
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<b>There are two general forms of clinical rabies in both animals and humans: furious rabies, and paralytic rabies</b>. <i>Furious rabies occurs in approximately 70% of human rabies cases and presents first with a prodrome typified by feelings of great anxiety</i>. Other symptoms during this phase are non-specific and may include headache, myalgia, and fever. Following the prodrome, the neurologic phase progresses with intermittent agitation and aggressive behavior. Hydrophobia is a common symptom due to spasms of muscle structures in the neck. Increased saliva is also a prominent feature of the neurologic phase. Coma then develops in a short time, typically within a few days from the onset of this phase. Other autonomic abnormalities are common and can include pulmonary edema, blood pressure variability, and cardiac arrhythmia. Interestingly, there can also be differences in presentation based on whether the human infection was acquired from a dog or a bat, the latter being associated with seizures and hallucinations. <i>Paralytic rabies occurs in approximately 30% of humans rabies cases, and is much more difficult to identify and diagnose</i>. This form of disease is very similar in clinical appearance to Guillain-Barre syndrome with respect to encephalopathy, paralysis, and electrophysiological findings.<br />
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<b>Post exposure prophylaxis (PEP) is critical to administer to any individual suspected of having been inoculated with the rabies virus</b>. There are two primary components to PEP. <b>First</b>, the bite wound, or suspected point of entry, must be thoroughly cleaned using soap and water as soon as possible after exposure. This can help to reduce the number of virus particles that can gain entry into cells. Second, vaccination must be provided as soon as possible following exposure. Rabies is one of the very few infections for which effective immunization can be administered <i>after</i> the exposure. This is due to the extended period of time required for the virus particles to reach the CNS and initiate pathogenesis. As such, PEP can be administered during the incubation period to effectively block pathogenesis. However, while the incubation period is typically a few weeks, it can be as short as a few days for some individuals. As such, it is critical to begin PEP as soon as possible following the exposure. In addition, the number of virions introduced to the infected individual as well as the site of introduction are important determinants of the duration of the incubation period. For example, individuals with multiple or severe bite wounds will typically have a larger inoculum, and those with bites on the hands, face, neck, or head will have a shorter distance for virions to travel before reaching the CNS. In either scenario, the incubation period can be reduced substantially. Children are also at greater risk because they typically experience bites on the face and head more frequently than adults.<br />
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A course of tissue culture vaccine should be administered, however it takes 1 to 2 weeks to mount an adequate humoral immune response. As such, the necessary antibodies may not be available in time for individuals with short incubation periods. Therefore, in addition to the tissue culture vaccine, we rely first on passive immunity by administering antirabies immunoglobulin (RIG) in and around all bite wounds. The passive antibodies must be injected at the wound sites, not intramuscularly at some site distal to the wounds.<br />
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The document below states the specific recommendations of the Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention (CDC):<br />
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<span style="font-size: x-small;"><a href="http://www.docstoc.com/docs/44927978/Rabies%20Post-Exposure%20Prophylaxis%20Schedule%20(PDF)">Rabies Post-Exposure Prophylaxis Schedule (PDF)</a></span><br />
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The problem with PEP is that it is expensive and often not available at all, or in part, in those areas of the world with high endemicity of rabies in dogs, particularly South and Southeast Asia and Africa. Thus, even if a rabies exposure is well documented and identified prior to the onset of symptoms, often supplies are inadequate to administer complete and effective PEP. <br />
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<b>Epidemiology and the Landscape</b>. Rabies virus is shed in the
saliva of symptomatic hosts and, as such, contact transmission <b>via biting</b> is the primary route of infection. Rabies virus only infects mammals and, while all mammals are
susceptible to infection, certain mammal species are particularly important as
reservoir hosts and vectors for human infection. In particular, dogs, cats,
domestic livestock, and bats are important sources of rabies infection to
humans. Dogs are by the most important source of human infection, accounting
for the vast majority of human infections worldwide (however, almost all human rabies infections in the United States are due to contact with wild animals, particularly raccoons, skunks, and bats). <b>Areas with large populations of free
roaming stray dogs have the largest occurrence of rabies in humans</b>. <i>The single most important feature defining
the landscape of human rabies infection is the spatial range of stray dogs</i>.
This feature is definitive because the range of stray dogs always intersects or
is in union with the human social landscape in either its residential or
occupational components, or both. Moreover, the spatial range of stray dogs often is in contact with sylvan or peri-sylvan landscapes at its boundaries, thus maintaining
both the primary domestic rabies reservoir, through contact between dogs and
other sylvan mammals, and the human transmission cycle, through regular contact
between dogs and humans. The map below shows the important mammal reservoirs and vectors for rabies virus (<span style="font-size: x-small;"><i>published in Lancet Infectious Diseases Volume 2, Issue 6, June 2002, Pages 327–343</i></span>).</div>
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Rabies exists in almost every country and landmass on earth
with the exception of Antarctica and some remote islands. The
regions of South Asia and sub-Saharan Africa experience the vast majority of
human rabies each year, with India alone accounting for approximately 20,000 of
the total 55,000 annual rabies deaths. The map below produced by the World Health Organization (WHO) shows the global distribution of rabies infection risk for humans: </div>
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The transmission of rabies by bite from sylvan hosts to
domestic livestock is another important route of transmission that can result
in secondary transmission to human hosts. In addition, airborne transmission is a possible, but rare, route of infection that can occur if the saliva of an infected host becomes
aerosolized and is subsequently inhaled by a susceptible host. Such cases
have been documented among individuals exploring caves that harbor bats, or
among people with bats in the home who were not bitten. However, airborne
transmission of rabies is exceptionally rare, at least among documented cases,
so it is difficult to know exactly whether or not transmission to humans with
no history of a bat bite acquired an aerosolized infection or acquired the
infection through the typical biting route, but from a bite that was
imperceptible as a bite. Indeed, it is not uncommon to experience a bite from
some bat species and be unaware of the incident, especially if the bite was
acquired during sleep and is not in a conspicuous position on the body.</div>
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<b>Control and Prevention</b>. <i>Control of animal vectors is the
primary strategy for the prevention of rabies in humans</i>. This strategy
typically targets dogs, as these are the most important animal vector for
transmission to humans, and involves two intervention components. The first is
the management of stray dog populations to reduce numbers, which may entail
culling. The management of stray dog populations is critical because 1) it
reduces the reservoir population and the potential effective contacts between
stray dogs and humans, and 2) smaller, managed populations of dogs can be more
easily administered the second intervention component. The second component
consists of canine vaccination. <b>Rabies can be controlled in the canine population if 70% of dogs are vaccinated using inactivated virus vaccine</b>. Immunity lasts for approximately 3 years in the animals.</div>
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As mentioned above, in the developed world and in the United States in particular, almost all rabies infections are due to contact with wild animals. Therefore, the best prevention strategy for rabies in these areas is to avoid contact with wild animals. This is a good general practice for many reasons, but it also serves to remove the potential for rabies transmission between infected animals and humans. And we should remember that contact with wildlife is much more likely in an urban landscape than a sylvan landscape for most people. For example, there is a large raccoon population in Manhattan in the heart of New York City and many of these animals have tested positive for rabies. One should be especially wary of any animal that is exhibiting unusual, erratic, or aggressive behavior. If any contact with such an animal does occur, seek medical consultation.<br />
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<i><span style="font-size: x-small;">Photo by umbrooklynborn.blogspot.com</span></i></div>
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Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com60tag:blogger.com,1999:blog-3492197469143963742.post-2815227929350630792013-04-18T13:13:00.000-04:002013-04-18T13:13:48.938-04:00Tuberculosis<div dir="ltr" style="text-align: left;" trbidi="on">
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This time on Infection Landscapes we are going to cover one of the most significant infectious diseases to affect humans: tuberculosis. Tuberculosis is an ancient disease and is currently the world's second leading cause of death due to an infectious disease.<br />
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<b>The Pathogen</b>. Tuberculosis is caused by bacteria in the Mycobacteriaceae family. This family is comprised of many slow growing, acid-fast bacilli, most of which live in soil and water and help to degrade organic material. However, there are five species that are capable of causing tuberculosis in humans, and three of these are highly pathogenic. <i>Mycobacterium tuberculosis</i>, <i>M. africanum</i>, <i>M. bovis</i> are the three highly pathogenic agents capable of causing tuberculosis in humans. <i>M. tuberculosis</i> causes the vast majority of human tuberculosis worldwide.<br />
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<span style="font-size: x-small;"><i>Mycobacterium tuberculosis</i></span></div>
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<i>M. canettii</i> and <i>M. microti</i> are also capable of causing tuberculosis in humans but these are rare etiologic agents. This group of 5 closely related bacteria that cause tuberculosis in humans are referred to collectively as the Mycobacterium complex. Because of the primacy in human infection and the global burden of disease, this discussion will focus on infections with <i>M tuberculosis</i>.<br />
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<b>Mycobacteria are thin rod-shaped bacteria and are approximately 4µm by 0.3 µm in size</b>. These bacteria are strictly aerobic and have a high concentration of high molecular weight lipids in their cell wall. As a consequence, these organisms are hydrophobic and thus resistant to water-based bactericidal agents, as well as drying out, which is very important to the infectivity of <i>M. tuberculosis</i>.<br />
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<b>Mycobacteria are very slow growing in culture</b>, which can impede diagnosis for people with active tuberculosis. Mycobacteria require 4 to 6 weeks to grow on solid media, and 9 to 16 days using rapid liquid cultures.<br />
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<b>The target cells for <i>M. tuberculosis</i> are macrophages in the alveoli deep in the the lungs</b>.<br />
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<b>The Disease</b>. Infection with <i>M. tuberculosis</i> begins with latent infection that can progress to active disease. Latent tuberculosis infection (LTBI) is asymptomatic and does not constitute active disease. Most people with LTBI do not know they are infected. Following initial infection in most people, the immune system will contain and control the infection, but, typically does not eliminate the infection. Approximately 5% to 10% of individuals are not able to control the initial infection and will develop <b>primary tuberculosis</b>, while a large proportion of the the remaining 90% to 95% of individuals are left with LTBI. Among this large group of people, <i>M. tuberculosis</i> can remain dormant in macrophages and other cells for decades. The dormant myocbacteria will become active again in approximately 5% to 10% of those with LTBI as a result of various factors that can lead to reduced vigilance of the immune system. Active tuberculosis among this group is referred to as <b>reactivation tuberculosis</b>.<br />
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Clinical tuberculosis most often affects the lungs and respiratory tract. However, it can affect almost any organ system. Active tuberculosis can manifest as pulmonary or extrapulmonary disease irrespective of whether the individual is a primary or reactivation case. However, approximately 80% of clinically manifested tuberculosis is pulmonary among individuals with good immune function, while extrapulmonary tuberculosis can be seen more frequently in immunocompromised people. Pulmonary tuberculosis can be mild or severe and present with any of the following symptoms: coughing with or without blood in the sputum, fever, night sweats, chills, weight loss, anorexia, fatigue, and chest pain. Extrapulmonary disease can also present with fever, fatigue, night sweats, and wasting, but prominent symptoms will typically stem from the affected organ system. Extrapulmonary tuberculosis will commonly involve the pericardium, genitourinary tract, gastrointestinal tract, vertebrae of the spine and other bones of the skeleton, the meninges, adrenal glands, lymph nodes, eyes, and skin. The figure below depicts common symptoms of different tuberculosis classifications by anatomical site. It shows how some symptoms are common across different classifications while others are specific to a particular classification of tuberculosis.<br />
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Systemic tuberculosis occurs when <i>M. tuberculosis</i> is disseminated throughout the body by way of the blood or lymph, with small lesions appearing in most organ systems. Disseminated tuberculosis was originally called miliary tuberculosis because the lesions appeared as grains of millet. When it does occur, miliary tuberculosis is more common in children and in immunocompromised people.<br />
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<b>The Epidemiology and the Landscape</b>. <i>Mycobacterium tuberculosis</i> is spread primarily by airborne transmission. People with LTBI do not transmit infection to others. People with <b>active pulmonary tuberculosis</b> release very small droplets into the air when they cough, talk, or sing. As these droplets evaporate in the air, the remaining droplet nuclei are comprised of the solid components of the mucous and, potentially, <i>M. tuberculosis</i>, which is capable of infecting a new host. <i>M. tuberculosis</i> is only moderately infectious as transmission occurs in only 20% to 30% of individuals exposed to someone with active tuberculosis. However, this is an average estimate, whereas any specific infection will depend on <i>effective contact</i> between an infected case and susceptible persons, which varies greatly by factors such as the immunocompetence of the susceptible host, frequency and intimacy of contact between infected and susceptible individuals, severity of disease in the infected individual, and housing, working, and other social conditions.<br />
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<i>M. tuberculosis</i> can also be transmitted by way of the gut, genitourinary tract, and eye, or through compromised skin. Transmission via these extrapulmonary, non-airborne, routes is relatively rare, but is more common in areas of high endemicity. Nevertheless, airborne transmission is still the most frequent route of infection across the world. The graphic below (<i><span style="font-size: x-small;">published in Chest. 2012;142(3):761-773. doi:10.1378/chest.12-0142</span></i>) presents a nice summary of the transmission and natural history of <i>M. tuberculosis</i>.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgG1LikPbxG5eDWACTTVTl8rCYs8e7RynFMiLjIhFkH4TRWKVZ49tkqHSQJWIp4I2d9VMqOuqPPRN1Z_8CbcLr3SU2H_dRkySQhXtwUNjzDE1T_3fzi1F6fMoDUnBAHZEALW_pwPTL8isc/s1600/tuberculosis_propogation.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgG1LikPbxG5eDWACTTVTl8rCYs8e7RynFMiLjIhFkH4TRWKVZ49tkqHSQJWIp4I2d9VMqOuqPPRN1Z_8CbcLr3SU2H_dRkySQhXtwUNjzDE1T_3fzi1F6fMoDUnBAHZEALW_pwPTL8isc/s640/tuberculosis_propogation.png" width="560" /></a></div>
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<b>Approximately one third of the population of the world is infected with <i>M. tuberculosis</i></b>. That sentence is worth a pause to consider its magnitude. While many of these are latent infections and thus do not represent active tuberculosis cases, <i>they do represent an incredibly large pool of infection from which an extremely large number of active cases emerge on an annual basis</i>. As a result, there are approximately 1.8 million deaths due to tuberculosis across the world each year. Globally, this is the second leading cause of death due to an infectious disease. The global distribution of tuberculosis incidence is depicted in the map below produced by the World Health Organization (WHO):<br />
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Of all WHO global regions, The Southeast Asia region has the largest absolute number of cases, while the Africa region has the highest incidence density. Together, the WHO Southeast Asia and Africa regions account for almost 70% of the world's active tuberculosis cases. In some areas of these regions 60% to 70% of the adult population is latently infected with <i>M. tuberculosis</i>. <br />
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The natural history of tuberculosis directly affects its propagation through a population. <b>Stage 1</b>: In a given population in a particular period of time, the pathogen's reservoir is comprised of all those people with LTBI. <b>Stage 2</b>: Each year some proportion of these individuals with LTBI develop reactivation tuberculosis. <b>Stage 3</b>: New infections occur when the individuals with active disease transmit <i>M. tuberculosis</i> to their susceptible contacts. An average of 10 contacts are infected before the infectious individual is treated with anti-tuberculosis medication and further transmission is arrested. <b>Stage 4</b>: Five to ten percent of the newly infected contacts (the secondary infections) will develop primary tuberculosis, and then will transmit new infections to their contacts (<b>Stage 3</b>). Most of the remaining newly infected retain LTBI and replenish the pathogen reservoir (<b>Stage 1</b>).<br />
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Perhaps the most important feature of the epidemiology of tuberculosis emerges at a critical point where the social and physical landscapes converge: the structure of population density. Overcrowding is a defining feature of areas of high tuberculosis endemicity. As described above, ongoing close contact between active cases and susceptible individuals is necessary to maintain endemicity in a population. Moreover, housing conditions characterized by a lack of quality materials and very dense construction are typically the same conditions that characterize poor ventilation in the home and extended close contact between members of the household as well as neighbors. This landscape epidemiology defines areas wherein <i>M. tuberculosis</i> can be easily transmitted and propagate through a population, even for an organism that is not necessarily highly transmissible.<br />
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It is also important to note that co-infection with the human immunodeficiency virus (HIV) is probably the most significant risk factor for developing active tuberculosis once infected with <i>M. tuberculosis</i>. The risk of reactivation tuberculosis ranges from 3% to 14% <i>per year</i>, and averages 10% per year, among individuals who had LTBI prior to their infection with HIV. Forty percent of new <i>M. tuberculosis</i> infections among individuals already infected with HIV will develop primary active tuberculosis (compared to 5% to 10% of new infections among those not infected with HIV). Tuberculosis is now the leading opportunistic infection associated with HIV infection in most areas of the developing world.<br />
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<b>Treatment</b>. Treating tuberculosis requires a long-term commitment. Specifically, at least 6 months of treatment are required because of the heterogeneous population of <i>M. tuberculosis</i> in an infected individual, which is comprised of active and dormant organisms. Medication that is effective against active mycobacteria may not be against latent mycobacteria and, thus, extended treatment ensures that the whole population of <i>M. tuberculosis</i> will eventually be exposed to the drug. However, undergoing treatment over a long time period also favors the emergence of drug-resistance gene mutations in the <i>M. tuberculosis</i> population. Thus, <b>at least two effective drugs must be administered</b>: this reduces the probability of developing drug-resistant bacilli. Adherence to treatment with the full regimen is essential for treatment success. Non-adherence can lead to treatment failure in the individual as well as the development of antibiotic resistant forms of <i>M. tuberculosis</i>. To effect complete resolution of infection in the individual and mitigate the spread of antibiotic resistance in the population, WHO recommends the short-course of directly observed therapy (DOTS) regimen, comprised of four drugs (typically isoniazid, rifampicin, pyrazinamide, and ethambutol) for two months, followed by two drugs (typically isoniazid and rifampicin) for four months. Directly observed therapy requires that a health care worker must monitor each tuberculosis patient closely and observe the patient take each dose of anti-tuberculosis medication.<br />
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Nevertheless, antibiotic resistance has been a difficult ongoing problem for many years and has now reached a point of crisis, whereby some strains of <i>M. tuberculosis</i> are resistant to at least two of the first-line, and most powerful, drugs (isoniazid and rifampicin). Disease caused by these strains is known as multi-drug resistant tuberculosis (MDR-TB). Worse still, other strains have developed even more extensive resistance as a result of the inadequate and under-resourced management of MDR-TB in many regions of the world. These strains are also resistant to isoniazid and rifampicin, as well as at least one of the quinolones and at least one of the second-line drugs kanamycin, capreomycin, or amikacin. Disease caused by these strains is known as extensively drug resistant tuberculosis (XDR-TB).<br />
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<b>Control and Prevention</b>. There are several critical factors that need to be implemented to realize an effective tuberculosis control and prevention program. <b>First</b>, rigorous case finding and treatment is obviously critical to save the individual as well as to stop transmission of infection to contacts. Case identification must combine microscopy and clinical symptoms, and treatment should be comprised of the short-course of directly observed therapy (DOTS). <b>Second</b>, exhaustive contact tracing for contacts of each active tuberculosis case should be carried out in the field so that new infections can be identified and treated before becoming active cases. <b>Third</b>, a good surveillance system is fundamental to the control of any infectious disease. An administrative system for recording cases and monitoring outcomes is necessary to estimate the occurrence of disease and identify temporal trends and spatial clusters. Furthermore, good surveillance instruments combined with molecular epidemiology are also necessary to monitor antibiotic resistance in <i>M. tuberculosis</i>. <b>Fourth</b>, an adequate supply of tuberculosis medications must be available to populations with endemic tuberculosis. This may seem obvious, and it is, but unfortunately the lack of a consistent supply of medication has hampered many control programs particularly in poor areas of the developing world. <b>Fifth</b>, there must be a government commitment to tuberculosis control. Significant resources and public health infrastructure and personnel are required to implement and sustain tuberculosis control programs, and sustainability is critical because control of this disease requires a long-term effort. As such, a strong commitment by government agencies, which can mobilize the necessary resources and infrastructure, is essential to regional control of tuberculosis.<br />
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Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com61tag:blogger.com,1999:blog-3492197469143963742.post-26298196259863189402013-03-20T14:21:00.001-04:002013-10-09T12:37:15.919-04:00Influenza<div dir="ltr" style="text-align: left;" trbidi="on">
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This week at Infection Landscapes we will cover influenza, one of the most significant respiratory diseases to affect humans, and which does so on an annual basis. Influenza causes substantial morbidity and mortality each year in both the developing and developed world.<br />
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The name "influenza" is derived from the Italian word for <i>influence</i> because, centuries ago, it was believed that this disease occurred as a result of the influence of the movement of the sun and the stars given its seasonal nature.<br />
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<b>The Pathogen</b>. Influenza is caused by one of three genera of influenza viruses in the Orthomyxoviridae family: influenza A, influenza B, and influenza C. Of these three, influenza A is the most virulent and thus is responsible for the greatest burden of disease. As such, most of this discussion will focus on influenza A.<br />
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<b>Influenza A viruses are enveloped and have an RNA genome in 8 segments</b>. The genome is single stranded and negative sense, and is enclosed in a helical capsid:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhjijStBkmKciRCLyiDyE7Oo7bwDZXupkpdSZi2mIR1ZGcMe2Ii2fKY7XFZU-LLQ6Pb3LL9HE7ZLqbyyDKh8cYbkv1VCWPHqx0qBF5IRw8EYYtueJv41W4MwotFQVy3kWsrX-svMTXEq-M/s1600/Influenza_virus_3D.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhjijStBkmKciRCLyiDyE7Oo7bwDZXupkpdSZi2mIR1ZGcMe2Ii2fKY7XFZU-LLQ6Pb3LL9HE7ZLqbyyDKh8cYbkv1VCWPHqx0qBF5IRw8EYYtueJv41W4MwotFQVy3kWsrX-svMTXEq-M/s400/Influenza_virus_3D.png" width="400" /></a></div>
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<b>Hemagglutinin (HA) and neuraminidase (NA) are important surface glycoproteins that facilitate virion entry into and exit from the host cell</b>. As such, these surface structures are key features of virus infectivity and pathogenicity. HA functions as the attachment glycoprotein to the cellular receptor, sialic acid, on columnar epithelial cells of the respiratory tract. Thus, HA specificity for receptor binding is a determinant of which species can be infected, i.e. the host range, which will be discussed in more detail later. Specific antibodies to HA epitopes prevent attachment and entry of the influenza virus particle into the host cells, and are thus an important aspect of immune protection against infection. NA cleaves sialic acid residues to allow virus particle release from the host epithelial cell. It is suspected that specific anti-NA antibodies diminish the release of new virions from host cells, thus curtailing an infection. The infection cycle of the virus in the host cell is very nicely depicted in the graph below published by Influenza Report:</div>
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The animated video below also provides a nice depiction of the infectivity, pathogenicity, and immunogenicity of influenza A. </div>
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Antigenic variation is very important to influenza A evolution, particularly as this relates to the annual epidemics and multidecadal pandemics experienced by humans. Before talking more specifically about these two phenomena, it will be helpful to highlight two features of the molecular biology of the virus that are particularly important to its rate of genetic change. First, the genome is comprised of RNA molecules. Many such RNA viruses, including influenza A, exhibit low fidelity and, thus, a high rate of mutation because they lack the proofreading provided by DNA polymerase, which is a necessary enzyme for DNA virus assembly. Second, the genome of influenza A virus is segmented, which further contributes to the high rate of genomic change because the genes encoded on particular segments of one genome can more easily be exchanged with segments of other influenza A genomes from multiple virus particles that happen to infect the same host cell.</div>
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<b>There are two fundamental evolutionary genetic processes at play in the antigenic properties of influenza A virus</b>. <i><u>The first is antigenic drift</u></i>. Antigenic drift defines the minor yet frequent genetic changes in the HA and NA surface antigens that occur on an annual or near-annual basis. Antigenic drift leads to approximately 1% change in the HA antigen per year. <b>This rate of mutation is the leading force driving the annual epidemics experienced every year around the world during the regular influenza season</b>. However, there is a second, equally important, process involved. <i><u>The second is antigenic shift</u></i>. Major changes in the amino acid composition for the HA or NA surface antigens, or both, can lead to a new viral subtype. These new subtypes will present (in most instances) to a completely immunologically naive population wherein everyone, or nearly everyone, is susceptible to infection. It is believed that after several decades (typically between 10 and 30 years) of circulation of a specific influenza A subtype, most members of the population will have antibody to that subtype. This accumulated population immunity places selective pressure on the virus and leads to new shift variants that emerge by way of reassortment. The new subtypes lead to pandemic influenza events.</div>
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The patterns of transmission during the annual epidemics that correspond to antigenic drift, and the multidecadal pandemics that correspond to antigenic shift will be described later in the epidemiology section.</div>
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<b>The Disease</b>. Clinical disease typically presents with abrupt onset of fever and respiratory symptoms, including cough, rhinorrhea and sore throat. Malaise and prostration are very common. Myalgia and headache are more common with influenza than with other respiratory infections. In addition, gastrointestinal symptoms are not common in adults, but 50% of infant and child infections may have vomiting, abdominal pain and diarrhea. However, none of these symptoms are definitive for influenza infection. Only cell culture demonstrating influenza A virus can distinguish influenza from other agents causing respiratory infection, such as a rhinovirus (a frequent source of the "common cold"). Nevertheless, influenza infection is on average associated with more severe disease than the pathogens responsible for the common cold. Symptomatic disease usually lasts 3 to 5 days, but complications can prolong the illness.</div>
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The complications associated with influenza make the infection particularly dangerous, especially for infants, the elderly, and individuals who are immunocompromised. Some individuals can develop primary viral pneumonia, which frequently can be fatal. However, primary viral pneumonia is not very common. Secondary bacterial pneumonia is much more common, particularly among the susceptible groups mentioned above, and can occur up to two weeks after the acute viral infection. In infants and children, otitis media and croup are common complications. Myocarditis, myositis and encephalitis are less frequent complications.</div>
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<b>The Epidemiology and the Landscape</b>. Influenza A virus is spread via droplet, airborne and contact transmission, with droplet transmission probably serving as the most important during seasonal transmission. The overall attack rate in large populations is typically between 10% to 20% during the annual epidemics (seasonal flu), however some subpopulations or local outbreaks can have attack rates approaching 40%. These higher attack rates usually occur in children and, as such, they play a critical role in the spread of influenza in communities during the annual epidemics. Indeed, schools and/or daycare centers will often serve as the primary loci of infection transmission during these epidemics. This is reflected in the typical peak incidence of infection occurring in young school age children prior to the peak in any other age group. The annual global incidence of influenza is unknown given the extreme difficulty in recording and classifying respiratory infections that do not result in hospitalization in most parts of the world. However, the annual global mortality attributable to influenza is estimated to be between 250,000 and 500,000 deaths. In the United States, the annual incidence is estimated to be between 35 and 50 million cases, with between 200,000 and 250,000 hospitalizations and 36,000 deaths.<br />
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<span style="font-size: x-small;"><i>The prevalence of influenza in a single simulation of the United States 100 days after the start of an influenza epidemic with <span style="font-family: Calibri, sans-serif; line-height: 16.363636016845703px;">R</span><sub style="font-family: Calibri, sans-serif; line-height: 15.454545021057129px;">0</sub>=1.6. The color of each dot corresponds to the illness prevalence in a census tract.</i></span></div>
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The above map (published in<i> <span style="font-size: x-small;">PLoS Comput Biol 6(1): e1000656. doi:10.1371/journal.pcbi.1000656</span></i>) simulates the typical distribution of prevalent influenza cases in the US once the seasonal epidemic has begun, given that each infectious case will, on average, lead to more than one new infectious case in a completely susceptible population (<span style="font-family: Calibri, sans-serif; font-size: 11pt; line-height: 115%;">R</span><sub style="font-family: Calibri, sans-serif; line-height: 115%;">0</sub>=1.6). <b>The map demonstrates the high level of transmission, as well as the potential need for the mobilization of resources, in urban areas</b>.<br />
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<b>Seasonal, or epidemic, influenza follows a annual, roughly predictable, pattern each year in the temperate regions of the northern and southern hemispheres</b>. In the southern hemisphere, epidemics usually occur in the May to September winter season, while in the northern hemisphere they occur from October to May. For example, in China, Europe, and North America, the epidemic peak(s) usually occurs between November and March: manifested first by high rates of school and industrial absenteeism, followed by an increase in visits to health care facilities, an increase in pneumonia and influenza hospital admissions, and finally an increase in deaths from pneumonia or influenza. In any specific locality, epidemic influenza often begins abruptly, reaches a peak within three weeks, and usually ends by 8 weeks. A given region can also experience 2 epidemic peaks with different virus strains, either in sequence or with overlap. In tropical climates influenza can occur in seasonal epidemics, often during the monsoon or rainy seasons, or endemic transmission can occur throughout the year. The former tropical pattern may suggest that, in these areas of high humidity, powerful climatic forces such as a monsoon may cause people to spend more time indoors in close proximity to each other and thus facilitate spread of disease. Regardless of the time of year, geography, or climate, epidemic influenza occurs because of antigenic drift, i.e. the slow incremental changes that accrue in the viral genome by way of mutation as described above.<br />
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<b>Pandemic influenza does not occur in a regular predictable pattern each year, but rather occurs only periodically over the course of decades and can be much more severe because all or a large proportion of the the population is immunologically naive and clinically susceptible to the new emerging virus</b>. These are the antigenic shift events, i.e. widespread global infection following those changes in the viral genome that are due to reassortment. Over the course of the last one hundred years, 5 such shift events have occurred that have lead to 5 subsequent pandemics. The most devastating of these was the 1918 shift to the H1N1 subtype, which resulted in the death of approximately 50 million people worldwide. In 1957, influenza A shifted from the H1N1 to the H2N2 subtype, but with a much lower global burden of disease than the previous 1918 pandemic. In 1968, influenza A H2N2 was replaced by influenza A H3N2, which circulated for the next decade until, in 1977, the influenza A H1N1 subtype re-emerged. This re-emergence was associated with very high attack rates (~50%) in individuals born after 1956 as they had not been exposed because the H1N1 subtype had been replaced by the H2N2 subtype in 1957. For the next three decades, from 1977 until 2009, the re-emerged H1N1 and H3N2 subtypes co-circulated in the population causing the annual influenza epidemics each year. Then, in 2009, a new influenza A H1N1 subtype emerged in Mexico and subsequently replaced the earlier H1N1 subtype. This most recent pandemic in 2009 did not cause the extensive morbidity and mortality that was feared at the beginning of the outbreaks in North America. Overall, morbidity and mortality were lower than in previous pandemics. It is believed that this may have been due in part to the reduced morbidity and mortality among people over the age of 65 years. Nevertheless, there was substantive morbidity and mortality associated with this pandemic and it followed atypical patterns. For example, the vast majority of deaths (~96%) occurred in people under the age of 65, whereas the majority of deaths (~90%) occur in people over the age of 65 during seasonal influenza epidemics. Moreover, the number of deaths due to influenza in children was 4 times greater during the 2009 pandemic than what it is during seasonal influenza epidemics. <br />
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<b>It is important to discuss the ecologic relationship between human epidemic influenza and pandemic influenza</b>. To begin, there are strains of influenza A virus that infect humans, there are strains that infect birds, and there are strains that infect pigs. Nevertheless, all influenza A viruses circulating today are evolutionarily derived from bird influenza A. Birds, and in particular waterfowl, are the natural primary reservoir host for all current circulating bird inlfuenza A. These birds are also, either directly or indirectly via another intermediate host (generally pigs), the historic reservoir for all influenza A that subsequently adapted to other animals. New subtypes of human influenza A typically emerge when the genome of a current circulating human influenza A subtype reassorts with the genome of a subtype of current circulating bird influenza A or the genome of a subtype of current circulating pig influenza A. Pigs can harbor infection with several influenza subtypes because they have the epithelial cell receptors for both bird and human HA. As such, pigs are considered important "mixing vessel" hosts for reassortment events. However, in order for a new human subtype to become a pandemic virus it must 1) be new to a relatively large proportion of the population; i.e. the global population must be relatively immunologically naive to the new subtype, 2) it must be able to replicate and cause disease in humans, and 3) it must be easily transmissible between humans. The last point is particularly important as the new subtype will not become a human inlfuenza A subtype if it cannot be transmitted between people, even if human infection is possible zoonotically. Infection with the highly pathogenic avian influenza A H5N1 (commonly referred to as bird flu) exemplifies this. This is a bird inlfuenza A subtype, not a human inlfuenza A subtype. While this bird subtype is capable of infecting and causing severe disease in some humans, it is not currently capable of causing a pandemic because it cannot be transmitted efficiently from person to person. The graphic below produced by the National Institute of Allergy and Infectious Diseases nicely depicts the species and transmission pathways that can lead to antigenic shift in the influenza A virus and subsequent pandemics.</div>
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The mixing of different influenza A subtypes from different animal species is central to producing new and potentially dangerous subtypes that can result in new human influenza A, which can subsequently lead to new pandemics. Moreover, the nature of such genetic exchange makes the elimination of human influenza A virtually impossible. There are two primary landscapes that converge to optimize reassortment of influenza A subtypes: 1) the sylvan landscapes and migratory paths of waterfowl and, 2) the agricultural lands and markets, both subsistence and industrial, of humans. The spaces where these converge are places where sylvan birds can come into contact with domestic birds (e.g. chickens), which may also be in direct contact with pigs. As such, these landscapes can be important sources of diverse influenza A subtype circulation among multiple hosts and may serve as important sources of human exposure.<br />
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<b>Control and Prevention</b>. There are four important tactics that have demonstrated effectiveness in either preventing infection or mitigating the effects of an active infection. The <b>first</b> is very simple: <i>regular hand washing during the flu season</i>. This certainly need not be obsessive, but the regular practice of washing your hands with regular bar soap (NOT antibacterial soaps or hand sanitizers, which can be harmful to our microbiome) after returning home from populated public spaces during flu season makes good sense. The <b>second</b> is even more simple, though rarely followed: <i>stay home when sick</i>. The likelihood of transmitting influenza virus to susceptible people is quite high during illness. In addition, given that influenza virus is typically more virulent than many of the respiratory pathogens associated with the common cold, an infected individual requires significant rest to convalesce. As such, going in to work or school during a respiratory illness can be dangerous both to oneself and one's peers. <b>Third</b>, <i>the use of antiviral drugs can be used to reduce the duration of symptoms among infected individuals and may help prevent transmission to their susceptible contacts</i>. There are two classes of these drugs: the neuraminidase inhibitors, oseltamivir and zanamivir, and the M2 inhibitors, amantadine and rimantadine. The neuraminidase inhibitors block the release of new virions from the surface of infected host cells. The M2 inhibitors block the release of viral RNA into the host cell after the virion has entered the cell. The <b>fourth</b> <i>important measure of control and prevention is vaccination</i>.<br />
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<b>The previous discussion of antigenic drift highlighted the importance of influenza virus mutability</b>. This requires that a new vaccine is produced each year because the vaccines stimulate an immune response that targets those same components of HA and NA antigens whose genes are subject to the high rate of mutation. The process of having to renew vaccine production with new strains of virus on an annual basis has made achieving a consistently high level of vaccine effectiveness difficult. Nevertheless, it is currently the best we have and the vaccine effectiveness is not negligible.<br />
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<b>There are two types of vaccine: an inactivated vaccine (the injection) and a "live" attenuated vaccine (nasal spray)</b>. <i>Neither of these vaccines are capable of causing influenza</i>. The overall vaccine effectiveness for the inactivated vaccine against seasonal influenza based on recent meta-analyses is approximately 60% (the "live" vaccine seems to have a higher effectiveness, however the data are much more limited because so much less of the this vaccine is produced). While this is certainly not ideal, it still does provide a level of protection that can have some important implications. <b>First</b>, specific subpopulations, such as school children, can be very important for targeted vaccination as these are typically the loci of epidemic transmission and community dissemination of seasonal influenza. Moreover, there is evidence that the vaccine effectiveness is markedly better in children. Blocking transmission in this setting, even with imperfect effectiveness, can have important implications for the epidemic curves of localized outbreaks, as well as the national incidence of severe illness and hospitalizations and deaths. <b>Second</b>, the vaccine, even when it does not prevent infection for a given individual, can still mitigate the severity of that infection. As such, the people who are vaccinated and do get infected still benefit from protection because they will generally experience illness that is less severe than those who were not vaccinated. And, as discussed above, the problem with influenza is the potential for developing complications when illness is severe. <b>Third</b>, there are subgroups in the population who are at particularly high risk for influenza infection. These are infants and small children, the elderly, and immunocompromised people. By getting vaccinated, we significantly reduce the risk of transmitting what could be a deadly infection to these high risk people by either preventing the infection in ourselves, or by limiting the severity of disease we experience if we do get infected and thus our transmissibility to others. If you are wondering whether or not the influenza vaccine is for you just read through the infographic below by TeleVox:<br />
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<img alt="Do I Need A Flu Vaccination?" class="visually_embed_infographic" rel="http://thumbnails.visually.netdna-cdn.com/do-i-need-a-flu-vaccination_50b62cbad2a47.jpg" src="http://thumbnails.visually.netdna-cdn.com/do-i-need-a-flu-vaccination_50b62cbad2a47_w587.jpg" />
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One caveat is that both inactivated and live attenuated vaccines use chicken eggs in their production and so both would be contraindicated for anyone with severe allergies to egg proteins. This caveat should soon be eliminated, however, as the US Food and Drug Administration has just recently approved the first cell-cultured vaccine.</div>
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Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com41tag:blogger.com,1999:blog-3492197469143963742.post-17998536467079926052013-02-13T12:12:00.000-05:002013-02-13T12:12:08.932-05:00American Hemorrhagic Fevers<div dir="ltr" style="text-align: left;" trbidi="on">
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This week we cover the American hemorrhagic fevers, which are a group of hemorrhagic fevers occurring primarily in different parts of South America. These are all caused by arenaviruses and will constitute the final installment of the extended series on hemorrhagic fevers.<br />
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<b>The Pathogen</b>. We are going to focus on the four major American hemorrhagic fevers (AHF): Bolivian hemorrhagic fever (BoHF), Argentinian hemorrhagic fever (ArHF), Venezuelan hemorrhagic fever (VHF), and Brazilian hemorrhagic fever (BrHF). BoHF is caused by Machupo virus, ArHF is caused by Junin virus, VHF is caused by Guanarito virus, and BrHF is caused by Sabia virus. All of these viruses are members of the Tacaribe (New World) serocomplex in the Arenaviridae family. They are enveloped viruses approximately 110 to 130 nanometers in diameter with single-stranded, ambisense RNA genomes in two segments:<br />
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<b>Macrophages are the primary target cells for these AHF-causing arenaviruses</b>. A membrane-bound glycoprotein (GP1) binds to the host receptor, and the virus enters the cell by endocytosis. Replication occurs in the cytoplasm of the host cell.<br />
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<b>There is typically strong upregulation of pro-inflammatory cytokines and altered coagulation</b> following dramatic increases in thrombopoietin and decreases in erythropoietin. Unlike some other hemorrhagic fevers, the endothelium typically experiences only minor damage in AHF.<br />
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<b>The Reservoir</b>. Rodents are the natural reservoirs for each of the viruses causing the four AHF. The reservoir for Machupo virus is <i>Calomys callosus</i>, commonly known as the large vesper mouse:<br />
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<span style="text-align: left;"><i><span style="font-size: x-small;">Calomys callosus</span></i></span></div>
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There are several important reservoirs for Junin virus. These are <i>Calomys musculinus</i> (drylands vesper mouse), <i>Calomys laucha</i> (small vesper mouse). <i>Akodon azarae</i> (Azara's grass mouse), and <i>Mus musculus</i> (house mouse).<br />
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<i style="text-align: left;"><span style="font-size: x-small;">Calomys musculinus</span></i></div>
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The reservoirs for Guanarito virus are <i>Zygodontomys brevicauda</i>, the cane mouse, and <i>Sigmodon alstoni</i>, the cotton rat:<br />
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<i style="text-align: left;"><span style="font-size: x-small;">Zygodontomys brevicauda</span></i></div>
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<i style="text-align: left;"><span style="font-size: x-small;">Sigmodon alstoni</span></i></div>
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The reservoir for Sabia virus is currently unknown but is strongly suspected to be another rodent species.<br />
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<b>The Disease</b>. The four AHF discussed here are similar to each other in presentation. Early symptoms include fever, headache, fatigue, myalgia, pharyngitis, and lymphadenopathy. Petechial and erythematous rash, vomiting and diarrhea are also common and can present early or late. Vascular complications begin to emerge later in the disease course. Thrombocytopenia can be extensive and typically leads to focal hemorrhage and potential necrosis in several organs systems, with the liver and spleen commonly affected. Bleeding from the nose and gums and hematemesis can be common later in the disease course, and gastrointestinal bleeding can be quite severe. Low blood pressure due to extensive bleeding and increased vascular permeability and subsequent leakage can lead to shock. Pulmonary, renal, and neurologic complications can also present. These can include pneumonia following pulmonary edema and secondary bacterial infection, frank proteinuria, and tremor, ataxia, convulsions, and coma. Recovery begins 1 to 2 weeks after the onset of symptoms and may require a month of convalescence. Those who recover do not typically suffer chronic disability. Nevertheless, the mortality attributable to AHF can be quite high. The mortality associated with BoHF is approximately 30%; ArHF ranges between 25% and 35%; VHF is approximately 34%; and BrHF is 33%, though this last estimate is based on very few cases.<br />
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<b>The Epidemiology and the Landscape</b>. The primary mode of transmission for the Tacaribe serocomplex is from infected rodents to humans via the airborne route. The virus is shed in the stool, urine, and saliva of the rodent reservoirs. As the excreta dry out, the virus remains viable in dust. If the the dust is disturbed, particularly by human activity, the virus particles can be inhaled as they are introduced into the air. Transmission through a common vehicle, such as contaminated food, has been documented for BoHF, but is not common. Person to person transmission is also possible for BoHF, but has not been documented for the other AHF. As such, nosocomial infection can be an important source of additional cases of BoHF particularly in an outbreak setting.<br />
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Most cases of AHF occur in rural settings in either agricultural landscapes or at the intersection of agricultural and residential landscapes. These spaces are most clearly delineated in ArHF, which follows a clear seasonal transmission cycle corresponding to the autumnal corn harvest in landscapes intersected by human maize agriculture and the drylands vesper mouse habitat. While there are several reservoir species for ArHF, the drylands vesper mouse is the most important for transmission to humans because of its extensive exploitation of agriculturally modified landscapes. Venezuelan HF also occupies a similar landscape at the intersection of cane and cotton agriculture and cane mouse and cotton rat habitats, respectively, across five states of the central plains in Venezuela. The physical processes of harvesting, whether manual or automated, are directly relevant to transmission as these create large amounts of dust, which can contain the dried excreta of infected rodent reservoirs and subsequently enter the respiratory tract of the agricultural laborers.<br />
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Transmission of virus for all AHF also can occur commonly in the home, particularly among agricultural communities where residential spaces may overlap or exist in close proximity to subsistence farming spaces. In these latter landscapes, some reservoir rodents may occupy both the agricultural and residential spaces.<br />
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<span style="font-family: inherit;"><b style="background-color: #fefdfa; line-height: 16.363636016845703px;">Control and Prevention</b><span style="background-color: #fefdfa; line-height: 16.363636016845703px;">. Because the reservoir host is ubiquitous in endemic areas, elimination of the reservoir is not possible</span><i style="background-color: #fefdfa; line-height: 16.363636016845703px;">. However, rodent control is still an important strategy to control human infection with the Machupo, Junin, Guanarito, and Sabia viruses</i><span style="background-color: #fefdfa; line-height: 16.363636016845703px;">. Taking precautions to eliminate safe spaces for rodents in the home or other structures of human habitation or occupation can reduce effective human to rodent contact and thus block this important mode of transmission.</span><br style="background-color: #fefdfa; line-height: 16.363636016845703px;" /><br style="background-color: #fefdfa; line-height: 16.363636016845703px;" /><b style="background-color: #fefdfa; line-height: 16.363636016845703px;">In order to eliminate safe spaces for mice the following steps can be employed</b><span style="background-color: #fefdfa; line-height: 16.363636016845703px;">:</span><br style="background-color: #fefdfa; line-height: 16.363636016845703px;" /><br style="background-color: #fefdfa; line-height: 16.363636016845703px;" /><b style="background-color: #fefdfa; line-height: 16.363636016845703px;">Remove all food sources</b><span style="background-color: #fefdfa; line-height: 16.363636016845703px;">: Food and garbage should always be kept in </span><b style="background-color: #fefdfa; line-height: 16.363636016845703px;">well-sealed containers</b><span style="background-color: #fefdfa; line-height: 16.363636016845703px;"> that cannot be breached by rodents. In addition, pet food and/or garden fruit and vegetables left unattended outside will often attract rodents.</span><br style="background-color: #fefdfa; line-height: 16.363636016845703px;" /><br style="background-color: #fefdfa; line-height: 16.363636016845703px;" /><b style="background-color: #fefdfa; line-height: 16.363636016845703px;">Household maintenance</b><span style="background-color: #fefdfa; line-height: 16.363636016845703px;">: Good maintenance both inside and outside the home can be very important in eliminating rodent habitat. On the outside, overgrown plants and shrubs, unattended woodpiles or debris, and unattended outdoor structures can all serve as welcome homes for rodents, and should be regularly maintained. On the inside, poorly sealed foundations, roofing, vents, and other household structures can provide easy access to the interior of the house and thus provide good rodent habitat. As such, it is very important to maintain good structural integrity of the house to keep the rodents out.</span></span><br />
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<span style="font-family: inherit;"><b>Occupational exposure</b>: Given the particular risk associated with occupational exposure in the agricultural setting, providing personal protective equipment for workers may mitigate exposure and reduce infections. For example, the use of fitted respirators may effectively block the inhalation of infectious virions as dust is generated during farm work. Nevertheless, there are little data providing solid evidence that the respirators reduce the incidence of AHF and, moreover, such protective equipment may be cost prohibitive especially among subsistence farmers. </span><br />
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<span style="font-family: inherit;"><b>Candid #1 Vaccine</b>: This vaccine was developed to prevent ArHF. It is a live attenuated vaccine based on the XJ strain of the Junin virus. It has demonstrated remarkably high efficacy, ranging between 95% and 98% with good long-term (9-10 years) immunity. The vaccine is also cross-protective against BoHF. While this vaccine has demonstrated good protection, there can still be disparities in accessibility, with poorer individuals living and working in more remote areas of Argentina missing opportunities for vaccination. <br style="background-color: #fefdfa;" /><br style="background-color: #fefdfa; line-height: 16.363636016845703px;" /><span style="background-color: #fefdfa; line-height: 16.363636016845703px;">While person to person transmission of Machupo virus is not common, during outbreaks of BoHF, or in any BoHF endemic health care setting, blocking nosocomial transmission by employing good barrier protection and patient isolation can also be important in preventing Machupo virus spread from infected patients to health care personnel and/or other non-infected patients.</span></span></div>
Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com16tag:blogger.com,1999:blog-3492197469143963742.post-77319728163855039072013-01-15T14:29:00.002-05:002013-01-23T13:16:04.331-05:00Lassa Hemorrhagic Fever<div dir="ltr" style="text-align: left;" trbidi="on">
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This week at Infection Landscapes we begin to discuss the last group of viruses to be considered in this extended series on hemorrhagic fevers: the arenaviruses. In general, there is a greater prevalence of human infection in endemic areas than the other viruses causing hemorrhagic fevers that we have discussed in this series. We begin the section on arenaviruses with Lassa fever and follow next time with the American areanaviruses.<br />
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Lassa fever is named after the town of Lassa in Nigeria where the disease was first documented in 1969.<br />
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<b>The Pathogen</b>. Lassa virus (LASV) is a member of the Arenaviridae family. These are enveloped viruses approximately 120 nanometers in diameter with single-stranded, ambisense RNA genomes in two segments:<br />
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<b>Monocytes, macrophages, dendritic cells, and endothelial cells are the target cells for LASV</b>. A membrane-bound glycoprotein (GP1) binds to the host receptor, and the virus enters the cell by endocytosis. Replication occurs in the cytoplasm of the host cell. Pathogenesis follows suppression of specific lymphocyte, platelet, and endothelial functions, rather than stimulating a hyper-inflammatory response. This results in the suppression of specific cytokines, diminished coagulation, and vascular leakage and hemorrhaging.<br />
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<b>The Reservoir</b>. The rodent, <i>Mastomys natalensis</i>, is the natural reservoir host for LASV:<br />
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<span style="font-size: x-small;"><i>Mastomys natalensis</i></span></div>
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Known as the common African rat, this rat is extraordinarily widespread throughout incredibly varied landscapes across sub-Saharan Africa. It can be found in tropical or subtropical dry and moist lowland forest, dry and moist savanna, tropical or subtropical dry and moist shrubland, agricultural land of varied type, and urban settings. As such, <i>this reservoir is well adapted to both sylvan and domestic landscapes and thus acts a a robust reservoir for human transmission</i>.<br />
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<b>The Disease</b>. Most LASV infections are asymptomatic. <b>Between 9% and 26% of those infected will present with clinical symptoms. While a minority, these individuals typically experience severe disease</b>. Approximately 1 to 3 weeks after initial infection, those developing clinically apparent Lassa hemorrhagic fever (LHF) typically present with fever, malaise, chills, and, commonly, a sore throat that is may be exudative. Following these initial symptoms, myalgia, arthralgia, headache, and cough are common. Abdominal pain with diarrhea and vomiting are also common. Renal dysfunction with frank proteinuria can present. Myocarditis and nose, gum, and pulmonary bleeding may follow. Petechiae can present on the trunk and neck. Moderate infections begin to resolve after approximately one week, while more severe infections continue to progress. Advanced complications can include bradycardia, extensive face and neck edema, mucosal and conjunctival bleeding, pleural effusion, encephalopathy, and hepatitis. Neurologic complications may include intention tremors, followed later by seizures.Vascular leakage and hemorrhage can lead to shock and death. The overall mortality for all infections is estimated at about 1%. However, among those hospitalized for their infections, the mortality is between 15% and 20%, and can be as high as 60% among those with severe infections who receive no medical attention.<br />
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In addition, long term disability is common in those with symptomatic LHF. The most common disability suffered is hearing loss. Approximately 25% who develop symptomatic disease will experience some degree of deafness due to the involvement of the eighth cranial nerve during infection. Incomplete hearing is recovered in only about 50% of these cases. The remainder suffer permanent hearing loss.<br />
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<b>The Epidemiology and the Landscape</b>. The primary mode of transmission for LASV is from infected rodents to humans via the airborne route, by direct contact with excretory substances containing virus that are shed from the reservoir host, or through a contaminated common vehicle, such as water or food. The virus is shed in the stool and urine of the rodent reservoirs and, when dust containing dried excreta is disturbed, can be inhaled by the human host. Lassa virus can also be transmitted directly from person to person by way of contaminated blood or body fluid exposure. This mode of transmission can be important for nosocomial spread of LASV, particularly during outbreaks. Finally, transmission from rodent to human can occur by way of a rat bite or, as these rodents are a delicacy in many endemic areas, during the processing or eating of infected rodents.<br />
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There are between 100,000 and 500,000 incident cases of LHF each year and about 5,000 deaths, making this the most common, though narrowly distributed, hemorrhagic fever to affect humans. Endemicity is limited to several countries in West Africa.<br />
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<b>The landscape of LASV infection is delineated primarily by the generalized range of the reservoir rodent host and the specific points of contact with humans</b>, which often intersect agricultural or domestic human spaces, determine local cultural preferences and/or practices, or generate sources of rodent contamination of food or water. The latter can be particularly important in areas with poor sanitation and water infrastructure, which are often the same areas endemic for LASV.<br />
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<b>Another important important feature of this landscape is defined by person to person transmission</b>. In this context, the essential human function of caring for the sick, whether in the home or in a clinical setting, can expand endemic rodent to human transmission into epidemic human to human transmission.<br />
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<b>Control and Prevention</b>. Because the reservoir host is ubiquitous in endemic areas, elimination of the reservoir is not possible<i>. However, rodent control is still an important strategy to control LASV infection in humans</i>. Taking precautions to eliminate safe spaces for rodents in the home or other structures of human habitation or occupation can reduce effective human to rodent contact and thus block this important mode of LASV transmission.<br />
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<b>In order to eliminate safe spaces for mice the following steps can be employed</b>:<br />
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<b>Remove all food sources</b>: Food and garbage should always be kept in <b>well-sealed containers</b> that cannot be breached by rodents. In addition, pet food and/or garden fruit and vegetables left unattended outside will often attract rodents.<br />
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<b>Household maintenance</b>: Good maintenance both inside and outside the home can be very important in eliminating rodent habitat. On the outside, overgrown plants and shrubs, unattended woodpiles or debris, and unattended outdoor structures can all serve as welcome homes for rodents, and should be be regularly maintained. On the inside, poorly sealed foundations, roofing, vents, and other household structures can provide easy access to the interior of the house and thus provide good rodent habitat. As such, it is very important to maintain good structural integrity of the house to keep the rodents out.<br />
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During outbreaks, or in any endemic health care setting, blocking nosocomial transmission by employing good barrier protection and patient isolation can also be very important in preventing LASV spread from infected patients to health care personnel and/or other non-infected patients.</div>
Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com12tag:blogger.com,1999:blog-3492197469143963742.post-53945626219199881312012-12-19T13:56:00.001-05:002012-12-19T13:57:41.884-05:00Marburg Hemorrhagic Fever<div dir="ltr" style="text-align: left;" trbidi="on">
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This week we are going to cover the second of the two Filoviruses included in our extended series on the viral hemorrhagic fevers: Marburg virus. Marburg hemorrhagic fever is another very serious disease, and it is clinically indistinguishable from Ebola hemorrhagic fever. Indeed, because the virology, epidemiology, and clinical symptoms are so similar between these two diseases, much of this discussion will be quite similar to what has been covered on Ebola hemorrhagic fever.<br />
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Marburg virus is named after the city of Marburg, Germany, which is where one of the first epidemics was identified following exposure to imported infected monkeys in 1967.<br />
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<b>The Pathogen</b>. Marburg hemorrhagic fever (MHF) is caused by Marburg virus (MARV), whose species name is <i>Marburg marburgvirus</i> and is in the Filoviridae family.<br />
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Like all the Filoviridae, MARV ranges between 790 and 1400 nanometers long (though MARV is typically about 200 nanometers shorter than the ebolaviruses) and 80 nanometers in diameter They are enveloped viruses with helical capsids and linear, negative-sense single-stranded RNA genomes.<br />
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<i><span style="font-size: x-small;">Marburg virus structure (published by ViralZone)</span></i></div>
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<b>Monocytes, macrophages, dendritic cells, liver cells, and endothelial cells are the primary target cells of MARV</b>. Virus is present in many tissues including kidney, liver, spleen, lymph nodes, and blood, as well as most body secretions. The viruses enter the cells by endocytosis, or by phagocytosis in the case of macrophages.<br />
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<b>The Reservoir</b>. The natural reservoir host for MARV remains unknown. However, several outbreak-associated and outbreak-independent seroepidemiology field investigations, as well as laboratory animal studies, strongly suggest that fruit bats are important natural reservoir hosts for MARV.<br />
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These are the the so-called megabats, i.e. the family Pteropodidae in the suborder known as Megachiroptera.<br />
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<span style="font-size: x-small;"><i>Megabat, or "fruit bat": Spectacled flying-fox (Pteropus conspicillatus)</i></span></div>
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Many of these bats are quite large relative to the other suborder of bats, the Microchiroptera, but this is not a defining feature as some species of megabats are as small or smaller than some microbats. An important distinction between these suborders is that megabats do not use echolocation (with the exception of the genus Rousettus) for navigation in flight and finding prey. Moreover, the megabats typically have very good vision. Megabats subsist solely on nectar and fruit, which is why they are commonly collectively referred to as "fruit bats", while most microbats eat insects and some will eat small vertebrates (reptiles, mammals, fish), mammalian blood or fruits and nectar.<br />
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The Egyptian fruit bat, <i>Rousettus aegyptiacus</i>, has been identified as a natural reservoir host for MARV. <br />
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<span style="font-size: x-small;"><i>Rousettus aegyptiacus</i></span></div>
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Like the reservoir fruit bats discussed for ebolaviruses, these bats are frugivores and are nocturnal. However, the Egyptian fruit bat is relatively small for a megabat, and it also uses echolocation, which is unique to <i>Rousettus</i> spp. among the megabats. These bats are gregarious and roost in large colonies in trees and caves.<br />
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Egyptian fruit bats can exploit very diverse ecological habitats, but stay away from desert landscapes. They are distributed extensively across subregions of Africa and narrow corridors of the Middle East. They can also be found in South Asia in Pakistan and northern India.<br />
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<b>The Disease</b>. Marburg hemorrhagic fever (MHF) is characterized by an abrupt onset presenting with myalgia, fever, and chills. Abdominal pain and/or nausea with diarrhea and/or vomiting are also common. There are two important features of MHF that are critical in its pathogenesis: 1) endothelial damage mediated by both the virus and the up-regulation of toxic cytokines, which leads to extensive vascular leakage, and 2) disseminated intravascular coagulation, which leads to severe thrombocytopenia. The graphic below published in <i>Nature Reviews Immunology</i> 7, 556-567 (July 2007) illustrates these key features of MARV pathogenesis:<br />
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<b>Hemorrhage, often severe, thus ensues and can be seen at several sites within approximately 5 to 7 days of the onset of symptoms</b>. Bleeding from the nose, gums, and eyes is common, and extensive gastrointestinal hemorrhage will often manifest as frank blood in the stool or hematemesis. Dehydration is very common.Significant lesions can be found in multiple organs including the kidneys, spleen, liver, and lymph nodes. Mortality is high, typically ranging from 50% to 90% depending on the species and strain of MARV.</div>
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<b>The Epidemiology and the Landscape</b>. Marburg virus is transmitted via contaminated body fluids. <b>Direct and indirect contact, and droplet transmission are the primary specific routes of viral spread between humans, and between other animals and humans</b>. Health care settings and subsistence hunting define the two primary paradigms for human infection, and therefore both human to human and zoonotic transmission are viable and important routes of human infection.<br />
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The global distribution of MARV is depicted in the following two map sets and the descriptions below each, all of which was published in <i>Emerging Infectious Diseases</i> 2004 Jan (http://wwwnc.cdc.gov/eid/article/10/1/03-0125.htm):<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjnhrOLqyBMJ7hs9loPunWh2hd6nLGoUx1f5f8jKqodEshKgDrtIEd8cdLDbccWDsbOT3FPH7n6oaAqiBAF_U4MwtuiYfHDvjG9ajs0M-B3qwdgra6XA98mEZRlMjBJetwqFq8afx_YQeU/s1600/Ecologic_and_Geographic_Distribution_of_Filovirus_Disease_in_Africa.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="312" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjnhrOLqyBMJ7hs9loPunWh2hd6nLGoUx1f5f8jKqodEshKgDrtIEd8cdLDbccWDsbOT3FPH7n6oaAqiBAF_U4MwtuiYfHDvjG9ajs0M-B3qwdgra6XA98mEZRlMjBJetwqFq8afx_YQeU/s400/Ecologic_and_Geographic_Distribution_of_Filovirus_Disease_in_Africa.jpg" width="400" /></a></div>
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<i>Summary of known and predicted geography of filoviruses in Africa. (A) Known occurrence points of filovirus hemorrhagic fevers (HFs) identified by virus species. (B) Geographic projection of ecologic niche model based on all known filovirus disease occurrences in Africa. (C) Geographic projection of ecologic niche model based on all known Ebola HF occurrences (i.e., eliminating Marburg HF occurrences). (D) Geographic projection of ecologic niche model based on all known occurrences of Marburg HF (i.e., eliminating Ebola HF occurrences). Darker shades of red represent increasing confidence in prediction of potential presence. Open squares, Ebola Ivory Coast; circles, Ebola Zaire; triangles, Ebola Sudan; dotted squares, Marburg HF</i> </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhIAetWX3lg7WdD9szpZqAgxAzki9Oa6pdTcyPrqerWFmylEvc8SmBrb-pPcNEnCmtlS8gBBNHsMqqhhWyUeUuQ0B8Qovaz8DsCDBoLMUKwFoYAb_wi_qfnCrDleZvZOi-ef-zS7rpre8k/s1600/Ecologic_and_Geographic_Distribution_of_Filovirus_Disease_in_SE_Asia.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhIAetWX3lg7WdD9szpZqAgxAzki9Oa6pdTcyPrqerWFmylEvc8SmBrb-pPcNEnCmtlS8gBBNHsMqqhhWyUeUuQ0B8Qovaz8DsCDBoLMUKwFoYAb_wi_qfnCrDleZvZOi-ef-zS7rpre8k/s640/Ecologic_and_Geographic_Distribution_of_Filovirus_Disease_in_SE_Asia.jpg" width="412" /></a></div>
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<i>Projection of filovirus ecologic niche models onto southeastern Asia and the Philippines to assess the degree to which possible Philippine distributional areas are predictable on the basis of the ecologic characteristics of African filovirus hemorrhagic fever (HF) occurrences. (A) Projection of model for Marburg HF occurrences (Figure 1D) to southeastern Asia. (B) Projection of model for all filovirus disease occurrences (Figure 1B) to southeastern Asia (the projection of models for Ebola HF occurrences is identical to this map). Inset: detail of projection to the island of Mindanao, in the Philippines. Darker shades of red represent increasing confidence in prediction of potential presence</i>.</div>
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The graphic below, and the description underneath, were published in the journal, <i>Emerging Infectious Diseases</i> (http://wwwnc.cdc.gov/eid/article/11/2/04-0533_article.htm). This is a depiction of the ecology and landscape epidemiology of ebolaviruses, but applies equally to MARV:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjaMV0zkRZ8DQB_DG5JMVaTzbD4MEO1rBTkgMqpOBPuIRYt22QHQD7BtPYY6cevBy4vTKbYF0XxPCDwgdpldfGMIuFEccTGyI4Q1W3RFDHZBT0sRUEm58BAuVJ1ZzHsb_93raZ9Bv5g-DQ/s1600/ebola+landscape.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="225" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjaMV0zkRZ8DQB_DG5JMVaTzbD4MEO1rBTkgMqpOBPuIRYt22QHQD7BtPYY6cevBy4vTKbYF0XxPCDwgdpldfGMIuFEccTGyI4Q1W3RFDHZBT0sRUEm58BAuVJ1ZzHsb_93raZ9Bv5g-DQ/s400/ebola+landscape.jpg" width="400" /></a></div>
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<i>Schematic representation of the Ebola cycle in the equatorial forest and proposed strategy to avoid Ebola virus transmission to humans and its subsequent human-human propagation. Ebola virus replication in the natural host (a). Wild animal infection by the natural host(s) (b), no doubt the main source of infection. Wild animal infection by contact with live or dead wild animals (c). This scenario would play a marginal role. Infection of hunters by manipulation of infected wild animal carcasses or sick animals (d). Three animal species are known to be sensitive to Ebola virus and to act as sources of human outbreaks: gorillas, chimpanzees, and duikers. Person-to-person transmission from hunters to their family and then to hospital workers (e). The wild animal mortality surveillance network can predict and might prevent human outbreaks. Medical surveillance can prevent Ebola virus propagation in the human population</i>.<br />
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As you can see from this depiction, the physical and social landscapes are both important in the epidemiology of MHF. In particular, 1) the interface between human subsistence economies and sylvan habitat generates critical index cases, and 2) the bare-essential act of care-giving, either in the home or in a clinical setting, generates the propagative secondary cases.<br />
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<b>Control and Prevention</b>. Control and prevention of MHF are typically focused on outbreak containment and control, and in only the second of the two primary paradigms of transmission described above. As such, this translates to blocking nosocomial transmission by employing good barrier protection and patient isolation to prevent spread from infected patients to health care personnel and/or other non-infected patients in a hospital or health care setting. This is the central component to MHF control and prevention as outbreaks often generate many secondary cases by human to human transmission during the care of infected individuals.<br />
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<b>Blocking transmission at the source of index cases is very difficult because there is no way that a primary source of subsistence, i.e. bush hunting, can be removed as a public health intervention for a community whose basis of existence is a subsistence economy</b>. Nevertheless, the Wild Animal Mortality Monitoring Network is an important surveillance instrument that has been developed to survey animal carcasses in sylvan habitat where Filoviruses, including Ebola virus and Marburg virus, have been identified in order to help predict and prevent future outbreaks. While of limited geographic and temporal implementation, the use of this kind of surveillance could be quite useful for the future identification of sylvan MARV foci and the possible interception of human contact with these cites before transmission occurs.</div>
Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com8tag:blogger.com,1999:blog-3492197469143963742.post-45379497347408660352012-11-26T12:57:00.002-05:002012-11-26T12:57:37.149-05:00Ebola Hemorrhagic Fever<div dir="ltr" style="text-align: left;" trbidi="on">
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This week we introduce the Filoviridae family of viruses, with perhaps its most infamous member: Ebola virus. This virus has gained popular attention because of its severe outbreaks, which are typically associated with a very high mortality. Unfortunately this attention has usually been amplified by sensationalism in news media and film. While this hemorrhagic fever is undoubtedly a very serious disease and needs to be treated as such, this post will strive to describe only what is currently known and avoid hyperbole.<br />
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<b>Ebola virus is named after the Ebola River in the Democratic Republic of Congo, which is one of the two places documented outbreaks first occurred in 1976</b>. At the time, the Democratic Republic of Congo was known as Zaire, while the other outbreak occurred in the Sudan. These two outbreaks occurred almost simultaneously but were caused by two distinct species of the virus, as described below. There have been about 25 outbreaks in central Africa since, and including, the first, and these have occurred on an annual or biannual basis since 1994. Some years, like 2012, have seen multiple outbreaks.<br />
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<b>The Pathogen</b>. Ebola hemorrhagic fever (EHF) is caused by by one of five species of <i>Ebolavirus</i>. These species are Bundibugyo ebolavirus, Coite d'Ivoire ebolavirus (CIEBOV), Sudan ebolavirus (SEBOV), Reston ebolavirus (REBOV), and Zaire ebolavirus (ZEBOV), which is the specific virus denoted by the name Ebola virus (EBOV). Through the remainder of this discussion we will simply refer generically to EBOV.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjlO53BCklR6pBFDgbOJ6BO1PVAcKqAiReHzl1Vja5pdody4BmnKNSvbnT57pFp0aYH9o_5p9XDQUKWBHmMpZf5THoGZ8DaS6n4JrFpI8XCRF7P2htiA9-XfvNqMurFHF0RsdoNO6LQKRw/s1600/Ebola_virus_em.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjlO53BCklR6pBFDgbOJ6BO1PVAcKqAiReHzl1Vja5pdody4BmnKNSvbnT57pFp0aYH9o_5p9XDQUKWBHmMpZf5THoGZ8DaS6n4JrFpI8XCRF7P2htiA9-XfvNqMurFHF0RsdoNO6LQKRw/s400/Ebola_virus_em.jpg" width="282" /></a></div>
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The ebolaviruses, and the Filoviridae, are typically between 790 and 1400 nanometers long and 80 nanometers in diameter They are enveloped viruses with helical capsids and linear, negative-sense single-stranded RNA genomes.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgvzzvlTBXYFuOrJRuS5Fy7oLXmAxemASwTpSpIXKe_HmWuLyhsF54bNs-IeIpBFexzWfZVceJ1Sg690zF3heyktBu_xgeF-o7jTGv_tWiOTppXCXcBKxYRcq_AaT5TzgV4ZgKYS-8AOXY/s1600/Filovirus_virion.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="243" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgvzzvlTBXYFuOrJRuS5Fy7oLXmAxemASwTpSpIXKe_HmWuLyhsF54bNs-IeIpBFexzWfZVceJ1Sg690zF3heyktBu_xgeF-o7jTGv_tWiOTppXCXcBKxYRcq_AaT5TzgV4ZgKYS-8AOXY/s400/Filovirus_virion.jpg" width="400" /></a></div>
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<i><span style="font-size: x-small;">Ebolavirus structure (published by ViralZone)</span></i></div>
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<b>Monocytes, macrophages, dendritic cells, liver cells, and endothelial cells are the primary target cells of ebolaviruses</b>. Virus is present in many tissues including kidney, liver, spleen, lymph nodes, and blood, as well as most body secretions. The viruses enter the cells by endocytosis, or by phagocytosis in the case of macrophages. The graphic below published by the Research Center for Zoonosis Control at Hokkaido University, nicely depicts the life cycle of ebolaviruses. </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi9ovK-6k-enT8hB441Og2RFuKMLdUayMIAETQGHmgC_aTzfJN2Qxa6sTxVMNYrGwkNIV_SD1dk3D2QS-N-XIyJI7KEUZLhAWiEkB1iszXYSv9ywq3ZPVk7_XxtEPogD35vPCaAszfo7eE/s1600/ebola+life+cycle+and+pathogenicity.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi9ovK-6k-enT8hB441Og2RFuKMLdUayMIAETQGHmgC_aTzfJN2Qxa6sTxVMNYrGwkNIV_SD1dk3D2QS-N-XIyJI7KEUZLhAWiEkB1iszXYSv9ywq3ZPVk7_XxtEPogD35vPCaAszfo7eE/s400/ebola+life+cycle+and+pathogenicity.png" width="322" /></a></div>
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<b>The Reservoir</b>. The natural reservoir host for EBOV remains unknown. However, several outbreak-associated and outbreak-independent seroepidemiology field investigations, as well as laboratory animal studies, <b>strongly suggest that fruit bats are important natural reservoir hosts for EBOV</b>. </div>
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These are the the so-called megabats, i.e. the family Pteropodidae in the suborder known as Megachiroptera. </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiWgMqTrge-nxC9AejG3Z109RBAdb6vwFBUexZwnQxavwHPPNpwVcKXgtFX5U9XImEBLxU9lboQyQ5rYPBujqOXP4SH9FHoU_y4EqPOpoESdR5mcBL2YnQOnvSimf9Rion-SkE-7oJJRP8/s1600/Pteropus_conspicillatus.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiWgMqTrge-nxC9AejG3Z109RBAdb6vwFBUexZwnQxavwHPPNpwVcKXgtFX5U9XImEBLxU9lboQyQ5rYPBujqOXP4SH9FHoU_y4EqPOpoESdR5mcBL2YnQOnvSimf9Rion-SkE-7oJJRP8/s400/Pteropus_conspicillatus.jpg" width="300" /></a></div>
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<span style="font-size: x-small;"><i>Megabat, or "fruit bat": Spectacled flying-fox (Pteropus conspicillatus)</i></span></div>
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Many of these bats are quite large relative to the other suborder of bats, the Microchiroptera, but this is not a defining feature as some species of megabats are as small or smaller than some microbats. An important distinction between these suborders is that megabats do not use echolocation (with the exception of the genus <i>Rousettus</i>) for navigation in flight and finding prey. Moreover, the megabats typically have very good vision. Megabats subsist solely on nectar and fruit, which is why they are commonly collectively referred to as "fruit bats", while most microbats eat insects and some will eat small vertebrates (reptiles, mammals, fish), mammalian blood or fruits and nectar.</div>
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There are three species distributed across tropical Africa that have demonstrated EBOV infection without disease. The first is <i>Hypsignathus monstrosus</i>, known commonly as the Hammer-headed bat:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg7RUMGX1bgS7KqXNuZTlv8uFaux3QHBzP9QIJaBzukyhmr3WvdVhZugIKP7Q4dHukYZJ68z2xZPMSiLuwuEI5pkti0wrsn3WjsvtXf27wn6iK9I0gMZwtJrrNNmMBswdwdk__4tWyNyLg/s1600/hammer-headed+bat.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg7RUMGX1bgS7KqXNuZTlv8uFaux3QHBzP9QIJaBzukyhmr3WvdVhZugIKP7Q4dHukYZJ68z2xZPMSiLuwuEI5pkti0wrsn3WjsvtXf27wn6iK9I0gMZwtJrrNNmMBswdwdk__4tWyNyLg/s400/hammer-headed+bat.jpg" width="250" /></a></div>
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<i><span style="font-size: x-small;">Hypsignathus monstrosus</span></i></div>
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The Hammer-headed bat has a long but very narrow distribution across the tropical belt of African rain forest:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEil9rA_Wg05diEjWVQasxyOf9yPDvg6GUMFe9SoHXKDecgxbMH-rfI_5VXHcdnWMPWdz8y1O8h6AP7DxEsePF-qVbT9IsbQiEG-5BwV25DbW-g5xAfmdV60QiU1-CK853ghGfTNufTS4lQ/s1600/Hammer-headed_Bat_area.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEil9rA_Wg05diEjWVQasxyOf9yPDvg6GUMFe9SoHXKDecgxbMH-rfI_5VXHcdnWMPWdz8y1O8h6AP7DxEsePF-qVbT9IsbQiEG-5BwV25DbW-g5xAfmdV60QiU1-CK853ghGfTNufTS4lQ/s400/Hammer-headed_Bat_area.png" width="356" /></a></div>
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These bats are exclusively fruit eating and are nocturnal. They roost in the tree canopy of forested habitat during the day, but are not selective about tree species other than they must be sufficiently high (20 to 30 meters).</div>
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The second of these potential important EBOV reservoirs is <i>Epomops franqueti</i>, which is known as the Franquet's Epauletted fruit bat:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEioCGvLwBasISG9O7DI1AnYVae_M8XNcMkTbgPlUBuBPM0WcAfgpDxFUELxoF34VygtALCriaTkL_6mQjzfK-xzv5Wy_7kPKHOHDNWUPYx02bN_H3Q1PPEhdmMXvVtJhxVyDtEsxflvmWc/s1600/EpomophorusFranqueti.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="195" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEioCGvLwBasISG9O7DI1AnYVae_M8XNcMkTbgPlUBuBPM0WcAfgpDxFUELxoF34VygtALCriaTkL_6mQjzfK-xzv5Wy_7kPKHOHDNWUPYx02bN_H3Q1PPEhdmMXvVtJhxVyDtEsxflvmWc/s320/EpomophorusFranqueti.jpg" width="320" /></a></div>
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<i><span style="font-size: x-small;">Epomops franqueti</span></i></div>
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These bat ares distributed across a wide, but slightly shorter, area of central Africa:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiOM4IebW56LYYAyqa7CBvnx8zJFxQQC1sVfgnvuY5XJTuwxU5iqVq31qpWQurHseefKj2urwK7KiWYUZAPCKRj8KUcsi8-of8XJxkKFYZSVfNNQDQNrJ6gJ4KyJqhSbBv8XaxRW7nAWfM/s1600/Franquet's_Epauletted_Fruit_Bat_area.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiOM4IebW56LYYAyqa7CBvnx8zJFxQQC1sVfgnvuY5XJTuwxU5iqVq31qpWQurHseefKj2urwK7KiWYUZAPCKRj8KUcsi8-of8XJxkKFYZSVfNNQDQNrJ6gJ4KyJqhSbBv8XaxRW7nAWfM/s320/Franquet's_Epauletted_Fruit_Bat_area.png" width="285" /></a></div>
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These bats can be found across a wide variety of landscapes, including wet, dry, and mangrove forests, swamps, and dry savanna. These bats are also nocturnal and frugivorous, but they are solitary and maintain diurnal roosts at a height of around 5 meters. </div>
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The third possible reservoir is <i>Myonycteris torquata</i>, known as the Little Collared fruit bat.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgrFVJ5K4d4CnisOT1whTpgKpLDGfX9jnRHgcqO_gG6qld9NSDlUClIM5rCx70NlKYNDXSblYaSS4yfsQ8JQgGOYssk4oXF-ruou8sfncSMQfg1xNMfVj-PPnc613qGHwqun3B1SgNoyCU/s1600/little+collared+fruit+bat.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="381" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgrFVJ5K4d4CnisOT1whTpgKpLDGfX9jnRHgcqO_gG6qld9NSDlUClIM5rCx70NlKYNDXSblYaSS4yfsQ8JQgGOYssk4oXF-ruou8sfncSMQfg1xNMfVj-PPnc613qGHwqun3B1SgNoyCU/s400/little+collared+fruit+bat.jpg" width="400" /></a></div>
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<i><span style="font-size: x-small;">Myonycteris torquata</span></i></div>
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These bats have a geographic distribution similar to the Franquet's Epauletted fruit bat in central Africa: </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj5bQkytmgGamIGirQAfwAlC3QxHifl-dvxXCmiYRYmx16kkoxF5rEs7OtG7M4eCET-Rwk8HBalbN7Kf3VgNiLfHby731pthc-Q4lZmCKdIoHbubBHrzqduHOxEH1EmM6pX0Ll7yWC-YKI/s1600/Little_Collared_Fruit_Bat_area.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj5bQkytmgGamIGirQAfwAlC3QxHifl-dvxXCmiYRYmx16kkoxF5rEs7OtG7M4eCET-Rwk8HBalbN7Kf3VgNiLfHby731pthc-Q4lZmCKdIoHbubBHrzqduHOxEH1EmM6pX0Ll7yWC-YKI/s320/Little_Collared_Fruit_Bat_area.png" width="285" /></a></div>
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However, the Little Collared fruit bat is somewhat more ecologically specialized in that it prefers wet lowland forests and wet savanna. These bats are also nocturnal frugivores.</div>
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<b>The Disease</b>. Ebola hemorrhagic fever (EHF) is characterized by an abrupt onset presenting with myalgia, fever, and chills. Abdominal pain and/or nausea with diarrhea and/or vomiting are also common. <b>There are two important features of EHF that are critical in its pathogenesis</b>: 1) endothelial damage mediated by both the virus and the up-regulation of toxic cytokines, which leads to extensive vascular leakage, and 2) disseminated intravascular coagulation, which leads to severe thrombocytopenia. The graphic below published in the <i>Lancet Student</i> <span style="font-family: inherit;">(<span style="background-color: white;">doi:10.1016/S0140-6736(10)60667-8Cite) illustrates these key features of EBOV pathogenesis<span style="font-size: x-small;">:</span></span></span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjICpA8vix7953Uz7s3TyPHxs5ojqKKMAXJk35o6ycGWBT3FXrD7T7_uBXRmOoWVK3YmnpV3TCqqMp_vNZoXKejh8QF0zaQY3WHy4sDym515DMfEAv548-k9FnQcOTHopwU3F9yPE8rHi8/s1600/Ebola-virus-pathogenesis.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="390" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjICpA8vix7953Uz7s3TyPHxs5ojqKKMAXJk35o6ycGWBT3FXrD7T7_uBXRmOoWVK3YmnpV3TCqqMp_vNZoXKejh8QF0zaQY3WHy4sDym515DMfEAv548-k9FnQcOTHopwU3F9yPE8rHi8/s400/Ebola-virus-pathogenesis.jpg" width="400" /></a></div>
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<b>Hemorrhage, often severe, thus ensues and can be seen at several sites within approximately 5 to 7 days of the onset of symptoms</b>. Bleeding from the nose, gums, and eyes is common, and extensive gastrointestinal hemorrhage will often manifest as frank blood in the stool or hematemesis. Dehydration is very common.Significant lesions can be found in multiple organs including the kidneys, spleen, liver, and lymph nodes. Mortality is high, typically ranging from 50% to 90% depending on the species and strain of <i>Ebolavirus</i>.<br />
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<b>The Epidemiology and the Landscape</b>. <i>Ebola virus is transmitted via contaminated body fluids</i>. <b>Direct and indirect contact, and droplet transmission are the primary specific routes of viral spread between humans, and between other animals and humans</b>. Health care settings and subsistence hunting define the two primary paradigms for human infection, and therefore both human to human and zoonotic transmission are viable and important routes of human infection.<br />
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The global distribution of EBOV human and animal outbreaks, seroprevalence and presumed reservoir host range is depicted in the map below produced by the World Health Organization:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgTk6WdC4GhPjxzACtC6Yiv3xg4VdQNHKsdFs_jdG3HiTZsFLXhQ2NLmzVH53lJyg_YEByeO240_TRZD9dPk6iiAcnNLTb6RtlSp0Ghgiq2KdZ3V0E56NdHzzgSnEPdAmyeonPFmmeGMwc/s1600/EbolaGlobalOutbreakRisk_20090510.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="268" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgTk6WdC4GhPjxzACtC6Yiv3xg4VdQNHKsdFs_jdG3HiTZsFLXhQ2NLmzVH53lJyg_YEByeO240_TRZD9dPk6iiAcnNLTb6RtlSp0Ghgiq2KdZ3V0E56NdHzzgSnEPdAmyeonPFmmeGMwc/s400/EbolaGlobalOutbreakRisk_20090510.png" width="400" /></a></div>
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Interestingly, the map demonstrates a very wide potential reservoir host distribution across much of South and Southeast Asia and Oceania, which includes several additional fruit bat species in the Pteropodidae family not described above. Moreover, REBOV has been found extensively in monkeys and domestic pigs in the Philippines, though no human infections have yet been observed. <br />
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The graphic below, and the description underneath, were published in the journal, <i>Emerging Infectious Diseases</i> (<span style="text-align: center;"><a href="http://wwwnc.cdc.gov/eid/article/11/2/04-0533_article.htm" style="text-align: left;">http://wwwnc.cdc.gov/eid/article/11/2/04-0533_article.htm</a></span>). This is a nice depiction of the ecology and landscape epidemiology of ebolaviruses, as we currently understand them:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjlZtX2g_xXCnKy9khnDuAt2TeeNXnFLqA3z7FZB4gPFBFu6HLJb8XR8GCPZzbMPROOgcxiW25EsNE4nBn9FTVAZRwz6kbDuCL3arl1lD04WSy261jNLCXXCBCUoHKiqP2dhYpvWRHM8lY/s1600/ebola+landscape.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="225" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjlZtX2g_xXCnKy9khnDuAt2TeeNXnFLqA3z7FZB4gPFBFu6HLJb8XR8GCPZzbMPROOgcxiW25EsNE4nBn9FTVAZRwz6kbDuCL3arl1lD04WSy261jNLCXXCBCUoHKiqP2dhYpvWRHM8lY/s400/ebola+landscape.jpg" width="400" /></a></div>
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<i>Schematic representation of the Ebola cycle in the equatorial forest and proposed strategy to avoid Ebola virus transmission to humans and its subsequent human-human propagation. Ebola virus replication in the natural host (a). Wild animal infection by the natural host(s) (b), no doubt the main source of infection. Wild animal infection by contact with live or dead wild animals (c). This scenario would play a marginal role. Infection of hunters by manipulation of infected wild animal carcasses or sick animals (d). Three animal species are known to be sensitive to Ebola virus and to act as sources of human outbreaks: gorillas, chimpanzees, and duikers. Person-to-person transmission from hunters to their family and then to hospital workers (e). The wild animal mortality surveillance network can predict and might prevent human outbreaks. Medical surveillance can prevent Ebola virus propagation in the human population</i>.</div>
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As you can see from this depiction, the physical and social landscapes are both important in the epidemiology of EHF. In particular, 1) the interface between human subsistence economies and sylvan habitat generates critical index cases, and 2) the bare-essential act of care-giving, either in the home or in a clinical setting, generates the propagative secondary cases.</div>
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<b>Control and Prevention</b>. Control and prevention of EHF are typically focused on outbreak containment and control, and in only one of the two primary paradigms of transmission described above. As such, this translates to blocking nosocomial transmission by employing good barrier protection and patient isolation to prevent spread from infected patients to health care personnel and/or other non-infected patients in a hospital or health care setting. This is the central component to EHF control and prevention as outbreaks often generate many secondary cases by human to human transmission during the care of infected individuals.<br />
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<b>Blocking transmission at the source of index cases is very difficult because there is no way that a primary source of subsistence, i.e. bush hunting, can be removed as a public health intervention for a community whose basis of existence is a subsistence economy</b>. Nevertheless, the Wild Animal Mortality Monitoring Network is an important surveillance instrument that has been developed to survey animal carcasses in sylvan habitat where EBOV has been identified in order to help predict and prevent future outbreaks. While of limited geographic and temporal implementation, the use of this kind of surveillance could be quite useful for the future identification of sylvan EBOV foci and the possible interception of human contact with these cites before transmission occurs. <br />
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Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com42tag:blogger.com,1999:blog-3492197469143963742.post-79108000310146657892012-10-30T14:15:00.000-04:002012-10-30T14:15:16.715-04:00Rift Valley Fever<div dir="ltr" style="text-align: left;" trbidi="on">
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This week we will cover the last of the Bunyaviridae in this extended series on the viral hemorrhagic fevers. This is the Phlebovirus that causes Rift Valley fever. Rift Valley fever is another zoonotic vector-borne infection and occurs throughout much of Africa and parts the Arabian Peninsula.<br />
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<b>The Pathogen</b>. Rift Valley fever (RVF) is caused by Rift Valley fever virus (RVFV), which is a Phlebovirus in the Bunyaviridae family. RVFV is approximately 90 to 110 nanometers in diameter. It is an enveloped virus with a single-stranded RNA genome in three segments. The three genome segments are circular and classified as large (L), medium (M), and small (S). The S segment is ambisense, while the L and M segments are negative-sense:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_HyZs_upwKJllzvKJ76QfKpHLumlRJBLRuLwp60WlYwQHr0EshJ9q1-NnfF9oeVncTgXvYBs1tedjZg1l0S-RzlYfSvbJeFzVgYbnGNRcW1VUnuHDJMXPO67hNohUfhOXxKcT2fw6g8o/s1600/RVFV+structure+2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_HyZs_upwKJllzvKJ76QfKpHLumlRJBLRuLwp60WlYwQHr0EshJ9q1-NnfF9oeVncTgXvYBs1tedjZg1l0S-RzlYfSvbJeFzVgYbnGNRcW1VUnuHDJMXPO67hNohUfhOXxKcT2fw6g8o/s400/RVFV+structure+2.jpg" width="386" /></a></div>
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<i><span style="font-size: x-small;">RVFV structure (Published in: Vet. Res. 2010. 41(6): 61.)</span></i></div>
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<b>Macrophages, hepatocytes and endothelial cells are the target cells in the human host</b> and, like hantaviruses and Crimean-Congo hemorrhagic fever virus, RVFV invades host cells by endocytosis and replicates via the ER-Golgi intermediate compartment.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgJa-Q8GbCPa3m6OnOQfmO9nbYJgqXgIujV_qJxbeI0aPO-ZbrvsVQyIRJ-wIt0YRP-plmkAt4nu7_pAEwR7Iael6Vbq963cO-hhJs6Qs0bjQnG1robSNkrhh04WhD0zBRg8_Njpi4EPc0/s1600/Bunyaviridae+infection+cycle.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="351" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgJa-Q8GbCPa3m6OnOQfmO9nbYJgqXgIujV_qJxbeI0aPO-ZbrvsVQyIRJ-wIt0YRP-plmkAt4nu7_pAEwR7Iael6Vbq963cO-hhJs6Qs0bjQnG1robSNkrhh04WhD0zBRg8_Njpi4EPc0/s400/Bunyaviridae+infection+cycle.jpg" width="400" /></a></div>
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<i><span style="font-size: x-small;">Bunyaviridae infection cycle (Published in: Antiviral Research, Volume 64, Issue 3, December 2004, Pages 145-160)</span></i></div>
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<b>The Vector</b>. RVFV is an exceptional virus in that it can be vectored by many, and quite varied, arthropods depending on the specific geographic location. For example, several species of mosquito, sandflies and ticks are all capable of transmitting RVFV between hosts. <b>Nevertheless, mosquitoes are far and away the primary and most important vector for this virus</b>. Mosquito vectors are central to the enzootic, epizootic, and epidemic ecology of the virus. In most of the geographic areas where RVFV is present, <i>Aedes</i> mosquitoes are the dominant mosquito vectors for enzootic transmission among animals, and for sporadic transmission among humans. These are the virus maintenance vectors. <i>Aedes mcintoshi</i> is the most important of these maintenance vectors.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEitZ1eyIueQwfRFPuFVEWwblGgLi-v1ULoU0Vo6D-v4CpT3k2o_FaPjMDFIFfyjnmzTyBtk92QXqlx5X5hz26oBXEbzuuaMoMgOGPE1RnjFy_7tjvzE6PHHqzj_398Yn04nEd2KOjmNopo/s1600/Aedes+mcintoshi.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="261" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEitZ1eyIueQwfRFPuFVEWwblGgLi-v1ULoU0Vo6D-v4CpT3k2o_FaPjMDFIFfyjnmzTyBtk92QXqlx5X5hz26oBXEbzuuaMoMgOGPE1RnjFy_7tjvzE6PHHqzj_398Yn04nEd2KOjmNopo/s400/Aedes+mcintoshi.jpg" width="400" /></a></div>
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<i><span style="font-size: x-small;">Aedes mcintoshi</span></i></div>
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On the other hand, when specific features of the landscape emerge, <i>Culex</i> mosquitoes serve as important amplifying vectors, which transition virus circulation and transmission in animals from enzootic conditions to epizootic conditions, and subsequently also increase the risk for human epidemics. These dynamic landscape features of mosquito and disease ecology will be discussed in greater detail below.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhZWnhoGiOVdIrnCSgAmCaoZUNf8aRKCkhNmTn0Gx4EfyNDTCdU2gl2UEYWiS4r97vRSvZhYq-CYHvUvMwYBC1SCQej1UHVyDW1Sdlepp0tdsbFhv-o2itLfGEe-ehV5oZLIHYD4xn104M/s1600/Culex_pipiens_2007-1.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhZWnhoGiOVdIrnCSgAmCaoZUNf8aRKCkhNmTn0Gx4EfyNDTCdU2gl2UEYWiS4r97vRSvZhYq-CYHvUvMwYBC1SCQej1UHVyDW1Sdlepp0tdsbFhv-o2itLfGEe-ehV5oZLIHYD4xn104M/s400/Culex_pipiens_2007-1.jpg" width="338" /></a></div>
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<i><span style="font-size: x-small;">Culex pipiens</span></i></div>
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<b>The Disease</b>. The vast majority of infections are mild or asymptomatic. <i>The mild disease course typically presents as an influenza-like illness with abrupt onset of fever, mylagia and arthralgia, and headache</i>. Some patients may additionally present with vomiting, neck stiffness, and photosensitivity, which may be initially identified incorrectly as meningitis. </div>
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Approximately 2% to 5% of infected individuals develop complicated RVF, which is comprised of three syndromes that may or may not occur in concert.</div>
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<b>Ocular disease</b> is marked by lesions on the retina appearing approximately 1 to 3 weeks following the onset of initial symptoms. These lesions are usually associated with blurred vision and/or mild to severe vision loss, which may or may not resolve during convalescence. The mortality associated with this syndrome, when it is not accompanied by either of the other two, is quite low. </div>
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<b>Meningoencephalitis</b> is marked by severe neurologic involvement approximately 1 to 4 weeks following the initial symptoms, but can even occur more than two months later. Confusion, loss of memory, convulsions, hallucination and headache are common features of this syndrome. Coma can also ensue. Mortality associated with this syndrome is also low, but chronic neurologic deficit often persists and can be quite severe.</div>
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<b>Hemorrhagic fever</b> is marked by serious hemorrhage. This syndrome typically begins much closer to the onset of initial symptoms. Approximately 2 to 4 days after initial symptoms appear, significant liver dysfunction, which may include jaundice, presents. Following the onset of liver involvement, widespread hemorrhage typically ensues. Bleeding from the nose and gums is common, as is hematemesis and blood in the stool (either melena or hematochezia). Purpuric rashes, which can develop into ecchymoses, are also frequently present with this syndrome. This syndrome is associated with a much higher mortality than the other two. Approximately 50% of those individuals who develop the hemorrhagic form of RVF succumb to the disease, and they typically do so within the first week of illness.</div>
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<b>Livestock disease</b> <i>can be quite devastating and is often responsible for the greatest burden of RVF</i>. Rift Valley fever typically causes severe disease in livestock animals much more frequently than it does in humans. In some domestic animals, the mortality attributable to RVF can approach 10%. In addition, spontaneous abortion occurs in almost all pregnant livestock if infection occurs during pregnancy. In fact, <b>widespread spontaneous abortion among livestock populations often signals an RVF epizootic and human epidemic to follow</b>.</div>
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<b>The Epidemiology and the Landscape</b>. The landscape epidemiology of RVF is extraordinarily complex. RVFV is transmitted to humans by way of mosquito vectors, primarily <i>Aedes</i> species, or through <b>direct or aerosol</b> contact with contaminated body fluids of infected livestock during animal husbandry or processing, or by consumption of contaminated animal products. <b>Zoonotic transmission from livestock accounts for the vast majority of human infections</b>. Human to human transmission has not been documented.</div>
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The map below produced by the Centers for Disease Control and Prevention shows the global distribution of RVF. Blue represents countries with endemic disease and substantial outbreaks of RVF, whereas green represents countries known to have some cases, periodic isolation of virus, or serologic evidence of RVF</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhpEdztI7HYO9fto4lGDuSxv37KUf3rY2AaxbLH7petZdSm5nTgR0AxCn3T4BtYLniJdZLKdpMYJYk5N3EsfGBGe4Ajxa4M3pllJ7phQVcXTxhp_YjocLCfQn9FZ6C4obudp9of2MK9ctU/s1600/Rift_valley_fever_distribution.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="203" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhpEdztI7HYO9fto4lGDuSxv37KUf3rY2AaxbLH7petZdSm5nTgR0AxCn3T4BtYLniJdZLKdpMYJYk5N3EsfGBGe4Ajxa4M3pllJ7phQVcXTxhp_YjocLCfQn9FZ6C4obudp9of2MK9ctU/s400/Rift_valley_fever_distribution.jpg" width="400" /></a></div>
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While RVF is demonstrated in much of the African continent, endemicity has only been documented in parts of West, East, southern African, and the Arabian Peninsula. </div>
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<b>The graphic below nicely depicts the key features of the landscape of RVFV transmission and disease ecology</b>. The sylvan infection cycle is maintained <i>directly by multiple mosquito vectors</i> and perhaps some combination of mammal hosts in varied terrain, the full compliment of which is unknown but may include ruminants and rodents as important hosts and perhaps bats to a lesser degree. Mosquitoes also act as bridge vectors for transmission of RVFV to livestock, or less commonly, directly to humans. <i>Transmission to humans occurs most frequently following exposure to their livestock</i>. Thus, animal husbandry is the most significant conduit to human infection in the landscape even though direct transmission from mosquitoes to humans remains a distinctly viable route of infection.</div>
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The complexity of RVF landscape epidemiology is further
compounded by the intersection of specific landscape features with climate factors
and diverse mosquito ecology. In particular, <i>Aedes</i> mosquitoes are primarily
responsible for maintaining endemicity in sylvan and domestic animal
populations. The virus is transmitted transovarially in these <i>Aedes</i> mosquitoes
and, because viremia remains relatively low among all mammalian hosts,
<b>ultimately the mosquitoes act as the primary natural reservoir for RVFV</b>. This
is unusual for arthropod-borne viruses as there is typically a vertebrate host
in the environment that serves as a natural reservoir. The relevant <i>Aedes</i> mosquito vectors oviposit on dry surfaces close to intermittent or standing bodies of water and require a period
of desiccation before hatching. Once they are newly submerged in water
following a period of rain the eggs can hatch and the life cycle can proceed. These mosquitoes, as mentioned, transmit the virus vertically and act as the
primary natural reservoir. These mosquitoes exploit dynamic water habitat in
the landscape, which fluctuates between intermediate dry and wet periods
according to the fluctuations in rainfall. Moreover, they tend to take their blood
meals in proximity to these water sources, which also serve as water sources
for ruminants (sylvan and domestic) and small mammals. These water features tend to be associated with geologic depressions that drain the landscape of water runoff, and are known locally as pans or Dambos.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEji-C1ZQojbBRAms8cFKYHsx_2VMJqJENhQ9qFoTVSwxBN7GkAhy3kn-YynMcFjQpM2F5G3YTpr7mqPRk_DV2ZC8Jd9YzxnoMuxWgaELymSLPjheWXhJgD6jG6YZ5w6rFFKlJXduR2aKgw/s1600/RVF+dambo.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="256" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEji-C1ZQojbBRAms8cFKYHsx_2VMJqJENhQ9qFoTVSwxBN7GkAhy3kn-YynMcFjQpM2F5G3YTpr7mqPRk_DV2ZC8Jd9YzxnoMuxWgaELymSLPjheWXhJgD6jG6YZ5w6rFFKlJXduR2aKgw/s400/RVF+dambo.jpg" width="400" /></a></div>
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<i><span style="font-size: x-small;">Flooded Dambo</span></i></div>
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Thus, as the mosquitoes
respond to and exploit the intermittent cycles of standing water in the
landscape in hyperlocalized habitat, and because they acquire RVFV transovarially, <b>they also maintain enzootic
disease in animals as those animals exploit and
share the same water resources</b>. However, when more extensive water accumulates
in the Dambos, due to periods of greater rainfall and flooding, the ecological
niche expands and allows for population explosions of <i>Culex</i> species. These
mosquitoes cannot transmit the virus vertically, but they do travel much
farther afield in the landscape. After taking blood meals from local mammal
populations whose enzootic levels of virus are maintained by the <i>Aedes</i>
mosquitoes, <i>Culex</i> mosquitoes can then distribute RVFV much more
widely and subsequently spark epizootic disease across a much larger
geographic space. This in turn increases
the likelihood of human epidemic disease. The graphic below visually depicts the nuance of RVF landscape epidemiology and disease ecology.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi7eAFz3Uap47LKFQCZ3SD8zXRgHRYsozmcs1jOU0N9vF5nfTqY6xUauUuTvQNbNk-Ii_tCOxWeQRuoy26VJGwzWXEVzrnhYsNTWmXzTS3S-jjDy8UqJXExHtL4nICtMpwqawib7iNVAxY/s1600/rift+valley+fever+cycle+2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi7eAFz3Uap47LKFQCZ3SD8zXRgHRYsozmcs1jOU0N9vF5nfTqY6xUauUuTvQNbNk-Ii_tCOxWeQRuoy26VJGwzWXEVzrnhYsNTWmXzTS3S-jjDy8UqJXExHtL4nICtMpwqawib7iNVAxY/s640/rift+valley+fever+cycle+2.jpg" width="396" /></a></div>
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<b>Control and Prevention</b>. Rift Valley Fever control is typically focused on livestock protection, which is accomplished through vaccination. There are two vaccines available. One is a single-dose live attenuated virus vaccine and provides good long-term immunity, although it causes spontaneous abortion in a small proportion of cattle. The other vaccine is inactivated and is not associated with aborted pregnancies in livestock, however it requires multiple doses to generate an effective immune response. Regardless of the vaccine used, any RVF intervention in livestock must be implemented before an epizootic emerges. Initiating a livestock vaccination campaign after an epizootic has begun in the livestock population can actually accelerate the outbreak. However, the implementation of these control methods require significant resources because of the costs of vaccination and good livestock infrastructure, neither of which are often available for poor subsistence farmers and herders in many areas where RVF is endemic.<br />
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Prevention of RVF in humans is focused on 1) maintaining hygienic animal processing techniques, particularly barrier protection and sanitary working conditions, to prevent or minimize contact with animal body fluids, 2) avoiding consumption of uncooked or undercooked animal products, and/or raw blood or milk, and 3) vector control, particularly around the home, which typically employs insecticide-treated bed nets and/or residual insecticide spraying.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgS_xKQjVhQE1rFt67Ut7lFedGx5foHZUX38Qmd9ZPYWzurQW7_GmgESmYaUU9UwWA30RNex2qXdmR8RBHoRMF8Vl7VZZiAsTGrsmCX-bjhaHRsGcqn90LzNrnFpTpM3q8dxaLgSMrRc-0/s1600/RVF+control.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="240" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgS_xKQjVhQE1rFt67Ut7lFedGx5foHZUX38Qmd9ZPYWzurQW7_GmgESmYaUU9UwWA30RNex2qXdmR8RBHoRMF8Vl7VZZiAsTGrsmCX-bjhaHRsGcqn90LzNrnFpTpM3q8dxaLgSMrRc-0/s400/RVF+control.jpg" width="400" /></a></div>
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While some of these strategies may be combined with other public health initiatives (e.g., malaria vector control programs), others may not be successfully combined with other programs and may not be adequately resourced to implement independently (e.g. providing rubber gloves, barrier gowns, and sanitary working conditions to all individuals who process cattle for human consumption). Moreover, some strategies may contradict social and cultural norms and thus unable to gain popular acceptance (e.g. consumption of raw cattle blood among some pastoral communities).<br />
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Given the complex landscape epidemiology of RVF with its multiple modes of transmission, mosquito ecology, and virus infection cycle, establishing complete prevention and control measures to effectively block RVFV along all transmission pathways will be very difficult.<br />
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Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com19tag:blogger.com,1999:blog-3492197469143963742.post-3916180986518170982012-10-11T12:13:00.002-04:002012-10-11T12:16:09.020-04:00Crimean–Congo Hemorrhagic Fever<div dir="ltr" style="text-align: left;" trbidi="on">
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This week we cover another virus in the Bunyaviridae family that causes hemorrhagic fever in humans: Crimean–Congo hemorrhagic fever virus. This is a zoonotic arbovirus vectored by ticks and demonstrates a wide geographic range from southern and eastern Europe, across the Middle East and western and central Asia, and down through sub-Saharan Africa. Human infection can be quite severe with high mortality.<br />
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<b>The Pathogen</b>. Crimean–Congo hemorrhagic fever (CCHF) is caused by Crimean–Congo hemorrhagic fever virus (CCHFV), which is a Nairovirus in the Bunyaviridae family. These viruses are approximately 80 to 120 nanometers in diameter. They are enveloped viruses with ambisense, single-stranded RNA genomes in three segments. The three genome segments are circular and are classified as large (L), medium (M), and small (S).<br />
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<span style="font-size: x-small;"><i><span style="text-align: left;">Crimean–Congo hemorrhagic fever virus </span>(Published in <span style="text-align: left; white-space: pre-wrap;">Antiviral Research, Volume 64, Issue 3, December 2004, Pages 145-160)</span></i></span></div>
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<b>Macrophages, hepatocytes and endothelial cells are the target cells in the human host</b> and, like hantaviruses, CCHFV invades host cells by endocytosis and replicates via the ER-Golgi intermediate compartment.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj3BDA4-181cHAXKZV3PPEOX3t5O-xSAb8KxXC3m2MdOQOUC3r_caUrMioNEt57bR7ZD-GY52CxW5LP1OqCDD_s7yb55FWJurq01u0qSG-_r00zgaV6OrKf7S6qnzQLzyOh65e0xJVIUTE/s1600/bunyaviridae+infection+cycle.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="351" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj3BDA4-181cHAXKZV3PPEOX3t5O-xSAb8KxXC3m2MdOQOUC3r_caUrMioNEt57bR7ZD-GY52CxW5LP1OqCDD_s7yb55FWJurq01u0qSG-_r00zgaV6OrKf7S6qnzQLzyOh65e0xJVIUTE/s400/bunyaviridae+infection+cycle.jpg" width="400" /></a></div>
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<span style="font-size: x-small;"><i>Bunyaviridae infection cycle (Published in: <span style="text-align: left; white-space: pre-wrap;">Antiviral Research, Volume 64, Issue 3, December 2004, Pages 145-160</span>)</i></span></div>
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<span style="font-size: x-small;"><span style="font-size: small;"><b>The Vector</b>. CCHFV is vectored by ticks between reservoir hosts, which maintains the natural sylvan infection cycle. However this vector is also very important in introducing the infection to domestic livestock. While tick-borne transmission is a relevant pathway to infection in humans, this mode of transmission generally accounts for sporadic human cases only. On the other hand, outbreaks in humans typically result from contact with infected livestock, which in turn are infected by ticks.</span></span><br />
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<span style="font-size: x-small;"><span style="font-size: small;">The most important tick vectors for CCHFV transmission are those of the genus <i>Hyalomma</i>.</span></span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjF0PJjZFps2Lz0dOXocusN7oQiqk1Zi_q2LnpPVM2SLEg3CgV9k4PwGVTpEvmobDCZxfzXq4iISFmb9VuuX1uX4eDjMGqOFDLyL4UPalOqUjyPKRuy0InU-7bETmPvChd-7xIncJJXRQ0/s1600/Hyalomma_marginatum.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="357" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjF0PJjZFps2Lz0dOXocusN7oQiqk1Zi_q2LnpPVM2SLEg3CgV9k4PwGVTpEvmobDCZxfzXq4iISFmb9VuuX1uX4eDjMGqOFDLyL4UPalOqUjyPKRuy0InU-7bETmPvChd-7xIncJJXRQ0/s400/Hyalomma_marginatum.jpg" width="400" /></a></div>
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<span style="font-size: x-small;"><span style="font-size: small;"> <span style="font-size: x-small;"><i>Hyalomma marginatum</i></span></span></span></div>
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<span style="font-size: x-small;"><span style="font-size: small;">These are hard-bodied ticks in the family Ixodidae. Unlike other hard-bodied ticks, the <i>Hyalomma</i> leave a moderately serious bite wound after detaching, which can often necrotize the surrounding tissue. These ticks are widely distributed throughout Europe, Africa, and Asia. The graphic below developed by the Centers for Disease Control and Prevention (CDC) nicely depicts the two year life cycle of the <i>Hyalomma</i> ticks. </span></span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgHfU2Bh_EYtX-qLIL6HEZVxbwX4rQZOTzSHkf5iAquBENgR2Ri8PZQfQnq92T9NPzKFs4SvywIp6QGDF1D8JhOAH7HoRsx-EYYpn4nKi_buPAxy2xQBJmdV4jNhrfseChKb49sZmxLJXI/s1600/two_host_tick_LifeCycle.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgHfU2Bh_EYtX-qLIL6HEZVxbwX4rQZOTzSHkf5iAquBENgR2Ri8PZQfQnq92T9NPzKFs4SvywIp6QGDF1D8JhOAH7HoRsx-EYYpn4nKi_buPAxy2xQBJmdV4jNhrfseChKb49sZmxLJXI/s400/two_host_tick_LifeCycle.gif" width="400" /></a></div>
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<b>The Reservoir</b>. Small mammals comprise the natural reservoir hosts of CCHFV, with rodents in the genus <i>Mastomys</i>:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjU5LWTMr4iNqOVSmnfeJmZF-wLVtjOfQg3FiWqCWumjmYZL05gS27Epg_pZm1LC5tgfxWK_duHnRzwxpvMSAomoKiet9tPckJGn-3jtinEK36k87HmTvylH-uQZcsTewbOgSROVXGye58/s1600/Mastomys.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="258" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjU5LWTMr4iNqOVSmnfeJmZF-wLVtjOfQg3FiWqCWumjmYZL05gS27Epg_pZm1LC5tgfxWK_duHnRzwxpvMSAomoKiet9tPckJGn-3jtinEK36k87HmTvylH-uQZcsTewbOgSROVXGye58/s400/Mastomys.jpg" width="400" /></a></div>
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the hedgehogs (Erinaceinae subfamily):<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgKm8GobPDOPSv_YBepfpFGqEsBEVQnq83VsG1WOI8mSs3cbKuMNQrskBxkTs5PiOqVO4QfKGqd25RrcvqZltqnP-Wn3nFS_98x9RfONJaaXgJmqs4osD3G874TumiN7TYvy-mOxq5VDw8/s1600/hedgehog.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="275" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgKm8GobPDOPSv_YBepfpFGqEsBEVQnq83VsG1WOI8mSs3cbKuMNQrskBxkTs5PiOqVO4QfKGqd25RrcvqZltqnP-Wn3nFS_98x9RfONJaaXgJmqs4osD3G874TumiN7TYvy-mOxq5VDw8/s400/hedgehog.jpg" width="400" /></a></div>
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and the European Hare (<i>Lepus europaeus</i>):<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEggWJe_R1MtD8DqCx2TYk72w2M-978uyDdJnN7k0aJ_Cspaz15G5-OWdWFl0l8JvQwnvetdUw9UcA7z3Ws-FyI9WTG8LwOAVIBA6E_y7yQC_m9hVqfpXGp-xCMlrxTQiCbenybvwhCPUkI/s1600/european+hare.JPG" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="343" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEggWJe_R1MtD8DqCx2TYk72w2M-978uyDdJnN7k0aJ_Cspaz15G5-OWdWFl0l8JvQwnvetdUw9UcA7z3Ws-FyI9WTG8LwOAVIBA6E_y7yQC_m9hVqfpXGp-xCMlrxTQiCbenybvwhCPUkI/s400/european+hare.JPG" width="400" /></a></div>
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acting as the primary reservoirs throughout most of the range of this virus. <br />
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<b>The Disease</b>. Symptoms typically present with an abrupt onset and include fever, malaise, muscle pain, and headache early in the clinical course. Abdominal pain and nausea, with associated diarrhea and vomiting, respectively, can also present early on in the disease. Hepatomegaly is also a common clinical feature. As the disease progresses in subsequent days confusion and aggression commonly occur in concert with mood swings. Several bleeding symptoms often present with this disease. Petechiae commonly occur on the skin and in the mouth and throat. Intestinal bleeding can produce black stools or frank blood, and hematuria can present with or without visible discoloration. Bleeding from the nose and gums is quite common. By or before the end of the first week of illness, hepatitis is common and liver, renal, and/or pulmonary failure may ensue in those with a severe clinical course. By 10 to 14 days affected individuals begin to recover, but approximately 30% succumb to the infection. <br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEggxSRc4nrN0lSaogIcKJ6AR4sAiEgjNJiTR8ghZb1ELFfUMhZr-vgg2DHrW9EuVlDsxng9MAtrCrPaqQ1fqeX-hgy-eSIO7RO_65DwytSiqdXszWssU0buvQUPz6XLUOD_H3eEfOlEryo/s1600/Crimean-Congo_Hemorrhagic_Fever.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="268" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEggxSRc4nrN0lSaogIcKJ6AR4sAiEgjNJiTR8ghZb1ELFfUMhZr-vgg2DHrW9EuVlDsxng9MAtrCrPaqQ1fqeX-hgy-eSIO7RO_65DwytSiqdXszWssU0buvQUPz6XLUOD_H3eEfOlEryo/s400/Crimean-Congo_Hemorrhagic_Fever.jpg" width="400" /></a></div>
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<span style="font-size: x-small;"><i>Patient with severe petechial rashes (ecchymoses)</i></span></div>
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<b>The Epidemiology and the Landscape</b>. CCHFV is transmitted to humans by the <i>Hyalomma</i> tick vector, as described above, from infected domestic livestock animals, or directly from person to person by way of contaminated blood or body fluid exposure. Vector-borne transmission is typically responsible for sporadic cases, whereas outbreaks typically follow from exposure to contaminated livestock during processing or consumption, or from exposure to contaminated body fluids during the care of infected patients in a clinical setting.<br />
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The map below produced by the World Health Organization (WHO) shows the global distribution of <i>Hyalomma</i> ticks (white and colors), viral- and seroprevalence (yellow), and incident cases (orange and red).<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEibFZMjVUIyLkUOgrUu3AdReUg1bSKx-vtQ6RxLtodQnBd6RF-UeXA2RWTI0KScYYtwsJFw0TYuOutlAqdBTvwc1PxBaFWrOAg5P5TbeAvG0m2E41kencxhwdtLEPj7o9nHkjvN4hNPNgU/s1600/Global_CCHFRisk.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="266" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEibFZMjVUIyLkUOgrUu3AdReUg1bSKx-vtQ6RxLtodQnBd6RF-UeXA2RWTI0KScYYtwsJFw0TYuOutlAqdBTvwc1PxBaFWrOAg5P5TbeAvG0m2E41kencxhwdtLEPj7o9nHkjvN4hNPNgU/s400/Global_CCHFRisk.png" width="400" /></a></div>
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<b>High concentrations of disease activity are apparent in parts of South, Central, and West Asia, and southeastern Europe</b>. While the virus is present in much of Africa, significant numbers of human cases are only seen in South Africa, although this apparent anomaly could be due to under-reporting in several African countries.<br />
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The graphic below nicely depicts the key features of the landscape of CCHFV transmission and disease ecology.<br />
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<i><span style="font-size: x-small;">Sylvan and Human Infection Cycles (Published in Perspectives in Medical Virology, Elsevier, 2006, Volume 16, Pages 299-324)</span></i></div>
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<b>The cycle above highlights different aspects of the complex landscape epidemiology of CCHF</b>. The sylvan infection cycle is maintained by the tick vector and extraordinarily diverse small mammal populations in varied terrain, though many of these species prefer open field and fringe forest and scrub habitats. The same ticks that maintain the sylvan cycle also act as bridge vectors for transmission of CCHFV to livestock, or less commonly, directly to humans. <i>Transmission to humans occurs most frequently following 1) exposure to their livestock or 2) exposure to each other in a health care setting following initial infection and presentation of index cases</i>. Thus, animal husbandry and nosocomial transmission are the most significant conduits to human infection in the landscape even though direct transmission from ticks to humans remains a distinctly viable route of infection.<br />
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<b>Control and Prevention</b>. While most human infections in the outbreak setting are not attributable to tick bites, <i>vector control is still a primary locus of prevention and control of human disease</i>. It is generally comprised of two strategies.<br />
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<b>The first vector control strategy</b> is to take the usual precautions to prevent tick bites in humans and, thus, prevent sporadic cases. Use of long-sleeved shirts and long pants are very effective control measures as these reduce tick access to human skin. However, this approach may not be realistic for those that live or work outdoors in endemic areas during hotter months. As such, <b>individuals who do spend time outside, and are at risk of exposure to ticks, should practice regular body tick checks</b>.<br />
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Here is a nice video on the proper way to remove ticks from the skin:<br />
<iframe allowfullscreen="allowfullscreen" frameborder="0" height="315" src="http://www.youtube.com/embed/0wotB38WrRY" width="420"></iframe>
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<b>The second vector control strategy</b> is to prevent or minimize tick bites in domesticated livestock. This usually includes government regulated tick removal prior to the transport and processing of livestock animals. Acaricides are also frequently used and probably constitute the largest agricultural prevention strategy in many areas. However, both the above livestock vector control methods require significant resources and good livestock production infrastructure, neither of which are often available for poor subsistence farmers and herders in many areas where CCHFV is endemic.<br />
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<b>Another important non-vector control strategy</b> employs good barrier protection and patient isolation to prevent nosocomial spread from infected patients to health care personnel and/or other non-infected patients in a hospital or health care setting. This is a critical component to CCHFV control and prevention as outbreaks often generate many secondary cases by human to human transmission during the care of infected individuals.</div>
Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com18tag:blogger.com,1999:blog-3492197469143963742.post-72464935123988843422012-09-17T12:40:00.001-04:002012-09-17T12:41:22.398-04:00Hantaviruses<div dir="ltr" style="text-align: left;" trbidi="on">
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This week we will discuss the hantaviruses. These viruses are found in three distinct, yet large, regions of the world: Asia, Europe, and the Americas. Moreover, they produce two distinct clinical syndromes delineated by these same regional geographies, hemorrhagic fever with renal syndrome in the Old World, and hantavirus pulmonary syndrome in the New World. These viruses can be highly virulent and result in high mortality.<br />
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<b>The Pathogen</b>. Hantaviruses are in the Bunyaviridae family of viruses. These spheroid viruses are approximately 95 to 110 nanometers in diameter. They are enveloped viruses with negative-sense, single-stranded RNA genomes in three segments. The three segments are classified as large (L), medium (M), and small (S). Each segment has an associated RNA polymerase:<br />
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<span style="font-size: x-small;"><i>Hantavirus structure (Published in JASN December 1, 2005 vol. 16 no. 12 3669-3679)</i></span></div>
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The viruses invade host cells by endocytosis and replicate via the ER-Golgi intermediate compartment. <b>Endothelial cells are the primary target host cells for hantaviruses</b>. <i>Vascular permeability is increased in both pathogenic forms of the disease, and is a key feature of the pathogenesis of these viruses</i>, though hemorrhage and frank renal failure are limited to hemorrhagic fever with renal syndrome (HFRS), while hantavirus pulmonary syndrome (HPS) is characterized by lung involvement.</div>
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<i><span style="font-size: x-small;">Hantavirus Life Cycle (Published in Clin. Microbiol. Rev. April 2010 vol. 23 no. 2 412-441)</span></i></div>
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There are scores of distinct hantavirus species, but the most relevant for human infection are the Hantaan virus of Asia and eastern Europe and the Dobrava virus of southern Europe, which cause HFRS, and the Sin Nombre virus of North America and the Laguna Negra virus and the Andes virus of the Southern Cone of South America, which cause HPS.</div>
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<b>The Reservoir</b>. Rodents serve as the natural reservoir for hantaviruses, though the relevant rodent species differ by geography and virus species.</div>
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The primary reservoir for the Hantaan virus is <i>Apodemus agrarius</i>, which is commonly known as the Striped Field Mouse:</div>
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<i style="text-align: left;"><span style="font-size: x-small;">Apodemus agrarius</span></i>
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This mouse is found from eastern Europe to Japan and is common in both forested and agricultural landscapes, and is, in fact, a common pest to agricultural communities across this very wide geographic region.</div>
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The primary reservoir for the Dobrava virus is <i>Apodemus flavicollis</i>, which is commonly known as the Yellow-necked Mouse:</div>
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<span style="text-align: left;"><i><span style="font-size: x-small;">Apodemus flavicollis</span></i></span>
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This mouse is found in southern Europe in mountainous, forested landscapes.</div>
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The primary reservoir for Sin Nombre virus is <i>Peromyscus maniculatus</i>, which is commonly known as the Deer Mouse:</div>
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<span style="text-align: left;"><i><span style="font-size: x-small;">Peromyscus maniculatus</span></i></span>
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This mouse is found throughout North America and is particularly common in the Mountain West, in forested, or mixed grassland-forested, landscapes.</div>
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The primary reservoir for Andes virus, and the many related viruses, is <i>Oligoryzomys longicaudatus</i>, which is commonly known as the long-tailed pygmy rice rat, or colilargo:</div>
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<i><span style="font-size: x-small;">Oligoryzomys longicaudatus</span></i></div>
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This mouse is common in the mountains regions of Argentina and Chile in forested and shrub landscapes. Several other species in the genus <i>Oligoryzomys</i> can also serve as reservoir species for Andes virus.</div>
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<span style="font-family: inherit;"><b>The Disease</b>. As mentioned above, hantaviruses cause two distinct clinical disease forms: </span>hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS).</div>
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<b>HFRS typically presents with high fever, severe lower back or abdominal pain, and bleeding, petechiae, and disseminated intravascular coagulation</b>. Intestinal problems are common with associated with nausea, vomiting, and diarrhea. Respiratory dysfunction can sometimes present if there is sufficient fluid accumulation in the lungs. <i>Renal dysfunction is the hallmark of HFRS</i>. Hypotension is also common, as is increased heart rhythm and decreased partial pressure of oxygen in the blood. Shock can occur and must be managed accordingly. Macroalbuminuria and renal failure usually present one to two weeks after the onset of initial symptoms. Thrombocytopenia and increased serum creatinine are common laboratory findings. The Hantaan virus and Dobrava virus are the primary species causing most HFRS cases.</div>
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<b>HPS typically presents with high fever, myalgia, headache, but bleeding is not common</b>. The intestinal problems described for HFRS can also present in HPS, including nausea, vomiting and diarrhea. <i>Respiratory symptoms are the hallmark of HPS, but generally NOT during the early period of the infection</i>. Leakage of the alveolar capillary beds leads to fluid accumulation in the alveoli and the later cardiopulmonary symptoms, which include elevated heart rate, rapid breathing, and hypoxia. Thrombocytopenia is common, as it is for HFRS, but hemorrhage is not. Continued loss of fluid into the lungs leads to pulmonary edema, which can be identified radiographically:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj_wLHMxtCmHsTLPDoh86SkpeJ4-cyGrXQGVW-oFQKiUZKxKrFX34K0Cj8wByN5cdV9h87G_T5zhOClCYE8HKxHNwvll58LG9dbAueA-9saDNVTOkTDuzkxIhEp-dh6XFKxS9qfplxEANQ/s1600/hantavirus+pulmonary+syndrome.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="247" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj_wLHMxtCmHsTLPDoh86SkpeJ4-cyGrXQGVW-oFQKiUZKxKrFX34K0Cj8wByN5cdV9h87G_T5zhOClCYE8HKxHNwvll58LG9dbAueA-9saDNVTOkTDuzkxIhEp-dh6XFKxS9qfplxEANQ/s400/hantavirus+pulmonary+syndrome.jpg" width="400" /></a></div>
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Cough and shortness of breath are late stage respiratory symptoms that are common to most patients. Metabolic acidosis can also occur in the later stages. While some degree of proteinuria is also common, extensive renal damage is rare.</div>
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<b>The Epidemiology and the Landscape</b>. The mode of transmission for hantaviruses is from infected rodents to humans via the airborne route. The virus is shed in the stool, urine, and saliva of the rodent reservoirs. As the excreta dry out, the virus remains viable in dust. If the the dust is disturbed, particularly by human activity in enclosed areas, the virus particles can be inhaled as they are introduced into the air. Hantaviruses are not transmissible from person to person.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgpECMcQhseBW2wX01_cK64XWxYqiRo0X85Kmhg_MA-KfjxLJq1hRYzLAs3u6MtgiFlrNg2gu8My4NTic7N1euFGxWe7LxA5K3iG9_iJWPWvsjMhFtuWFHW6T-do7xN-ryUowBgLf7cenA/s1600/hantavirus+landscape.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="308" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgpECMcQhseBW2wX01_cK64XWxYqiRo0X85Kmhg_MA-KfjxLJq1hRYzLAs3u6MtgiFlrNg2gu8My4NTic7N1euFGxWe7LxA5K3iG9_iJWPWvsjMhFtuWFHW6T-do7xN-ryUowBgLf7cenA/s400/hantavirus+landscape.jpg" width="400" /></a></div>
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There are approximately 100,000 incident cases of HFRS, with between 1% and 15% mortality associated with these cases. Good estimates for HPS incidence and HPS-associated deaths are not available, though the incidence is very low in North America. Nevertheless, the mortality attributable to HPS is generally much higher than that attributable to HFRS. Between 30% and 50% of admitted HPS cases do not survive the disease.<br />
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The approximate distribution of concentrated Old World hantaviruses is depicted below in the map by Ho Wang Lee:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEitLI7sB694XAgxgYs001LBY_9FOmUpbuVlHCje_Kj7mfjznyBNwsNlOuvk4ypAnwf8-QgvlTAlCuAvwn0DxRJIHbpk9tXCe_xceRBCG-xxXzQUnLOkKa9rsdDB-bUJrPa6Wk-CGS-1KaI/s1600/Hantaviruses_Asia_Europe.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="253" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEitLI7sB694XAgxgYs001LBY_9FOmUpbuVlHCje_Kj7mfjznyBNwsNlOuvk4ypAnwf8-QgvlTAlCuAvwn0DxRJIHbpk9tXCe_xceRBCG-xxXzQUnLOkKa9rsdDB-bUJrPa6Wk-CGS-1KaI/s400/Hantaviruses_Asia_Europe.gif" width="400" /></a></div>
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Hantaan virus is represented by the shaded areas in northeastern Asia and southeastern Russia, while the shaded areas in southern Europe represent Dobrava virus. The shaded areas in Scandinavia and northwestern Russia represent Puumala virus, which is a less significant cause of human infection. The map above is quite dated, as is obvious from the "U.S.S.R" label. While these approximate areas of concentration are still relevant for today, they are, nevertheless, only approximations and they do only represent the areas of greatest concentration.<br />
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The map below published in the journal <i>Emerging Infectious Diseases</i>, gives a much more accurate distribution of the range and concentration of Hantaan virus in China, as well as the primary rodent reservoir, <i>Apodemus agrarius</i>:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjfwP5BxLCgQewAS_Hw1kbW8mT-PvNhClPBzxOwhiICidoxbJ7s_OKWTDacYc5356dAo_Ezd9GmjpGwFIfy3FqFLQiWA_RZfBKPNwN-EZ9fTR2jHiOA2Ha4fZX5gc-gMDRADB3ooqsJC7I/s1600/hantavirus+china.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="368" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjfwP5BxLCgQewAS_Hw1kbW8mT-PvNhClPBzxOwhiICidoxbJ7s_OKWTDacYc5356dAo_Ezd9GmjpGwFIfy3FqFLQiWA_RZfBKPNwN-EZ9fTR2jHiOA2Ha4fZX5gc-gMDRADB3ooqsJC7I/s400/hantavirus+china.jpg" width="400" /></a></div>
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<span style="font-size: x-small;"><i>Distribution of Hantaan virus in China (Published in: <span style="background-color: white; font-family: Verdana, Arial, Helvetica, sans-serif; line-height: 15.949999809265137px; text-align: left;">Emerg Infect Dis. 2007 Sep)</span></i></span></div>
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The map below depicts the the distribution of New World hantaviruses, with their associated rodent reservoirs in italics.<br />
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<i><span style="font-size: x-small;">Distribution of hantaviruses and their reservoir species in the Americas (Published in: <span style="text-align: left; white-space: pre-wrap;">Virus Research, Volume 162, Issues 1–2, December 2011, Pages 138-147</span>)</span></i></div>
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<b>At its simplest, the landscape of hantavirus infections, whether they are located in the eastern or western hemispheres, is comprised of rodent and human habitats wherein their points of intersection can create loci of zoonotic transmission from the rodents to humans</b>. However, it is insufficient to claim that the landscape epidemiology of hantaviruses can simply be reduced to the contact between rodents (largely mice) and humans. There are, in fact, important features of both the physical and social landscape that determine the degree of contact between humans and the relevant rodent reservoirs.<br />
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<b>For the most part, hantavirus transmission occurs in rural settings regardless of the geographic region or virus species</b>. Nevertheless, the particular rural spaces that facilitate transmission can be different. For example, Hantaan virus infection in humans most commonly occurs in agrarian communities. This is driven in large part by the reservoir host, the Striped Field Mouse (<i>Apodemus agrarius</i>), which can exploit crop fields, and any human structures therein, as a readily available ecologic niche across a large portion of its range. As such, an agricultural landscape facilitates the potential contact between this particular reservoir species and human farmers sharing a common space. In addition, human Hantaan virus infection tends to occur in areas of mid to high precipitation.<br />
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<b>While still a rural infection, Sin Nombre virus, on the other hand, is most common in the arid and semi-arid regions of the mountain west in North America, which only encompasses a part of the wider range of the reservoir host, the Deer Mouse (<i>Peromyscus maniculatus</i>)</b>. Nevertheless, perturbations in climate that lead to higher than normal precipitation can cause dramatic changes in the landscape epidemiology of Sin Nombre virus. In 1993 following an El Nino Southern Oscillation (ENSO), higher than normal levels of precipitation led to exceptionally high production of pine nuts in the southwestern range of the Deer Mouse. Pine nuts are a preferred food source for this mouse and this abundance of food following the ENSO subsequently led to a population explosion in the reservoir host mouse. As such, the contact rate between humans and mice increased as the expanding population of the mice brought them into greater contact with humans in rural settings. This led to a large (and first documented) Sin Nombre virus outbreak in the Four Corners region of the American Southwest. People of the Navajo Nation in particular were greatly affected by this outbreak. <b>It is important to note that human hantavirus infection almost always occurs at the intersection between places of human habitation/occupation and the range of the mouse</b>. Sporadic human infection in a wilderness setting outside the context of a human constructed space is extremely rare. <br />
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<b>Control and Prevention</b>. <i>Rodent control is the primary strategy to control hantavirus infection in humans</i>. While rare in any context, taking precautions to eliminate safe spaces for mice in the home or other structures of human habitation or occupation will eliminate effective human to mouse contact and thus block transmission of hantaviruses. The image below depicts the many areas within household structures that can be exploited by mice: <br />
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<b>It is clear from the picture that a mouse has many opportunities for both food and habitation in and around the home</b>. In order to eliminate safe spaces for mice the following steps can be employed:<br />
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<b>Remove all food sources</b>: Food and garbage should always be kept in <b><u>well-sealed containers</u></b> that cannot be breached by rodents. In addition, as depicted above, pet food and/or garden fruit and vegetables left unattended outside will often attract rodents.<br />
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<b>Household maintenance</b>: Good maintenance both inside and outside the home can be very important in eliminating rodent habitat. On the outside, overgrown plants and shrubs, unattended woodpiles or debris, and unattended outdoor structures can all serve as welcome homes for rodents, and should be be regularly maintained. On the inside, poorly sealed foundations, roofing, vents, and other household structures can provide easy access to the interior of the house and thus provide good mouse habitat. As such, it is very important to maintain good structural integrity of the house to keep the rodents out.<br />
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<b>Pest control</b>: Directly controlling rodent populations can be accomplished by keeping pets, especially cats, in the home, or by setting bait and traps. <b>However, it is <u>extremely important to maintain barrier control</u> when disposing of rodent carcasses or when cleaning or setting traps</b>. <i>Rubber gloves, protective goggles, and a respirator should always be used</i>.<br />
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<b>Special case: Infrequently used or poorly ventilated spaces</b>: Some structures that are infrequently used or are poorly ventilated, such as vacation homes, cabins, workplaces, or even standard basements/cellars, may have rodents and be contaminated with excreta and saliva. When confronted with the need to clean these kinds of spaces, the same barrier protection described above should be used (i.e. rubber gloves, protective goggles, and a respirator). <b>In addition, it may be prudent to spray the floor with a disinfectant that is capable of lysing the envelopes of viral particles <u>before</u> sweeping and cleaning the space</b>.<br />
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Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com16tag:blogger.com,1999:blog-3492197469143963742.post-7623953346822869322012-09-06T10:34:00.000-04:002012-09-06T10:34:26.424-04:00The Hemorrhagic Fevers<div dir="ltr" style="text-align: left;" trbidi="on">
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This week begins a new series on the hemorrhagic fevers. These are typically viral infections that can frequently present with symptoms of bleeding and high fever. However, bleeding is not particularly sensitive or specific for many of the hemorrhagic fevers. Indeed, many of these infections initially present with much more generic, flu-like symptoms. Nevertheless, many of these infections do share two very important features. First, many (but, not all) of the viruses causing hemorrhagic fever are zoonotic in origin, which can create difficulty in identifying the sources of outbreaks, as well as implementing effective control measures. Second, many of these infections are highly virulent and potentially associated with high mortality in outbreak settings. Two of the hemorrhagic fevers have already been covered at Infection Landscapes, namely <a href="http://www.infectionlandscapes.org/2011/01/dengue-part-1-virus-and-global-burden.html" target="_blank">dengue fever</a> and <a href="http://www.infectionlandscapes.org/2011/07/yellow-fever.html" target="_blank">yellow fever</a>.<br />
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<b>Viral hemorrhagic fevers are caused by RNA viruses in the following four families</b>:<br />
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<b>Flaviviridae</b>: These are enveloped viruses with single-stranded RNA genomes. Those that cause hemorrhagic fever are generally arthropod-borne, and include <a href="http://www.infectionlandscapes.org/2011/01/dengue-part-1-virus-and-global-burden.html" target="_blank">dengue virus</a> and <a href="http://www.infectionlandscapes.org/2011/07/yellow-fever.html" target="_blank">yellow fever virus</a>.<br />
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<span style="font-size: x-small;"><i>Dengue virus (cluster of black spots)</i></span></div>
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<b>Bunyaviridae</b>: These are enveloped viruses with single-stranded RNA genomes in three segments. Most of those that cause hemorrhagic fever are arthropod-borne, except the Hantaviruses, which are rodent-borne. These viruses include the Hantaviruses, Nairoviruses, and Phleboviruses.</div>
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<span style="font-size: x-small;"><i>Hantavirus</i></span></div>
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<b>Filoviridae</b>: These are enveloped viruses with single-stranded RNA genomes, further characterized by a distinctive, pleomorphic thread-like structure that can take on circular, branched, or coiled shapes. These viruses cause severe infections in humans, while the natural reservoir is probably fruit bats. These viruses are transmitted zoonotically and nosocomially.</div>
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<span style="font-size: x-small;"><i>Ebolavirus</i></span></div>
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<b>Arenaviridae</b>: These are enveloped viruses with single-stranded RNA genomes in two segments. Those that cause hemorrhagic fevers are generally rodent-borne, and include Lassa virus, Machupo virus, Junin virus, Sabia virus, and Guanarito virus.</div>
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<span style="font-size: x-small;"><i>Lassa virus</i></span></div>
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We have already covered the major hemorrhagic fevers in the Flaviridae family, so these will not be revisited in this series. However, we will cover all the major viruses that cause hemorrhagic fevers in the remaining three families. <b>Next time, we will begin with the Bunyaviridae family, and with the hantaviruses in particular</b>.</div>
Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com4tag:blogger.com,1999:blog-3492197469143963742.post-4085917632472977002012-08-28T15:28:00.002-04:002012-08-28T15:32:13.564-04:00Tapeworms<div dir="ltr" style="text-align: left;" trbidi="on">
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This week at infection landscapes we enter into the second group of flatworms, and the last group of helminths that we will be considering in this extended series. These are the cestodes or, as they are more commonly known, tapeworms. The tapeworm species that most commonly infect humans are <i>Taenia solium</i> (pork tapeworm), <i>T. saginata</i> (beef tapeworm), <i>Diphyllobothrium latum</i> (fish tapeworm), and <i>Echinococcus granulosus</i> (dog tapeworm). Because only <i>T. solium</i> causes a significant public health burden, this species will be the focus of this discussion.<br />
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<b>The Worm</b>. <i>Taenia solium</i> is the pork tapeworm.The <i>Taenia</i> genus is comprised of over 100 species, some of which cause human infection and disease, including <i>T. solium </i>and<i> T. saginata</i>. "Pork" and "beef" tapeworms are actually misnomers, as both <i>T. solium</i> and <i>T. saginata</i> are human tapeworms whose intermediate hosts are pigs and cows, respectively. <b>The adult tapeworm of both species only occurs in the definitive host, which is humans for both helminths.</b><br />
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The <i>Taenia</i> genus is a member of the Taeniidae family, which is a member of the Cestoda class. Cestodes have a unique structure that is quite distinct in many ways from the trematode flatworms. <b>The length of their body is composed of segments, called proglottids</b>. At the anterior portion of the worm is the scolex, which the helminth uses to attach to its host's intestinal epithelium. These helminths do not have a gut tract.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi5Ymvl7NWj47gEd8OvyXZjJ-4_5pwtD6Ec9F6S8YKaPT5_NKFKUKuZQWJvJLZnjIfwFKphTX0UKNjRbNM07ePPBB3EezlzIOy-y1KlOPYse8J7Q7745FrPG8A-iUwBFNG5jRG1DPEkcQc/s1600/Taenia_solium+2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi5Ymvl7NWj47gEd8OvyXZjJ-4_5pwtD6Ec9F6S8YKaPT5_NKFKUKuZQWJvJLZnjIfwFKphTX0UKNjRbNM07ePPBB3EezlzIOy-y1KlOPYse8J7Q7745FrPG8A-iUwBFNG5jRG1DPEkcQc/s640/Taenia_solium+2.jpg" width="403" /></a></div>
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<i><span style="font-size: x-small;">Adult Taenia solium</span></i>
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Notice the individual proglottid segments in the picture above, as well as the scolex at the anterior tip, which appears as a small knob.<br />
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Let's consider the life cycle of <i>T. solium</i>. Embryonated eggs pass in gravid terminal proglottids from infected humans. When the gravid proglottids, or the eggs they contain, are ingested by pigs, porcine infection ensues. <b>The pig is the intermediate host for this helminth</b>.The eggs hatch in the small intestine of the pig, releasing oncospheres into the gut. These oncospheres are hooked larvae, which subsequently penetrate the epithelium of the intestine and migrate to various tissues, usually skeletal muscle tissue, by way of the blood circulation. These oncospheres encyst in the muscle tissue and develop into cysticerci (which is the stage infectious to humans), where they can remain viable for several years before calcifying. It is important to note that, while muscle tissue is the most common site for oncospheres to locate and encyst, they can potentially locate in many other tissues including liver and brain.Human infection occurs following consumption of undercooked pork products from pigs infected with cysticerci. Having reached their human definitive host, the encapsulated cysticerci lose their capsules in the stomach and subsequently enter the small intestine. In the small intestine, the juvenile cestode everts its scolex, which attaches to the intestinal epithelium using four suckers and a crown of small hooks known as the rostellum:<br />
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The juvenile grows into an adult as developing proglottids extend down the length of the small intestine. As described above these proglottids are the individual segments of the helminth:<br />
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<b>Cestodes do not have a digestive tract, so <i>T. solium</i> transport nutrients obtained from the host's meals across the surface of the tegument</b>. As they progress toward the terminal end of the helminth, the proglottids mature. The terminal proglottids are gravid with hundreds of embryonated eggs, which are infectious to the intermediate host (i.e. pig) and, in aberrant infections, they are also infectious to the definitive host (i.e. humans). These gravid proglottids can pass from the human host as single segments or as segment chains. Moreover, they can be expunged passively with feces or they can actively migrate out of the host:<br />
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<b>The adult tapeworm will only develop in humans, not pigs</b>. As described, humans are the definitive hosts, <i>for whom normal transmission of infection occurs following consumption of infectious cysticerci in infected pigs</i>. The adult tapeworms then develop in their definitive hosts following the standard life cycle of normal infections. </div>
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<b>However, humans can acquire aberrant infections outside the normal life cycle</b>. While only the intermediate developmental pathway can proceed in the intermediate pig host:. </div>
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<b><span style="font-size: large;">eggs <span style="font-family: Calibri, sans-serif; line-height: 115%;">→ </span>oncospheres <span style="font-family: Calibri, sans-serif; line-height: 115%;">→</span> cysticerci </span></b></div>
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both the definitive and intermediate developmental pathways can proceed in humans: </div>
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<b><span style="font-size: large;">cysticerci <span style="font-family: Calibri, sans-serif; line-height: 115%;">→</span> juvenile <span style="font-family: Calibri, sans-serif; line-height: 115%;">→</span> adult <span style="font-family: Calibri, sans-serif; line-height: 115%;">→</span> eggs</span></b>, </div>
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<b><span style="font-size: large;">eggs <span style="font-family: Calibri, sans-serif; line-height: 115%;">→ </span>oncospheres <span style="font-family: Calibri, sans-serif; line-height: 115%;">→</span> cysticerci </span></b></div>
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<b>Humans acquire intermediate host infection by consuming water or food that has been contaminated by embryonated eggs from another infected human</b>, or by autoinfection from the adult tapeworm already harbored in the definitive host. Ordinarily, the ingested eggs would simply pass out of the gut of the definitive host and not cause infection, as is the case when humans consume the eggs of the beef tapeworm, <i>T. saginata</i>. However, the oncospheres of <i>T. solium</i> can frequently mistake the human gut for the pig gut because of their similarity, and subsequently these larvae penetrate the gut and migrate to peripheral tissues as if the definitive host were the intermediate host. These aberrant infectious are the source of the major clinical disease and public health burden associated with pork tapeworms. The graphic below developed by the Centers for Disease Control and Prevention (CDC) nicely depicts the life cycle of T. solium:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgVnehyhZvGrn5W2J16QWuhAkfN44Jvut0ZCO-38YOepwwR5N0usnrpIxzTXUbWuD1l-G12WqshrWZOIIvBMfdKt5attxbYO0-aZuS6OFXSDPgQ1fAHrQe747KRwEdq5uJRTIjcFId4GtU/s1600/taenia-solium-life-cycle.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgVnehyhZvGrn5W2J16QWuhAkfN44Jvut0ZCO-38YOepwwR5N0usnrpIxzTXUbWuD1l-G12WqshrWZOIIvBMfdKt5attxbYO0-aZuS6OFXSDPgQ1fAHrQe747KRwEdq5uJRTIjcFId4GtU/s400/taenia-solium-life-cycle.gif" width="312" /></a></div>
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For comparison, another graphic developed by the CDC depicts the life cycle of both <i>T. solium</i> and <i>T. saginata</i> under normal infection cycles: </div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_ijBX6lrzfS7eJwvCBoC6SgXE0tAsU839xyfBcZBpy3YHMHBXb6Q7DAmcyEjZLaYrHgM8EYPqbfm61CqnlVovbGTApJfByVWfa9Oa43lNQAiMqpaCfanAGNbxZ_5_qRe5GnWYYCsc538/s1600/Taenia_LifeCycle.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="315" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_ijBX6lrzfS7eJwvCBoC6SgXE0tAsU839xyfBcZBpy3YHMHBXb6Q7DAmcyEjZLaYrHgM8EYPqbfm61CqnlVovbGTApJfByVWfa9Oa43lNQAiMqpaCfanAGNbxZ_5_qRe5GnWYYCsc538/s400/Taenia_LifeCycle.gif" width="400" /></a></div>
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<b>The Disease</b>. Most taeniasis is asymptomatic. In normal definitive host infections, in which the adult tapeworm inhabits the small intestine, no symptomatic disease occurs, though there is histologic evidence of minor cellular damage at the site of attachment of the scolex. <b>Taeniasis refers specifically to infection with the adult tapeworm in the gut of the definitive host</b>. As such, taeniasis only occurs in humans. The quantity of nutrients the adult helminth takes from the definitive host is negligible. The same is true for <i>T. saginata</i> (beef tape worm), but <b>not</b> <i>D. latum</i> (fish tapeworm), which can deplete the host of vitamin B12 and eventually lead to megaloblastic anemia over a period of years. So, contrary to popular belief, <i>infection with the adult tapeworm does not make you excessively hungry or cause you to lose weight</i>.</div>
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<b>Cysticercosis, on the other hand, is infection with the larval stage tapeworm in peripheral tissues in the intermediate host</b>. Pigs are the normal intermediate hosts and, therefore, the hosts normally affected by cysticercosis. However, as described above, humans can be accidental intermediate hosts if they ingest eggs deposited from another human. Cysticercosis generally presents in muscle tissue, subcutaneously, or in the brain. Subcutaneous and muscle cysticercosis may present with fever and/or pain in nodules under the skin or in muscle tissue, respectively, but these infections are generally mild or asymptomatic. Below is a nice chart that summarizes the transmission cycles and differentiates between taeniasis and cysticercosis (<i>Published in: </i><span style="white-space: pre-wrap;"><i>Sumit Sinha, B.S. Sharma, Neurocysticercosis: A review of current status and management, Journal of Clinical Neuroscience, Volume 16, Issue 7, July 2009, Pages 867-876</i>)</span>:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi4-Ttrx4pmwEjPmCho0IJqh3nKUh8nAwssA6Yu2plQquwYTCPB1eDl-ApVo0MoynYLTEBlmQpWKxpt2IBdG0Q29qhhqtfEaF1J8fpHcYPguoFrQ9kLXmJT2UdTY7cyCxqZi15etBw_r0w/s1600/T.+solium+infection+cycle.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="287" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi4-Ttrx4pmwEjPmCho0IJqh3nKUh8nAwssA6Yu2plQquwYTCPB1eDl-ApVo0MoynYLTEBlmQpWKxpt2IBdG0Q29qhhqtfEaF1J8fpHcYPguoFrQ9kLXmJT2UdTY7cyCxqZi15etBw_r0w/s400/T.+solium+infection+cycle.jpg" width="400" /></a></div>
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<b>Cysticercosis in the brain is referred to as neurocysticercosis and constitutes the most important clinical manifestation of this infection in humans</b>. Oncospheres can locate and encyst in brain parenchyma, in the subarachnoid space, or in the ventricles. Here is an example of extensive infection with intraparenchymal cysts:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjlSqTK5UTP-bN0Oj71XfsWvKe237Xk0S4sfE3g8iHOBHZRVrZ94gS1Uz-Wx_ZZR6bF2hSqu7gmLnAPMZM5VaTwWM63ZRpU8PjKF3AnOmrQ1omrKzqA5qJFMrR8RtcSx33OTfnr3G9A7Vs/s1600/neurocysticercosis.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="271" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjlSqTK5UTP-bN0Oj71XfsWvKe237Xk0S4sfE3g8iHOBHZRVrZ94gS1Uz-Wx_ZZR6bF2hSqu7gmLnAPMZM5VaTwWM63ZRpU8PjKF3AnOmrQ1omrKzqA5qJFMrR8RtcSx33OTfnr3G9A7Vs/s400/neurocysticercosis.jpg" width="400" /></a></div>
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The inflammatory response to intraparenchymal cysts, or later edema surrounding calcified lesions, is the primary mediator of symptoms. The most common clinical presentation of neurocysticercosis is seizure. When cysts grow in the subarachnoid space or the ventricles, cerebral spinal fluid can be blocked leading to hydrocephalus and/or intracranial hypertension, which are associated with greater mortality. Psychiatric disorders and neurologic deficits can also present. </div>
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<b>The Epidemiology and the Landscape</b>. There are an estimated 50 million people infected with neurocysticercosis across the world, with approximately 50,000 deaths each year, though these are both likely to be underestimated, particularly the prevalence. Globally, <i>T. solium</i>, and cysticercosis in particular, is widely distributed across Latin America, South, Southeast, and East Asia, most of sub-Saharan Africa, and some islands of the Pacific, wherever pigs are part of the agricultural landscape and raised for food. The map below produced by the World Health Organization displays the global distribution of cysticercosis risk based on country-specific prevalence:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEie14WOK4AJtu_1QyxF_UE8baxsWPfDX96iCstRrw_mcJMmuBAqZ2g9tTiJEqLBERXnP01eC8XRCbqq18j6nfMP-QcccX47Mi9J9vVPoZpMOKQRVmSv9PcPMUqIlF9MT_4exUgAaR8DmYQ/s1600/Global_cysticercosis_2009.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="280" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEie14WOK4AJtu_1QyxF_UE8baxsWPfDX96iCstRrw_mcJMmuBAqZ2g9tTiJEqLBERXnP01eC8XRCbqq18j6nfMP-QcccX47Mi9J9vVPoZpMOKQRVmSv9PcPMUqIlF9MT_4exUgAaR8DmYQ/s400/Global_cysticercosis_2009.png" width="400" /></a></div>
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<b>The landscape of <i>Taenia</i> infections is fundamentally one of animal husbandry</b>. Perhaps more than any other helminth infection, human tapeworms are both culturally and evolutionarily derived from the relationship between humans and their livestock. This is the case for both human tapeworms, <i>T. solium</i> and <i>T. saginata</i>. This unique relationship between definitive and intermediate hosts, wherein the former consumes the latter, is necessary for the helminth to complete its life cycle. Infection derives from two fundamental points of intersection in the landscape: 1) the move to agricultural economies with the domestication of subsistence animals in the course of human evolution, and 2) the contamination of the human environment with human feces due to a lack of sanitation and good water infrastructure.</div>
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<b>Control and Prevention</b>. Given that there are multiple modes of transmission of <i>T. solium</i> to humans, there are also multiple potential points to block transmission. Let's discuss these in the context of the two types of human infection, 1) as definitive host, and 2) as accidental intermediate host.<br />
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1) As described above, human infection with the adult tapeworm is essential to the tapeworm's life cycle since humans are the sole definitive host. Thorough cooking or freezing of pork products destroys cysticerci and prevents infection with the adult tapeworm in humans.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjcxbQC_R778v2dnXKAlgXmrFpTYOqzdZktKxunF8F3_72ghyphenhyphen6rKGm7uWAKKMvmQvJyRAeUTah1SkDrRY_ujRwKgfIvSJzH1PZruS3Ssrbnbl4j8rA28kgZhJZRK8T_A_uxcgULaSCkoVo/s1600/Pork_Cuts.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="205" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjcxbQC_R778v2dnXKAlgXmrFpTYOqzdZktKxunF8F3_72ghyphenhyphen6rKGm7uWAKKMvmQvJyRAeUTah1SkDrRY_ujRwKgfIvSJzH1PZruS3Ssrbnbl4j8rA28kgZhJZRK8T_A_uxcgULaSCkoVo/s400/Pork_Cuts.png" width="400" /></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhD0gUIGVRqFiBhTe9SulLoYvkfiimVtyBErGeKvCutZv7H47-vOipHV7E1HU-WVi98ouBph2O3OXdeoVTNFpoh4AQCvVlik8d_YrWqSooKJccmNHBQf4NMBMaW643tV7umCM_gO97oRzw/s1600/pork_ribs.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="240" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhD0gUIGVRqFiBhTe9SulLoYvkfiimVtyBErGeKvCutZv7H47-vOipHV7E1HU-WVi98ouBph2O3OXdeoVTNFpoh4AQCvVlik8d_YrWqSooKJccmNHBQf4NMBMaW643tV7umCM_gO97oRzw/s320/pork_ribs.jpg" width="320" /></a></div>
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This intervention, while fairly simple, is the only one which can be implemented on an individual basis at the level of the household. To block other transmission pathways, larger community-wide strategies are required.<br />
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2) As described above, humans are also capable of being infected as intermediate hosts when they ingest the eggs of <i>T. solium </i>(or also possibly by autoinfection following infection as the definitive host). Because only humans harbor the adult tapeworm, only humans pass eggs in their feces, which means human feces are the essential source of infectious embryonated eggs. As such, good sanitation and water infrastructure are important in blocking the transmission of the eggs to both humans and pigs, and would thus have wide impact on reducing intermediate host infection in both pigs and humans.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjr5DX5U2_Mgxd9626TSWxuUX-8-AKf9KiULGSLiplCui0u92hfC81wNYVwc73CEbTA36YyYrJggsXKJhGrvLbImG_2HjTryY9M7eHl1eRQ6VoBss2GA2FR0KxcE-kSQ34sJ2uaKIi3Xo0/s1600/toilet+1.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjr5DX5U2_Mgxd9626TSWxuUX-8-AKf9KiULGSLiplCui0u92hfC81wNYVwc73CEbTA36YyYrJggsXKJhGrvLbImG_2HjTryY9M7eHl1eRQ6VoBss2GA2FR0KxcE-kSQ34sJ2uaKIi3Xo0/s400/toilet+1.jpg" width="300" /></a></div>
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<i><span style="font-size: x-small;">Western-style flush toilet</span></i></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEie5vwMv-Dw_BX7yBL1twcu0hO_XjkyJiZjZ3Bpkjho1ePeinV6Y1fjJ_D7ga9JqzBkOX7uR2gjuY_sTK5sAw0kOopgVEjUJYUb0YYTq4Vu_4E8tvoAKZqTkbt7RCvS4ranim3CEn0xuNs/s1600/toilet+2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="240" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEie5vwMv-Dw_BX7yBL1twcu0hO_XjkyJiZjZ3Bpkjho1ePeinV6Y1fjJ_D7ga9JqzBkOX7uR2gjuY_sTK5sAw0kOopgVEjUJYUb0YYTq4Vu_4E8tvoAKZqTkbt7RCvS4ranim3CEn0xuNs/s320/toilet+2.jpg" width="320" /></a></div>
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<b>Of course, maintaining vigilance in personal hygiene is also critical to stop human to human transmission of aberrant infections at the level of the household</b>. However, while good personal hygiene will block aberrant human infections and thus prevent human cysticercosis, it will not block normal infections with the adult tapeworm, and thus cannot be expected by itself to contribute substantively to reducing the global burden of pork tapeworm infections. </div>
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Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com35tag:blogger.com,1999:blog-3492197469143963742.post-59748128320770647232012-08-07T10:57:00.000-04:002012-08-07T10:57:07.489-04:00Lung Flukes: Paragonimiasis<div dir="ltr" style="text-align: left;" trbidi="on">
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This week at Infection Landscapes we will cover the last of the trematodes included in the extended series on helminths. Paragonimiasis is caused by several species of the genus <i>Paragonimus</i>. <i>Paragonimus westermani</i> causes most human infections, and is commonly known as the lung fluke. Lung flukes are probably the most widely distributed trematodes in the world.<br />
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<b>The Worm</b>. <i>Paragonimus westermani</i> is a trematode helminth and, because it is responsible for most human infections, this species will be the focus of the current discussion:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjXky_WWPJvKQ2csV4HdaUj3jXjzPbSwW4Qssj1GZPxlEIp8RRX3pl2qC2g6JXLYYIfsSNW87AMG4KvJJvmShPpiQK9c7FDYtfSr92TsfAYZ3efAd_xBvdGprIrmuC7Rx4h9WKeUPIxxvY/s1600/Paragonimus+westermani+2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="266" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjXky_WWPJvKQ2csV4HdaUj3jXjzPbSwW4Qssj1GZPxlEIp8RRX3pl2qC2g6JXLYYIfsSNW87AMG4KvJJvmShPpiQK9c7FDYtfSr92TsfAYZ3efAd_xBvdGprIrmuC7Rx4h9WKeUPIxxvY/s400/Paragonimus+westermani+2.jpg" width="400" /></a></div>
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<span style="font-size: x-small;"><i>Adult Paragonimus westermani</i></span></div>
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<b>This helminth's life cycle requires 2 intermediate hosts and a definitive host, the latter of which includes many mammal species including humans</b>.<br />
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Unembryonated ova are expunged in the sputum or feces of an infected definitive host, which may be a human or one of several mammal species. The ova embryonate in freshwater, thus after being expunged from the host they must come into contact with an appropriate water source in the environment. After approximately three weeks, the eggs hatch and the miracidia emerge, which are motile and subsequently seek their first intermediate host. Freshwater snails of the <i>Melanoides</i>, <i>Semisulcospira</i>, and <i>Thiara</i> genera are the most common first intermediate hosts, depending on the the local biogeography and ecology. After penetrating the snail, the miracidia migrate to the hepatopancreas
where the develop first into sporocysts, then into rediae, and finally
into cercariae. The cercariae then exit the snail returning to the aquatic environment. As with the other trematodes we have covered, these cercariae are motile but they are not swimmers. Instead the cercariae of <i>P. westermani</i> are crawlers and seek out their second intermediate hosts by crawling along the bed of their local body of water. Crustaceans serve as the second intermediate host, particularly freshwater crabs or crayfish. The cercariae penetrate their crustacean hosts and then encyst (usually in muscle tissue, but also under the shell), subsequently developing into metacercariae, which is the stage that is infectious to their definitive hosts. When raw or undercooked crabs or crayfish are eaten by humans (or other definitive hosts), viable metacercariae are ingested with the crustaceans. These metacercariae excyst in the small intestine, penetrate the epithelium of the gut, and enter the abdominal cavity where they develop into immature flukes. The immature flukes migrate up to and penetrate the diaphragm and enter the lungs. In the lungs the flukes complete their development, form adult pairs, and encapsulate in peripheral lung tissue. The mature adult pairs begin cross-fertilization and subsequent release of eggs into the lung tissue surrounding the trematode capsule. Approximately one months is required from the time of ingestion of the metacercariae to the time when adult flukes begin releasing eggs into host tissue. These eggs eventually reach the bronchioles and are coughed up with sputum, which may also contain blood. The eggs can contaminate water directly by the introduction of the sputum to the relevant water source, or they can be swallowed and passed in the feces of the host. The graphic below developed by the Centers for Disease Control and Prevention nicely depicts this life cycle:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiZn05DH9LzkqRoe_Xpuks4I25_WUOtmh5iW1VuB2YHOzTYj97wYQ2TX7GyVnHBE3jZ8XFbzj7Ip_5vLtyr_oQNdaLnlo6mv6caqDI5l7ah9nPWRwxJgoE0FOV7tduagLcfOwWKLPmJ9kY/s1600/Paragonimus_LifeCycle.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="335" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiZn05DH9LzkqRoe_Xpuks4I25_WUOtmh5iW1VuB2YHOzTYj97wYQ2TX7GyVnHBE3jZ8XFbzj7Ip_5vLtyr_oQNdaLnlo6mv6caqDI5l7ah9nPWRwxJgoE0FOV7tduagLcfOwWKLPmJ9kY/s400/Paragonimus_LifeCycle.gif" width="400" /></a></div>
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<b>The Snail.</b> Species in the
<i>Melanoides</i>, <i>Semisulcospira</i>, and <i>Thiara</i> genera are
the preferred first intermediate host for <i>Paragonimus</i> spp.
These are all freshwater snails that can exploit lentic and lotic aquatic environments, and some (<i>Melanoides</i>) are burrowers:</div>
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<i>Melanoides tuberculata</i></div>
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<b>These snails are widely distributed throughout the world</b>. <i>Melanoides tuberculata</i>,
in particular, is distributed as a native species across most of
sub-Saharan Africa and many micro-environments of North Africa, and most
countries of South, Southeast, and East Asia. The species has been
introduced into the western hemisphere and is now also widely
distributed across North, Central, and South American, and across many
islands of the Caribbean.</div>
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<b>The Crustacean</b>. Where most human
infections occur by consumption of undercooked crab meat (East
Asia), species in the <i>Eriocheir</i>, <i>Potamon</i>, <i>Potamiscus</i> genera are important second intermediate hosts for <i>Paragonimus</i> spp. These
are freshwater crabs that also are widely distributed and serve as food species for humans.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_aCh9Y1eOGTKd3nhqDnXLM3homdZIirbg-CvnO_KgT1HHH_qRBBiuKYG5H3rmeWbmC5yYjBOGJA9IQ6Sx_ExWKJYqXHQZ3cZkcG8HTWLQ48F5olKrXqIdKfK0q2_lXqpMoSTDnIdsvgI/s1600/EriocheirSinensis.jpg" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="260" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_aCh9Y1eOGTKd3nhqDnXLM3homdZIirbg-CvnO_KgT1HHH_qRBBiuKYG5H3rmeWbmC5yYjBOGJA9IQ6Sx_ExWKJYqXHQZ3cZkcG8HTWLQ48F5olKrXqIdKfK0q2_lXqpMoSTDnIdsvgI/s400/EriocheirSinensis.jpg" width="400" /></a></div>
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<span style="font-size: x-small;"><i>Eriocheir sinensis</i></span><br />
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Crayfish,
which are crustaceans in the superfamilies Astacoidea and
Parastacoidea, are also important second intermediate hosts for <i>Paragonimus</i> spp. As these crustaceans also serve as food items, these too can be important sources of transmission to humans.</div>
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<b> </b><span style="font-size: x-small;"><i>Austropotamobius pallipes</i></span></div>
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<b>The Disease</b>. The adult stage of
<i>P. westermani</i> forms cysts in pulmonary tissue, which can
breach the bronchioles.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhZrr4LIMG2Ky1nW3_-inBSgqeoOpcn0c0Sffa5M8Vy8_ZIMQF4HrBlbozn5AEmvRsdiUB1Kd83F5dAhOzwG9BZz5iUkfOwVR3Wbcr7cJRd6ycBSIf0UskTkc1l1QNhfvGC2HVSRYPi3Hw/s1600/paragonimiasis+in+dog+lung.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="290" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhZrr4LIMG2Ky1nW3_-inBSgqeoOpcn0c0Sffa5M8Vy8_ZIMQF4HrBlbozn5AEmvRsdiUB1Kd83F5dAhOzwG9BZz5iUkfOwVR3Wbcr7cJRd6ycBSIf0UskTkc1l1QNhfvGC2HVSRYPi3Hw/s400/paragonimiasis+in+dog+lung.jpg" width="400" /></a></div>
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<i><span style="font-size: x-small;">Dog lung with many P. westermani cysts (From the Web Atlas of Medical Parasitology)</span></i></div>
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Light infections are often asymptomatic.
However, symptomatic cough is not uncommon even in low volume
infections. With higher volume infections, cough can become chronic
with hemoptysis. Chest pain and difficulty breathing can also
present, which are often more common following secondary bacterial
infection and abscess development. With severe infections, particularly in
the presence of frequent secondary bacterial infection, pneumothorax and
pleural effusion are significant complications.</div>
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<i><span style="font-size: x-small;">Arrows pointing to the position of Paragonimus flukes in lung tissue</span></i></div>
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<b>The Epidemiology and the Landscape</b>.
<i>Paragonimus</i> spp. are the most widely distributed trematode
helminths in the world. These flukes are endemic in a great
diversity of reservoir hosts across South, Southeast, and East Asia,
the Pacific Islands, North and sub-Saharan Africa, and North and
South America. Definitive reservoir hosts include dogs and cats,
pigs, leopards, tigers, foxes, wolves, opossums and minks. Lung
flukes constitute an incredibly adapted helminth capable of
exploiting a great diversity of ecologic niches across incredibly
varied geography. There are approximately 22 million human infections
worldwide, but most occur in East and Southeast Asia. In
some communities in China, the prevalence of human infection
approaches 20%. The map below, produced by the Imaging of Tropical Diseases, depicts the global distribution of human infection with <i>P. westermani</i>:<br />
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You can see in the map that most human cases are concentrated in South, Southeast, and East Asia, with additional clusters in the tropical and subtropical belts of Africa and Central and South America. Nevertheless, given the extremely wide geographic distribution of this and other <i>Paragonimus</i> species, these areas of endemicity do not define strict limits of occurrence.</div>
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<span style="font-family: inherit;"><span style="background-color: white; color: #333333; line-height: 18px;">The landscape epidemiology of lung flukes in general, and <i>P. westermani</i> in particular, shows that these trematodes require a second intermediate host, which transfers the infectious metacercariae passively (through consumption) to the definitive host. This means that the point of intersection between pathogen and host in the landscape derives from a complex and layered ecologic framework. <b><i>Paragonimus</i> trematodes require a nuanced and specific engagement of the definitive host with the aquatic environment, i.e. through the harvesting of food from the water</b>. However, this landscape, as narrowly described so far, is not sufficient by itself for infection transmission to humans. For human transmission to occur, the physical landscape that defines the geography and structure of <i>Paragonimus</i> ecology must intersect the human social landscape. <b>This is because human, or other animal reservoir, feces (or, less likely, sputum) must first contaminate the same water sources that humans then subsequently harvest for food</b>. This happens primarily through 1) poor sanitation and water infrastructure, and 2) contamination of water sources by domestic or sylvan animals that serve as the natural reservoirs for this trematode. </span><span style="background-color: white; color: #333333; line-height: 18px;">Regardless, even given the correct environmental circumstances for transmission to humans, <i>eating the metacercariae-infested crustaceans need not transmit the infection to humans</i>. <b>It does so only because of the method of preparation of the crustaceans</b>. </span><span style="background-color: white; color: #333333; line-height: 18px;">I</span><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">n many places where <i>P. westermani</i> is endemic, raw crab or crawfish is a key ingredient in some local delicacies (e.g. drunken crab), so food preparation, as determined by cultural preference, becomes</span><span style="background-color: white; color: #333333; line-height: 18px;"> a key aspect of the social landscape that converges with the physical landscape to effect</span><span style="background-color: white; color: #333333; line-height: 18px;"> transmission.</span></span>
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<b>Control and Prevention</b>.</div>
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<i><u><span style="font-family: inherit;">Snail Control</span></u></i></div>
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<span style="font-family: inherit;">Early (and some ongoing) attempts at lung fluke<i> </i>elimination focused on gastropod control in various surface water sources. Typically, these control campaigns have involved the chemical treatment of freshwater sources to eliminate the local snail population, thus blocking the transmission of <i>P. westermani</i> at the first intermediate host. However, two important problems make gastropod control unrealistic in many settings. </span></div>
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<span style="font-family: inherit;"><b>First</b>, the chemical treatment of water sources can have much broader ecologic impact than what is intended by the public health initiative. Introducing toxic agents into surface water may kill the snails, but it can also harm other organisms in the aquatic ecosystem and result in unanticipated and detrimental ecologic effects. Some investigations have explored the possibility of introducing biologic mechanisms of control to supplant chemical treatment with more "natural" mechanisms. However, these approaches can also be dangerous if the natural biologic mechanisms involve the introduction of non-native invasive species into the aquatic environment. </span></div>
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<span style="font-family: inherit;"><b>Second</b>, whether chemical or natural, snails in most areas prove robust to elimination. Both their high reproductive capacity and diffuse distribution within the aquatic system usually allow some members of the population to survive, which can then re-populate the local environment fairly quickly.</span></div>
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<u><i><span style="font-family: inherit;">Food Preparation</span></i></u></div>
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<span style="font-family: inherit;"><b><span style="line-height: 18px;">Thorough cooking of all freshwater crustaceans is very important for blocking transmission of </span><i style="line-height: 18px;">P. westermani</i></b><b> to humans</b>. Cooking kills the metacercariae and, thus, directly prevents infection in humans. Cooking is probably the most effective method of control and prevention of <i>P. westermani </i>infection. However, in many places where this helminth is endemic, certain local delicacies require raw crustaceans as central ingredients. As such, consistent cooking of crustaceans in each household becomes an individual choice that may be <span style="line-height: 18px;">superseded by cultural dietary norms and preferences.</span> </span></div>
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<br />
<br /></div>Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com3tag:blogger.com,1999:blog-3492197469143963742.post-43056398512163125052012-07-19T12:08:00.001-04:002012-07-19T12:08:09.577-04:00Liver Flukes Part 2: Fascioliasis<div dir="ltr" style="text-align: left;" trbidi="on">
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This week at Infection Landscapes we will cover another group of liver flukes, the trematodes <i>Fasciola hepatic</i> and <i>Fasciola gigantica</i>, which cause fascioliasis. These liver flukes cause enzootic disease, so human disease results from zoonotic infection. Globally, <i>Fasciola</i> liver flukes are also the most widely distributed, although they do not cause the largest overall burden of liver fluke disease.<br />
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<b>The Worm</b>. As mentioned above, these two <i>Fasciola</i> species are trematode flatworms.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgx2JzYlF5aJh43cWpPcclulaZiMQTj3e9wDQyv1M3LcRmRQB6HDgFYHsKJr-lIFikyOcfcCx-4_cE2cHqYRlmtZIJA0PyJ5B7glppDXmthXDgzdukEZakupFJSTTu0N3Mmsao_AsDxzTE/s1600/Fasciola_hepatica.JPG" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgx2JzYlF5aJh43cWpPcclulaZiMQTj3e9wDQyv1M3LcRmRQB6HDgFYHsKJr-lIFikyOcfcCx-4_cE2cHqYRlmtZIJA0PyJ5B7glppDXmthXDgzdukEZakupFJSTTu0N3Mmsao_AsDxzTE/s400/Fasciola_hepatica.JPG" width="400" /></a></div>
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<span style="font-size: x-small;"><i>Fasciola hepatica adult</i></span></div>
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<i>F. hepatica</i> and <i>F. gigantica</i> have very similar life cycles (although they probably have different intermediate host preferences based on the differences in the geographic distribution of freshwater nails), so we will consider their life cycle in common.<br />
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<b>Unembryonated eggs are passed in the feces of an infected definitive host, the natural reservoir of which is ruminants</b>. The eggs embryonate in freshwater and miracidia emerge over the course of one to two weeks. These miracidia then seek out and penetrate their intermediate hosts, freshwater snails. After entry into the snail, the miracidia migrate to the hepatopancreas where the develop first into sporocysts, then into rediae, and finally into cercariae. The motile cercariae exit the snail and seek out the littoral zone, attach to vegetation, usually aquatic, and encyst. Encysted, the cercariae develop into metacercariae, which is infective to the definitive host. When these encysted metacercariae are eaten by a ruminant (or human) incidental to the ingestion of the food vegetation, infection is initiated. Infection can also occur by drinking water contaminated with encysted metacercariae, which is also fairly common. The metacercariae excyst in the small intestine, penetrate the epithelium of the gut, and migrate intraperitoneally to the liver. The metacercariae then gain the liver directly by piercing the collagenous capsule surrounding it. Development is completed in the liver tissue and requires approximately four months to adulthood. At this point, the adults typically reside in the bile ducts. These trematodes feed directly on the liver tissue and on the epithelium of the bile ducts. Tens to hundreds of thousands of eggs can be produced per day, depending on the infection volume, and infections can last years. A nice graphic below produced by the Centers for Disease Control and Prevention depicts the life cycle:<br />
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<b>The Snail</b>. Freshwater snails of the family Lymnaeidae serve as the intermediate host for <i>F. hepatica</i>. There are many species in this family that are capable of serving as the intermediate host. One of the most common freshwater snail host species is <i>Galba truncatula</i>:<br />
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<i>Galba truncatula</i></div>
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This freshwater snail is an air breather and prefers shallow lentic or wetland environments.</div>
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<b>The Disease</b>. Most light infections are asymptomatic. Clinical disease presents in two forms, acute and chronic. </div>
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<b>Acute disease results from the the migration of the metacercariae through liver tissue</b> (or other organ tissue if other organs are invaded). Common symptoms in acute disease include fever, abdominal discomfort, hepatomegaly and/or splenomegaly, anemia, nausea, anorexia, and jaundice, though this last symptom may or may not present. </div>
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<b>Chronic disease results from the adult trematodes taking up residence in the bile ducts</b>. Their presence induces inflammation and an epithelial hyperplasia of the bile duct, which, in concert with the adults' large size, obstruct the passage of bile from the liver.<br />
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Symtpoms include chronic and pronounced abdominal pain, nausea, hepatomegaly, and a greater likelihood of jaundice. Calculi formation in the gall bladder and bile ducts is also common in chronic disease, which further contributes to intolerance of foods with high fat content.<br />
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<b>The Epidemiology and the Landscape</b>. Globally, there are between 2 and 3 million people infected with <i>Fasciola</i> spp. The occurrence of human fascioliasis is highly variable across geography, but livestock farming is central to the epidemiology and ecology of this infection. The greatest burden in the world occurs in the Andean region of Peru, Ecuador, and Bolivia, where the prevalence in some communities can range between 75% and 100%. Prevalence can also be locally high in parts of some Caribbean islands, particularly Cuba and Puerto Rico. On the other hand, while animal husbandry is quite common across much of the southern cone of South America, North America, and much of Asia, these are typically areas of very low endemicity or only sporadic incidence. Countries of the Mediterranean can have high levels of endemicity depending on the specific region. For example, some communities in the Nile delta, Turkey, and Iberian Peninsula have relatively high prevalence. In Asia, the greatest prevalence occurs in Iran, while countries in east Asia only demonstrate sporadic human cases.<br />
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In contrast to human fascioliasis, enzootic disease is very widely distributed across all of Africa, Asia, and the Americas, demonstrating endemicity in livestock in most regions of the world where livestock is present.<br />
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<b>Animal husbandry underlies the ecology and epidemiology of fascioliasis</b>. Human infection is fundamentally zoonotic, passed to humans from their livestock animals (although, in hyper- or holoendemic areas transmission between humans via contaminated water sources may play a significant role). Most frequently, the natural reservoirs are sheep or cattle, though many other ruminants are capable of becoming infected. Nevertheless, there is great geographic variation in the occurrence of human fascioliasis even among countries or regions that exhibit similar levels of livestock farming. <i>Therefore, while the presence of livestock is a necessary, and perhaps defining, component of the landscape for the transmission of F. hepatica to humans, it is not sufficient for transmission</i>. Critically there must also be regular points of contact between livestock and surface water. Moreover, the surface water must comprise an appropriate lentic environment with sufficient vegetation in the littoral zones and the presence of the appropriate snail populations:<br />
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As such, areas of high endemicity typically demonstrate a lack of adequate protection of surface water, which allows regular contamination of the water by livestock animals. The effects of such contaminated water may be less among communities that do not draw domestic water supplies from surface water, but those that do are at much greater risk because their water supply has not been protected, and also because of the poorer water infrastructure and sanitation overall.<br />
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Finally, the degree of subsistence on vegetation obtained in the littoral zone (e.g. watercress) will also contribute to the prevalence of human fascioliasis, as this is the most direct mode of transmission and the one which largely defines the infection ecology for ruminants.<br />
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<b style="background-color: white;">Control and Prevention</b><span style="background-color: white;">.</span><br />
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<i><u><span style="font-family: inherit;">Snail Control</span></u></i></div>
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<span style="font-family: inherit;">As with other trematodes, early (and some ongoing) attempts at fascioliasis<i> control</i> focused on gastropod control in various surface water sources. Typically, these control campaigns have involved the chemical treatment of freshwater sources to eliminate the local snail population, thus blocking transmission of <i>Fasciola</i> spp. at the intermediate host. However, two important problems make gastropod control unrealistic in many settings. </span></div>
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<span style="font-family: inherit;"><b>First</b>, the chemical treatment of water sources can have much broader ecologic impact than what is intended by the public health initiative. Introducing toxic agents into surface water may kill the snails, but it can also harm other organisms in the aquatic ecosystem and result in unanticipated and detrimental ecologic effects. Some investigations have explored the possibility of introducing biologic mechanisms of control to supplant chemical treatment with more "natural" mechanisms. However, these approaches can also be dangerous if the natural biologic mechanisms involve the introduction of non-native invasive species into the aquatic environment. </span></div>
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<span style="font-family: inherit;"><b>Second</b>, whether chemical or natural, snails in most areas prove robust to elimination. Both their high reproductive capacity and diffuse distribution within the aquatic system usually allow some members of the population to survive, which can then re-populate the local environment fairly quickly.</span></div>
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<i><u>Environmental Maintenance and Livestock Surveillance</u></i><br />
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<b>Focusing on the aquatic environment can be a useful approach to preventing human fascioliasis</b>. For example, thinning aquatic plants in the littoral zones of surface water can remove a major exposure point for humans and their livestock. This is especially relevant for agricultural and pastoral communities that may come into frequent contact with these zones. However, any such "aquatic gardening" should be conducted in an ecologically informed and sensitive way so that the larger lentic ecosystem is not damaged by the helminth control measure. <b>In addition, direct protection of the water supply can be effective in blocking transmission</b>. Restricting contact between livestock and the water sources used for household consumption or crops is the primary means of water protection. However, in communities hyperendemic for fascioliasis, protecting the water supply from livestock will not be sufficient to block transmission. These communities also face the problem of water contamination with human feces. Hyperendemic areas are also typically areas of poor sanitation and water infrastructure, so blocking transmission in this setting will be more difficult without infrastructural development.<br />
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Surveillance of cattle for infection with <i>Fasciola</i> spp. can dramatically help to reduce the burden of disease in livestock, which can then secondarily reduce the burden in humans. A good surveillance system will employ regular serology screening to monitor infection in livestock animals and administer treatment to the infected animals. However, this kind of surveillance is very expensive as it requires laboratory technicians and supplies, highly trained field personnel, and veterinary treatment on a large scale. While high income countries with sporadic cases may be able to afford these methods, they will obviously be cost prohibitive in low income areas, which are precisely the areas where the greatest number of human cases occur. </div>Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com14tag:blogger.com,1999:blog-3492197469143963742.post-4020436440804105352012-06-26T16:32:00.001-04:002012-07-19T12:06:27.452-04:00Liver Flukes Part 1: Clonorchis sinensis<div dir="ltr" style="text-align: left;" trbidi="on">
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<span style="background-color: white;">This week at Infection Landscapes we begin to cover another group of trematodes, the liver flukes.We will cover two species separately as their life cycles and landscape epidemiology are different enough to warrant distinct entries. The first liver fluke species we will cover is </span><i style="background-color: white;">Clonorchis sinensis</i><span style="background-color: white;">.</span><br />
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<b>The Worm</b>. <i>Clonorchis sinensis</i> is a flatworm in the class Trematoda.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhc7hkTzGBzWqGtBDx0l373OovcsNuT2gCavWHZmsZFTLrhotXRXykG5X3TsDHC_R__QTj6nhm5ARQBBw7x6gW0ZqP73Xy2ktQa3VXsn4cJQNJL26dk_GnafXVA6AdxomNuButbF6hmYxY/s1600/Clonorchis_sinensis.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhc7hkTzGBzWqGtBDx0l373OovcsNuT2gCavWHZmsZFTLrhotXRXykG5X3TsDHC_R__QTj6nhm5ARQBBw7x6gW0ZqP73Xy2ktQa3VXsn4cJQNJL26dk_GnafXVA6AdxomNuButbF6hmYxY/s640/Clonorchis_sinensis.png" width="216" /></a></div>
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<i><span style="font-size: x-small;">Clonorchis sinensis</span></i></div>
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<b>This helminth's life cycle requires two intermediate hosts and a definitive host</b>. This is a human parasite and humans constitute the definitive host species in its life cycle. Let's consider this life cycle.<br />
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Embryonated ova are expunged from an infected definitive host (human) and are infectious to the first intermediate host, i.e. freshwater snails, most commonly <i>Parafossarulus</i> spp. As the freshwater snails are the first intermediate host, the embryonated eggs must encounter a water environment to move to the next stage of development, which means that the human feces must come into contact with this water source. The eggs are eaten by the freshwater snails, and subsequently the miracidia emerge and relocate to the hepatopancreas, where they develop into sporocysts. After approximately 3 weeks of development in the hepatopancreas, cercariae are fully formed and exit the snail. These cercariae are highly motile in water, similar to the analogous stage of schistosomes. However, <i>C. sinensis</i> cercariae do not penetrate human skin. Rather, <i>C. sinensis</i> cercariae seek out a second intermediate host. When the cercariae encounter a fish of the Cyprinidae family, which are important freshwater food fish in many parts of the world, they burrow into the muscle tissue of the fish, or simply locate under the scales, and encyst. They subsequently transform into the metacercariae, which the infectious stage for humans. Alternatively, the cercariae can also encyst under the exoskeleton in the muscle tissue of freshwater crustaceans, such as crabs or crayfish. Human infection occurs following the ingestion of undercooked fish or crustaceans that harbor encysted metacercariae. These metacercariae then excyst in the small intestine and migrate up the bile duct where they will continue to develop into adult flukes over the course of several weeks. Adults live in the lumen of the bile duct in the liver and are thought to feed directly on the bile. <i>C. sinensis</i> adults contain both male and female reproductive organs, so no sex pairing is required of these trematodes to produce and fertilize the eggs. Embryonated eggs pass out of the common bile duct and into the small intestine and are eventually expunged in the feces of the host. The graphic below produced by the Centers for Disease Control and Prevention nicely depicts this trematode's complex life cycle:<br />
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<b>The Snail</b>. Freshwater snails are the first intermediate hosts of <i>C. sinensis</i>. There are several genera capable of filling this role, but the most common is <i>Parafossarulus</i>, and the most common species in endemic areas is <i>Parafossarulus manchouricus</i>.<br />
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<i style="text-align: left;"><span style="font-size: x-small;">Parafossarulus manchouricus</span></i>
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These snails are aquatic, breathe with gills, and are ciliary feeders. They are widely distributed throughout Asia.<br />
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<b>The Fish</b>. The Cyprinidae family of fish serve as the second intermediate hosts of <i>C. sinensis</i>. This fish family is the largest and is comprised of the carps and minnows. They are freshwater fish and, being toothless, primarily eat gastropods and aquatic vegetation, though some will eat algae, small fish, or other molluscs. Given their great diversity, wide geographic distribution (extensive in Europe, Asia, Africa, and North America), and preferred food, <b>and given that these fish are one of the most important food fish for humans in much of the world</b>, including much of Asia, these fish are an ideal intermediate host for <i>C. sinensis</i>.<br />
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In addition to these fish, crustaceans, such as crabs and crayfish, are also capable of serving as the second intermediate hosts.<br />
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<b>The Disease</b>. Most infections with <i>C. sinensis</i> are asymptomatic. Pathogenesis stems from this trematode locating in the bile duct:<br />
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Acute illness typically involves moderate, non-specific symptoms: abdominal pain, diarrhea, nausea. In high volume infections the proliferation of adults can progress to more severe pathology for two reasons. <b>First</b>, the large number of adult trematodes can consume substantive amounts of bile and subsequently disrupt the digestion and absorption of dietary nutrients. <b>Second</b>, in high volume infections the bile duct can become blocked usually due to the large egg volume produced by the adults, which can lead to inflammation, secondary bacterial infection (cholangitis), fibrosis, and hyperplasia.<br />
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In chronic infections, weight loss, lack of energy, and chronic diarrhea are common due to the ongoing digestive interruption, and carcinoma can develop in the bile duct due to the chronic obstruction and tissue damage.<br />
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<b>The Epidemiology and the Landscape</b>. <i>C. sinensis</i> is the most prevalent liver fluke in the world with approximately 30 million people currently infected, <i>but it is not the most widely distributed</i> (<i>Fasciola hepatica</i> is the most geographically widespread liver fluke). <i>C. sinensis</i> is endemic in East and Southeast Asia, particularly in Japan, Korea, China, Vietnam, Laos, and Cambodia.<br />
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<span style="background-color: white;">We do not have good surveillance data describing concrete measures of the burden of disease. However, areas of high endemicity do correspond to a relatively high incidence of cholangiocarcinoma.</span><br />
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<span style="background-color: white;">The landscape epidemiology of liver flukes in general, and <i>C. sinensis</i> in particular, differs from that of the schistosomes in that cercariae do not infect their definitive host directly, but rather require a second intermediate host, which transfers the metacercariae passively (through consumption) to the definitive host. This means that the point of intersection between pathogen and host in the landscape is fundamentally different and derives from a unique ecological framework. <b>Whereas, schistosome transmission occurs simply by way of contact with cercariae-infested freshwater bodies, <i>C. sinensis</i> trematodes require a more nuanced and specific engagement of the human host with the aquatic environment, i.e. through the harvesting of food from the water</b>. However this terrain, as narrowly described so far, is not sufficient by itself for infection transmission. In addition, the physical landscape that defines the geography and structure of <i>C.sinensis</i> ecology must intersect the uniquely human social landscape for transmission to occur and the life cycle to be completed. <b>This is because human feces must first contaminate the same water sources that humans then subsequently harvest for food</b>. This can happen through 1) poor sanitation and water infrastructure, 2) the use of human feces for the fertilization of crops, or 3) both. </span><br />
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<span style="background-color: white;">Moreover, eating metacercariae-infested fish (or crustaceans) need not transmit the infection to humans, <b>but does because of the method of preparation of the fish</b>. </span><span style="background-color: white;">I</span><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">n many places where <i>C. sinensis</i> is endemic, raw fish is a key ingredient in some local delicacies, so food preparation, as determined by cultural preference, becomes</span><span style="background-color: white;"> another aspect of the social landscape that converges with the physical landscape to effect</span><span style="background-color: white;"> transmission.</span><br />
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<span style="font-family: inherit;"><b>Control and Prevention</b>. </span></div>
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<i><u><span style="font-family: inherit;">Snail Control</span></u></i></div>
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<span style="font-family: inherit;">As with the schistosomes, early (and some ongoing) attempts at liver fluke<i> </i>elimination focused on gastropod control in various surface water sources. Typically, these control campaigns have involved the chemical treatment of freshwater sources to eliminate the local snail population, thus blocking the transmission of <i>C. sinensis</i> at the intermediate host. However, two important problems make gastropod control unrealistic in many settings. </span></div>
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<span style="font-family: inherit;"><b>First</b>, the chemical treatment of water sources can have much broader ecologic impact than what is intended by the public health initiative. Introducing toxic agents into surface water may kill the snails, but it can also harm other organisms in the aquatic ecosystem and result in unanticipated and detrimental ecologic effects. Some investigations have explored the possibility of introducing biologic mechanisms of control to supplant chemical treatment with more "natural" mechanisms. However, these approaches can also be dangerous if the natural biologic mechanisms involve the introduction of non-native invasive species into the aquatic environment. Nevertheless, the use of some plants in specific aquatic environments has been quite successful. For example, planting <span style="background-color: white; line-height: 19px; text-align: -webkit-auto;"><span style="font-style: italic;">Sarcoca dodecandra</span>,<b style="font-style: italic;"> </b>i.e. the </span>gopo berry shrub, in water sources kills any snails present. </span></div>
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<span style="font-family: inherit;"><b>Second</b>, whether chemical or natural, snails in most areas prove robust to elimination. Both their high reproductive capacity and diffuse distribution within the aquatic system usually allow some members of the population to survive, which can then re-populate the local environment fairly quickly.</span></div>
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<span style="font-family: inherit;"><u><i>Food Preparation</i></u></span></div>
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<b><span style="color: #333333; font-family: inherit;"><span style="line-height: 18px;">Thorough cooking of all freshwater fish and crustaceans is very important for blocking transmission of </span></span><i style="color: #333333; font-family: inherit; line-height: 18px;">C. sinensis</i></b><span style="color: #333333; font-family: inherit;"><span style="line-height: 18px;"><b> to humans</b>. Cooking kills the metacercariae and, thus, directly prevents infection in humans. Cooking is probably the most effective method of control and prevention of <i>C. sinensis </i>infection. However, in many places where this helminth is endemic, certain local delicacies require raw fish as central ingredients. As such, consistent cooking of fish in each household becomes an individual choice that may be </span></span><span style="color: #333333;"><span style="line-height: 18px;">superseded by cultural dietary norms and preferences.</span></span><span style="color: #333333; font-family: inherit;"><span style="line-height: 18px;"> </span></span></div>
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<i><u>Farming Practice</u></i></div>
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<span style="font-family: inherit;">Finally, <b>changing agricultural practices that rely on human feces for fertilization of crops could help reduce infection with <i>C. sinensis</i> in some</b> <b>agricultural subsistence communities</b>.</span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhOq1cVJSMxkFydHTXhn-Q_C9XrwoKoPHXWhKi2reml5eoPCBAri6vlhXeSxqmxnQrU1RZTVkXZ_8ful83dLEw908vTyzPpv8tnH89mcclw0GKlYEyKcc9xuSmD82NyK1jBsCwBQxbrRVQ/s1600/hookworm+human+feces+fertilizer.jpg" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><span style="font-family: inherit;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhOq1cVJSMxkFydHTXhn-Q_C9XrwoKoPHXWhKi2reml5eoPCBAri6vlhXeSxqmxnQrU1RZTVkXZ_8ful83dLEw908vTyzPpv8tnH89mcclw0GKlYEyKcc9xuSmD82NyK1jBsCwBQxbrRVQ/s400/hookworm+human+feces+fertilizer.jpg" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-color: white; background-position: initial initial; background-repeat: initial initial; border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-top-left-radius: 5px; border-top-right-radius: 5px; border: 1px solid rgb(204, 204, 204); box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding: 8px; position: relative;" width="400" /></span></a></div>
<span style="font-family: inherit;"><br />Unfortunately this, too, can be a difficult practice to disengage since human feces serves as a very rich fertilizer and, thus, can form a critical component to subsistence farming in many parts of the world where other fertilizers or farming technologies are cost prohibitive. And, of course, without an affordable substitute, refraining from human feces fertilization could very well lead to starvation. As such, this may not be a viable option for some subsistence farmers.</span></div>Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com19tag:blogger.com,1999:blog-3492197469143963742.post-62646349114308337402012-06-06T16:51:00.001-04:002012-07-16T16:24:40.124-04:00Schistosomiasis<div dir="ltr" style="text-align: left;" trbidi="on">
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This week we begin to explore a new phylum, the Platyhelminths, or flatworms. This phylum contains two major classes of parasitic worms, the cestodes (Cestoda) and the trematodes (Trematoda). These animals are physiologically much simpler than the nematodes, as they do not have a digestive tract or a circulatory system. In this ongoing series, we first cover the trematodes (blood flukes and liver flukes) and then we will cover the cestodes (tapeworms). Schistosomiasis, which we are going to cover this week, is responsible for a substantive burden of disease across large areas of Africa, Asia, and South America.<br />
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<b>The Worm</b>. Schistosomiasis, also known as bilharzia, is caused by trematodes of the genus <i>Schistosoma</i>, also commonly referred to as blood flukes. There are three main species that cause human infection, <i>Schistosoma mansoni</i>, <i>S. haematobium</i>, and <i>S. japonicum</i>. <i>S mekongi</i> and <i>S. intercalatum</i> also infect humans, but are of lesser importance. There are also several additional species that infect other animals, most often livestock. In this discussion we will focus on the three primary schistosome species that cause most human infections.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj9dOxrN0s4BlHUnMP70c7QMCxXiT9u6IMOztBf4MdQGp3IHTL7tdSX9IuPtLzLRMEl8W-guqtpPTKeirlos0N-El38zzk0WMjlNKMwJjDxr19hkyGJCvJAFsU1bxYvampsHUt-tsA5Sw4/s1600/Schistosoma_mansoni.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="273" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj9dOxrN0s4BlHUnMP70c7QMCxXiT9u6IMOztBf4MdQGp3IHTL7tdSX9IuPtLzLRMEl8W-guqtpPTKeirlos0N-El38zzk0WMjlNKMwJjDxr19hkyGJCvJAFsU1bxYvampsHUt-tsA5Sw4/s400/Schistosoma_mansoni.jpg" width="400" /></a></div>
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<i><span style="font-size: x-small;">S. mansoni male-female pair</span></i></div>
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The life cycle of these three (as well as the other two species that infect humans) follow the same general developmental stages. <i>Schistosoma</i> ova are expelled in the definitive host feces for all three schistosome species, and in the urine for <i>S. haematobium</i> and <i>S. japonicum</i>. In fresh water, these eggs will hatch and release the miracidia, which are motile in water. Subsequently, these miracidia seek out the intermediate host, which is one of several species of freshwater snail depending on the specific environment, geographic location, and schistosome species. The miracidia penetrate the foot of the snail and develop into sporocysts, which then produce daughter sporocysts that make their way to the snail's hepatopancreas. In the hepatopancreas these second generation sporocysts develop into cercariae, which is the larval stage that is infective to humans. The cercariae have evolved several remarkable strategies to find and infect their definitive hosts. Anatomically, the cercariae are equipped with a long forked tail that provides for prodigious swimming capacity after they exit the snail. The cercariae migrate out of the snail according to a diurnal pattern that follows light cues. <b>The cercariae swim upward, following wave vibrations, chemical trails, and obstructed light patterns in the water</b>, all of which can indicate the presence of their human (or other mammal) host. Upon finding a host, the cercariae penetrate the skin, lose their tail, and transform into schistosomulae, which migrate through the skin seeking out capillary beds and venules. Once they gain the venous circulation, the schistosomulae are transported to the lungs, where they develop further, and then move on to the liver, where, in the sinusoids, males and females pair off. The helminths feed on red blood cells in the sinusoids. Among mating pairs the female is enclosed in the gynaecophoric channel of the male:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhxpYuWlABmu9rch-_J-L14A8uzjqqUtDMaNyrdSKwQ_GSY5vIUSc6nkmuJ9ZksueBMyudtSlNfw3QPp0AZHuXNeyi4V9iaUnl9jb1jgP5660LWig-NvrhbGrOlOOvh-PKcwQBm9H7Ccj0/s1600/Schistosoma_mansoni_adult_pair.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhxpYuWlABmu9rch-_J-L14A8uzjqqUtDMaNyrdSKwQ_GSY5vIUSc6nkmuJ9ZksueBMyudtSlNfw3QPp0AZHuXNeyi4V9iaUnl9jb1jgP5660LWig-NvrhbGrOlOOvh-PKcwQBm9H7Ccj0/s400/Schistosoma_mansoni_adult_pair.jpg" width="400" /></a></div>
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After pairing these male-female schistosome pairs remove from the liver to the mesenteric veins where they will mate for life. The schistosomes require approximately 2 months to become fully mature, which marks the point when females begin to release eggs. These eggs, when mature, are able to pass through the endothelium of the veins and the epithelium of the intestine (or bladder) where they pass out of the host in the feces (or urine). The graphic below by the Centers for Disease Control and Prevention (CDC) nicely depicts the general life cycle of schistosomes:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhY0KPP07NWv4gNX82pqpLV2iTf_RRcapUnBTRcgQzp2gnhCgWcELhwmv0c5LysOqnQvv0KVLsXAo3udA44NTQ76k5AyWXE_7_v7NGqoqu9LIvZx29CqDmaLO8lcvQHQmUIXu0ddgtF6c0/s1600/Schistosoma_Life_Cycle.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="318" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhY0KPP07NWv4gNX82pqpLV2iTf_RRcapUnBTRcgQzp2gnhCgWcELhwmv0c5LysOqnQvv0KVLsXAo3udA44NTQ76k5AyWXE_7_v7NGqoqu9LIvZx29CqDmaLO8lcvQHQmUIXu0ddgtF6c0/s400/Schistosoma_Life_Cycle.png" width="400" /></a></div>
<b>The Snail</b>. Freshwater snails are the <b>intermediate hosts</b> of schistosomes. There are four main genera of these freshwater gastropods that are capable of serving as the intermediate hosts for schistosomes. <i>Biomphalaria</i> are the intermediate hosts for <i>S. mansoni</i>:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhDnPvRLYmp84vIpn9MTpbztebfGJIxZBPrP7KX9a8mdn29PihvheMMPPwQa-sxHqUdg-YB1ZYMNc-oMdpuZ-n1lTYoV2nqE2iOQvmbCTQbpS5IKwMFqXOsdtvrIgEBkrq7lLrDDbzOEg4/s1600/Snails+Biomphalaria.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhDnPvRLYmp84vIpn9MTpbztebfGJIxZBPrP7KX9a8mdn29PihvheMMPPwQa-sxHqUdg-YB1ZYMNc-oMdpuZ-n1lTYoV2nqE2iOQvmbCTQbpS5IKwMFqXOsdtvrIgEBkrq7lLrDDbzOEg4/s400/Snails+Biomphalaria.jpg" width="316" /></a></div>
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<i><span style="font-size: x-small;">Biomphalaria snail</span></i></div>
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These snails are aquatic but air-breathing. They prefer slow moving or stagnant surface water systems and are distributed in tropical areas in South America and Africa. <i>Bulinus</i> snails are the intermediate hosts for <i>S. haematobium</i>:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjbkG0U1WgSBXZiNUdZbgEXhsLxDfZ8p-EHRjTCfpab4g1bjVcEoMofR37BN4E9I8llEbs-RD00Hp9w9UqMmsvilcQF9P9-GsZ4g-MGuIKwhXezL7y2bfiobTsm3tgLeTihUX-oE985r7c/s1600/Snails+Bulinus.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="240" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjbkG0U1WgSBXZiNUdZbgEXhsLxDfZ8p-EHRjTCfpab4g1bjVcEoMofR37BN4E9I8llEbs-RD00Hp9w9UqMmsvilcQF9P9-GsZ4g-MGuIKwhXezL7y2bfiobTsm3tgLeTihUX-oE985r7c/s320/Snails+Bulinus.png" width="320" /></a></div>
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<i><span style="font-size: x-small;">Bulinus snail</span></i></div>
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These snails are aquatic, air-breathing, and also prefer stagnant or slow moving water systems. These snails are distributed throughout Africa and the Middle East. <i>Oncomelania</i> snails are the intermediate hosts for <i>S. japonicum</i>:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiMcnBb1qnPIlcrba6apsguoNWwTkHfFR4FkVMiUJl8JkJbX1xIZ8lY8mNKGzBsVUZXZGu3yyMGyRCT0M4azaD3TfkRXfpBydM46vKzEhybMdRfxW36g1r1YUIk8iMM4-yqxT54QVO9lrA/s1600/Snails+Oncomelania.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiMcnBb1qnPIlcrba6apsguoNWwTkHfFR4FkVMiUJl8JkJbX1xIZ8lY8mNKGzBsVUZXZGu3yyMGyRCT0M4azaD3TfkRXfpBydM46vKzEhybMdRfxW36g1r1YUIk8iMM4-yqxT54QVO9lrA/s320/Snails+Oncomelania.jpg" width="245" /></a></div>
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<i><span style="font-size: x-small;">Oncomelania snail</span></i></div>
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These snails are aquatic, breathe with gills and prefer fast moving, lotic water systems. They are distributed throughout east and southeast Asia.<br />
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<b>The Disease</b>. <i>The clinical spectrum of schistosomiasis is extraordinarily complex and encompasses both acute and chronic disease, which differ by schistosome species</i>. Most low volume acute infections are asymptomatic, and will not present with either acute or chronic disease. However, high volume acute infections, especially in naive hosts, will frequently manifest acute clinical disease. A syndrome consisting of some combination of cough, fever, malaise, hyper-eosinophilia, lymphadenopathy, and hepatosplenomegaly appear anywhere between 2 to 12 weeks following exposure to infectious cercariae.This syndrome is known as <b>Katayama fever</b> (after a valley in Japan, from which early descriptions of the disease were reported). This acute syndrome likely results from the migration of the schistosomulae through multiple organ tissues (see life cycle above).<br />
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<b>Chronic infection and subsequent disease is responsible for the great global burden attributable to schistosomiasis</b>. Chronic disease is primarily due to years of the deposition of eggs by reproductively active females in the tissues of the host. As females release their eggs, only approximately 50% make their way into the lumen of the intestine (in <i>S. mansoni</i> and <i>S. japonicum</i> infections) or urinary tract (in <i>S. haematobium</i>) and exit the host. The remaining eggs stay embedded in host tissues. <i>Chronic symptoms are associated with both the expunged and embedded eggs and manifest according to Schistosoma species</i>.<br />
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<b><u><i>Schistosoma mansoni</i> and <i>Schistosoma japonicum:</i></u></b><br />
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<span style="background-color: white;">The paired adults of these species are located in the mesenteric veins, where females release their eggs into the lumen.</span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj43LWm8x57Q-Ohqxx29P-U2Ey1LcmLphcApoqMXny_hVXplaeTSnROXQ4zqFCrtQstwtFjDhm4neTD8DlBdzmRnVAXdE7s_Z2sQxt0sqGL6HXrxuteBC4Id-xay6RKpRHohfg3U1a-ST0/s1600/schistosomes+anatomy.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj43LWm8x57Q-Ohqxx29P-U2Ey1LcmLphcApoqMXny_hVXplaeTSnROXQ4zqFCrtQstwtFjDhm4neTD8DlBdzmRnVAXdE7s_Z2sQxt0sqGL6HXrxuteBC4Id-xay6RKpRHohfg3U1a-ST0/s640/schistosomes+anatomy.png" width="418" /></a></div>
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About half of these will make their way into the lumen of the intestine and are expunged from the host. The breach of intestinal epithelium by the the eggs results in bleeding into the intestinal space leading to blood in the stool and diarrhea, which are common symptoms in chronic infections. In high volume chronic infections, intestinal blood loss can be substantive and lead to anemia. The consequences of "hidden" schistosomiasis in young children with heavy infections can be particularly severe with impaired physical and cognitive development.<br />
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<b>The approximately 50% of schistosome eggs that are not expunged stay embedded in the intestinal epithelium or liver parenchyma</b>. These embedded eggs stimulate potent inflammatory responses in the host and lead to granulomas and fibrotic lesions.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjPGSpfjkAJHSbjlNCoPOASFAngAiPLdg6JSPsHqhgh2YGhkLm3QWBKisZqpH3f4l1iEo8AzvjQ2V6oGbDBLdg3rPA4oR_gHirxvHZtMp5kA6dzZk4sKZ-ctfqWLTpRiOKqI1W5qFqQvFY/s1600/Schistosoma_japonicum_(3)_histopathology.JPG" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="301" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjPGSpfjkAJHSbjlNCoPOASFAngAiPLdg6JSPsHqhgh2YGhkLm3QWBKisZqpH3f4l1iEo8AzvjQ2V6oGbDBLdg3rPA4oR_gHirxvHZtMp5kA6dzZk4sKZ-ctfqWLTpRiOKqI1W5qFqQvFY/s400/Schistosoma_japonicum_(3)_histopathology.JPG" width="400" /></a></div>
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Portal fibrosis leads to hepatomegaly and splenomegaly. Subsequent obstruction of the portal circulation can lead to both portal hypertension and esophageal varices, which in turn can manifest in the transport of schistosome eggs to the lungs and hematemesis, respectively. The re-deposition of eggs in the lungs can also stimulate inflammation locally, resulting in pulmonary granulomas and pulmonary heart disease.<br />
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Chronic high volume <i>S. japonicum</i> infections seem to <b>present greater risk for liver cirrhosis and hepatic cancer, as well as colon cancer</b>, because this species produces up to 10 times more eggs than <i>S. mansoni</i>, which subsequently lead to a far greater number of granulomas.<br />
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<i><b><u>Schistosoma haematobium</u></b></i>:<br />
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The paired adults of this species are located in the venous plexus of the bladder. As with the other <i>Schistosoma</i> species, only about 50% of the eggs are successfully expunged from the host. These eggs are released into the vasculature, where they penetrate the endothelium of the blood vessel and then the wall of the bladder. In these infections, the breach of the bladder wall by the emerging eggs leads to hematuria, polyuria and dysuria.<br />
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Again, approximately 50% of the schistosome eggs are not expunged and remain embedded in the wall of the bladder.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi6kaMC6mju-ovOhxu57P7rTQW0OcjOd3ozBuC5fRZ-N9CvVWcY147r5K7DWizp4jKTCXMCX3oBGQal3eT0CBJQ1Kmwxxgk-74eufn35Qc_HZRBI9jk7Uo4NH3viVE39J98QZiy-F8ydps/s1600/Schistosoma_bladder_histopathology.jpeg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="270" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi6kaMC6mju-ovOhxu57P7rTQW0OcjOd3ozBuC5fRZ-N9CvVWcY147r5K7DWizp4jKTCXMCX3oBGQal3eT0CBJQ1Kmwxxgk-74eufn35Qc_HZRBI9jk7Uo4NH3viVE39J98QZiy-F8ydps/s400/Schistosoma_bladder_histopathology.jpeg" width="400" /></a></div>
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As with the other <i>Schistosoma</i> species, these embedded eggs are potent stimulators of inflammation, which leads to fibrotic lesions in the bladder and calcification:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhgRrSxQluvof5vDbrmGL3k_Dxq_N9FP58hiEXjfWxTN5my_H9xz_ITEkPD_ahjMFhyphenhyphenGFOo-_-3Z0JPziMn9MNnSqh-rWFkULYu3MOFkfCSnwt66c01auAnie6NjeI1-xaYZBgf13XIAEw/s1600/Schistosomiaisis_Bladder_Calcifications.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="162" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhgRrSxQluvof5vDbrmGL3k_Dxq_N9FP58hiEXjfWxTN5my_H9xz_ITEkPD_ahjMFhyphenhyphenGFOo-_-3Z0JPziMn9MNnSqh-rWFkULYu3MOFkfCSnwt66c01auAnie6NjeI1-xaYZBgf13XIAEw/s400/Schistosomiaisis_Bladder_Calcifications.png" width="400" /></a></div>
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In high volume chronic infections, urinary fibrosis can obstruct the urinary tract leading to urinary stasis and secondary bacterial infections.<br />
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Chronic high volume <i>S. haematobium</i> infections are also associated with a <b>relatively high risk of squamous cell carcinoma of the bladder</b>.<br />
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<b>The Epidemiology and the Landscape</b>. The are currently over 200 million people throughout the world infected with at least one species of <i>Schistosoma</i> helminth. There are 76 endemic countries, but the greatest burden (≥ 1 million infections) occurs in 30 African countries and Brazil. Approximately 20 to 50 million people experience substantive disability due to their infections. The map below, published in <i>Acta Tropica</i> (Volume 120, Supplement 1, September 2011, Pages S121–S137), depicts this global distribution including those areas where schistosomiasis has been eliminated: <br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgGKgoH8hh7lA8z53lg0J0Th5o2ALeS_8vJIoR9VB-yV8-p_wX15u_EkvLdcxhkOd3J02g-UYD0cyM_sKkWkGYKOY-QqXORRWNMjBSh9hGXRHfygw44tmbW_sgbQZxJ65tIIM3DApBVIb8/s1600/schistosomiasis+global+distribution+2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="158" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgGKgoH8hh7lA8z53lg0J0Th5o2ALeS_8vJIoR9VB-yV8-p_wX15u_EkvLdcxhkOd3J02g-UYD0cyM_sKkWkGYKOY-QqXORRWNMjBSh9hGXRHfygw44tmbW_sgbQZxJ65tIIM3DApBVIb8/s400/schistosomiasis+global+distribution+2.jpg" width="400" /></a></div>
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The distribution of disability-adjusted life years associated with schistosomiasis reflects the distribution of endemicity:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiMEB_4ofi_cwwVXOn80ek5_r6LNUrNvYn6WC5bRdpksWZ6OpNG9NKTP5o74JreueynWg_tMvtFm8Md6Q4vQws2Z59beOsSUFJNe21tsN42VP6i1AMiwyrYCxfIZ0Vu3OlkYtvYzQQH1Jw/s1600/Schistosomiasis_world_map_DALY_WHO2002.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="176" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiMEB_4ofi_cwwVXOn80ek5_r6LNUrNvYn6WC5bRdpksWZ6OpNG9NKTP5o74JreueynWg_tMvtFm8Md6Q4vQws2Z59beOsSUFJNe21tsN42VP6i1AMiwyrYCxfIZ0Vu3OlkYtvYzQQH1Jw/s400/Schistosomiasis_world_map_DALY_WHO2002.png" width="400" /></a></div>
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<div class="description en" lang="en" style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;" xml:lang="en">
<span class="description"><a class="extiw" href="http://en.wikipedia.org/wiki/Age_adjustment" style="background-image: none; background-position: initial initial; background-repeat: initial initial; color: #663366; text-decoration: none;" title="en:Age adjustment">Age-standardised</a> <a class="extiw" href="http://en.wikipedia.org/wiki/DALY" style="background-image: none; background-position: initial initial; background-repeat: initial initial; color: #663366; text-decoration: none;" title="en:DALY">disability-adjusted life year</a> (DALY) rates from <b>Schistosomiasis</b> by country (per 100,000 inhabitants).</span></div>
<div style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #b3b3b3; border: 1px solid rgb(128, 128, 128); display: inline-block; width: 2.4em;"> </span></span> no data</div>
<div style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffff65; border: 1px solid rgb(128, 128, 128); display: inline-block; width: 2.4em;"> </span></span> less than 50</div>
<div style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #fff200; border: 1px solid rgb(128, 128, 128); display: inline-block; width: 2.4em;"> </span></span> 50-75</div>
<div style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffdc00; border: 1px solid rgb(128, 128, 128); display: inline-block; width: 2.4em;"> </span></span> 75-100</div>
<div style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffc600; border: 1px solid rgb(128, 128, 128); display: inline-block; width: 2.4em;"> </span></span> 100-150</div>
<div style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffb000; border: 1px solid rgb(128, 128, 128); display: inline-block; width: 2.4em;"> </span></span> 150-200</div>
<div style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff9a00; border: 1px solid rgb(128, 128, 128); display: inline-block; width: 2.4em;"> </span></span> 200-250</div>
<div style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff8400; border: 1px solid rgb(128, 128, 128); display: inline-block; width: 2.4em;"> </span></span> 250-300</div>
<div style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff6e00; border: 1px solid rgb(128, 128, 128); display: inline-block; width: 2.4em;"> </span></span> 300-350</div>
<div style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff5800; border: 1px solid rgb(128, 128, 128); display: inline-block; width: 2.4em;"> </span></span> 350-400</div>
<div style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff4200; border: 1px solid rgb(128, 128, 128); display: inline-block; width: 2.4em;"> </span></span> 400-450</div>
<div style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff2c00; border: 1px solid rgb(128, 128, 128); display: inline-block; width: 2.4em;"> </span></span> 450-500</div>
<div style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #cb0000; border: 1px solid rgb(128, 128, 128); display: inline-block; width: 2.4em;"> </span></span> more than 500</div>
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The distribution of schistosomiasis is primarily a function of the distribution of the intermediate host snails. The maps below, which were produced by the Schistosomiasis Research Group at Cambridge University, depict the geographic distribution of species-specific schistosomiasis:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhTEVwyi_jP9epcU4dxnhhvUCarSQt_c-khfjjUaXz0dXltgP3Ds-2ADnEUxH91ubcnYZ1BXt6yH0KKIeiBdmSWo2qg1ripiQEW-MGUO-W0X7w359ZlR68ri296OLS5WU_OMtMbY5O-kIQ/s1600/S+mansoni+map.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="185" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhTEVwyi_jP9epcU4dxnhhvUCarSQt_c-khfjjUaXz0dXltgP3Ds-2ADnEUxH91ubcnYZ1BXt6yH0KKIeiBdmSWo2qg1ripiQEW-MGUO-W0X7w359ZlR68ri296OLS5WU_OMtMbY5O-kIQ/s320/S+mansoni+map.gif" width="320" /></a></div>
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<i><span style="font-size: x-small;">Global distribution of S. mansoni infections</span></i> </div>
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Notice how the geography of schistosomiasis caused by <i>S. mansoni</i> conforms to the distribution of <i>Biomphalaria</i> snails described above.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjwo19O1YRYr39x50PCczbLs0ci6jNU-m8f8ZyR4Bj3DcTDxPwCOFfFlVkuJwsFHSES_ks5TlGvpkQOT3hJERD93NyMS5ymcLonRNYkTkdBUkX5FRlOgOQexsTI6rDSuqrk2WJT4ij1YkI/s1600/S+haematobium+map.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjwo19O1YRYr39x50PCczbLs0ci6jNU-m8f8ZyR4Bj3DcTDxPwCOFfFlVkuJwsFHSES_ks5TlGvpkQOT3hJERD93NyMS5ymcLonRNYkTkdBUkX5FRlOgOQexsTI6rDSuqrk2WJT4ij1YkI/s320/S+haematobium+map.gif" width="300" /></a></div>
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<i><span style="font-size: x-small;">Global distribution of S. haematobium infections</span></i></div>
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Notice, here, how the geography of schistosomiasis caused by <i>S. haematobium</i> conforms to the distribution of <i>Bulinus</i> snails described previously.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhsU6fjWWy2YdTTz7Tpsp1FIx9PHSV0txlPh2lWWiGmmDda4bajnc_SsuV7pvHiyc2LNG-bsKzyeXKwdgq_rBV1RK0IGBUFTNzJa8fc-vTNeMgcGxsk5ByXlKNfw5pelZAlx8ziFmugzpk/s1600/S+japonicum+map.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="200" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhsU6fjWWy2YdTTz7Tpsp1FIx9PHSV0txlPh2lWWiGmmDda4bajnc_SsuV7pvHiyc2LNG-bsKzyeXKwdgq_rBV1RK0IGBUFTNzJa8fc-vTNeMgcGxsk5ByXlKNfw5pelZAlx8ziFmugzpk/s200/S+japonicum+map.gif" width="196" /></a></div>
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<i><span style="font-size: x-small;">Global distribution of S. japonicum infections</span></i>
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Finally, notice how the geography of schistosomiasis caused by <i>S. japonicum</i> conforms to the distribution of <i>Oncomelania</i> snails described previously.
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<b>The landscape epidemiology of schistosomiasis is a confluence of the schistosome relationship with its preferred intermediate host, local snail habitat and water environment, and, finally, the human activity (occupational, domestic, and/or recreational) that creates contact points with this habitat</b>. So, as with so many human infections, the disease ecology is really defined by the intersection of the physical landscape and the human social landscape.<br />
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<b>Control and Prevention</b>. </div>
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<i><u>Snail Control</u></i></div>
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Early (and some ongoing) attempts at schistosomiasis elimination focused on gastropod control in various surface water sources. Typically, these control campaigns have involved the chemical treatment of freshwater sources to eliminate the local snail population, thus blocking transmission of the schistosomes at the intermediate host. However, two important problems make gastropod control unrealistic in many settings. </div>
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<b>First</b>, the chemical treatment of water sources can have much broader ecologic impact than what is intended by the public health initiative. Introducing toxic agents into surface water may kill the snails, but it can also harm other organisms in the aquatic ecosystem and result in unanticipated and detrimental ecologic effects. Some investigations have explored the possibility of introducing biologic mechanisms of control to supplant chemical treatment with more "natural" mechanisms. However, these approaches can also be dangerous if the natural biologic mechanisms involve the introduction of non-native invasive species into the aquatic environment. Nevertheless, the use of some plants in specific aquatic environments has been quite successful. For example, planting <span style="background-color: white; line-height: 19px; text-align: -webkit-auto;"><span style="font-family: inherit; font-style: italic;">Sarcoca dodecandra</span><span style="font-family: inherit;">,</span><span style="font-size: 14px;"><b style="font-family: sans-serif; font-style: italic;"> </b><span style="font-family: inherit;">i.e. the </span></span></span>gopo berry shrub, in water sources kills any snails present. </div>
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<b>Second</b>, whether chemical or natural, snails in most areas prove robust to elimination. Both their high reproductive capacity and diffuse distribution within the aquatic system usually allow some members of the population to survive, which can then re-populate the local environment fairly quickly.</div>
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<i><u>Deworming</u></i></div>
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<b>The World Health Assembly has adopted deworming treatment with praziquantel as the primary approach to schistosomiasis control</b>. According to the goals of the World Health Assembly and the Schistosomiasis Control Initiative, between 75% and 100% of school-age children in endemic areas should be treated with praziquantel. In highly endemic areas, large-scale, population-based, systematic therapeutic and prophylactic treatment of the population has proven far more effective than selective treatment of diagnosis-confirmed individuals.</div>
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<b style="background-color: #fefdfa;"><span style="color: #333333; font-family: inherit;"><span style="line-height: 18px;">De-worming campaigns do offer some hope for area-specific elimination, since there is a safe, effective, easily administered, and fairly cheap anti-helminthic drug available (i.e. </span></span><span style="color: #333333;"><span style="line-height: 18px;">praziquantel</span></span><span style="color: #333333; font-family: inherit;"><span style="line-height: 18px;">)</span></span></b><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">. However, as one might expect, there are obstacles to overcome in de-worming. </span><b style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">First</b><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">, praziquantel is not free and, while the price dropped by over 90% in the 1990s, without adequate funding poor communities will not be able to prioritize the cost, especially since many infections are generally asymptomatic. </span><b style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">Second</b><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">, effective ways to deliver the de-worming medications to communities need to be implemented, which can be logistically challenging particularly in remote communities or during times of the year when travel may be restricted (i.e. during the rainy season). </span><b style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">Third</b><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">, the extensive use, or misuse, of these drugs will likely lead to antihelminthic-resistance in the schistosomes, thus making the drugs ineffective. Nevertheless, if adequate resources can be put behind de-worming campaigns, and if delivery systems can be adapted to </span><i style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">actively engage community members in the delivery and monitoring of these de-worming medications</i><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;"> to simultaneously circumvent logistical obstacles and reduce the development of resistance, then substantial reductions in schistosomiasis may still be possible.</span>
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</div>Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com23tag:blogger.com,1999:blog-3492197469143963742.post-39352297135598520682012-05-16T11:20:00.000-04:002012-12-19T12:51:50.262-05:00Lymphatic Filariasis<div dir="ltr" style="text-align: left;" trbidi="on">
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This week at Infections Landscapes, I will cover the last of the nematode infections in this extended helminth series. Lymphatic filariasis, which includes the advanced form, elephantiasis (often <b>incorrectly</b> referred to as elephantitis), causes extensive disability in several tropical and sub-tropical regions of the world. Like onchocerciasis, lymphatic filariasis is caused by filarial worms and is vector-borne.<br />
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<b>The Worm</b>. Lymphatic filariasis is caused primarily by three main helminth species in the Onchocercidae family of nematodes: <i>Wuchereria bancrofti</i>, <i>Brugia malayi</i>, and <i>Brugia timori</i>. Approximately 90% of infections are caused by <i>W. bancrofti</i>, while most of the remaining infections are caused by <i>B. malayi</i> (~9%) and <i>B. timori</i> (~1%). Humans are the reservoir for <i>W. bancrofti</i>, while non-human hosts serve as reservoirs for <i>Brugia</i> species, and thus infections with the latter result from zoonotic transmission.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgQjX5-eZCQMzKj3LYDHR2yiMUwNJ1cku0I_opNvVlYSoV5QiKgpZvbkhZPKOlOm3EdUYyBaQcvIIRHVf5iNqr2z3DhgC04b-lTbybac1vLmpFvG8Z1BJs1SvfNz5LqkY6h2UK6ICwX7Qg/s1600/Wuchereria_bancrofti.JPG" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="302" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgQjX5-eZCQMzKj3LYDHR2yiMUwNJ1cku0I_opNvVlYSoV5QiKgpZvbkhZPKOlOm3EdUYyBaQcvIIRHVf5iNqr2z3DhgC04b-lTbybac1vLmpFvG8Z1BJs1SvfNz5LqkY6h2UK6ICwX7Qg/s400/Wuchereria_bancrofti.JPG" width="400" /></a></div>
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<span style="font-size: x-small;"><i>Wuchereria bancrofti</i></span></div>
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<b>In the human host, the adult worms concentrate in the vessels and nodes of the lymphatic system</b>. Gravid females release motile sheathed microfilariae, which migrate to the peripheral circulation. It takes approximately 6 to 12 months from initial infection to the time when the microfilariae begin to appear in the periphery. These peripheral microfilariae exhibit a fascinating circadian rhythm, wherein they migrate at night into the peripheral blood via the circulation, returning to the arterioles in the lungs during the day. This migration to the periphery aids in the transmission of the microfilariae to the vectors, which are primarily, though not exclusively, night-biting mosquito species. After the microfilariae are ingested by the mosquito, the sheath is lost and they migrate out of the mosquito stomach and into the flight muscle tissues of the thorax. At this loaction, the microfilariae will molt three times, developing into the infectious 3rd stage larvae (L3) after approximately 10 to 20 days. The exact time required is dependent on the density of infection in the mosquito and the local climate conditions at the time of development. Infectious L3 larvae migrate to the proboscis of the mosquito. The larvae are not directly injected into the human host by the mosquito, but rather are deposited on the skin and migrate into the bite wound. The L3 larvae then migrate through subcutaneous tissues to gain the lymphatic system, where they will develop into adults over the course of approximately 1 year. Male and female adults will mate soon after reaching maturity and gravid females subsequently release their motile microfilariae. The following graphic developed by the Centers for Disease Control and Prevention (CDC) nicely depicts the life cycle of the nematodes that cause lymphatic filariasis:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEihfQXMhm2KsHsbzaA2WBnHIQyYB6vN6BY4jnx93VvUINa4rSMOBzK_gFjrVhDoW-Gf3jUwiwAmQwh1YFq7srhUl4BwH6F4q20QL1aQjCG6TmEUqC48ZdgR1X4E4Kqy8l0jz0qhtWj8-JM/s1600/Filariasis_life_cycle.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="315" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEihfQXMhm2KsHsbzaA2WBnHIQyYB6vN6BY4jnx93VvUINa4rSMOBzK_gFjrVhDoW-Gf3jUwiwAmQwh1YFq7srhUl4BwH6F4q20QL1aQjCG6TmEUqC48ZdgR1X4E4Kqy8l0jz0qhtWj8-JM/s400/Filariasis_life_cycle.png" width="400" /></a></div>
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<span style="font-family: inherit;"><b style="background-color: #fefdfa; color: #333333; line-height: 18px;">The symbiotic relationship between this helminth and a bacterium constitutes another critical, and fascinating, component to the worm's life cycle</b><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">. </span><i style="background-color: #fefdfa; color: #333333; line-height: 18px;">Wolbachia</i><span style="background-color: #fefdfa; color: #333333; line-height: 18px;"> is a genus of bacteria that commonly infects many species of insects, and a few species of nematodes. These ubiquitous bacteria can engage either parasitic or symbiotic relationships with their hosts. In the case of <i>W. bancrofti</i>, L3 larvae cannot complete their adult development w</span><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">ithout this bacterial infection, and, as such, the helminth's life cycle is arrested in the human host.</span></span>
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<b>Because the vast majority of infections are caused by <i>W. bancrofti</i>, this discussion will focus primarily on bancroftian lymphatic filariasis</b>. However, certain aspects of infections caused the <i>Brugia</i> spp. (i.e. brugian lymphatic filariasis) will be discussed where noted.</div>
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<b>The Vector</b>. <i>Mosquitoes are the vectors for the helminths that cause lymphatic filariasis</i>. The species capable of transmitting these filarial nematodes are many and varied, making the medical ecology of lymphatic filariasis extraordinarly complex, and the landscape epidemiology hyperlocal. <i>W. bancrofti</i> is vectored by <i>Culex</i> mosquitoes (primarily <i>Culex quinquefasciatus</i>) in most urban and semiurban areas of the world where this helminth is endemic. However, anopheline mosquitoes are important vectors in rural areas, especially in rural areas of sub-Saharan Africa, and <i>Aedes</i> mosquitoes are important vectors in southeast Asia and the endemic islands of the Pacific. The primary vectors for <i>Brugia</i> nematodes, however, are <i>Mansonia</i> mosquitoes. We'll briefly examine the ecology of each genus of mosquito below, although it is important to keep in mind that the behavior of species within genera can also vary widely, especially for anopheline mosquitoes. </div>
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<i>Culex Mosquitoes</i></div>
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<i><span style="font-family: inherit; font-size: x-small;">Culex mosquito taking a blood meal</span></i></div>
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<span style="color: #333333; font-family: inherit; line-height: 18px;"><i>Culex</i> mosquitoes seek out dirty water, </span><span style="background-color: transparent; line-height: 18px;"><span style="color: #333333;">rich in decayed nutrients,</span></span><span style="color: #333333; font-family: inherit; line-height: 18px;"> for oviposition, and lay their eggs on the water's surface in the form of an egg raft</span><span style="color: #333333; font-family: inherit; line-height: 18px;">. </span><i style="color: #333333; font-family: inherit; line-height: 18px;">Culex</i><span style="color: #333333; font-family: inherit; line-height: 18px;"> mosquitoes bite primarily at night, and also during the dusky times of dawn and sunset</span><span style="color: #333333; font-family: inherit; line-height: 18px;">. Different <i>Culex</i> species have very different preferences with respect to their hosts.</span></div>
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<i><span style="font-family: inherit; font-size: x-small;">Culex life cycle</span></i></div>
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<i>Culex quiquefasciatus</i> is the most important <i>Culex</i> mosquito vector for lymphatic filariasis. This <i>Culex</i> species is highly <b>anthropophilic</b>, and so prefers to take its blood meals from humans, unlike other <i>Culex</i> vectors that are <b>ornithophilic</b> (e.g. <i>Culex pipiens pipiens</i>). This preference for humans, and stagnant water around human habitation for larval development, make this mosquito's ecology very similar to <i>Aedes aegypti</i>, which is another prominent disease vector for humans. <i>C. quiquefasciatus</i> is responsible for a substantive burden of lymphatic filariasis in South Asia.<br />
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<i>Anopheles Mosquitoes</i><br />
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<i><span class="Apple-style-span" style="font-size: xx-small;">Anopheles gambiae</span></i></div>
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<span style="font-family: inherit;"><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">Anopheline mosquitoes are quite heterogeneous and so exhibit tremendous differences across species in their preference of vertebrate hosts, biting and resting behavior, and selection of sites for oviposition.</span><br style="background-color: #fefdfa; color: #333333; line-height: 18px;" /><br style="background-color: #fefdfa; color: #333333; line-height: 18px;" /><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">Of course, the anopheline mosquitoes require the same transition through four stages of development to complete the life cycle. Here is a comparison between three mosquito genera, with </span><i style="background-color: #fefdfa; color: #333333; line-height: 18px;">Anopheles</i><span style="background-color: #fefdfa; color: #333333; line-height: 18px;"> on the far left. All four stages of the life cycle are depicted for each genus:</span></span><br />
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<b style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">Notice the adult mosquitoes in the picture above</b><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">. One of the distinguishing features of anopheline mosquitoes is the roughly 45 degree angle their abdomen forms with respect to the surface on which they land. This is unique to </span><i style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">Anopheles</i><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;"> and can be used to identify the mosquito. Keep in mind however that after taking a blood meal the abdomen will be heavy and weighed down form the extra mass, and so will likely no longer form this distinguishing 45 degree angle.</span><br />
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<span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">Most anophelines feed during the night, but some will also feed during the dusky hours of morning and evening. As with with <i>C. quinquefasciatus</i>, the night biting preference of anophelines means that humans are at greatest risk of infection during sleep, when we are at our most vulnerable. Some</span><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;"> anopheline species are </span><b style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">zoophilic</b><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">, while other species are </span><b style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">anthropophilic</b><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">. Some anopheline mosquitoes are endophagic, prefering to take their blood meal indoors. </span><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">Others are </span><b style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">exophagic</b><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">, meaning they prefer to take the blood meal outside. Another important distinction among species is determined by what they do after they take their blood meal. Adding further heterogeneity to this genus, some anopheline species are </span><b style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">endophilic</b><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;"> rest-ers, meaning they prefer to rest inside, while others are </span><b style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">exophilic</b><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">, which means they prefer to rest outside. </span><i style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">This aspect of mosquito behavior is very important for mosquito control efforts, which may include residual spraying and thus would need to target inside or outside the home depending on the resting preference</i><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">.</span><br />
<span style="font-family: inherit;"><br style="background-color: #fefdfa; color: #333333; line-height: 18px;" /><b style="background-color: #fefdfa; color: #333333; line-height: 18px;">Most species of <i>Anopheles</i> mosquitoes prefer to lay their eggs in <i>clean water</i></b><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">, which is quite different to the </span><i style="background-color: #fefdfa; color: #333333; line-height: 18px;">Culex</i><span style="background-color: #fefdfa; color: #333333; line-height: 18px;"> and </span><i style="background-color: #fefdfa; color: #333333; line-height: 18px;">Aedes</i><span style="background-color: #fefdfa; color: #333333; line-height: 18px;"> species. While this helps to characterize anopheline ecology somewhat, there can still be great differences between individual </span><i style="background-color: #fefdfa; color: #333333; line-height: 18px;">Anopheles</i><span style="background-color: #fefdfa; color: #333333; line-height: 18px;"> species with respect to their water preferences for oviposition. Here is a depiction of some different potential breeding sites published in: </span><span class="Apple-style-span" style="background-color: #fefdfa; color: #000033;">Keating J, Macintyre K, Mbogo CM, Githure JI, Beier JC. <i style="font-style: normal; font-weight: bold;">Characterization of potential larval habitats for Anopheles mosquitoes in relation to urban land-use in Malindi, Kenya.</i> <i><a class="external" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC419712/?tool=pubmed" style="background-color: inherit; color: #3300cc; font-weight: bold; text-decoration: none;" target="_blank">Int J Health Geogr. 2004 May 4;3(1):9. (PMID: 15125778)</a></i></span></span><br />
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<span class="Apple-style-span" style="color: #000033; font-family: sans-serif;"><span class="Apple-style-span" style="font-size: xx-small;"><i style="font-style: normal; font-weight: bold;">Pictures illustrating the types of habitat identified by strata during this study:</i> (A) Swimming pool in well drained tourist area; (B) Broken water pipe in well drained residential area; (C) Open water tank in poorly drained area; (D) Pond in poorly drained area; (E) Drainage channel in well drained area; and (F) Ditch and tire tracks in poorly drained area.</span></span></div>
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<span style="font-family: inherit;"><b style="background-color: #fefdfa; color: #333333; line-height: 18px;">Let's talk a little more specifically about water preference</b><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">. For example, </span><i style="background-color: #fefdfa; color: #333333; line-height: 18px;">Anopheles gambiae</i><span style="background-color: #fefdfa; color: #333333; line-height: 18px;"> one of the most important vectors for transmitting lymphatic filariasis in sub-Saharan Africa. It prefers small sunlit pools, and it's natural habitat is tropical forest. In natural, undisturbed habitat, this mosquito is limited in abundance by the distribution of breaks in the tree canopy that allow the sun to reach the forest floor. However, when habitat is disturbed, due to deforestation or agriculture, for example, much larger areas of land cover become exposed. In this situation any pools of collected rainwater can receive direct sunlight and provide ideal and abundant breeding for </span><i style="background-color: #fefdfa; color: #333333; line-height: 18px;">A. gambiae</i><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">. Such habitat disturbances often also coincide with increased human proximity, and so more and more people come into greater contact with more and more of this efficient vector of <i>W. bancrofti</i>. Here are a few CDC pictures of some diverse land cover that </span><i style="background-color: #fefdfa; color: #333333; line-height: 18px;">A. gambiae</i><span style="background-color: #fefdfa; color: #333333; line-height: 18px;"> can make use of:</span></span><br />
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<i><span class="Apple-style-span" style="font-size: xx-small;">Irrigation in forest ecotones</span></i></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiib_FiP2zGr06odQ4tpOhTHydi4waEp7rJAd8hqOVO97izGjPcRHbLLGzlMzCSlInra4KtBqKb78XX3bGCKQQrLJ9ZwSgdNSNK8yK3LpVSPmTif-fdZjAZf6K0JM093AoLJWHnonX3FvY/s1600/Anopheles_gambiae_larval_habitat_2_100h.jpg" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><img border="0" height="200" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiib_FiP2zGr06odQ4tpOhTHydi4waEp7rJAd8hqOVO97izGjPcRHbLLGzlMzCSlInra4KtBqKb78XX3bGCKQQrLJ9ZwSgdNSNK8yK3LpVSPmTif-fdZjAZf6K0JM093AoLJWHnonX3FvY/s320/Anopheles_gambiae_larval_habitat_2_100h.jpg" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="320" /></a></div>
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<i><span class="Apple-style-span" style="font-size: xx-small;">Rice fields</span></i></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj48fFIwlFe63lAxyLcwiw-CMweIa6DeE9_uMQxQHBX6dZpS-PQuZtYx0tP6x7pWghyphenhyphenH-p59Mmr23SvRr6vnXs9kP7mzPt0AS9u2ES72Jf1HVO95PnX4XJVe5B2nOrxhhOQdKFTWSndue8/s1600/Anopheles_gambiae_larval_habitat_2_100h_3.jpg" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><img border="0" height="240" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj48fFIwlFe63lAxyLcwiw-CMweIa6DeE9_uMQxQHBX6dZpS-PQuZtYx0tP6x7pWghyphenhyphenH-p59Mmr23SvRr6vnXs9kP7mzPt0AS9u2ES72Jf1HVO95PnX4XJVe5B2nOrxhhOQdKFTWSndue8/s320/Anopheles_gambiae_larval_habitat_2_100h_3.jpg" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="320" /></a></div>
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<i><span class="Apple-style-span" style="font-size: xx-small;">Tire tracks</span></i></div>
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<span style="font-family: inherit;"><span style="background-color: #fefdfa; color: #333333; line-height: 18px;"><i>Aedes Mosquitoes</i></span></span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgXez-g548rygoSIGhgHoXgkqrn0_BizBALlopB5p8QiQWZrpMygM5jRl6AqI9Kx03rspQsTRO2atMWD3sTCCVVcLQP3tcQTANZPKv_fkWi5YtqwfZ_YkXK_eB6-NndlDoFxMxNqrLhU0w/s1600/Aedes_aegypti_mosquito2.jpg" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><img border="0" height="260" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgXez-g548rygoSIGhgHoXgkqrn0_BizBALlopB5p8QiQWZrpMygM5jRl6AqI9Kx03rspQsTRO2atMWD3sTCCVVcLQP3tcQTANZPKv_fkWi5YtqwfZ_YkXK_eB6-NndlDoFxMxNqrLhU0w/s400/Aedes_aegypti_mosquito2.jpg" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></a></div>
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<span style="font-family: inherit;"><i>Aedes aegypti</i> mosquito</span></div>
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<i style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">A. aegypti</i><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;"> mosquitoes have a very particular preference for the water environment it selects for laying its eggs. </span><i style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">It likes SMALL containers that collect rainwater</i><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">. And the mechanics work as follows. This mosquito </span><i style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">does not lay its eggs either in the water or on the surface of the water</i><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">, as most other species do. Instead, </span><i style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">A. aegypti</i><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;"> lays its eggs </span><i style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">above the water</i><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;"> on the interior wall of the vessel containing the water so that when the water vessel is refilled, from the water line at which the mosquito laid its eggs to the lip of the vessel, the eggs will have enough time to complete their developmental cycle to adulthood before evaporation depletes the water source. A truly incredible evolutionary adaptation.</span><br />
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<span style="font-family: inherit;">This mosquito is originally adapted to a forest habitat wherein it would seek out holes in trees that would regularly collect rainwater. Tree holes are much more ubiquitous than you might think in a forest (think woodpeckers), and so this is quite an effective niche for this mosquito. As humans encroached more and more on forest habitat establishing agriculture, and building increasingly dense communities and living conditions, <i>A. aegypti</i> readily adapted to the new circumstances. The mosquitoes found an abundance of new and highly effective small containers strewn in and around households that can easily collect, or are intended to store, water. The mass production of plastics has been a major factor in the proliferation of potential water containers. Today <i>A. aegypti</i> is just as much an urban mosquito as it is a forest mosquito and probably more so. As such, <i>A. aegypti</i> is now adapted to the human environment. They will often live in the household with humans, and can complete their whole life cycle here. They also bite during the day, so they have unlimited access to humans for taking blood meals. And finally, this mosquito is anthropophilic so its preferred host is humans.</span><br />
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<span style="font-family: inherit;">While, <i>A. aegypti</i> is a vector of lesser importance for <i>W. bancrofti</i> across southeast Asia, <i>Aedes polynesiensis</i> is a very important vector of <i>W. bancrofti</i> in the South Pacific Islands of Polynesia, and shares similar characteristics with <i>A. aegypti</i>.</span></div>
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<span style="font-family: inherit;"><i>Mansonia Mosquitoes</i></span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEir-KC8ERdNGW7SFHWIFov8BEwyFPVwpxBnjyf_1Dn4xzIkTpmWMa-uKjNVSCt7PorVAXQ4dvOBYG5p8TNIH8i4rf7cOFCcv5YrbxeEncc_CzE_dxrdqfga_aDq_HCyKJAlNK2izFWlc2o/s1600/Mansonia_Mosquito_adult.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEir-KC8ERdNGW7SFHWIFov8BEwyFPVwpxBnjyf_1Dn4xzIkTpmWMa-uKjNVSCt7PorVAXQ4dvOBYG5p8TNIH8i4rf7cOFCcv5YrbxeEncc_CzE_dxrdqfga_aDq_HCyKJAlNK2izFWlc2o/s400/Mansonia_Mosquito_adult.jpg" width="300" /></a></div>
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<i><span style="font-size: x-small;">Adult Mansonia Mosquito</span></i></div>
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<i>Mansonia</i> mosquitoes are the primary vectors of brugian filariasis, and they are partial to stagnant water, typically in swamp, marsh, or rice field habitats. <i>Mansonia</i> mosquitoes have adopted a unique exploitation of these specific aquatic environments during larval development. The larvae and pupae attach and fix to the aquatic plant stems or roots below the surface of the water, acquiring oxygen directly from these plants:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiqT7MIwTAHYSmVgd2cLArlM-LvxCLo8XpIEkMfnEabZVxI-iBxPSUMrKceJpo_dg9BqzE-nW4-NoNFg0ley5pQoHGSko_YwRT5yd9e59lVAYrRBmfeuV1NLV_1fXyRgRDIxPBJ3nLhRTQ/s1600/Mansonia+mosquito+larva.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="265" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiqT7MIwTAHYSmVgd2cLArlM-LvxCLo8XpIEkMfnEabZVxI-iBxPSUMrKceJpo_dg9BqzE-nW4-NoNFg0ley5pQoHGSko_YwRT5yd9e59lVAYrRBmfeuV1NLV_1fXyRgRDIxPBJ3nLhRTQ/s400/Mansonia+mosquito+larva.jpg" width="400" /></a></div>
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<span style="font-family: inherit;"><b>The Disease</b>. Lymphatic filariasis is comprised of a very wide spectrum of clinical disease. Most endemic infections occur in children and young adults who are asymptomatic. This level of infection is referred to as <b>asymptomatic microfilaremia</b>.</span></div>
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<span style="font-family: inherit;">Acute clinical disease can present in several forms. <b>The most common acute presentation (~97%) is acute dermatolymphangioadenitis (ADLA)</b>. Fever is a common symptom, often accompanied by some lymphedema at a site (or sites) that is typically associated with lymph centers in the extremities. The draining lymph nodes swell and can become quite sore, possibly with redness and warm skin at the affected area. Depending on the volume of infection and the degree of lymphedema associated with the acute episode, lymphangitis, lymphadenitis and cellulitis are possible sequelae in ADLA. Interestingly, ADLA attacks are largely due to secondary bacterial infections. With high grades of lymphedema, affected limbs are more susceptible to breaches in the skin due cuts, drying cracks, or fungal infections, especially between the toes. Invading bacterial pathogens take advantage of the comprised skin integrity and cause additional infection secondary to the filariasis, ultimately leading to persistent cycles of ADLA. </span></div>
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<span style="font-family: inherit;"><b>Acute filarial lymphangitis occurs when the adult worms die in the host</b>, either naturally or by pharmacological treatment. Nodules form at the lymph centers where the worms die. Lymph nodes can become swollen and painful, and large tracts of the lymphatic system can actually stand out under the skin due to the inflammatory response that follows the death of the worms. These acute episodes are rare, and typically do not present with fever as does ADLA, and neither are they associated with secondary bacterial infection.</span></div>
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<span style="font-family: inherit;"><b>Elephantiasis is the primary chronic manifestation of lymphatic filariasis and is strongly associated with ongoing lymphedema and the cycles of ADLA described above</b>. This clinical manifestation is responsible for extraordinary disfigurement and disability in the host. The progression of lymphedema is graded as follows:</span></div>
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<span style="font-family: inherit;"><b>Grade 1</b>: Pitting edema, reversible on elevation of the affected limb</span></div>
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<span style="font-family: inherit;"><b>Grade 2</b>: Pitting or non-pitting edema that does not reverse on elevation of the affected limb; no skin changes</span></div>
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<span style="font-family: inherit;"><b>Grade 3</b>: Non-pitting edema that is not reversible; thickening of the skin</span></div>
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<span style="font-family: inherit;"><b>Grade 4</b>: Non-pitting edema that is not reversible; thickening of the skin, with nodular or warty excrescences:</span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiClV7I0Fcnwm7SytTPgacUNNsXZbjwLXS2E4U_KQYlP7YYyXrfd0asRkBxrttLYDoiBqWI-7wRiXeLp1pqa0vIuTMhjJg2HDBRWbMwiVo6B3atZjwKAK3wgUA1A_SbKbIVAgl7FK4LFrQ/s1600/filariasis+non-pitting+edema.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiClV7I0Fcnwm7SytTPgacUNNsXZbjwLXS2E4U_KQYlP7YYyXrfd0asRkBxrttLYDoiBqWI-7wRiXeLp1pqa0vIuTMhjJg2HDBRWbMwiVo6B3atZjwKAK3wgUA1A_SbKbIVAgl7FK4LFrQ/s640/filariasis+non-pitting+edema.jpg" width="420" /></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgLQUI3clsOLJYL0MqfCw4cVGyn_3DGYCQyriWCBewyRqHxDG-KrNNgA2raPT2VVHnjJEdT5nheR08ZlMgF_uujIMyXn_h0CdMXQI_T_fNj3cJXRKgwmckLQxEROC633bggBru4aCU_WAQ/s1600/filariasis+non-pitting+edema+2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgLQUI3clsOLJYL0MqfCw4cVGyn_3DGYCQyriWCBewyRqHxDG-KrNNgA2raPT2VVHnjJEdT5nheR08ZlMgF_uujIMyXn_h0CdMXQI_T_fNj3cJXRKgwmckLQxEROC633bggBru4aCU_WAQ/s640/filariasis+non-pitting+edema+2.jpg" width="480" /></a></div>
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<span style="font-family: inherit;">With progressive chronic infection and advanced lymphedema, thickening of the skin also advances until extensive folding occurs in concert with increasing nodular development, and ulceration, ultimately leading to severe disability and immobility:</span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi8gevGZgkzjifLPzUEO2BeaAnlwFgP49aCfES-ARHqAqk5AP7H5lrVq9eNsm0-3zKP3AzEiTfKicgaxfHuqIO8lsS3VW43uBwkXSmaKIZZkH3TdcQwB_cqem-YqvOJY7jZgJSVkayV-bI/s1600/elephantiasis+1.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi8gevGZgkzjifLPzUEO2BeaAnlwFgP49aCfES-ARHqAqk5AP7H5lrVq9eNsm0-3zKP3AzEiTfKicgaxfHuqIO8lsS3VW43uBwkXSmaKIZZkH3TdcQwB_cqem-YqvOJY7jZgJSVkayV-bI/s400/elephantiasis+1.jpg" width="286" /></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi6TohSDbVNQvzQYkVvS8xdtxoufmBVy5HrwiOhWDZRkU1q4SqhrcI1S2lrhc3o2etfdb_nDpoKkhhyphenhyphenT_6oM04ZRs8TTpkM74JbOT9wv-IXkoJvqVXO-iq4bhp5WoSnh1SSrg_8BwJZCFU/s1600/elephantiasis+2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi6TohSDbVNQvzQYkVvS8xdtxoufmBVy5HrwiOhWDZRkU1q4SqhrcI1S2lrhc3o2etfdb_nDpoKkhhyphenhyphenT_6oM04ZRs8TTpkM74JbOT9wv-IXkoJvqVXO-iq4bhp5WoSnh1SSrg_8BwJZCFU/s400/elephantiasis+2.jpg" width="280" /></a></div>
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Hydrocele is another common clinical manifestation of chronic infection with <i>W. bancrofti</i>. This condition results from the accumulation of fluid in the serous membrane surrounding the testes. Swelling increases over the period of the chronic infection and, when left untreated, leads to very large growth of the scrotum. This can be very painful and another severe impediment to mobility:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh7FM38LpJFmdfac1EyDFrWNAeIVjI_zA_kNr6GtWIyLjFpq8vE8J4c8ZXlJcjg7aF_6hUG6ECCy1YPFDfespA17lkbfofrDip5FbR2wx1EhWka6nasio2BWeTvNneb_vFkSkP6GiBnbKg/s1600/filariasis+hydrocele.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh7FM38LpJFmdfac1EyDFrWNAeIVjI_zA_kNr6GtWIyLjFpq8vE8J4c8ZXlJcjg7aF_6hUG6ECCy1YPFDfespA17lkbfofrDip5FbR2wx1EhWka6nasio2BWeTvNneb_vFkSkP6GiBnbKg/s320/filariasis+hydrocele.jpg" width="248" /></a></div>
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<span style="color: #333333;"><span style="line-height: 18px;">The pathogenesis of these filarial helminths in the lymphatic system begins with dilation of the lymph vessels where the adult worms are located. This early, often asymptomatic, damage seems to be present among individuals with adult worms as well as those with only microfilariae present. With extended exposure to the worms, the vessel damage proliferates throughout the lymphatics of the affected limb(s). <b>In high volume chronic infection, occlusion of the lymphatic vessels plays a role in the progression to the more profound clinical manifestation of elephantiasis. However, secondary bacterial infection, as described above, likely plays the most important role in the progression of lymphatic filariasis</b>.</span></span></div>
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<span style="color: #333333;"><span style="line-height: 18px;"><b>The Epidemiology and the Landscape</b>. There are approximately 120 million prevalent infections with the filarial worms that cause lymphatic filariasis, most of which are <i>W. bancrofti</i>. These infections occur in at least 83 countries, where it is estimated that over 1 billion people are at risk for infection. There are approximately 40 million people who experience severe disability due to their lymphatic filariasis. Approximately 1/3 of the cases occur in Africa, 1/3 occur in India, and the remaining 1/3 occur throughout Southeast Asia, the Pacific Islands, and in the Americas. Just four countries alone, India, Bangladesh, Nigeria, and Indonesia, account for 70% of the world's total infections. The map below by the World Health Organization shows the countries that are endemic for lymphatic filarisis:</span></span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgk1psy4J4FzXJJxvmqdQXl5oFT-o6Qav2o8uXlmnYgHTme8HMY11mvSzrjcQQPT9QWE2Le-pb1nM17VnMWnKS95pCIn_hm1xCLZBFjidygqqQ05s33UzhGYWHf5ptfu_3VI7tCaVaHz2A/s1600/filariasis+endemic+countries+WHO.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="263" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgk1psy4J4FzXJJxvmqdQXl5oFT-o6Qav2o8uXlmnYgHTme8HMY11mvSzrjcQQPT9QWE2Le-pb1nM17VnMWnKS95pCIn_hm1xCLZBFjidygqqQ05s33UzhGYWHf5ptfu_3VI7tCaVaHz2A/s400/filariasis+endemic+countries+WHO.jpg" width="400" /></a></div>
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However the map below, produced by the CDC, depicts a more specific distribution of lymphatic filariasis as it occurs in endemic countries:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhEEc0zWuaZpn4MlILTZDobGeE6sXyn61SWPLyeOjx2ZEOyh1LwnVINngO4x_6l7eQJeSwfKfCWwxR2eeykj8YJ8gRiuI-K8G8X52Jk1qFFDfmUi14u5g8wcQNzLY0jgQeNEYfqjEp3yF8/s1600/filariasis+global+distribution.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="217" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhEEc0zWuaZpn4MlILTZDobGeE6sXyn61SWPLyeOjx2ZEOyh1LwnVINngO4x_6l7eQJeSwfKfCWwxR2eeykj8YJ8gRiuI-K8G8X52Jk1qFFDfmUi14u5g8wcQNzLY0jgQeNEYfqjEp3yF8/s400/filariasis+global+distribution.jpg" width="400" /></a></div>
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The disability-adjusted life years associated with lymphatic filariasis are quite significant:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgj0UzaNqnhh7WPMxesGwFb3mNaU3SAZZcylmvP9Cww8UojfZ4zqcjsZiW3EzKbYqR0sneeMH7DjxglZXaanS7EqNRygP69UfZtxAkTSh5uIXcGzGgYcfERhIXIDCdE9cLasTxCU4yZQh0/s1600/filariasis_world_map_-_DALY_-_WHO2002.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="176" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgj0UzaNqnhh7WPMxesGwFb3mNaU3SAZZcylmvP9Cww8UojfZ4zqcjsZiW3EzKbYqR0sneeMH7DjxglZXaanS7EqNRygP69UfZtxAkTSh5uIXcGzGgYcfERhIXIDCdE9cLasTxCU4yZQh0/s400/filariasis_world_map_-_DALY_-_WHO2002.png" width="400" /></a></div>
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<div class="description en" lang="en" style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;" xml:lang="en">
<span class="description"><a class="extiw" href="http://en.wikipedia.org/wiki/Age_adjustment" style="background-attachment: initial; background-clip: initial; background-color: initial; background-image: none; background-origin: initial; background-position: initial initial; background-repeat: initial initial; color: #663366; text-decoration: none;" title="en:Age adjustment">Age-standardised</a> <a class="extiw" href="http://en.wikipedia.org/wiki/DALY" style="background-attachment: initial; background-clip: initial; background-color: initial; background-image: none; background-origin: initial; background-position: initial initial; background-repeat: initial initial; color: #663366; text-decoration: none;" title="en:DALY">disability-adjusted life year</a> (DALY) rates from <b>Lymphatic filariasis</b> by country (per 100,000 inhabitants).</span></div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #b3b3b3; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> no data</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffff65; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> less than 10</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #fff200; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 10-50</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffdc00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 50-70</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffc600; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 70-80</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffb000; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 80-90</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff9a00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 90-100</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff8400; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 100-150</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff6e00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 150-200</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff5800; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 200-300</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff4200; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 300-400</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff2c00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 400-500</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #cb0000; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> more than 500</div>
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<span style="color: #333333; font-family: inherit; line-height: 18px;"><b>Control and Prevention</b>. Unfortunately, the transmission of lymphatic filariasis is not limited to one vector. Rather, there are several genera of mosquitoes capable of transmitting infectious larvae to humans, and these mosquitoes demonstrate extraordinarily different behaviors in the widely varied landscapes they inhabit and ecologies they </span><span style="color: #333333; line-height: 18px;">exploit</span><span style="color: #333333; font-family: inherit; line-height: 18px;">. As such, while vector control should never be ruled out as a means of blocking transmission, there can also never be a universal approach to vector control that can be expected to be effective. Instead, any such vector control strategies must be hyperlocal, considering the specific mosquito species that transmit infection in the endemic local landscape.</span></div>
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<span style="color: #333333;"><span style="line-height: 18px;">The primary <i>Aedes</i> (<i>A. polynesiensis</i> and <i>A. aegypti</i>) and <i>Culex</i> (<i>C. quiquefasciatus</i>) mosquito vectors <i>can be controlled with vigilant maintenance of open water containers in the home and its surroundings</i>. The emphasis must be placed on "vigilant control" because it takes everyone in a community to be dedicated to eliminating this water source to reduce transmission in most places in the world where lymphatic filariasis is endemic. Pesticides can be used, and they are effective as well, but their application is cost prohibitive to control efforts in most places in the world. Instead, by changing the landscape of the mosquito where that landscape intersects with the human landscape, we can expect some results in transmission reduction where these species are important vectors.</span></span></div>
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<span style="color: #333333;"><span style="line-height: 18px;">The logistics of Anopheles vector control are not as straightforward. </span></span></div>
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<span style="color: #333333; font-family: inherit;"><b>Control of anopheline mosquitoes typically is comprised of several domains</b>. The first entails control of breeding sites, i.e. water sources. The second entails control of the larval stage of the mosquito as it lives and develops in the water. The third entails control of the adult mosquitoes, either prior to taking a blood meal or following the blood meal.</span></div>
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<span style="color: #333333; font-family: inherit;">Control of breeding sites requires the elimination of viable water sources for <i>Anopheles</i> oviposition. This can be quite a daunting task because of the immense diversity in preferred water habitat across the different species of <i>Anopheles</i> mosquito. Nevertheless, limiting human impact on natural resources, particularly forest transformation, can go a long way. This is, however, a long-term approach that must overcome societal, governmental, and economic constraints that simply may not be amenable to change for the sake of lymphatic filariasis reduction. Nevertheless, more localized efforts may focus on minimizing the number of potential rainwater collection areas in and around areas close to human habitation. The task is still incredibly daunting, especially given the sheer amount of rainfall in tropical climates.</span></div>
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<span style="color: #333333; font-family: inherit;"><b>While elimination of water sources suitable to mosquito breeding may not be possible in most circumstances for <i>Anopheles</i>, targeting the water source can still be a viable means to control the mosquito larvae</b>. Instead of eliminating the water source, such interventions take advantage of the larval water environment by introducing agents that can kill the larvae. These may include chemical agents, such as pesticides, but often they may include options that do not pollute potentially important water sources with chemical substances. For example, predatory animals, such as certain kinds of fish or other insects, can be introduced to feed on the larvae and thus reduce the numbers of mosquitoes reaching adulthood.</span></div>
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<span style="color: #333333; font-family: inherit;">Here is one researcher who is exploring pathogens and predators as viable non-chemical means of mosquito control:</span></div>
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<span style="color: #333333; font-family: inherit;">Notice the emphasis on "natural enemies" for mosquito control. The use of natural enemies is very important as the introduction of an alien, potentially invasive, species may control mosquito populations, but may also have damaging effects on the larger ecosystem.</span></div>
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<span style="color: #333333; font-family: inherit;">Control of adult mosquitoes can take various forms depending on when they are targeted with respect to taking the blood meal.</span></div>
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<span style="color: #333333; font-family: inherit;">I<b>ntercepting the mosquito with insecticide treated bed nets (ITNs) before it can take a blood meal from sleeping humans has become a major staple of malaria intervention, and is also relevant to the control of lymphatic filariasis</b>. ITNs can be quite effective, but they need to be used correctly and they need to be widely distributed, adopted, and correctly maintained in order to translate to reduced transmission. For example, some barriers to ITN effectiveness can be comfort and cleanliness. In many tropical areas, the temperatures are often quite high and the tight mesh of the ITNs typically does not allow much breeze to pass through in the night. As a consequence, sleeping under an ITN can be quite uncomfortable in endemic areas where they are most needed. People may opt for comfort over protection if it improves their sleep. Similarly, the ITNs easily collect dust and become dirty, which means people want to wash the nets regularly. However, if the ITNs are washed without being impregnated again with the insecticide, they will not effectively kill landing mosquitoes and some will be able to access the sleeping person beneath the net.</span></div>
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<span style="color: #333333; font-family: inherit;"><b>The resting mosquito offers another point of intervention</b>. You will recall that immediately after taking a blood meal, the mosquito must rest. Some rest indoors and some rest outdoors. Targeted insecticide spraying will aim to cover the resting surfaces of the mosquitoes so that they are killed after taking the blood meal. This will not prevent infection in the person from whom the blood meal was taken, but it will stop transmission by killing the mosquito before it can infect someone else. Residual spraying on walls in the home is a particularly common control measure, though this is of course limited to endophilic <i>Anopheles</i> species. However, residual spraying can be quite effective against <i>A. aegypti</i> and <i>C. quinquefasciatus</i>, which are more likely to reside in or close to the human residence. Targeting of exophilic anopheline mosquitoes is more difficult because potential resting surfaces are much more dispersed in the outside environment.</span></div>
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<span style="color: #333333;"><b>Chemotherapy/chemoprophylaxis is another major component of control and prevention of lymphatic filariasis</b>. Indeed, while vector control by itself, or in concert with de-worming drugs, is implemented in some settings, prophylaxis has become the foundation for most elimination efforts. This is largely due to the problems described above with widely varied vector control initiatives requiring hyperlocalized implementation to interrupt transmission in distinct ecologic niches. The Global Programme for the Elimination of Lymphatic Filariasis (PELF) was launched following the resolution of the World Health Assembly to eradicate this disease. Treatment and chemoprophylaxis with one of two drug regimens comprise the primary approach to this initiative. The first regimen is albendazole plus diethylcarbamazine, and the second is albendazole plus ivermectin. The implementation of these regimens, without specific universal vector control (although vector control in specific geographic locations can often supplement the de-worming campaigns), constitute the current major global eradication initiative under PELF.</span></div>
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Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com26tag:blogger.com,1999:blog-3492197469143963742.post-35689125481068350192012-04-25T15:23:00.000-04:002012-04-25T15:23:31.201-04:00Onchocerciasis<div dir="ltr" style="text-align: left;" trbidi="on">
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This week at Infection Landscapes I will cover onchocerciasis, which is more commonly known as "river blindness" for reasons that will shortly become clear. The helminth causing this infection is vector-borne, adding further complexity to its transmission dynamics. As the second leading infectious cause of blindness in the world, onchocerciasis is also associated with a large burden of disease, particularly in sub-Saharan Africa.<br />
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<b>The Worm</b>. Onchocerciasis is caused by <i>Onchocerca volvulus</i>, which is a nematode, and transmitted to humans by <i>Simulium</i> black flies. The microfilarial larvae of this helminth are the source of the pathology in humans:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgSqiSxpexFH2kyl87X_AkXeyPYqlDsyxrPaeou6JvnSbrtgNULyfdV_MTkf1Ls9uyn3KILshEtI_bTH1FoTcRXJA2djE7zZR0oLrMmRjyE2GLmQNyAG8f5ImNpmK04jkGdJpVw1jxHR64/s1600/Onchocerca_volvulus.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="267" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgSqiSxpexFH2kyl87X_AkXeyPYqlDsyxrPaeou6JvnSbrtgNULyfdV_MTkf1Ls9uyn3KILshEtI_bTH1FoTcRXJA2djE7zZR0oLrMmRjyE2GLmQNyAG8f5ImNpmK04jkGdJpVw1jxHR64/s400/Onchocerca_volvulus.jpg" width="400" /></a></div>
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<i><span style="font-size: x-small;">Microfilariae of Onchocerca volvulus</span></i></div>
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<b>The life cycle of <i>O. volvulus</i> requires both a definitive host, i.e. humans, and an intermediate host, i.e. black flies</b>. Fully formed microfilariae are released from gravid adult females in an infected human host. When a susceptible <i>Simulium</i> black fly takes a blood meal from this infected human host, the fly ingests the microfilariae with the blood. Upon reaching the gut of the fly, the microfilariae pass out of the gut and migrate to the thoracic flight muscles, where they proceed with their first (J1) and second (J2) larval stages of development. J2 larvae migrate to the saliva of the fly where they further develop into the infectious third stage larvae (J3). When the black fly with infectious J3 larvae takes a blood meal from a susceptible human host, these larvae enter the bite wound and migrate to subcutaneous tissues, where they form nodules and undergo their final developmental stage into adult worms. This last developmental stage requires between 6 and 12 months. The adult worms will mate when they reach maturity. The adult males leave their nodules and seek out females in the subcutaneous tissue. After mating, females produce an average of 700 eggs per day over the course of their adult lives, which average 8 to 10 years. Each microfilaria produced can live for an average of 1 to 2 years before it dies, giving these organisms ample time to encounter another black fly and carry on through the life cycle. The graphic below, produced by the Centers for Disease Control and Prevention (CDC) is a nice depiction of the life cycle of <i>O. volvulus</i>.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgiOdaNp1udIY8KTo9kzkHT3gamgZ5a1Ybib8GKjK35V7SBwhhGD891IZb6bl5DsN_Ou_kQf_O_FFJtJNDkU8F5s8Q4mGFcJZqXrxlQ0pVpvNfXGnxJ3ZjvJn78jIlRnmD7ZeOBC6XKtI0/s1600/Onchocerca_volvulus_LifeCycle.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="331" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgiOdaNp1udIY8KTo9kzkHT3gamgZ5a1Ybib8GKjK35V7SBwhhGD891IZb6bl5DsN_Ou_kQf_O_FFJtJNDkU8F5s8Q4mGFcJZqXrxlQ0pVpvNfXGnxJ3ZjvJn78jIlRnmD7ZeOBC6XKtI0/s400/Onchocerca_volvulus_LifeCycle.gif" width="400" /></a></div>
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<b>The symbiotic relationship between this helminth and a bacterium constitutes another critical, and fascinating, component to the worm's life cycle</b>. <i>Wolbachia</i> is a genus of bacteria that commonly infects many species of insects, and a few species of nematodes. These ubiquitous bacteria can engage either parasitic or symbiotic relationships with their hosts. In the case of the <i>Wolbachia</i>-<i>Onchocerca</i>-<i>Simulium</i> triad, an extraordinarily complex symbiosis has evolved wherein <i>O. volvulus</i> requires infection with <i>Wolbachia</i> bacteria in order to complete its larval development in the black fly. Without this bacterial infection, the helminth larvae cannot develop and their life cycle is arrested.<br />
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<b>The Vector</b>. Human infection with <i>O. volvulus</i> is vectored by the black fly, i.e. a member of the Simuliidae family. Black flies that transmit <i>Onchocerca</i> infections are members of the genus <i>Simulium</i>, which is comprised of hundreds of different species, many of which are capable of serving as vectors for this helminth:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjvPoDjebswxui_VgGTaKnh3NXoVFVuA68L0806MfIRq8oWON9DJdaZnm7w5NFzfYUP_95EsLr-rRO5eKT9qJRtww0R6Y5RPPK0gqVVzCKM6Mfv6kD6pwq32NH24ucd-E8Gn6tfaSH-40U/s1600/Simulium.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjvPoDjebswxui_VgGTaKnh3NXoVFVuA68L0806MfIRq8oWON9DJdaZnm7w5NFzfYUP_95EsLr-rRO5eKT9qJRtww0R6Y5RPPK0gqVVzCKM6Mfv6kD6pwq32NH24ucd-E8Gn6tfaSH-40U/s400/Simulium.jpg" width="400" /></a></div>
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Black flies occupy a fascinating ecology, which conforms to specific features of the landscape even though they are widely distributed throughout the world. <b>Black flies oviposit in flowing water systems</b>. When the larvae emerge from the eggs they remain submerged and anchor themselves to fixed objects, typically rocks, in the bed of the lotic environment. The larvae employ a system of passive "fishing" to feed, whereby extendable-retractable mouth fans are used to catch food items, such as bacteria and algae, as they are carried past by the water current:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjYAs2PxokYRZBGe_4YLs8uGJgtTKpcawFpFUl7Ql8tPoSSV_kt8I0UiiwPcRnz7V6_8kYNieaFn1GBULDjk8JtFvC0JJzlK2l3LxFZ9kxpWHWVsXMuKpXll2BTZ_Bj0_SE7zT8GtFO2Cw/s1600/Simulium_fly_larva_and_pupa.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjYAs2PxokYRZBGe_4YLs8uGJgtTKpcawFpFUl7Ql8tPoSSV_kt8I0UiiwPcRnz7V6_8kYNieaFn1GBULDjk8JtFvC0JJzlK2l3LxFZ9kxpWHWVsXMuKpXll2BTZ_Bj0_SE7zT8GtFO2Cw/s640/Simulium_fly_larva_and_pupa.png" width="396" /></a></div>
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<i><span style="font-size: x-small;">1. Pupa 2. Larva</span></i></div>
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<i><span style="font-size: x-small;">Notice the mouth fans on the larva that are used for catching food in moving water</span></i></div>
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The larvae further develop into pupae under the water and finally emerge from the water as adults in a bubble of air.<br />
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The adult flies' diets differ by sex. Much like most adult mosquitoes, the males subsist on plant juices alone while females also seek out the blood of vertebrate hosts. Thus, blood proteins are also likely important for egg production in females. The females are day biters and host preferences differ by <i>Simulium</i> species, as does their geographic range.<br />
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<b>The Disease</b>. Onchocerciasis pathogenesis is due to the microfilariae and the <i>Wolbachia</i> that infect them. The adult worms are effectively sealed off from the host's immune system in their subcutaneous nodules. The microfilariae, on the other hand, are in direct contact with blood and tissue and, thus, with the host's immune system. As such, the microfilariae are capable of stimulating a potent inflammatory response in the host, which leads to disease.<br />
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<i>There are typically three main organ systems that are involved in O. volvulus infection: the skin, the lymphatics, and the eye.</i><br />
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<b>Onchocerciasis involving the skin is known as onchodermatitis</b>. In minor, low volume infections, the infection may be entirely subclinical, but can also present with mild itching or discoloring of the skin. As the number of nodules increases, however, symptoms become more pronounced. Intense pruritus is a defining clinical characteristic of moderate to severe infections. The intense itching and associated scratching usually also present with a papular rash. In high volume infections, the itching can be so severe that it renders those affected physically disabled and can sometimes even result in suicide. With chronic infection, onchodermatitis can be quite taxing on the skin, with a general thickening and hardening and subsequent development of a "lizard skin" appearance. Depigmentation is also common in chronic infections wherein the skin can take on a leopard-like appearance. As the skin continues to degrade, it will wrinkle and age prematurely:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjVABAP47lx8FAWpvlaz_pyclTSkzzR6uk8_w7CeXU1FhZUn-Vl-l0CzX4DO4iloC5N3rJnfp2aQ15bQnwbhmNNu3pm0jOnPnnMhBjViUh9THxJZIzd_a3Vp9W_IHWpv_UtL8UhBRIj0bg/s1600/Onchocerciasis-onchodermatitus.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjVABAP47lx8FAWpvlaz_pyclTSkzzR6uk8_w7CeXU1FhZUn-Vl-l0CzX4DO4iloC5N3rJnfp2aQ15bQnwbhmNNu3pm0jOnPnnMhBjViUh9THxJZIzd_a3Vp9W_IHWpv_UtL8UhBRIj0bg/s400/Onchocerciasis-onchodermatitus.jpg" width="338" /></a></div>
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<b>Lymphadenopathy</b> presents as the microfilariae locate in lymph nodes, with pronounced nodules commonly developing at these sites. Interestingly, there are geographic differences in the lymphatic sites that are most often involved. For example, in the Americas the lymph nodes of the head and neck are more frequently affected, whereas in sub-Saharan Africa the femoral and inguinal lymph nodes are more commonly affected.<br />
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<b>Ocular onchocerciasis</b> is the second leading infectious cause of blindness in the world. All parts of the eye can be affected. Ocular infection begins with microfilariae migration to the cornea. Early infection usually presents with a tearing, irritated conjunctivitis, often with a hypersensitivity to light. Keratitis lesions are also typically apparent on the cornea at this time. This stage of infection is probably an inflammatory response similar to that induced in the skin. At this stage, the infection can clear, inflammation subside, and full recovery ensue. However, a sclerosing keratitis develops among those with chronic infection, which is common in areas of high endemicity. Over time, as the the cornea continues to sclerose it becomes increasingly opaque until light is effectively blocked altogether:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh7zt48BlyrTRCXGzeiATz4qLF468GmLNeoFztl-48arAJc4PVeu2Qfb4WSMiJejLM5gJdt2KQPLQi6np9R9TtNEpirccwVmhl2PkQSLmQmVY1nC2Vn4a2J4_bpRESB2hHy-ZjPUxNEdn4/s1600/Onchocerciasis-eye.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh7zt48BlyrTRCXGzeiATz4qLF468GmLNeoFztl-48arAJc4PVeu2Qfb4WSMiJejLM5gJdt2KQPLQi6np9R9TtNEpirccwVmhl2PkQSLmQmVY1nC2Vn4a2J4_bpRESB2hHy-ZjPUxNEdn4/s400/Onchocerciasis-eye.jpg" width="400" /></a></div>
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This pathology is the primary cause of blindness in onchocerciasis. However, because the microfilariae can invade any structure in the eye, pathology can also derive from damage to the posterior eye, including the retina and optic nerve.<br />
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<b>There is increasing evidence that the potent inflammatory response stimulated by the microfilariae is due to <i>O. volvulus</i>' symbiont, <i>Wolbachia</i></b>. As mentioned above, these bacteria are necessary catalysts to the larval development of this helminth in the black fly. However, these bacteria produce potent molecules that are proinflammatory to the human host. As the microfilariae die, these bacteria are released and subsequently interact with the human immune system, thus leading to the inflammatory responses associated with onchocerciasis. In fact, antibiotic treatment to eliminate the <i>Wolbachia</i> from the microfilariae has been associated with a drastic reduction in blindness among the chronically infected even without clearance of the helminths.<br />
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<b>The Epidemiology and the Landscape</b>. Worldwide, there are approximately 37 million people infected with <i>O. volvulus</i>. The vast majority of these occur in sub-Saharan Africa, however, there are small localized areas of endemicity in Central America and in the warm, moist, yet mountainous altitudes of northern South America. Of those who are infected, between 300,000 and 500,000 are visually impaired, and the disability-adjusted life years associated with general infection are substantive, with approximately 60% attributable to non-ocular skin-involved pruritis:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj2O7PWfocbAZmEUgEO8rxVUmP5npwsfZa2OMNrgt5eB8duNTFHVlv82PL5Qy-IRD_UG3sMdgXqpKDSbqM03GL3AWRmpyp0t2STGrh9NMG65dfTED1bF_9EhuAo4wP4hh9UEhxDoPbDCEw/s1600/Onchocerciasis_world_map_-_DALY_-_WHO2002.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="175" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj2O7PWfocbAZmEUgEO8rxVUmP5npwsfZa2OMNrgt5eB8duNTFHVlv82PL5Qy-IRD_UG3sMdgXqpKDSbqM03GL3AWRmpyp0t2STGrh9NMG65dfTED1bF_9EhuAo4wP4hh9UEhxDoPbDCEw/s400/Onchocerciasis_world_map_-_DALY_-_WHO2002.png" width="400" /></a></div>
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<div class="description en" lang="en" style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;" xml:lang="en">
<span class="description"><span class="language en" title=""><b>World Health Organization estiated:</b></span> <a class="extiw" href="http://en.wikipedia.org/wiki/Age_adjustment" style="background-attachment: initial; background-clip: initial; background-color: initial; background-image: none; background-origin: initial; background-position: initial initial; background-repeat: initial initial; color: #663366; text-decoration: none;" title="en:Age adjustment">Age-standardised</a> <a class="extiw" href="http://en.wikipedia.org/wiki/DALY" style="background-attachment: initial; background-clip: initial; background-color: initial; background-image: none; background-origin: initial; background-position: initial initial; background-repeat: initial initial; color: #663366; text-decoration: none;" title="en:DALY">disability-adjusted life year</a> (DALY) rates from <b>Onchocerciasis</b> by country (per 100,000 inhabitants).</span></div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #b3b3b3; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> no data</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffff65; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> less than 10</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #fff200; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 10-50</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffdc00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 50-60</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffc600; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 60-70</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffb000; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 70-80</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff9a00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 80-90</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff8400; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 90-100</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff6e00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 100-150</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff5800; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 150-200</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff4200; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 200-300</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff2c00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 300-400</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #cb0000; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> more than 400</div>
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Because of the reproductive ecology of <i>Simulium</i> flies, fast moving water is the central feature of the landscape required for transmission of <i>O. volvulus</i> to humans:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjJR8rZuYRS8NRbvWz3yWZQPXq1zmz20YxyJFioPo0cjTCmihk24ySLCR7H_uVlla-0OPyz7Wds0uxO_QxUuNXdUHUAtoBbRxFQN__vQlgnNtPg9-FC25VSOJ6LxgduucoiaXkRfoRdrts/s1600/Simulium_breeding_site_large.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="270" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjJR8rZuYRS8NRbvWz3yWZQPXq1zmz20YxyJFioPo0cjTCmihk24ySLCR7H_uVlla-0OPyz7Wds0uxO_QxUuNXdUHUAtoBbRxFQN__vQlgnNtPg9-FC25VSOJ6LxgduucoiaXkRfoRdrts/s400/Simulium_breeding_site_large.jpg" width="400" /></a></div>
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<b>Accordingly, in endemic areas, infection transmission is associated with residential or occupational distance to flowing rivers and streams in mountainous terrain</b>. As such, communities in close proximity to moving water are at high risk in topographically varied areas of endemicity. However, transmission is not exclusive to these sites because some <i>Simulium</i> species have broad flight ranges that extend well beyond (up to 40 miles for some species) their reproductive sites. Therefore, while risk of infection is certainly concentrated at the reproductive sites of fast moving water, the overall endemicity is typically more diffuse, and geographic risk more extensive, than the narrow corridor delineated by the waterway. <br />
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These features of black fly ecology and subsequent landscape of transmission make vector control an extraordinarily difficult, and largely unfeasible, approach to the prevention of onchocerciasis.<br />
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<b>Prevention and Control</b>. As described above, vector control of onchocerciasis is too difficult to achieve success at the population level. Currently, prevention and control strategies, primarily led by the African Programme for Onchocerciasis Control (APOC) and Onchocerciasis Elimination Program for the Americas (OEPA), employ therapeutic and prophylactic administration of ivermectin, which is very effective against filarial helminths, but cannot be administered to individuals who are infected with <i>Loa loa</i> nematodes as it causes severe reactions in the host that can lead to extensive secondary disease.<br />
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<span style="font-family: inherit;"><b style="background-color: #fefdfa; color: #333333; line-height: 18px;">More generally, de-worming campaigns do offer some hope, even for regional elimination of onchocerciasis</b><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">. However, as one might expect, there are obstacles to overcome in de-worming. </span><b style="background-color: #fefdfa; color: #333333; line-height: 18px;">First</b><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">, ivermectin is not free, so without adequate funding poor communities will not be able to prioritize the cost. </span><b style="background-color: #fefdfa; color: #333333; line-height: 18px;">Second</b><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">, effective ways to deliver ivermectin to communities need to be implemented, which can be logistically challenging particularly in remote communities or during times of the year when travel may be restricted (i.e. during the rainy season). </span><b style="background-color: #fefdfa; color: #333333; line-height: 18px;">Third</b><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">, the extensive use, or misuse, of ivermectin will likely lead to resistance in <i>O. volvulus</i>, thus making the drug ineffective. Nevertheless, if adequate resources can be put behind de-worming campaigns, and if delivery systems can be adapted to </span><i style="background-color: #fefdfa; color: #333333; line-height: 18px;">actively engage community members in the delivery and monitoring of ivermectin</i><span style="background-color: #fefdfa; color: #333333; line-height: 18px;"> to simultaneously circumvent logistical obstacles and reduce the development of resistance, then substantial reductions in onchocerciasis may still be possible.</span></span> </div>Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com11tag:blogger.com,1999:blog-3492197469143963742.post-69523840469712662882012-04-10T11:22:00.000-04:002012-04-10T11:24:38.605-04:00Trichinellosis<div dir="ltr" style="text-align: left;" trbidi="on">
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This week at Infection Landscapes I will cover trichinellosis, which is another roundworm infection. This roundworm does not cause a substantial burden throughout the world, but it is worth describing here because it does occupy some unique landsdcapes at the interface between human and animal ecology in both domestic and sylvan habitats.<br />
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<b>The Worm</b>. Trichinellosis is cause by nematode helminths of the genus <i>Trichinella</i>. While there are eight known species of the genus, only three are of major importance in causing human infection: <i>Trichinella spiralis</i>, <i>T. nativa</i>, and <i>T. britovi</i>. The majority of human infections are caused by <i>T. spiralis</i>.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg0SL9rsexxLWQHfyrzOoNOPeQba3Kw0EMzFwmbdj2bI1kddUytMQ9aNpKKsMnFZsBVZ0KnBq9n9KRmB7QotgpL8tKz79WcRQshw049AsGmTR3vIwe9UKg2j4fD0SuDO_VRVj8bgXK06CY/s1600/Trichinella_spiralis_larva.JPG" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg0SL9rsexxLWQHfyrzOoNOPeQba3Kw0EMzFwmbdj2bI1kddUytMQ9aNpKKsMnFZsBVZ0KnBq9n9KRmB7QotgpL8tKz79WcRQshw049AsGmTR3vIwe9UKg2j4fD0SuDO_VRVj8bgXK06CY/s320/Trichinella_spiralis_larva.JPG" width="320" /></a></div>
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<span style="font-size: x-small;"><i>Trichinella spiralis</i> <i>larva</i></span></div>
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<b>Let's consider the life cycle</b>. <i>The defining feature of the T. spiralis life cycle is that larvae encyst in the skeletal muscle tissue of the host, wherein they await the consumption of their current host by another predatory or scavenging host to infect that new host and complete the life cycle</i>. First, infection occurs when a new host ingests raw meat (i.e. the raw muscle tissue) containing the infectious encysted larvae. Upon reaching the stomach of the new host, the larvae excyst triggered by the acid and pepsin in the gastric environment. The free larvae subsequently make their way to the small intestine where they penetrate the mucous membrane of the epithelium and develop into adults after four molts. As adults, males and females mate and the females produce motile larvae after approximately one week. These larvae then penetrate the epithelium and ultimately gain the circulation (lymph and blood) to seek out skeletal muscle tissue. When the larvae reach the muscle tissue each larva will invade a single skeletal muscle cell wherein they encyst and become the infectious larvae capable of infecting new hosts. The process of encystation is unique in that the worm hijacks the host muscle cell and creates a new intracellular environment, call a <b>nurse cell</b>, which encapsulates and maintains the viability of the infectious larvae for many years until, one day, it finds itself in the stomach of a new host after being eaten raw along with its previous host:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiBZ8aEBigCyfwKxADyzjE8CZpHFGzHqZ5UVIQpOjovy0HQWSDPqCG7uCWvXJ70TecR5E71sugwDcMpNyn_BFRGyaLCFr99dP0T0ER8A1FEJqLapsxdfKR7oM_Ysy_LDfSapZ9Cmi8Hnwg/s1600/Trichinella_spiralis_larvae_within_muscle.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiBZ8aEBigCyfwKxADyzjE8CZpHFGzHqZ5UVIQpOjovy0HQWSDPqCG7uCWvXJ70TecR5E71sugwDcMpNyn_BFRGyaLCFr99dP0T0ER8A1FEJqLapsxdfKR7oM_Ysy_LDfSapZ9Cmi8Hnwg/s400/Trichinella_spiralis_larvae_within_muscle.jpg" width="400" /></a></div>
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<i><span style="font-size: x-small;">Trichinella spiralis larvae encapsulated in nurse cells within the skeletal muscle tissue of the host</span></i></div>
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Below is nice graphic from the Centers for Disease Control and Prevention (CDC) depicting the life cycle of this helminth:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiQ9gA_KMiUPOvsWyoe1tOS8X5MiQIlekRzS-syt_-OJiQpdEzTdgPaBf4BYbune6NFbDiNRwk3DP1PxFnoQqpjl1UlBGJhNoKBgJFi0Jyu0EneDIZLGeLn6bOshrYNYku728JHI-Qpa_Y/s1600/Trichinella_LifeCycle.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="363" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiQ9gA_KMiUPOvsWyoe1tOS8X5MiQIlekRzS-syt_-OJiQpdEzTdgPaBf4BYbune6NFbDiNRwk3DP1PxFnoQqpjl1UlBGJhNoKBgJFi0Jyu0EneDIZLGeLn6bOshrYNYku728JHI-Qpa_Y/s400/Trichinella_LifeCycle.gif" width="400" /></a></div>
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<b>Note that <i>Trichinella</i> does not require intermediate hosts. It is capable of completing its life cycle in a single species of either its primary hosts, such as rodents, pigs, or wild game, or incidental hosts, such as humans.</b><br />
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<b>The Disease</b>. The vast majority of <i>Trichinella</i> infections are asymptomatic. When clinical disease does occur, it follows one or both of two courses: <i>enteral or parenteral disease</i>.<br />
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<b>Enteral disease</b> will typically present in association with high volume infections and symptoms include diarrhea and gastric discomfort such as dyspepsia and nausea fairly soon (within ~ 1 week) after infection.<br />
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<b>Parenteral disease</b> is also associated with high volume infections and results from the migration of large numbers of larvae out of the small intestine and into the circulation with potential dissemination to many different organ systems. Fever, muscle pain, edema and vasculitis are typical presentations of parenteral disease, which follow from the systemic inflammation induced by the circulating larvae. Periorbital edema is considered a classic sign of parenteral trichinellosis, however it is not pathognomonic:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhcfMktzXaRBlGlT6pUVAn_7TSvVa-apk2b4h2tlI1Tkov_85s20LZr_xLUXPZTyshKvH7MaWssYntrW0ImX3K2pNoudE5C1kRUrALvC32AEYZd1kjg_dJtSmYcyOPMN0xfbL0uqDiR8JM/s1600/trichinellosis+periorbital+edema.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhcfMktzXaRBlGlT6pUVAn_7TSvVa-apk2b4h2tlI1Tkov_85s20LZr_xLUXPZTyshKvH7MaWssYntrW0ImX3K2pNoudE5C1kRUrALvC32AEYZd1kjg_dJtSmYcyOPMN0xfbL0uqDiR8JM/s400/trichinellosis+periorbital+edema.jpg" width="320" /></a></div>
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If the worms invade the central nervous system encephalitis can develop, as can other severe neurologic pathology involving pulmonary function and/or motor coordination. Although quite rare, when it does occur death is most often due to encephalitis, myocarditis or pneumonia following the extensive inflammatory responses associated with high volume infection.<br />
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<b>The Epidemiology and the Landscape</b>. As mentioned above, trichinellosis does not constitute a large global burden of disease. There are approximately 10,000 new infections each year and the vast majority of these are asymptomatic or of mild presentation. Currently, there are likely over 11 million people infected globally, with most infections occurring in China and Southeast Asia. The maps below published in Clinical Microbiology Reviews show the global distribution of <i>Trichinella</i> species:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgzeCM9fz_h-fSGAXjH67-xzWTWvCb79y29LnVGNZU4D9zxXGe2Wwu4DjKYDH1ajrVDHx5AgKYxHsIcWZ0EdfnUX9r24hq_aB7gwQh5kQpqn9xg6gY_6CnAde1DDs9FtdPOf0S-IKKhDQA/s1600/Trichinella+global+distribution.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="210" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgzeCM9fz_h-fSGAXjH67-xzWTWvCb79y29LnVGNZU4D9zxXGe2Wwu4DjKYDH1ajrVDHx5AgKYxHsIcWZ0EdfnUX9r24hq_aB7gwQh5kQpqn9xg6gY_6CnAde1DDs9FtdPOf0S-IKKhDQA/s400/Trichinella+global+distribution.jpg" width="400" /></a></div>
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<span style="font-size: x-small;"><i>World map showing the distribution areas of Trichinella spiralis (Tsp), Trichinella pseudospiralis from north America (TpsN), T. pseudospiralis from Europe and Asia (TpsP), T. pseudospiralis from Tasmania (TpsA), Trichinella papuae (Tpa), and Trichinella zimbabwensis (Tzi) (Clin. Microbiol. Rev. January 2009 vol. 22 no. 1 127-145)</i></span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjerGVuWt48QXHs_tn-8BEwgIA2crsjTQ1UlhKIHyh5emb06D9U5lWzpedg6UA84GDTLMA0dIMNFFFXqBg8CYubwYw5wNeHKDtEF8CzmvHfaEwGKYYfbfblj4CMrnWv1E-TllKYk9HRw1I/s1600/Trichinella+global+distribution+2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="206" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjerGVuWt48QXHs_tn-8BEwgIA2crsjTQ1UlhKIHyh5emb06D9U5lWzpedg6UA84GDTLMA0dIMNFFFXqBg8CYubwYw5wNeHKDtEF8CzmvHfaEwGKYYfbfblj4CMrnWv1E-TllKYk9HRw1I/s400/Trichinella+global+distribution+2.jpg" width="400" /></a></div>
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<i><span style="font-size: x-small;">World map showing the distribution areas of Trichinella nativa (Tna), Trichinella britovi (Tb), Trichinella murrelli (Tm), Trichinella nelsoni (Tne), Trichinella genotype T6 (T6), Trichinella genotype T8 (T8), and Trichinella genotype T9 (T9). In some regions, the distribution areas of these encapsulated species and genotypes overlap between them (Clin. Microbiol. Rev. January 2009 vol. 22 no. 1 127-145)</span></i></div>
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<b>Transmission to humans occurs within two fairly distinct landscapes, one domestic and one sylvan</b>. <i>The vast majority of infections in the world are transmitted by consuming inadequately prepared pork.</i> Domestic pigs, and particularly the ways in which pigs feed under specific farming practices, are the common vehicle responsible for most human infection. You will recall from the description above that a critical and defining feature of trichinellosis is that an infected host <b>must be consumed</b> by a new host for transmission of the helminth to occur in the new host. As such, two additional features immediately emerge in shaping the ecology of transmission. First, the eating habits of key reservoir hosts (and the farming practices that maintain these habits for domestic animals); and, second, the eating habits of humans, particularly with respect to food preparation.<br />
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Domestic pig farming practices vary dramatically across the world. In many low and middle income countires, where most trichinellosis infections occur, as well as in some high income countries, garbage feeding is a common practice in raising domestic animals. As such, pigs will very often encounter dead rodents, which they eat, in these food sources. Rodents are a common reservoir host for <i>T. spiralis</i> and serve as important hosts in maintaining infection in pigs. Moreover, while sources of garbage are prime locations for rodents, and thus encounters with the pigs who might feed on the garbage, this rodent-pig cycle is by no means limited to such loci. Indeed, better resourced farms that can afford better quality feed can also be quite attractive sources of food to rodent species. Finally, the rodents are not essential to maintain infection in pigs. Pig cannibalism, either as it occurs naturally or due to specific farming practices of adding pig remains to feed, can be an important source of transmission for pigs, which can maintain infection within a pig community without any external hosts. Of course, if pig products used for human consumption are properly cooked then transmission is blocked and the pig infection cycle is irrelevant. However, in addition to varied farming practices throughout the world, there are also varied food preparation practices when it comes to pork, which brings us back to the second important feature in transmission.<br />
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So, the domestic landscape epidemiology of trichinellosis is defined by the intersection of farming and food preparation in the geographic spaces where <i>T. spiralis</i> is endemic. Below is a nice graphic developed by G.J. Jackson at the Division of Microbiology, US Food and Drug Administration and published by the Food and Agriculture Organization of the United Nations, which depicts this domestic cycle and the sylvan cycle to be described below:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgCSWuX5uRufbk5A54w4MAE8wNdsPs3FdmoF7qAFEdTT_W1JH6Ep5cs0XAYE6qy2FrtMjka0mPsa6uIMW9D90bS226uDbfP4JDHpYtigEnpcArVf2KBQGCWibbC_CCkIb7kwv-3A2qSrMI/s1600/trichinellosis+cycles.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgCSWuX5uRufbk5A54w4MAE8wNdsPs3FdmoF7qAFEdTT_W1JH6Ep5cs0XAYE6qy2FrtMjka0mPsa6uIMW9D90bS226uDbfP4JDHpYtigEnpcArVf2KBQGCWibbC_CCkIb7kwv-3A2qSrMI/s640/trichinellosis+cycles.gif" width="518" /></a></div>
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<b>In the developed world, many human infections result from contact with the sylvan cycle</b>. Game animals, particularly bears, are frequently infected, albeit with different species of <i>Trichinella</i>. If these game meats are not properly prepared by cooking, then humans can ingest the intramuscular larvae and become infected. While this sylvan transmission cycle accounts for many infections in some developed countries, for example in the United States, this transmission cycle is by no means limited to developed countries. Indeed, the sylvan cycle can be an active transmission route in many developing regions as well. For example, the consumption of wild cat meats or feral pigs in sub-Saharan Africa can lead to human infection.<br />
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While the largest absolute number of incident and prevalent cases occur in Southeast Asia and are mostly transmitted via the domestic cycle, the largest density of human infection may be among arctic indigenous communities, where transmission occurs following consumption of polar and brown bears, foxes, and pinniped marine mammals:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjvkQnukaE-2nj-F3SqekNfz3ihjC6MaN1LJAAFlZDAJfqZ2KofPKagrT2WlS7cvAqY68i4doY7Jp6Pl9XafPAfFapdOfAcROqwNpKQ7Mt23yReqj6Qur13JwmYoaJKYAqDSsIfxCIa6-Q/s1600/trichinellosis+wild+game.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="232" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjvkQnukaE-2nj-F3SqekNfz3ihjC6MaN1LJAAFlZDAJfqZ2KofPKagrT2WlS7cvAqY68i4doY7Jp6Pl9XafPAfFapdOfAcROqwNpKQ7Mt23yReqj6Qur13JwmYoaJKYAqDSsIfxCIa6-Q/s400/trichinellosis+wild+game.jpg" width="400" /></a></div>
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<b>Prevention and Control</b>. <i>Prevention of trichinellosis in humans is comprised of 2 primary strategies: management of farming practices and preparation of meat products</i>. Where domestic pigs are raised for human consumption care should be taken to employ some basic control measures. The adoption of the following control regulations should apply universally, and are especially important when garbage feeding is used: 1) prevent pigs from eating any dead animal carcasses, 2) strictly control rodent populations, 3) prevent contact between pigs and sylvan animal species, and 4) prevent pigs from eating other pigs, either dead or alive. </div>
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The second prevention strategy consists of proper food preparation. <b>Thoroughly cooking all pork and game meats at 165 degrees F (74 degrees C) is the most effective way of killing the larvae in the meat and, thus, blocking transmission</b>. Freezing pork (but not game meats) can also kill <i>T. spiralis</i>, however freezing must occur at 5 degrees F (-15 degrees C) for at least 20 days, or -4 degrees F (-20 degrees C) for at least 3 days, in cuts of meat that are <i>less than 6 inches in thickness</i>. Other species of <i>Trichinella</i> are much more resistant to freezing and, thus, this method is not useful for game meats. </div>
</div>Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com12tag:blogger.com,1999:blog-3492197469143963742.post-64845396179870918242012-03-29T10:02:00.000-04:002012-03-29T10:04:17.006-04:00Guinea Worm<div dir="ltr" style="text-align: left;" trbidi="on">
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This week at Infection Landscapes I will cover dracunculiasis, more commonly known as Guinea worm or the "fiery serpent". Dracunculiasis is an ancient disease, so embedded in human experience that it is stylistically represented as the very symbol of medicine and health across much of the world. Probably. It is also likely to become only the second human infection ever eradicated through public health effort (smallpox was, of course, the first and only human infectious disease eradicated).<br />
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<b>The Worm</b>. Dracunculiasis is caused by <i>Dracunculus medinensis</i>, which is a nematode and an obligate helminth:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjoGpP0zN36MnNnA27JJBt_EpGMn-CFKQjeeNYjAc-xur5-7UeMfBWrcznaW2PITq-_Cb-8TvAEzookaHSXKlo7K3hJGWtyaUzTs1IqYVTbVgp5hcB9fw-56UD17FO1R2_KoI3dMACZHYo/s1600/Dracunculus_medinensis_larvae.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="270" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjoGpP0zN36MnNnA27JJBt_EpGMn-CFKQjeeNYjAc-xur5-7UeMfBWrcznaW2PITq-_Cb-8TvAEzookaHSXKlo7K3hJGWtyaUzTs1IqYVTbVgp5hcB9fw-56UD17FO1R2_KoI3dMACZHYo/s400/Dracunculus_medinensis_larvae.jpg" width="400" /></a></div>
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<i style="text-align: left;"><span style="font-size: x-small;">Dracunculus medinensis larvae</span></i> </div>
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<b>Let's examine the complex life cycle of this waterborne worm</b>. <i>D. medinensis</i> infects both a definitive host, humans, and an intermediate host, copepods, to complete its life cycle. I'll begin this helminth's developmental story in medias res: a mature adult female occupying an infected human host releases fully motile infective larvae into a community water supply by way of a blister on the host's skin. This blister is formed, and burrowed into, by the female worm. As the larvae are released from the human host, they enter the freshwater source and await their intermediate hosts, the <b>copepods</b>. Copepods are microscopic crustaceans that are ubiquitous in bodies of freshwater throughout the world. There are roughly 2800 species of copepods that occupy freshwater habitats, but those of the genus <i>Cyclops</i>, which alone comprises about 400 species, are probably the most important for maintaining the life cycle of <i>D. medinensis</i>.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh94rRksh_qRsXNYn2m7ICMnVPaVCHNnXD5JSQE_awQ4BtccSTU5r_hhI91rEpiQkMSQUavCibrL1U2Am4Sgp-iI3eMv0uxaMjRoTythnLMVSdQkF2iMUQm_1w6C-k5hjkIJ42QHjls-kU/s1600/Copepod_Cyclops.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh94rRksh_qRsXNYn2m7ICMnVPaVCHNnXD5JSQE_awQ4BtccSTU5r_hhI91rEpiQkMSQUavCibrL1U2Am4Sgp-iI3eMv0uxaMjRoTythnLMVSdQkF2iMUQm_1w6C-k5hjkIJ42QHjls-kU/s400/Copepod_Cyclops.jpg" width="400" /></a></div>
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<span style="font-size: x-small;"><i>Cyclops</i> copepod</span></div>
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These copepods ingest, and are subsequently infected by, the larvae that have been introduced into the body of freshwater by the infected human host. A further 2 to 3 weeks of larval development are then required in the copepod host before the larvae reach their 3rd stage, which is then infectious to new susceptible human hosts. <b>The infectious larvae are transmitted to humans when people consume the same water that is contaminated with the <i>D. medinensis</i>-infected copepods</b>. Thus, transmission is exclusively by way of the common vehicle, water. In fact, this helminth infection is the only worm we will cover in this series that is strictly waterborne. After consumption of the contaminated water, the copepods are digested and the <i>D. medinensis</i> larvae are released in the small intestine. The larvae then migrate out into the abdominal cavity where they begin their migration to and within connective tissue, mature to the adult stage, and mate. Males die after mating, but females continue their subcutaneous migration, usually, but not exclusively, moving distally toward peripheral structures in the lower limb, i.e. bottom parts of the leg or the foot. After approximately one year following the initial infection, the female adult worm, who now harbors the live 1st stage larvae, begins to form an induration on the surface of the host's skin. Underneath, a fluid-filled blister forms into which the tip of the worm protrudes. At this point, the blister causes a very painful, burning sensation that is typically relieved with cooling water. When the blister is submerged in water, it breaks and the larvae are released instantaneously into the body of freshwater from the protruding worm. Thus a new generation is introduced into the water and is capable of infecting new copepods and, thus, recontaminating the water. Here is a nice graphic developed by the Centers for Disease Control and Prevention (CDC) that nicely depicts the life cycle of <i>D. medinensis</i>:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiv_6lRvSvidObhyphenhyphenHsYVj5q9HpT5kggTpcVvfAWCstUJ0Z4dlsQkkJMO7mAfhIaWE3Bs5DlS1Z-J3t-LD7kA53J71tl4d3RVQr72HBNW8-gJDKQUp3uULCn26pEl8J7prT61Q-q7qJkohE/s1600/Dracunculus_medinensis_life_cycle.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="291" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiv_6lRvSvidObhyphenhyphenHsYVj5q9HpT5kggTpcVvfAWCstUJ0Z4dlsQkkJMO7mAfhIaWE3Bs5DlS1Z-J3t-LD7kA53J71tl4d3RVQr72HBNW8-gJDKQUp3uULCn26pEl8J7prT61Q-q7qJkohE/s400/Dracunculus_medinensis_life_cycle.gif" width="400" /></a></div>
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<b>The Disease</b>. Dracunculiasis does not typically cause life-threatening illness, unless the worm is removed incorrectly and dies within the host leading to extensive secondary infection. Nevertheless, because of the pain that is almost always associated with mature infections, particularly in the extremities, the disability that attends dracunculiasis can be severe during the eruptive stage, lasting approximately 3 to 10 weeks.</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg-r36V7OYRFqnnKwq69YBQB-I5JMQfj4o-MzJlExpmmzzyVZ5DaxXyxnMNe-eAeZVgzInsRpirx3pmX0k1Oh97H3sEUI4jIp6tGThfsO44wd-2h88G8BwoJqSnaRUjstLDGh2IP7QZfS8/s1600/dracunculiasisfoot.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="257" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg-r36V7OYRFqnnKwq69YBQB-I5JMQfj4o-MzJlExpmmzzyVZ5DaxXyxnMNe-eAeZVgzInsRpirx3pmX0k1Oh97H3sEUI4jIp6tGThfsO44wd-2h88G8BwoJqSnaRUjstLDGh2IP7QZfS8/s400/dracunculiasisfoot.jpg" width="400" /></a></div>
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In addition, chronic musculoskeletal dysfunction is not uncommon due to a hypersensitivity reaction, secondary infections, or if the worm fails to complete its migration and dies and calcifies in musculoskeletal tissue. When the migratory track of the worm intersects the articulation of bones, then joint problems can ensue:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhBj1gMOTe9oxQD8sc3eLSEL-lj8STysdBuFQa_APcrkXUUxiY_TOYZ9iqp6GC6Qh8Q72QClupxZbb1HM4FKPOPkSc-2dJKoLimUFniN3BT9vALh9NRDcEREOqA0GQGXh3NHxX-VfqyC44/s1600/Dracunculiasis+2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhBj1gMOTe9oxQD8sc3eLSEL-lj8STysdBuFQa_APcrkXUUxiY_TOYZ9iqp6GC6Qh8Q72QClupxZbb1HM4FKPOPkSc-2dJKoLimUFniN3BT9vALh9NRDcEREOqA0GQGXh3NHxX-VfqyC44/s640/Dracunculiasis+2.jpg" width="436" /></a></div>
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Finally, secondary infection of the ulcer that forms at the site of the blister can be quite serious if this vulnerable tissue is not carefully managed. Such secondary infections can indeed cause fatal disease. </div>
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<b>The Epidemiology and the Landscape</b>. This is an ancient disease. At one time this infection was a scourge that disrupted the lives of many across a vast expanse extending from West Africa, across the Middle East, South Asia, and into Southeast Asia. It also occurred in parts of the Americas. Before the beginning of the global eradication campaign (discussed in the Control and Prevention section below) estimates had the global prevalence of disease anywhere between 3 and 4 million cases. It was likely substantively higher than this at various points in history. Today we may be down to the last couple thousand cases in a few localized parts of a couple of sub-Saharan African countries. Dracunculiasis may become only the second human infection to be eradicated. Time and human experience will tell.</div>
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Around the turn of the 21st century the global burden of dracunculiasis was roughly geographically distributed as depicted in the map below published in the Canadian Medical Association Journal (CMAJ February 17, 2004 vol. 170 no. 4 495-500):</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEifKEkawIGgw_FAci6WFD28_i667S-JESIMZbZvUNIzPHmTRAJwGkj6zYiil7CLXjseDeKLbk2nIauUf-wkRliO0KIKS2RSpzc97C-De7no-3zUzjtPmgPyaN8OAKnERnB0W9XJaT0Ir9I/s1600/Dracunculiasis+distribution+2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="256" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEifKEkawIGgw_FAci6WFD28_i667S-JESIMZbZvUNIzPHmTRAJwGkj6zYiil7CLXjseDeKLbk2nIauUf-wkRliO0KIKS2RSpzc97C-De7no-3zUzjtPmgPyaN8OAKnERnB0W9XJaT0Ir9I/s400/Dracunculiasis+distribution+2.jpg" width="400" /></a></div>
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By the close of 2007, a much reduced distribution was apparent as depicted in this map published in the American Journal of Tropical Medicine and Hygiene (Am J Trop Med Hyg October 2008 vol. 79 no. 4 474-479):</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhNQtx7PwBUFfMFZbBLRx6c8rgey1Umc_vmquDRc3w4l29I-ChixXHsNb4B9WaQNda9oBuHqmiMuK8gvMVKMcrCgkN7zwiyVib6GVfYKOPmPP7Dd-E0wjz0uf2XwNjk2gPgRJV5Yw4G_xs/s1600/Dracunculiasis+distribution.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="307" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhNQtx7PwBUFfMFZbBLRx6c8rgey1Umc_vmquDRc3w4l29I-ChixXHsNb4B9WaQNda9oBuHqmiMuK8gvMVKMcrCgkN7zwiyVib6GVfYKOPmPP7Dd-E0wjz0uf2XwNjk2gPgRJV5Yw4G_xs/s400/Dracunculiasis+distribution.gif" width="400" /></a></div>
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<b>Official reporting has the number of incident cases identified in 2011 at close to 1100, most of which occurred in small pockets of South Sudan, but a small handful came from Mali, Chad and Ethiopia</b>. These numbers are likely under-reported especially in the areas of conflict in South Sudan, where most of the current cases still occur. Nevertheless, while complete eradication still requires vigilance and is by no means inevitable, it certainly does seem that dracunculiasis is now within reach of genuine eradication. Let's explore the landscape epidemiology more closely to get a better sense of how this worm effectively occupies a shared ecology with humans, and how this can be targeted to block transmission.</div>
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As described above in the life cycle of <i>D. medinensis</i>, <b>water is of the essence</b>. Water <i>is</i> the shared ecology between this worm and humans. In fact, it is the way in which water occupies both the physical and social landscapes that is responsible for transmission of infection.<br />
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<b>First, by adapting to intermediate copepod hosts, <i>D. medinensis</i> has located within specific bodies of freshwater</b>. In the areas of the world where dracunculiasis is endemic, this fundamental landscape requirement, i.e. bodies of freshwater, frequently overlaps the human social landscape in that high concentrations of infected copepods are found in important water sources for human consumption. For example, stepwells were a critical source of infection in India before dracunculiasis was eliminated in that country at the turn of the 21st century. These sites are typically artesian aquifers, which essentially provide reliable sources of surface water from the groundwater under pressure due to its geologic confinement underground:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjOdD6MLsLsv84vcnjk1L4xjDYcW9FZbevgZIvXr-rLLRXVpiPtOQhF-S1rk5Ol1cWUwrFm_U0Ep9RCngFGWj2kFbQDKenGAb-0ZnyAnzO2qJIye4kikyeeFiOhgpmllwb_YiGajwpIY-s/s1600/Dracunculiasis_Artesian_Well.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="245" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjOdD6MLsLsv84vcnjk1L4xjDYcW9FZbevgZIvXr-rLLRXVpiPtOQhF-S1rk5Ol1cWUwrFm_U0Ep9RCngFGWj2kFbQDKenGAb-0ZnyAnzO2qJIye4kikyeeFiOhgpmllwb_YiGajwpIY-s/s400/Dracunculiasis_Artesian_Well.png" width="400" /></a></div>
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These are known as <i>confined aquifers</i>, but unconfined aquifers can also be important constant sources of water, and can sometimes provide larger sources of surface water because they delineate the <i>water table</i>:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi14fUxB6AeKq3-YVn46S2ap8dhGJq7E6rS495IcXMaj0kMibepZyJonvEpnLj4nXPQir6ZeQ6VL_KyY9pYAt3M-CeMJ6P0fn5VmPjwk_VBatyIc3h5Mmx0KbJraKDHeLIJgx1TGonPU4k/s1600/Dracunculiasis_Groundwater_flow.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="258" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi14fUxB6AeKq3-YVn46S2ap8dhGJq7E6rS495IcXMaj0kMibepZyJonvEpnLj4nXPQir6ZeQ6VL_KyY9pYAt3M-CeMJ6P0fn5VmPjwk_VBatyIc3h5Mmx0KbJraKDHeLIJgx1TGonPU4k/s400/Dracunculiasis_Groundwater_flow.png" width="400" /></a></div>
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The main point is that these water sources are constant over long periods of time, and they stem from those specific points in the landscape where the groundwater breaches the surface and establishes a constant (relative in geologic time) source of freshwater. Because of the geologic structure of these aquifers, they provide extremely reliable sources of water to communities, in contrast to those unpredictable water sources that are more dependent on seasonal precipitation. <b>Furthermore, because these aquifers have typically been reliable across many human generations in the communities where they occur, they are also frequently centers of social gathering and exchange in addition to being fundamental sources of water for consumption</b>. India provides some amazing examples of the extent to which these overlapping geologic/hydrologic systems can intersect with social systems to provide unique landscapes that ultimately provided ecologic niches favorable to <i>D. medinensis</i>. Here is a picture of what is probably the most impressive stepwell in India, the Chand Baori, which was built in Abhaneri in Rajasthan in the 9th century. This stepwell is a full 100 feet deep and its architecture reflects a design that is intended to allow for relaxation and recreation among community members who come to use the well:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgeUfpOQsiA47qj-3kjUcpMCsjTfZuA1wDO2C3awsIjSZVb25j9n27CE8DGoMtiCoVzKUmFZDRul7Ds1siOUqMMYhuT6KQbO7eFVof5IGwyTV1MWH8RLETGw1kldXay0pMKEP4rokV87Mg/s1600/Dracunculiasis_ChandBaori.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="257" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgeUfpOQsiA47qj-3kjUcpMCsjTfZuA1wDO2C3awsIjSZVb25j9n27CE8DGoMtiCoVzKUmFZDRul7Ds1siOUqMMYhuT6KQbO7eFVof5IGwyTV1MWH8RLETGw1kldXay0pMKEP4rokV87Mg/s400/Dracunculiasis_ChandBaori.jpg" width="400" /></a></div>
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<b>In the days before dracunculiasis was eliminated from India, these kinds of water sources, which were already places of social gathering, served as the prefect relief for blistering worms</b>. Once infected individuals would seek relief in the water, the worms released their larvae, which readily infected copepods in the water and were subsequently consumed by the many people gathered at the well. This represents an incredible exploitation by this helminth of this unique landscape that represented the overlapping of geology, hydrology and society to form a very specialized ecologic niche. As mentioned, dracunculiasis is no longer endemic in India, so these stepwells are no longer sources of infection. However, in those parts of the world where dracunculiasis persists, similar hydrogeographic features in the landscape, representing constant water sources derived from aquifers, remain very relevant for continued transmission:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh7sADGfOTLFpK6zLO8w6y-vevO9HgE7PRvt-kJ94RqPgJEJQbwOn7RWxRlzpk7Jfho0iM3qMYX3xJmj6qjCxBd3n0kexZN_xzz9tArojMtP8VFlOxTJ3u1CgKE3SX8mMaIjrl8q5d62iQ/s1600/Dracunculiasis_prevention.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="264" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh7sADGfOTLFpK6zLO8w6y-vevO9HgE7PRvt-kJ94RqPgJEJQbwOn7RWxRlzpk7Jfho0iM3qMYX3xJmj6qjCxBd3n0kexZN_xzz9tArojMtP8VFlOxTJ3u1CgKE3SX8mMaIjrl8q5d62iQ/s400/Dracunculiasis_prevention.jpg" width="400" /></a></div>
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<b>Control and Prevention</b>. <i>The primary approaches to preventing transmission of D. medinensis infection are comprised</i> <i>of</i> 1) stopping the consumption of contaminated water sources, and 2) preventing contamination of water sources by implementing strictly controlled water submersion for infected individuals with blistering worms. In addition, the use of larvicidal agents to kill the larvae as they enter water sources from blistering worms, as well as the use of bore wells as primary water sources, can be important implementations that effectively block transmission. However, the latter two approaches are significantly more costly than the former two approaches.<br />
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<b>Water filtering is a common way to prevent the consumption of contaminated water</b> and can be achieved by using any fine mesh cloth (nylon is best) over the opening of an empty water vessel and pouring the potentially contaminated water through the mesh-cloth covering. This technique is very good at filtering out the larvae-infected copepods and blocks transmission by removing the intermediate host from the water. In some communities, filtering straws have been distributed that allow individuals to drink directly from the water source without ingesting the copepods (this is depicted in the photo above). Boiling is also an effective way to prevent infection as this kills the larvae before consumption.<br />
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<b>Management of infected individuals is equally important in the control and prevention of dracunculiasis</b>. These individuals must be prevented from contaminating the water sources used by the community. In order to break the life cycle of the worm and block transmission, infected individuals with blisters submerge their painful limbs in an isolated water container to allow the blister to burst and the adult female to release her larvae. The contaminated water is then sterilized and disposed of to prevent contamination of community water sources. The water can also be disposed of on dry ground as this will kill the copepods and the larvae they carry.<br />
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In addition, a combination of community education to prevent individuals from entering water sources, and ongoing rigorous field surveillance to detect any and all new cases of dracunculiasis are two important features of larger elimination programs. Indeed, the extraordinary effectiveness of water filtration and case management to prevent further infections, in concert with good field surveillance, epidemiology and community education are greatly responsible for the widespread successes of regional elimination programs in many parts of the world where dracunculiasis was previously endemic. Only four countries are still reporting cases: Mail, Chad, Ethiopia, and South Sudan, and most of these are coming from South Sudan. While there is still serious work to be done, we are on the verge of the global eradication of dracunculiasis. As mentioned before, global eradication of a human infectious disease is something that has been achieved only once before with smallpox.<br />
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<b>The possibility of eradication in the case of dracunculiasis is borne of its epidemiology</b>. <b>First</b>, <i>this worm has no definitive host reservoir other than humans</i>. While an intermediate host exists in copepods, and is required for the completion of the life cycle, without the human reservoir the worm cannot reach adulthood and reproduce. This makes transmission to humans essential for its survival. Pathogens that cause human disease, but which have animal reservoirs outside the human host are probably not eradicable because they don't require humans to replicate. <b>Second</b>, it is much easier to apply effective surveillance (an essential ingredient to any regional elimination program, and thus by extension to any global eradication program). <i>Ongoing surveillance is required in order to monitor geographic and epidemiologic sources of current and new infections</i>. Without this critical knowledge, it is impossible to direct control efforts, and without directed control efforts, you cannot eliminate a disease from a region. Dracunculiasis surveillance is made easier because cases are not easily missed. Infected individuals become clearly identifiable as the worm breaks through the skin, so case detection for this infection has much greater validity and reliability than many other infectious agents. Thus, with good case detection, it is possible to implement good surveillance. <b>Third</b>, there are no asymptomatic infectious individuals because the worm must penetrate the skin in order to release its larvae, without which no new infections can occur. As such, there is no possibility of missing infectious individuals who are capable transmitting infection subclinically. And, <b>fourth</b>, it is relatively simple and cheap to block transmission by 2 routes: 1) once identified, infectious individuals can be managed with relatively little cost to control the release of larvae from their worms and thus prevent further transmission, and 2) contaminated water can be easily decontaminated by filtering or boiling the water.<br />
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<b>Treatment</b>. Dracunculiasis requires a treatment that has transited many thousands of years. It is an ancient treatment for an ancient disease. Their is no modern drug that can be used, particularly because of the dangers to the host if the adult worm dies while occupying the musculoskeletal tissues. Some medications can be used to alleviate symptoms, but not to kill the worm. As such, the traditional approach to eliminating this pathogen, which transcends temporal, geographic, and cultural boundaries, is <b>the stick</b>. Yes, you read that correctly. As the worm begins to emerge from the surface of the infected individual's skin, the end of the worm is wound around a small stick. This is done very slowly, gradually winding only a centimeter or two per hour, or even per day, over the course of what can take days to weeks to complete:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjLhvvBLvoN6LwKmxFm4MjGgPhGg83nCprCiWpTV8qu4p3R-CmOaxAzzv46nO_OQ52G7WXyoaSN30tH4wwOC_ff4lTv02ZIdHWqObp_XUke2OhVVMZFBt5zj5F-NgdNnVvXonAuaN9sg0U/s1600/Dracunculus_medinensis_treatment.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="261" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjLhvvBLvoN6LwKmxFm4MjGgPhGg83nCprCiWpTV8qu4p3R-CmOaxAzzv46nO_OQ52G7WXyoaSN30tH4wwOC_ff4lTv02ZIdHWqObp_XUke2OhVVMZFBt5zj5F-NgdNnVvXonAuaN9sg0U/s400/Dracunculus_medinensis_treatment.jpg" width="400" /></a></div>
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The slow process is required because it is critical not to break the worm, which would kill it and present a far greater danger to the host than the mere presence of the worm.<br />
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This ancient treatment method for what was once an extraordinarily common disease across much of the world is likely the source of the symbolism in the Staff of Asclepius, who was the god of healing and medicine in Greek mythology:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjU7l2w7WDGWXnEh6A8CvLYuLoydGo0XjagYqAWA9Ro5gPgvs8DFIUrmlSZsE0OkEpAvENbwfJLj0KFQni52WTNLo_dNYG5U6vuLHRgjW-6jpjbp78chUG-O0Yk7H7LK2QoNyZmanLPdRk/s1600/Dracunculiasis_Rod_of_asclepius.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjU7l2w7WDGWXnEh6A8CvLYuLoydGo0XjagYqAWA9Ro5gPgvs8DFIUrmlSZsE0OkEpAvENbwfJLj0KFQni52WTNLo_dNYG5U6vuLHRgjW-6jpjbp78chUG-O0Yk7H7LK2QoNyZmanLPdRk/s320/Dracunculiasis_Rod_of_asclepius.png" width="124" /></a></div>
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<i><span style="font-size: x-small;">The Staff of Asclepius</span></i></div>
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And which today likely serves as the basis for the symbol of healing for many health and health care organizations around the world:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi1U6ojdQo_C4CvSwTUIpFgIqaNG2BIxnrDGEh2sdU2NKe83j2D1L3dYZ5fj-NpNTtNlODX5uHX5_BWzHChjpaGRfLJXciA46wmqfHdL0uZYZREee9Y1Qw_hsQHY5WxxBWgGRe2F7AU6ik/s1600/Dracunculiasis_Star_of_life2.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi1U6ojdQo_C4CvSwTUIpFgIqaNG2BIxnrDGEh2sdU2NKe83j2D1L3dYZ5fj-NpNTtNlODX5uHX5_BWzHChjpaGRfLJXciA46wmqfHdL0uZYZREee9Y1Qw_hsQHY5WxxBWgGRe2F7AU6ik/s320/Dracunculiasis_Star_of_life2.png" width="320" /></a></div>
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<span style="font-size: x-small;"><i>The Star of Life: International and United States symbol for the emergency medical services</i></span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi4rXitOyY0Hm4BU87PCnxAzIjPG4i0qUPvdZTSepc-r66LqkRBcZRVQr3Rnrwv38q0P009bPESXJ5mv45G2RtM5QTx6JPinvzOFZW_vSkpPFvg62IO57dqSnk7MxFf6ZQZD6ZQRhZhWMQ/s1600/Dracunculiasis_Flag_of_WHO.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="213" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi4rXitOyY0Hm4BU87PCnxAzIjPG4i0qUPvdZTSepc-r66LqkRBcZRVQr3Rnrwv38q0P009bPESXJ5mv45G2RtM5QTx6JPinvzOFZW_vSkpPFvg62IO57dqSnk7MxFf6ZQZD6ZQRhZhWMQ/s320/Dracunculiasis_Flag_of_WHO.png" width="320" /></a></div>
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<i><span style="font-size: x-small;">Flag of the World Health Organization</span></i></div>
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</div>Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com32tag:blogger.com,1999:blog-3492197469143963742.post-53599097731328688292012-03-14T12:11:00.001-04:002012-03-29T10:04:00.667-04:00Strongyloidiasis<div dir="ltr" style="text-align: left;" trbidi="on">
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This week at Infection Landscapes I am going to cover another nematode infection: strongyloidiasis. This infection is not nearly as prevalent as the three major soil-transmitted helminths, which, together, constitute probably the greatest global burden of disease attributable to the neglected tropical diseases. Nevertheless, strongyloidiasis currently infects up to 100 million people in the world, and can have very serious consequences among immunocompromised individuals. As such, this is both a substantive and serious disease for many people in the world, especially those in the developing world who are co-infected with the human immunodeficiency virus (HIV).<br />
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<b>The Worm</b>. Strongyloidiasis is caused by the nematode <i>Strongyloides stercoralis</i>:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhTfv0d50w2ECcL42igfzqvKyvQqypwaPI4d2QeU8jUsWAhlLHy4ZLAr5gaJFIDW7CSRViEvBzQTwr8aEsKOfn3WnDVOruQ07Zj4Cbv-8-6hcDhErOexuBoUAVp5bpAvyIxvAExKzHDEy8/s1600/Strongyloides+stercoralis.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="640" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhTfv0d50w2ECcL42igfzqvKyvQqypwaPI4d2QeU8jUsWAhlLHy4ZLAr5gaJFIDW7CSRViEvBzQTwr8aEsKOfn3WnDVOruQ07Zj4Cbv-8-6hcDhErOexuBoUAVp5bpAvyIxvAExKzHDEy8/s640/Strongyloides+stercoralis.jpg" width="531" /></a></div>
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<b>This worm has one of the most complex, and fascinating, life cycles of all the nematodes we will consider</b>. What makes this helminth particularly interesting is <i>its ability to complete its life cycle as either a parasitic worm, or a free living worm in the soil</i>. Let's take a close look at the stages of this worm's life cycle so we can fully appreciate its evolutionary adaptation.<br />
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<b>There are two key features to this worm's life cycle that allow it to organize itself into two parallel developmental regimes such that it can either 1) live entirely outside, and without need of, the host, or 2) live entirely within the host without need of secondary or intermediate hosts</b>. <i>The former describes the free-living non-parasitic form of the worm, while the latter describes the autoinfective helminth</i>. Moreover, the two forms do not define mutually exclusive life cycles. Rather, autoinfection can certainly lead to the introduction of free living organisms into the environment, and free-living organisms can produce infective larvae that are capable of infecting new susceptible hosts. Here is a nice graphic developed by the Centers for Disease Control and Prevention (CDC) that depicts the complex life cycle of <i>S. stercoralis</i>:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh__T2Q2TKdot7Qq4CP7UpLESz3-UUlevX0l21M5grLvVS915fn98vYGC24_DvB8qh5UT-q2wVAjiqcrKRTaZ8W791LXZg3PIb5OBhhrNi8xxCB3O-wfaF11w8ELn4e9EvxF776ZtAtZVM/s1600/Strongyloides_LifeCycle.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="313" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh__T2Q2TKdot7Qq4CP7UpLESz3-UUlevX0l21M5grLvVS915fn98vYGC24_DvB8qh5UT-q2wVAjiqcrKRTaZ8W791LXZg3PIb5OBhhrNi8xxCB3O-wfaF11w8ELn4e9EvxF776ZtAtZVM/s400/Strongyloides_LifeCycle.gif" width="400" /></a></div>
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As a starting point in this life cycle let's examine the point of human infection. The infectious form of <i>S. stercoralis</i> is the filariform larva. These larvae initiate infection by penetrating the skin of the host, in much the same way that we saw hookworm initiates infection. These larvae migrate through the subcutaneous tissue to reach the capillary beds where they gain access to the circulation. By passive transport through the circulation they reach the capillary beds in contact with the alveoli in the lungs and migrate into these air sacs. From this position deep in the lungs the larvae migrate up the bronchioles, bronchii, and trachea, over the throat and are then swallowed. The larvae pass through the stomach and, upon reaching the small intestine, begin to mature into adults, where they will remain for the rest of the their life course as helminths woven into the villi of the epithelium. The adult females oviposit in the mucous membrane of the intestinal epithelium. Subsequently, after these eggs hatch, the 1st stage larvae emerge in the lumen of the small intestine and migrate to the large intestine. In the large intestine, the 1st stage larvae molt and transform into the rhabditiform larvae. <b>This is a critical stage</b>, as these rhabditiform larvae can follow one of three courses in the continued development of <i>S stercoralis</i>. They can 1) develop into filariform larvae, penetrate the gut wall, gain the circulation, remove to the alveoli, and, via migration up the respiratory tract, over the throat, and down the alimentary tract, regain the small intestine to begin a new infection in the adult stage. <i>This intra-host infection cycle is known as autoinfection</i> and can continue for many years through many generations of the worm; <b>or</b> 2) pass out of the host as rhabditiform larvae in the stool and develop into filariform larvae in the soil. These filariform larvae can then infect new hosts by penetrating the skin as described above; <b>or</b> 3) pass out of the host as rhabditiform larvae in the stool and develop into the next stage, again in the soil, but this time developing into free-living adults. <i>These adults are not parasitic and so will complete their life course in the external environment with no need of a host</i>. The free-living female adults oviposition directly in the soil where the eggs hatch and a new generation of rhabditiform larvae emerge. These rabditiform larvae can subsequently follow one of two courses to complete their life cycle. They can either develop into adults and continue as free living worms in the soil, or they can develop into filariform larvae and infect new hosts. The former, free-living, life cycle can continue indefinitely, producing subsequent cycles of free-living non-parasitic organisms. Whereas, a proliferation of filariform larvae are typically a response to unfavorable environmental cues such as a change in soil composition, moisture, or temperature, or a reduction in available food (i.e. bacteria) in the soil. However, with each subsequent generation of free-living worms, some of the rhabditiform larvae that emerge from the eggs will develop into filariform larvae so the potential for helminth development if the infectious larvae are able to contact a susceptible human host is always present even in the free-living community of <i>S. stercoralis</i>. Here again is the CDC graphic to help visualize this life cycle:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh__T2Q2TKdot7Qq4CP7UpLESz3-UUlevX0l21M5grLvVS915fn98vYGC24_DvB8qh5UT-q2wVAjiqcrKRTaZ8W791LXZg3PIb5OBhhrNi8xxCB3O-wfaF11w8ELn4e9EvxF776ZtAtZVM/s1600/Strongyloides_LifeCycle.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="313" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh__T2Q2TKdot7Qq4CP7UpLESz3-UUlevX0l21M5grLvVS915fn98vYGC24_DvB8qh5UT-q2wVAjiqcrKRTaZ8W791LXZg3PIb5OBhhrNi8xxCB3O-wfaF11w8ELn4e9EvxF776ZtAtZVM/s400/Strongyloides_LifeCycle.gif" width="400" /></a></div>
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<i>S. stercoralis</i> is remarkable in that it has developed an opportunistic dual life course, such that it has the ability to exploit two distinct ecologic niches, engaging either as one or the other becomes available to the worm. Moreover, this organism maintains a bridge between these two disparate ecologic niches by way of the dual development potential of the free-living rhabditiform larvae. This is truly an extraordinarily adapted worm and a marvel of evolutionary biology. Unfortunately, <i>S. stercoralis</i> is capable of causing severe disease, so appreciation of the biology is quite tempered by the sobering morbidity for which this worm is responsible.<br />
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<b>The Disease</b>. Strongyloidiasis is comprised of a spectrum of disease. Many infections with <i>S. stercoralis</i> are asymptomatic. Because of the expansive migration of the worm throughout the human host, symptoms can present at multiple sites.<br />
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<b>Common clinical disease includes</b> 1) diarrhea, typically without dysentery, which results from the infection with the adult worms in the small intestine, 2) pulmonary symptoms in conjunction with the hypereosinophilia in the lungs, which results from the filariform migration into the alveoli and up the<br />
respiratory tract, 3) hive-like rashes on the skin, which are a hypersensitivity reaction following the subcutaneous migration of the filariform larvae:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEirCIrPN-Z70ri-D4vWImasEylA6xMqIh5mZQbfwS_ys3HLilspvkQWaaxT9ToO4uxHl3i9DPiUh-nvUQkFPWQN5opzgIV4EqqiRTql-uyt__tb6UsK_QVTWSU-UreM4_fr_0IYnIKXUVc/s1600/strongyloidiasis+2.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="215" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEirCIrPN-Z70ri-D4vWImasEylA6xMqIh5mZQbfwS_ys3HLilspvkQWaaxT9ToO4uxHl3i9DPiUh-nvUQkFPWQN5opzgIV4EqqiRTql-uyt__tb6UsK_QVTWSU-UreM4_fr_0IYnIKXUVc/s400/strongyloidiasis+2.jpg" width="400" /></a></div>
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<i><span style="font-size: x-small;">(A) Strongyloides pneumonitis associated with hyperinfection in a kidney transplant recipient. (B) Migrating larvae in subcutaneous lymphatics (arrows). (C) Hatching eggs in human intestine. </span><span style="font-size: xx-small;">(Published in: Parasitic infections in transplant recipients. Rashad S Barsoum. Nature Clinical Practice Nephrology (2006) 2, 490-503 doi:10.1038/ncpneph0255)</span></i></div>
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<b>Strongyloidiasis can be either transient or chronic</b>. Due to the autoinfection cycle described above, chronic infections do not necessarily require repeated points of contact with infectious filariform larvae in the environment. In other words, they do not require ongoing transmission. Nevertheless, the majority of chronic infections, more so than transient infections, are asymptomatic.<br />
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The <i>S. stercoralis</i> infections described thus far are, more or less, uncomplicated. Uncomplicated strongyloidiasis constitutes the large majority of the morbidity associated with this helminth. Whether symptomatic or asymptomatic, transient or chronic, most of these infections will not produce a severe life-threatening disease. However, complicated strongyloidiasis is a far more serious entity that can present in those with chronic infection.<br />
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<b>Complicated, or disseminated, strongyloidiasis occurs when an individual with a chronic infection becomes immunocompromised</b>. The suppressed immune response slackens the host's control over the infection and results in a hyperinfection, i.e. a massive proliferation <i>S. stercoralis</i> larvae. As the increased numbers of filariform larvae penetrate the epithelium of the large intestine and enter the circulation they likely carry some gut bacteria with them. This allows for the natural gut flora to access the blood and results in a dangerous septicemia. These bacteria can locate in organ systems throughout the body resulting in additional localized infection (thus the disseminated descriptor), with central nervous system involvement fairly common. Complicated strongyloidiasis can thus manifest with severe intestinal involvement directly due to the massive proliferation of larvae, or with disseminated disease due to the indirect transport of gut bacteria in the circulation. Complicated strongyloidiasis constitutes a life-threatening emergency and is associated with a high mortality when it occurs, which can be many years following the initial infection.<br />
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<b>Individuals infected with HIV are at high risk of complicated strongyloidiasis if they are co-infected with <i>S. stercoralis</i></b>. Because strongyloidiasis is most prevalent in developing countries, these also may represent areas with a high occurrence of HIV infection depending on the specific location. Severe malnutrition can also lead to the kind to immunocompromise that would put someone with chronic strongyloidiasis at risk for complicated disease.<br />
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In addition, transplant patients who undergo immunosuppressive therapy following the transplant will be in danger of complicated strongyloidiasis if they are infected with <i>S. stercoralis</i>.<br />
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<b>The Epidemiology and the Landscape</b>. The current global prevalence of strongyloidiasis is estimated between a few tens of millions of cases to up to 100 million cases. These are primarily concentrated in the tropical and subtropical regions of the world, but can also be transmitted in some temperarte regions as well.<br />
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The highest prevalences of infection today are found in South and Southeast Asia, and in parts of Central and South America. Strongyloidiasis is endemic in much of Africa but the prevalence is typically quite low throughout the continent.<br />
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<span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">As we saw with both hookworm and whipworm, the range of <i>S. stercoralis</i> is determined by important aspects of the physical landscape and because of this, as well as critical overlapping characteristics of the human social landscape,</span><b style="background-color: #fefdfa;"><span style="color: #333333; font-family: inherit;"><span style="line-height: 18px;"> the occurrence of </span></span><span style="color: #333333;"><span style="line-height: 18px;">strongyloidiasis</span></span><span style="color: #333333; font-family: inherit;"><span style="line-height: 18px;"> follows similar lines of geography</span></span></b><span style="background-color: #fefdfa;"><span style="color: #333333; font-family: inherit;"><span style="line-height: 18px;">. Soil and climate are two critical landscape features that influence the distribution of <i>S. stercoralis</i>. Because passaged </span></span><span style="color: #333333;"><span style="line-height: 18px;">rhabditiform</span></span><span style="color: #333333; font-family: inherit;"><span style="line-height: 18px;"> larvae can develop into free-living adults, and maintain a free-living cycle indefinitely, the non-parasitic ecology is distinctly characterized by specific environmental requirements. Whether free living or parasitic, the rhabditiform larvae that pass out in the host require</span></span></span><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;"> sandy, loamy soils in order to develop into either filariform larvae, which can then infect humans, or into free-living adults. In addition, the soils must be moist and the temperature must be warm. As such, the specific climatic conditions limit the range of the worms to the tropical and subtropical regions of the world that receive significant amounts of precipitation on an annual basis, while the pedological and edaphological constraints further define the microgeography of these worms. Notice below the global distribution of soil morphology in the map produced by the Natural Resources Conservation Service (NRCS) of the United States Department of Agriculture:</span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiLaBGhGBF3ojzvLNJsuxODgoR9_t8I8jdIq8OKupuCifbPzV04_szRhI1qv1MNFgyIe8sN-KyyiBDb5xHMGJ1FVOtUGbbLFr0faMJmbEMLt4f2KERnSwxksTK7Wc81fvHPJVx2SACwQqw/s1600/Hookworm_Global_Soil_Orders_Map.jpg" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><span style="font-family: inherit;"><img border="0" height="310" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiLaBGhGBF3ojzvLNJsuxODgoR9_t8I8jdIq8OKupuCifbPzV04_szRhI1qv1MNFgyIe8sN-KyyiBDb5xHMGJ1FVOtUGbbLFr0faMJmbEMLt4f2KERnSwxksTK7Wc81fvHPJVx2SACwQqw/s400/Hookworm_Global_Soil_Orders_Map.jpg" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></span></a></div>
<span style="font-family: inherit;"><br style="background-color: #fefdfa; color: #333333; line-height: 18px;" /><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">And this NRCS map below depicting the global distribution of soil moisture:</span></span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjnT9krfCQtHrojZql9KlR73akURSnEJ5QKLkb_OzXqDfMSA4ft7Q1Q5EIoAEfv9Ire6OHEDzf2TpRM0AC1sCAbp0yd6r7b14DDMzvqp2A7ZYt4tDlu5n6fC8edxBYulJNJKwYDEu6JccU/s1600/hookworm_map_soil_moisture_regimes.jpg" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><span style="font-family: inherit;"><img border="0" height="247" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjnT9krfCQtHrojZql9KlR73akURSnEJ5QKLkb_OzXqDfMSA4ft7Q1Q5EIoAEfv9Ire6OHEDzf2TpRM0AC1sCAbp0yd6r7b14DDMzvqp2A7ZYt4tDlu5n6fC8edxBYulJNJKwYDEu6JccU/s400/hookworm_map_soil_moisture_regimes.jpg" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></span></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj-ysq1UR21HtysVbNDy4VxLS0y51CvQhTtFCUQGru6TII0SLR89tNFdwo-subTJYHO8Wl07gd1zzfHMa8CJU5fY2fJwMrtm0GQSPdHZRSbg0Yp4RkAP1VLEIwytgJSCTN_9qsvdGkA5pc/s1600/hookworm+soil+moisture+map+legend.jpg" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><span style="font-family: inherit;"><img border="0" height="185" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj-ysq1UR21HtysVbNDy4VxLS0y51CvQhTtFCUQGru6TII0SLR89tNFdwo-subTJYHO8Wl07gd1zzfHMa8CJU5fY2fJwMrtm0GQSPdHZRSbg0Yp4RkAP1VLEIwytgJSCTN_9qsvdGkA5pc/s400/hookworm+soil+moisture+map+legend.jpg" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></span></a></div>
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<span style="font-family: inherit;">And, finally, the map below by the United Nations Food and Agriculture Organization depicts the global distribution of the annual mean temperature:</span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiTNpRXRloXclznDe63YfIwxCgdpMyBudGcJ5wUIMvRK3aypIKtQ-HwcvhXE0T23Y8yAoOwS-xwPkRD3D8ZT4hTmXO9bdBqnVKnMwom2zeEB2cU8v8C4JPm98ZivxbmzBnzS9bRXHQhyphenhyphen3E/s1600/hookworm-world-temperature-map.png" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><span style="font-family: inherit;"><img border="0" height="166" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiTNpRXRloXclznDe63YfIwxCgdpMyBudGcJ5wUIMvRK3aypIKtQ-HwcvhXE0T23Y8yAoOwS-xwPkRD3D8ZT4hTmXO9bdBqnVKnMwom2zeEB2cU8v8C4JPm98ZivxbmzBnzS9bRXHQhyphenhyphen3E/s400/hookworm-world-temperature-map.png" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></span></a></div>
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<span style="font-family: inherit;">It is worth noting how closely the global distribution of <i>S. stercoralis</i> coincides with the global distributions of soil regimes, moisture, and temperature. Finally, the filariform larvae are able to survive in, and are quite motile in, water, which greatly increases their versatility and transmission potential in comparison with hookworm.</span></div>
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<span style="font-family: inherit;"><b>There are three important factors from the <i>S. stercoralis</i> life cycle that are critical to the landscape epidemiology of human transmission</b>. <b>First</b>, the rhabditiform larvae pass out into the environment in the feces of the human host. <b>Second</b>, these larvae live in the soil and can either develop into free-living adults, OR develop into filariform larvae, which can infect humans. <b>Third</b>, infectious filariform larvae must make contact with the skin of a new human host. These three factors determine how the social landscape intersects with the physical landscape to enable transmission to humans. </span></div>
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<span style="font-family: inherit;">Lack of sanitation infrastructure, and especially a means by which human waste can be removed from sites of human occupation, results in feces being distributed directly in the human environment or in proximal spaces. Also, poor water quality is important for transmission. Conditions of poverty that are associated with the lack of municipal resources for infrastructural development often coincide with a lack of personal resources for adequate waste disposal, adequate water, and adequate clothing. As such, repeated exposure to filariform larvae is common in the same human environments (both the home and places of work) in which rhabditiform larvae-laden human feces are deposited on a daily basis. This leads to an abundance of points of contact for transmission between <i>S. stercoralis</i> and human hosts in those intersecting landscapes of warm, moist, structurally rich soils and conditions of poverty. This intersection currently defines a geography that encompasses, almost exclusively, the developing world. </span></div>
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<span style="font-family: inherit;">In many poor subsistence agricultural communities, farmers use human feces as a fertilizer to enhance the growth of their crops. This readily available fertilizer provides a cheap, yet very rich, source of critical nutrients to the soil, which can mean the difference between a crop yield that provides the farmer with a livelihood and a yield that does not. Unfortunately, in areas where strongyloidiasis is endemic, the use of human feces as fertilizer means a constant and widespread distribution of rhabditiform larvae throughout the farming community, and thus a steady source of new infections. </span></div>
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<span style="font-family: inherit;"><b>Control and Prevention</b>. Control and prevention of strongyloidiasis begins by following the usual guidelines: <b>improving sanitation and water infrastructure in resource poor areas</b>. In most settings in the world where strongyloidiasis is a significant problem, improved infrastructure that can adequately remove human feces from the spaces of human occupation is a first priority in its prevention.</span></div>
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<span style="font-family: inherit;"><b>Where large-scale municipally-resourced sanitation infrastructure is not available, individual pit privies can be constructed for single homes, or clusters of homes</b>. Here is a graphic that depicts the dimensions and structural components of such a privy:</span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi_2TieUbkMsR8vh3Cii8co4jCk8M6felns_QU9uOlRN4-M0OyfXx9BW_X3aECOcDMvquxuqcp_IqLcZ8LVCqa4NrKnpDnRoCnpMqdA6Qa4_4RcFEOAVViLkyvMzNiOtDmHrmawHxB5txc/s1600/pit+privy.gif" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><span style="font-family: inherit;"><img border="0" height="247" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi_2TieUbkMsR8vh3Cii8co4jCk8M6felns_QU9uOlRN4-M0OyfXx9BW_X3aECOcDMvquxuqcp_IqLcZ8LVCqa4NrKnpDnRoCnpMqdA6Qa4_4RcFEOAVViLkyvMzNiOtDmHrmawHxB5txc/s400/pit+privy.gif" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></span></a></div>
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<span style="font-family: inherit;"><b style="background-color: #fefdfa; color: #333333; line-height: 18px;">Wearing good shoes without holes while outside in endemic areas is another critical step in the prevention of new <i>S. stercoralis</i> infections</b><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">. Unfortunately, footwear is often simply not available for those people who need it most, and as such this very simple transmission block cannot be utilized.</span></span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgB9OHhk77ukMYLYQgFu1M7K_tSMVUxGt6Vo60eoTbTF_ZhNo5SiBVATWadueEvCkIskDW_BbfrYfbnaFR9zsEc38mPt3wTBr7Nr0bUIsxIRcCcuGjFmQU9VI3Bm-WlgO6T9S9wlnUqHos/s1600/hookworm+barefoot.jpg" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><span style="font-family: inherit;"><img border="0" height="292" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgB9OHhk77ukMYLYQgFu1M7K_tSMVUxGt6Vo60eoTbTF_ZhNo5SiBVATWadueEvCkIskDW_BbfrYfbnaFR9zsEc38mPt3wTBr7Nr0bUIsxIRcCcuGjFmQU9VI3Bm-WlgO6T9S9wlnUqHos/s400/hookworm+barefoot.jpg" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></span></a></div>
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<i><span style="font-family: inherit;"><a href="http://www.flickr.com/photos/matthetube/2436062056/" style="color: #7d171d; text-decoration: none;" target="_blank">Photo</a> by Peter Byrne</span></i></div>
<span style="font-family: inherit;"><br style="background-color: #fefdfa; color: #333333; line-height: 18px;" /><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">Also, </span><b style="background-color: #fefdfa; color: #333333; line-height: 18px;">changing agricultural practices that rely on human feces for fertilization of crops could dramatically help reduce the distribution of <i>S. stercoralis</i> in soils</b><span style="background-color: #fefdfa; color: #333333; line-height: 18px;"> in many agricultural subsistence communities.</span></span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhOq1cVJSMxkFydHTXhn-Q_C9XrwoKoPHXWhKi2reml5eoPCBAri6vlhXeSxqmxnQrU1RZTVkXZ_8ful83dLEw908vTyzPpv8tnH89mcclw0GKlYEyKcc9xuSmD82NyK1jBsCwBQxbrRVQ/s1600/hookworm+human+feces+fertilizer.jpg" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><span style="font-family: inherit;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhOq1cVJSMxkFydHTXhn-Q_C9XrwoKoPHXWhKi2reml5eoPCBAri6vlhXeSxqmxnQrU1RZTVkXZ_8ful83dLEw908vTyzPpv8tnH89mcclw0GKlYEyKcc9xuSmD82NyK1jBsCwBQxbrRVQ/s400/hookworm+human+feces+fertilizer.jpg" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></span></a></div>
<span style="font-family: inherit;"><br style="background-color: #fefdfa; color: #333333; line-height: 18px;" /><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">Unfortunately this, too, can be a difficult practice to disengage since human feces serves as a very rich fertilizer and, thus, can form a critical component to subsistence farming in many parts of the world where other fertilizers or farming technologies are cost prohibitive. And, of course, without an affordable substitute, refraining from human feces fertilization could very well lead to starvation. </span></span><br />
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<span style="background-color: #fefdfa;"><span style="color: #333333; font-family: inherit;"><span style="line-height: 18px;">Finally, the unique circumstances of immunosuppression that lead to severe disease require that strongyloidiasis is given special consideration under conditions of malnutrition and/or co-infection with HIV or other immunosuppressive infections such as measles. Because all of these are of greater prevalence in the developing world where </span></span><span style="color: #333333;"><span style="line-height: 18px;">strongyloidiasis</span></span><span style="color: #333333; font-family: inherit;"><span style="line-height: 18px;"> can also be endemic, severe disease is much more likely to affect these areas, especially in children. As such, it would be good practice to screen, and treat if necessary, individuals who have immunocompromising conditions in areas where strongyloidiasis is endemic.</span></span></span><br />
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<br /></div>Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com12tag:blogger.com,1999:blog-3492197469143963742.post-82787619958090756382012-02-27T12:32:00.001-05:002012-02-27T12:33:34.144-05:00Whipworm<div dir="ltr" style="text-align: left;" trbidi="on">
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This week at Infection Landscapes, I will cover the nematode that causes trichuriasis: whipworm. This worm is one of the three major soil-transmitted helminths, and as such causes one of the most important neglected tropical diseases in the world today.<br />
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<b>The Worm</b>. Trichuriasis is caused by <i>Trichuris trichiura</i>, and is frequently known by its common name, whipworm. The common name comes from the worm's morphology, which displays a fine, whip-like anterior section, and a more robust posterior section:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhYv7hThjAjeLhsPzlGlFrI7gRkmE9Lk09tUiSi84VMXBAwyTaB9pxAv8C_w8vAn88l-MOXtJXCYTFYGh8KiigBbn8oPc7153lXv57ouGlg7YqpjWzQPOamM1jfxrlbhWp7KRDZ3W81wT0/s1600/Trichuris_trichiura.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="128" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhYv7hThjAjeLhsPzlGlFrI7gRkmE9Lk09tUiSi84VMXBAwyTaB9pxAv8C_w8vAn88l-MOXtJXCYTFYGh8KiigBbn8oPc7153lXv57ouGlg7YqpjWzQPOamM1jfxrlbhWp7KRDZ3W81wT0/s400/Trichuris_trichiura.jpg" width="400" /></a></div>
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The life cycle of <i>T. trichiura</i> is significantly less complex than that of the giant intestinal roundworm (<i>A. lumbricoides</i>) or that of the hookworms. Whipworm eggs are deposited with human feces into the environment. These eggs are not embryonated at the time of passage from the human host and are not infectious at this time. Instead, they embryonate in the soil after approximately 2-3 weeks (but may require up to one month). These eggs do not hatch in the soil, but do become infectious following embryonation. Once these eggs are ingested by a new host, they will hatch in the small intestine and the larvae emerge and develop into immature adults in the epithelium over the following couple days. Subsequently these immature adults begin their descent to the colon. Once the adults gain the large intestine, the thin anterior portion of their body, which constitutes the esophagus (see photo above), penetrates the mucous membrane and embeds in the columnar epithelium of the gut wall. The worm then fashions its own essential environment in the human host by inducing a proliferation of host cells within the gut wall in which its anterior portion is embedded. The posterior section now extends out into the lumen of the colon, whereby it releases its eggs. An adult female whipworm does not begin depositing new eggs until approximately 2 to 3 months after the worm's life cycle began in the small intestine. Once the females reach sexual maturity they will produce about 5000 eggs per day for the remainder of their lives, which can last a year or more inside the human host. Below is a nice graph by the Centers for Disease Control and Prevention that depicts the life cycle of <i>Trichuris trichiura</i>:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj3DYr79Rx5PVICxSYN7Pj1WugWmu3Kg50yPAamSOM4np9quEmMCb9JCWs85htK6EE0oUlhoBikvkMCkn6UfWuGA06OFMBzyU6Hak6iJBXjYVZSd3qa2VDU_BejB-kRMzLCFSb6hlEWWCA/s1600/Trichuris_LifeCycle.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj3DYr79Rx5PVICxSYN7Pj1WugWmu3Kg50yPAamSOM4np9quEmMCb9JCWs85htK6EE0oUlhoBikvkMCkn6UfWuGA06OFMBzyU6Hak6iJBXjYVZSd3qa2VDU_BejB-kRMzLCFSb6hlEWWCA/s400/Trichuris_LifeCycle.gif" width="381" /></a></div>
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<b>The Disease</b>. As with the other major soil-transmitted helminths of significance, whipworm infection is usually asymptomatic, although this also contributes to its insidious nature during chronic infections. The whipworm's mucosal attachment and embedding in the epithelium of the large intestine described above leads to pathogenesis. Diarrhea and abdominal discomfort are the most common presentations for symptomatic infections and frank dysentery is not uncommon with high volume infections. In addition, rectal prolapse can also present with high volume infections because of the frequent physical straining during defecation. This straining results from the massive rectal inflammatory response in heavy infections, which gives the infected person the sensation to defecate even when feces are absent. The most significant presentation at the population level is iron-deficiency anemia associated with chronic and/or high volume infections. The anemia is brought on by the large quantity of blood loss in the colon due to the infestation of worms embedded in the epithelium and the subsequent damage to the gut wall and underlying vasculature. As is the case with hookworm, chronic whipworm-associated anemia frequently leads to arrested growth with associated physical and cognitive developmental delay and impairment.<br />
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<b>The Epidemiology and the Landscape</b>. Trichuriasis is one of the most important neglected tropical diseases in the world today and is probably the third most common roundworm infection in humans with approximately just under 1 billion prevalent infections worldwide. However, the prevalence of both hookworm and whipworm is very close in magnitude so it is difficult to say which of the two is currently more abundant, though both of these infections are less prevalent than infection with <i>Ascaris lumbricoides</i>. Nevertheless, whipworm and hookworm are, together, probably the largest contributor after malnutrition to poor physical and cognitive development in children worldwide. The current global distribution is pictured in the map below:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhgEQHo4IZjpFBqD8Nv_T4XgaGjYpMc5jQGrIc_3MaUIuZKrIByny8fCC05_F2QmlUr8gqE6bqBhVkb8fsDI03vaEO8F6ledrBLF5HJe8LHc2PHQBwza5s8JdclFYgHdQbWgRfZmT99OqQ/s1600/trichuriasis+global+distribution.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="200" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhgEQHo4IZjpFBqD8Nv_T4XgaGjYpMc5jQGrIc_3MaUIuZKrIByny8fCC05_F2QmlUr8gqE6bqBhVkb8fsDI03vaEO8F6ledrBLF5HJe8LHc2PHQBwza5s8JdclFYgHdQbWgRfZmT99OqQ/s400/trichuriasis+global+distribution.jpg" width="400" /></a></div>
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<span style="background-color: #fefdfa; color: #333333; line-height: 18px;"><span style="font-family: inherit;">As mentioned above, the morbidity associated with a high burden of trichuriasis is predominantly manifested as impaired physical and cognitive development in children. When this morbidity is translated into disability-adjusted life years we can see below that sub-Saharan Africa and especially Southeast Asia are saddled with a disproportionate burden of disease, and we can also see that this burden is quite substantive:</span></span>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj3Die11F7UAM3Zt4JH8awmMlfRc1nrEVpGwmDrQJz90lCZhkoT3VeKjHNEZuLFAv-ymJmhyphenhyphenB4uIgjd7yMrCbHt1mLMOwU8gRAtzZVKOwhjDbVBpqjD8zaDdF7fCBthm71y1NT_0o2U9Pw/s1600/Trichuriasis_world_map_-_DALY_-_WHO2002.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="176" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj3Die11F7UAM3Zt4JH8awmMlfRc1nrEVpGwmDrQJz90lCZhkoT3VeKjHNEZuLFAv-ymJmhyphenhyphenB4uIgjd7yMrCbHt1mLMOwU8gRAtzZVKOwhjDbVBpqjD8zaDdF7fCBthm71y1NT_0o2U9Pw/s400/Trichuriasis_world_map_-_DALY_-_WHO2002.png" width="400" /></a></div>
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<div class="description en" lang="en" style="background-color: #f9f9f9; direction: ltr; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;" xml:lang="en">
<span class="description"><span class="language en" title=""><b>English:</b></span> <a class="extiw" href="http://en.wikipedia.org/wiki/Age_adjustment" style="background-attachment: initial; background-clip: initial; background-color: initial; background-image: none; background-origin: initial; background-position: initial initial; background-repeat: initial initial; color: #663366; padding-bottom: 0px; padding-left: 0px; padding-right: 0px; padding-top: 0px; text-decoration: none;" title="en:Age adjustment">Age-standardised</a> <a class="extiw" href="http://en.wikipedia.org/wiki/DALY" style="background-attachment: initial; background-clip: initial; background-color: initial; background-image: none; background-origin: initial; background-position: initial initial; background-repeat: initial initial; color: #663366; padding-bottom: 0px; padding-left: 0px; padding-right: 0px; padding-top: 0px; text-decoration: none;" title="en:DALY">disability-adjusted life year</a> (DALY) rates from <b>Trichuriasis</b> by country (per 100,000 inhabitants).</span></div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #b3b3b3; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> no data</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffff65; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> less than 5</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #fff200; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 5-10</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffdc00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 10-15</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffc600; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 15-20</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffb000; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 20-25</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff9a00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 25-30</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff8400; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 30-35</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff6e00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 35-40</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff5800; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 40-45</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff4200; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 45-50</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff2c00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 50-60</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #cb0000; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> more than 60</div>
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While the life cycles are different between whipworm and hookworm, particularly given that hookworm undergoes two larval stages in the soil, these two groups of worms nevertheless have similar soil requirements, which delineate their global distributions and define their landscape epidemiology in similar ways.<br />
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<span style="font-family: inherit;"><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">The range of <i>T. trichiura</i> is determined by important aspects of the physical landscape and because of this, as well as critical overlapping characteristics of the human social landscape,</span><b style="background-color: #fefdfa; color: #333333; line-height: 18px;"> the occurrence of trichuriasis in humans is distinctly delineated by geographic features</b><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">. Soil and climate are two critical landscape features that determine the distribution of <i>T. trichiura</i>. Following the passage of nonembryonated eggs with feces into the soil, these eggs require several weeks in this specific environment before they embryonate and become infectious. Sandy loamy soils, rather than hard clay soils provide a more suitable habitat for these eggs</span><span style="background-color: #fefdfa; color: #333333; line-height: 18px;">. In addition, the soils must be moist and the temperature must be warm. As such, the specific climatic conditions limit the range of the worms to the tropical and subtropical regions of the world that receive significant amounts of precipitation on an annual basis, while the pedological and edaphological constraints further define the microgeography of these worms. Notice below the global distribution of soil morphology in the map produced by the Natural Resources Conservation Service (NRCS) of the United States Department of Agriculture:</span></span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiLaBGhGBF3ojzvLNJsuxODgoR9_t8I8jdIq8OKupuCifbPzV04_szRhI1qv1MNFgyIe8sN-KyyiBDb5xHMGJ1FVOtUGbbLFr0faMJmbEMLt4f2KERnSwxksTK7Wc81fvHPJVx2SACwQqw/s1600/Hookworm_Global_Soil_Orders_Map.jpg" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><img border="0" height="310" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiLaBGhGBF3ojzvLNJsuxODgoR9_t8I8jdIq8OKupuCifbPzV04_szRhI1qv1MNFgyIe8sN-KyyiBDb5xHMGJ1FVOtUGbbLFr0faMJmbEMLt4f2KERnSwxksTK7Wc81fvHPJVx2SACwQqw/s400/Hookworm_Global_Soil_Orders_Map.jpg" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></a></div>
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<span style="background-color: #fefdfa; color: #333333; line-height: 18px;"><span style="font-family: inherit;">And this NRCS map below depicting the global distribution of soil moisture:</span></span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjnT9krfCQtHrojZql9KlR73akURSnEJ5QKLkb_OzXqDfMSA4ft7Q1Q5EIoAEfv9Ire6OHEDzf2TpRM0AC1sCAbp0yd6r7b14DDMzvqp2A7ZYt4tDlu5n6fC8edxBYulJNJKwYDEu6JccU/s1600/hookworm_map_soil_moisture_regimes.jpg" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><img border="0" height="247" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjnT9krfCQtHrojZql9KlR73akURSnEJ5QKLkb_OzXqDfMSA4ft7Q1Q5EIoAEfv9Ire6OHEDzf2TpRM0AC1sCAbp0yd6r7b14DDMzvqp2A7ZYt4tDlu5n6fC8edxBYulJNJKwYDEu6JccU/s400/hookworm_map_soil_moisture_regimes.jpg" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj-ysq1UR21HtysVbNDy4VxLS0y51CvQhTtFCUQGru6TII0SLR89tNFdwo-subTJYHO8Wl07gd1zzfHMa8CJU5fY2fJwMrtm0GQSPdHZRSbg0Yp4RkAP1VLEIwytgJSCTN_9qsvdGkA5pc/s1600/hookworm+soil+moisture+map+legend.jpg" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><img border="0" height="185" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj-ysq1UR21HtysVbNDy4VxLS0y51CvQhTtFCUQGru6TII0SLR89tNFdwo-subTJYHO8Wl07gd1zzfHMa8CJU5fY2fJwMrtm0GQSPdHZRSbg0Yp4RkAP1VLEIwytgJSCTN_9qsvdGkA5pc/s400/hookworm+soil+moisture+map+legend.jpg" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></a></div>
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<span style="font-family: inherit;">And, finally, the map below by the United Nations Food and Agriculture Organization depicts the global distribution of the annual mean temperature:</span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiTNpRXRloXclznDe63YfIwxCgdpMyBudGcJ5wUIMvRK3aypIKtQ-HwcvhXE0T23Y8yAoOwS-xwPkRD3D8ZT4hTmXO9bdBqnVKnMwom2zeEB2cU8v8C4JPm98ZivxbmzBnzS9bRXHQhyphenhyphen3E/s1600/hookworm-world-temperature-map.png" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><img border="0" height="166" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiTNpRXRloXclznDe63YfIwxCgdpMyBudGcJ5wUIMvRK3aypIKtQ-HwcvhXE0T23Y8yAoOwS-xwPkRD3D8ZT4hTmXO9bdBqnVKnMwom2zeEB2cU8v8C4JPm98ZivxbmzBnzS9bRXHQhyphenhyphen3E/s400/hookworm-world-temperature-map.png" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></a></div>
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These elements described above define the critical features of the physical landscape, but there are also important features of the social landscape that must operate in order for trichuriasis to become endemic.</div>
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<span style="font-family: inherit;">Lack of sanitation infrastructure, and especially a means by which human waste can be removed from sites of human occupation, results in feces being distributed directly in the human environment or in proximal spaces. When a high degree of local fecal contamination occurs, <b>especially in combination with a lack of rigorous hand and food preparation hygiene</b>, this leads to an abundance of points of contact between embryonated, infectious <i>T. trichiura</i> eggs acquired from the soil and their human hosts. The intersecting landscapes of warm, moist, structurally rich soils and conditions of poverty</span><span style="font-family: inherit;"> currently define the geography of trichuriasis, as it does hookworm. It is a geography that encompasses, almost exclusively, the developing world. </span></div>
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<span style="font-family: inherit;">In many poor subsistence agricultural communities, farmers use human feces as a fertilizer to enhance the growth of their crops. This readily available fertilizer provides a cheap, yet very rich, source of critical nutrients to the soil, which can mean the difference between a crop yield that provides the farmer with a livelihood and a yield that does not. Unfortunately, in areas where trichuriasis is endemic, the use of human feces as fertilizer means a constant and widespread distribution of whipworm eggs throughout the farming community, and thus a steady source of new infections.</span></div>
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<b style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">Control and Prevention</b><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">. Control and prevention of trichuriasis begins by following the usual guidelines: </span><b style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">improving sanitation in resource poor areas</b><span style="background-color: #fefdfa; color: #333333; font-family: inherit; line-height: 18px;">. In most settings in the world where trichuriasis is a significant contributor to morbidity, improved infrastructure that can adequately remove human feces from the spaces of human occupation is a first priority in its prevention.</span><br />
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<span style="font-family: inherit;"><b>Where large-scale municipally-resourced sanitation infrastructure is not available, individual pit privies can be constructed for single homes, or clusters of homes</b>. Here is a graphic that depicts the dimensions and structural components of such a privy:</span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi_2TieUbkMsR8vh3Cii8co4jCk8M6felns_QU9uOlRN4-M0OyfXx9BW_X3aECOcDMvquxuqcp_IqLcZ8LVCqa4NrKnpDnRoCnpMqdA6Qa4_4RcFEOAVViLkyvMzNiOtDmHrmawHxB5txc/s1600/pit+privy.gif" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><img border="0" height="247" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi_2TieUbkMsR8vh3Cii8co4jCk8M6felns_QU9uOlRN4-M0OyfXx9BW_X3aECOcDMvquxuqcp_IqLcZ8LVCqa4NrKnpDnRoCnpMqdA6Qa4_4RcFEOAVViLkyvMzNiOtDmHrmawHxB5txc/s400/pit+privy.gif" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></a></div>
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<span style="font-family: inherit;">Finally, <b>changing agricultural practices that rely on human feces for fertilization of crops could dramatically help reduce the widespread distribution of whipworm in soils</b> in many agricultural subsistence communities.</span><br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhOq1cVJSMxkFydHTXhn-Q_C9XrwoKoPHXWhKi2reml5eoPCBAri6vlhXeSxqmxnQrU1RZTVkXZ_8ful83dLEw908vTyzPpv8tnH89mcclw0GKlYEyKcc9xuSmD82NyK1jBsCwBQxbrRVQ/s1600/hookworm+human+feces+fertilizer.jpg" imageanchor="1" style="color: #7d171d; margin-left: 1em; margin-right: 1em; text-decoration: none;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhOq1cVJSMxkFydHTXhn-Q_C9XrwoKoPHXWhKi2reml5eoPCBAri6vlhXeSxqmxnQrU1RZTVkXZ_8ful83dLEw908vTyzPpv8tnH89mcclw0GKlYEyKcc9xuSmD82NyK1jBsCwBQxbrRVQ/s400/hookworm+human+feces+fertilizer.jpg" style="-webkit-box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; background-attachment: initial; background-clip: initial; background-color: white; background-image: initial; background-origin: initial; background-position: initial initial; background-repeat: initial initial; border-bottom-color: rgb(204, 204, 204); border-bottom-left-radius: 5px; border-bottom-right-radius: 5px; border-bottom-style: solid; border-bottom-width: 1px; border-color: initial; border-image: initial; border-left-color: rgb(204, 204, 204); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(204, 204, 204); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(204, 204, 204); border-top-left-radius: 5px; border-top-right-radius: 5px; border-top-style: solid; border-top-width: 1px; border-width: initial; box-shadow: rgba(0, 0, 0, 0.199219) 0px 0px 20px; padding-bottom: 8px; padding-left: 8px; padding-right: 8px; padding-top: 8px; position: relative;" width="400" /></a></div>
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<span style="font-family: inherit;">Unfortunately this, too, can be a difficult practice to disengage since human feces serves as a very rich fertilizer and, thus, can form a critical component to subsistence farming in many parts of the world where other fertilizers or farming technologies are cost prohibitive. And, of course, without an affordable substitute, refraining from human feces fertilization could very well lead to starvation. The massive scope of the problem presented by soil-transmitted helminths in general, and whipworm in particular, should now be coming into focus.<br /><br /><b>De-worming campaigns do offer some hope, since there are safe, effective, and fairly cheap anti-helminthic drugs available</b>. However, as one might expect, there are obstacles to overcome in de-worming. <b>First</b>, these drugs are not free and, while cheap they may be, without adequate funding poor communities will not be able to prioritize the cost, especially since most infections are generally asymptomatic. <b>Second</b>, effective ways to deliver the de-worming medications to communities need to be implemented, which can be logistically challenging particularly in remote communities or during times of the year when travel may be restricted (i.e. during the rainy season). <b>Third</b>, the extensive use, or misuse, of these drugs will likely lead to antihelminthic-resistance in the worms, thus making the drugs ineffective. Nevertheless, if adequate resources can be put behind de-worming campaigns, and if delivery systems can be adapted to <i>actively engage community members in the delivery and monitoring of these de-worming medications</i> to simultaneously circumvent logistical obstacles and reduce the development of resistance, then substantial reductions in whipworm infections may still be possible.</span>
</div>Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com10tag:blogger.com,1999:blog-3492197469143963742.post-34142920616573001872012-02-13T11:07:00.001-05:002012-02-13T11:09:12.779-05:00Hookworm<div dir="ltr" style="text-align: left;" trbidi="on">
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This week at Infection Landscapes I will cover another of the soil-transmitted helminths, and another of the important neglected tropical diseases: <b>hookworm</b>. Hookworm is a major contributor to morbidity in the developing world, particularly with respect to growth and development in children.<br />
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<b>The Worm</b>. Human hookworm infections can be caused by two different species, both of which are nematodes. <i>Necator americanus</i> and <i>Ancylostoma duodenale</i> are the two main hookworm species that cause human infection. <i>N. americanus</i> has the greatest global distribution, and is responsible for the greatest prevalence of infection, whereas the prevalence of <i>A. duodenale</i> infection is more focally clustered across Africa, South Asia, China and a few foci in the Americas.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhcR3cu1DzUKnTZTfUrQKK-DP40WXL8OYl5BUaQG26TbqbHjhhuHte1VhIwtz49Ut30bQSQzSX0J6DJKTT1IltbGUldgANIBrb0AqjG1HrpV6-dDFoIz9iVWlD98c9EYLVGSr1fYo-iN9Y/s1600/hookworms+A.+duodenale.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="330" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhcR3cu1DzUKnTZTfUrQKK-DP40WXL8OYl5BUaQG26TbqbHjhhuHte1VhIwtz49Ut30bQSQzSX0J6DJKTT1IltbGUldgANIBrb0AqjG1HrpV6-dDFoIz9iVWlD98c9EYLVGSr1fYo-iN9Y/s400/hookworms+A.+duodenale.jpg" width="400" /></a></div>
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<span style="font-size: x-small;"><i>Ancylostoma duodenale</i> (photo by <a href="http://www.flickr.com/photos/34542202@N08/5218201316/" target="_blank">Jay Reimer</a>)</span></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgbf0YNp7FXAPKWwiZQoq5ha3eo5y_YmhBhWnsEUsZJF-q9GVH1x6WyIYSTeGMIXBzuzO3oxJ9olAsOxTCVrN1JP1UaHX0nvFZKf5E-q02c6kOZB9iaoeUUMGHfeT1ohnZ9HUXlM5iGQxY/s1600/hookworms+N.+americanus.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgbf0YNp7FXAPKWwiZQoq5ha3eo5y_YmhBhWnsEUsZJF-q9GVH1x6WyIYSTeGMIXBzuzO3oxJ9olAsOxTCVrN1JP1UaHX0nvFZKf5E-q02c6kOZB9iaoeUUMGHfeT1ohnZ9HUXlM5iGQxY/s400/hookworms+N.+americanus.jpg" width="378" /></a></div>
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<span style="font-size: x-small;"><i>Necator americanus</i> (photo by <a href="http://www.sciencephoto.com/media/366460/enlarge" target="_blank">David Scharf</a>)</span></div>
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<b>Both species employ complex life cycles</b>, as we saw with <i>A. lumbricoides</i>, however the pathway is somewhat different for the life cycle of hookworms and, subsequently, so is the resulting disease ecology. Let's describe the life cycle. The eggs of both species are deposited in the feces of an infected host and, following deposition, embryonate. The eggs require warm and moist soil that is sandy or loamy in composition. If these immediate ecologic needs are met, in about 2 days the eggs will develop into the first stage (L1), rhabditoform larvae, which are not infective and subsist on the microbial contents of the soil. These larvae will molt twice, the first time (L2) resulting in a second soil-stage rhabditoform, and the second time (L3) resulting in the infective filariform larvae. This stage of development no longer feeds, but its mobility increases dramatically so that it can remove itself from within the soil and relocate to high points above the soil horizon, such as rocks or grass. By moving above the soil horizon, the larvae are able to increase the likelihood that they will successfully engage the skin of their host. Once the larvae make contact with the skin, they penetrate by way of hair follicles or through open wounds or lesions on the skin's surface. Having achieved cutaneous and subcutaneous penetration, the filariform larvae must reach the lung to continue the next stage of the their life cycle. They do this by passive transfer through the venous circulation, which the larvae access by way of the capillary beds under the skin. The vasculature ultimately deposits these L3 larvae in the capillary beds of the lung from which they penetrate into the alveoli and migrate up the bronchii and trachea until they reach the throat. From here the larvae are swallowed and, thus, finally gain access to the alimentary tract of the host. In the small intestine the larvae molt for the third and final time forming the adult worm, which is the parasitic feeding stage of this worm. In this stage the adult worm targets the intestinal mucosa where it attaches and feeds on both the villi of the epithelium and the blood which it sucks from the blood vessels of the submucosa. The total infective process (skin penetration to intestinal feeding adult) typically requires 1 to 2 months to complete. Adult females and males mate in the host intestine and produce several thousand fertilized eggs per day. <i>N. americanus</i> females will produce up to 10,000 eggs each day, while <i>A. duodenale</i> females can produce three times as many eggs per day. These eggs are passed into the environment with the host's stool and the cycle continues. Below is a nice graph by the Centers for Disease Control and Prevention that depicts the complex life cycle of both hookworm species:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhQ_RLEWXTLxQcZbTGwJYfxRd38R0xzzG-59Kuw-o-XQuhyphenhyphenn-CdZemkw9ujX4W7rVu2zrZB7y3IxAsksJIWfgXl7_DY41X_7k3iMTA1J-rfEY9ffOXS6J5CcyzLRhXTUAVCtW0XVQnufFw/s1600/Hookworm_LifeCycle+2.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="300" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhQ_RLEWXTLxQcZbTGwJYfxRd38R0xzzG-59Kuw-o-XQuhyphenhyphenn-CdZemkw9ujX4W7rVu2zrZB7y3IxAsksJIWfgXl7_DY41X_7k3iMTA1J-rfEY9ffOXS6J5CcyzLRhXTUAVCtW0XVQnufFw/s400/Hookworm_LifeCycle+2.gif" width="400" /></a></div>
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And here is another nice graph by MetaPathogen.com that nicely contextualizes the life cycle within transmission:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjXtMgTHr6oNfyGxhv02qe4WLSsKwTPyKAxmLYAsG7refDo7t6vSCuQyfTnuQkUUAxWXx7xJu19dWWxd4TqfyNG_E4enT-Ajw4U7RwmFq5qW9uzxrbpYXD0CZHlV-ZvYZvjfhfB-zbR9z4/s1600/hookworm+life+cycle+3.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="400" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjXtMgTHr6oNfyGxhv02qe4WLSsKwTPyKAxmLYAsG7refDo7t6vSCuQyfTnuQkUUAxWXx7xJu19dWWxd4TqfyNG_E4enT-Ajw4U7RwmFq5qW9uzxrbpYXD0CZHlV-ZvYZvjfhfB-zbR9z4/s400/hookworm+life+cycle+3.png" width="400" /></a></div>
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It is important to note that the life cycle stages above describe the strategies employed by both <i>N. americanus</i> and <i>A. duodenale</i>. Transmission by skin penetration is the only mode of transmission for <i>N. americanus</i>, and it is the most common mode of transmission for <i>A. duodenale</i>. However, <i>A. duodenale</i> can also transmit by ingestion of the larvae. When the latter strategy is employed the life cycle is shortened since the lung stage is bypassed and the larvae develop directly into the adult stage in the small intestine of the host. <br />
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<b>The Disease</b>. Most hookworm infections are asymptomatic. When symptoms do occur, they typically involve 1) the subcutaneous migration of the larvae, 2) the larval development within the lungs, and/or 3) the attachment of the adult worms in the small intestine. Subcutaneous larvae migration can cause a hypersensitivity reaction in the course of the migrating worms that produces very itchy lesions on the skin:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj4U8sv673S43uCbKnnTTHpDod78-gmG1f5mEYiFejaxWsNN9Z5BhTOwZ6m4cdgV-bJkPW5Vno2flIt9c4_-GvifXIIuMnZnKTG3HBMzmlHvGBxxo17oYMoPpXnLVpbsdErJq1PBaN2vI0/s1600/Hookworm+Foot.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="240" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj4U8sv673S43uCbKnnTTHpDod78-gmG1f5mEYiFejaxWsNN9Z5BhTOwZ6m4cdgV-bJkPW5Vno2flIt9c4_-GvifXIIuMnZnKTG3HBMzmlHvGBxxo17oYMoPpXnLVpbsdErJq1PBaN2vI0/s320/Hookworm+Foot.jpg" width="320" /></a></div>
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Hypersensitivity reactions involving pruritic lesions are more common in hyperendemic areas following repeated infections over time. Larval infection in the lungs can produce cough and hypereosinophilia, and even mimic pneumonia with radiographically apparent chest infiltrates and fever. However, these more severe pulmonary symptoms are also usually only associated with high volume infections. Abdominal pain is the most common intestinal symptom, but irregular stool, with either diarrhea or constipation, and vomiting are also possible presentations. But again, symptomatic gut infection is more common in high volume infections.<br />
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<b>The most important clinical consequence of hookworm infection at the population level is anemia</b>. An iron-deficiency anemia results from the blood lost into the lumen of the gut, and which is ultimately passaged in stool, as the adult worms feed in the small intestine. Protein deficiency is also an important consequence of long-term or high volume infection. <i>Because of the iron-deficiency anemia and protein deficiency, chronic hookworm infection is particularly damaging to children, often leading to arrested musculoskeletal growth and cognitive development</i>. As such, children account for a large preponderance of the overall morbidity experienced by a population and so are typically the age group targeted in de-worming campaigns. This is the typical practice even though adults can often acquire higher volume infections under some circumstances. For example, due to the widespread use of human feces as fertilizer in farming among poor agricultural communities, adults working the fields contaminated by hookworm may have much more extensive exposures and subsequent infections.<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZUkllRvisCJmAJbwvMagxnY-Pn75uz-Jm6xXuxpP2FUkHyq7XSBgC_3rrx44PezNiM1lwGT2Q0O2CbsV608eJekMFL3bTkO4648fIiH2_Ac8-QF7Hq9JVdgFgzCOLn2qP0dCJpn9JZPQ/s1600/Hookworms+attached.JPG" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="266" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZUkllRvisCJmAJbwvMagxnY-Pn75uz-Jm6xXuxpP2FUkHyq7XSBgC_3rrx44PezNiM1lwGT2Q0O2CbsV608eJekMFL3bTkO4648fIiH2_Ac8-QF7Hq9JVdgFgzCOLn2qP0dCJpn9JZPQ/s400/Hookworms+attached.JPG" width="400" /></a></div>
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<b>The Epidemiology and the Landscape</b>. <i>There are likely close to one billion prevalent infections with hookworm in the world today</i>. The vast majority of these occur in sub-Saharan Africa, Southeast, South and East Asia, and parts of South America:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgCuOlFgLf6TYAhkMkVm_8vdhc6pyynJfmwNpuv4yawUl720tFcul5PdpxfFReMkLcaBN18iG-vyHn4LqQ2B9klNpdRk3ii_5V4qKGV4XLn8PcVTUGkMMS907nHf5gh-_kg_T16Bs-Dkug/s1600/hookworm+global+prevalence.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="211" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgCuOlFgLf6TYAhkMkVm_8vdhc6pyynJfmwNpuv4yawUl720tFcul5PdpxfFReMkLcaBN18iG-vyHn4LqQ2B9klNpdRk3ii_5V4qKGV4XLn8PcVTUGkMMS907nHf5gh-_kg_T16Bs-Dkug/s400/hookworm+global+prevalence.jpg" width="400" /></a></div>
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As mentioned above, the morbidity associated with such a high burden of infection is predominantly manifested as impaired physical and cognitive development in children. When this morbidity is translated into disability-adjusted life years we can see below that sub-Saharan Africa and Southeast Asia are saddled with a disproportionate burden of disease, and we can also see that this burden is quite substantive:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj7rzdsjzHBpPZvSzXLd41slxMY1EJUXu0_G6CVW9KiqyU1GrfN8d7zTSR7wbofCwk6OKMEvbNCqTjZDZrScLkTnMgpoO_LAZ6uof6ArRYwhObh3x0r5YhoEjJW78hfNEB8sEtXi18SqSc/s1600/Hookworm_disease_world_map_-_DALY.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="176" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj7rzdsjzHBpPZvSzXLd41slxMY1EJUXu0_G6CVW9KiqyU1GrfN8d7zTSR7wbofCwk6OKMEvbNCqTjZDZrScLkTnMgpoO_LAZ6uof6ArRYwhObh3x0r5YhoEjJW78hfNEB8sEtXi18SqSc/s400/Hookworm_disease_world_map_-_DALY.png" width="400" /></a></div>
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<div class="description en" lang="en" style="background-color: #f9f9f9; direction: ltr; line-height: 19px; text-align: -webkit-auto;" xml:lang="en">
<span style="font-family: inherit;"><span style="color: black;">Age-standardised disability-adjusted life year</span> (DALY) rates from <b>Hookworm disease</b> by country (per 100,000 inhabitants).</span></div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #b3b3b3; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> no data</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffff65; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> less than 10</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #fff200; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 10-15</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffdc00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 15-20</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffc600; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 20-25</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ffb000; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 25-30</div>
<div style="background-color: #f9f9f9; font-family: sans-serif; font-size: 12px; line-height: 19px; text-align: -webkit-auto;">
<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff9a00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 30-35</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff8400; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 35-40</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff6e00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 40-45</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff5800; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 45-50</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff4200; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 50-55</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #ff2c00; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> 55-60</div>
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<span style="display: inline-block; text-align: center; width: 2.8em;"><span style="background-color: #cb0000; border-bottom-color: rgb(128, 128, 128); border-bottom-style: solid; border-bottom-width: 1px; border-image: initial; border-left-color: rgb(128, 128, 128); border-left-style: solid; border-left-width: 1px; border-right-color: rgb(128, 128, 128); border-right-style: solid; border-right-width: 1px; border-top-color: rgb(128, 128, 128); border-top-style: solid; border-top-width: 1px; display: inline-block; width: 2.4em;"> </span></span> more than 60</div>
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The morbidity that attends hookworm infection in areas of high endemicity makes this one of the most significant infections currently affecting humans. This is further highlighted by the fact that this infection is one of the primary <b>neglected tropical diseases</b>, meaning it typically draws little consideration and/or resources in the overall global fight against infectious disease.<br />
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The range of hookworm species is determined by important aspects of the physical landscape and because of this, as well as critical overlapping characteristics of the human social landscape,<b> the occurrence of hookworm in humans is distinctly delineated by geographic features</b>. Soil and climate are two critical landscape features that determine the distribution of hookworm species. During the first two larval stages of development in the life cycle of both <i>A. duodenale</i> and <i>N. americanus</i>, the larvae require sandy, loamy soils in order to undergo the first two molts to the L3 stage, which can then infect humans. If the hookworm eggs hatch and find themselves in hard clay soils then the larvae will not reach the L3 developmental stage and thus they cannot infect humans and they cannot complete their life cycle. In addition, the soils must be moist and the temperature must be warm. As such, the specific climatic conditions limit the range of the worms to the tropical and subtropical regions of the world that receive significant amounts of precipitation on an annual basis, while the pedological and edaphological constraints further define the microgeography of these worms. Notice below the global distribution of soil morphology in the map produced by the Natural Resources Conservation Service (NRCS) of the United States Department of Agriculture:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiLaBGhGBF3ojzvLNJsuxODgoR9_t8I8jdIq8OKupuCifbPzV04_szRhI1qv1MNFgyIe8sN-KyyiBDb5xHMGJ1FVOtUGbbLFr0faMJmbEMLt4f2KERnSwxksTK7Wc81fvHPJVx2SACwQqw/s1600/Hookworm_Global_Soil_Orders_Map.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="310" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiLaBGhGBF3ojzvLNJsuxODgoR9_t8I8jdIq8OKupuCifbPzV04_szRhI1qv1MNFgyIe8sN-KyyiBDb5xHMGJ1FVOtUGbbLFr0faMJmbEMLt4f2KERnSwxksTK7Wc81fvHPJVx2SACwQqw/s400/Hookworm_Global_Soil_Orders_Map.jpg" width="400" /></a></div>
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And this NRCS map below depicting the global distribution of soil moisture:<br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjnT9krfCQtHrojZql9KlR73akURSnEJ5QKLkb_OzXqDfMSA4ft7Q1Q5EIoAEfv9Ire6OHEDzf2TpRM0AC1sCAbp0yd6r7b14DDMzvqp2A7ZYt4tDlu5n6fC8edxBYulJNJKwYDEu6JccU/s1600/hookworm_map_soil_moisture_regimes.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="247" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjnT9krfCQtHrojZql9KlR73akURSnEJ5QKLkb_OzXqDfMSA4ft7Q1Q5EIoAEfv9Ire6OHEDzf2TpRM0AC1sCAbp0yd6r7b14DDMzvqp2A7ZYt4tDlu5n6fC8edxBYulJNJKwYDEu6JccU/s400/hookworm_map_soil_moisture_regimes.jpg" width="400" /></a></div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj-ysq1UR21HtysVbNDy4VxLS0y51CvQhTtFCUQGru6TII0SLR89tNFdwo-subTJYHO8Wl07gd1zzfHMa8CJU5fY2fJwMrtm0GQSPdHZRSbg0Yp4RkAP1VLEIwytgJSCTN_9qsvdGkA5pc/s1600/hookworm+soil+moisture+map+legend.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="185" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj-ysq1UR21HtysVbNDy4VxLS0y51CvQhTtFCUQGru6TII0SLR89tNFdwo-subTJYHO8Wl07gd1zzfHMa8CJU5fY2fJwMrtm0GQSPdHZRSbg0Yp4RkAP1VLEIwytgJSCTN_9qsvdGkA5pc/s400/hookworm+soil+moisture+map+legend.jpg" width="400" /></a></div>
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And, finally, the map below by the United Nations Food and Agriculture Organization depicts the global distribution of the annual mean temperature:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiTNpRXRloXclznDe63YfIwxCgdpMyBudGcJ5wUIMvRK3aypIKtQ-HwcvhXE0T23Y8yAoOwS-xwPkRD3D8ZT4hTmXO9bdBqnVKnMwom2zeEB2cU8v8C4JPm98ZivxbmzBnzS9bRXHQhyphenhyphen3E/s1600/hookworm-world-temperature-map.png" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="166" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiTNpRXRloXclznDe63YfIwxCgdpMyBudGcJ5wUIMvRK3aypIKtQ-HwcvhXE0T23Y8yAoOwS-xwPkRD3D8ZT4hTmXO9bdBqnVKnMwom2zeEB2cU8v8C4JPm98ZivxbmzBnzS9bRXHQhyphenhyphen3E/s400/hookworm-world-temperature-map.png" width="400" /></a></div>
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It is worth noting how closely the global distribution of hookworm coincides with the global distributions of soil regimes, moisture, and temperature, with one exception: the southeastern Untied States. Indeed, this geographic region was, at one time, highly endemic for hookworm infection. Why no longer? The answer to this question lies within the context of the social landscape of this infection. </div>
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<b>There are three important factors from the hookworm life cycle that are critical to the landscape epidemiology of human transmission</b>. <b>First</b>, the eggs pass out into the environment in the feces of the human host. <b>Second</b>, the larvae live in the soil during the first two larval stages of the life cycle. <b>Third</b>, the larvae must make contact with the skin of a new human host. These three factors determine how the social landscape intersects with the physical landscape to enable transmission to humans. </div>
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Lack of sanitation infrastructure, and especially a means by which human waste can be removed from sites of human occupation, results in feces being distributed directly in the human environment or in proximal spaces. Conditions of poverty that are associated with the lack of municipal resources for infrastructural development often coincide with a lack of personal resources for adequate clothing. As such, a barefoot lifestyle may be ubiquitous in the same human environments (both the home and places of work) in which hookworm egg-laden human feces are deposited on a daily basis. This leads to an abundance of points of contact for transmission between hookworm larvae and human hosts in those intersecting landscapes of warm, moist, structurally rich soils and conditions of poverty. This intersection currently defines a geography that encompasses, almost exclusively, the developing world. However, this geography did include the southeastern United States where the same intersection of the key physical and social landscapes was present until the early 20th century. When adequate sanitation became widespread in this region of the US, human hookworm largely disappeared.</div>
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In many poor subsistence agricultural communities, farmers use human feces as a fertilizer to enhance the growth of their crops. This readily available fertilizer provides a cheap, yet very rich, source of critical nutrients to the soil, which can mean the difference between a crop yield that provides the farmer with a livelihood and a yield that does not. Unfortunately, in areas where hookworm is endemic, the use of human feces as fertilizer means a constant and widespread distribution of hookworm eggs throughout the farming community, and thus a steady source of new infections. </div>
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<b>Control and Prevention</b>. Control and prevention of hookworm begins by following the usual guidelines: <b>improving sanitation in resource poor areas</b>. In most settings in the world where hookworm is a significant contributor to morbidity, improved infrastructure that can adequately remove human feces from the spaces of human occupation is a first priority in its prevention.</div>
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<b>Where large-scale municipally-resourced sanitation infrastructure is not available, individual pit privies can be constructed for single homes, or clusters of homes</b>. Here is a graphic that depicts the dimensions and structural components of such a privy:</div>
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi_2TieUbkMsR8vh3Cii8co4jCk8M6felns_QU9uOlRN4-M0OyfXx9BW_X3aECOcDMvquxuqcp_IqLcZ8LVCqa4NrKnpDnRoCnpMqdA6Qa4_4RcFEOAVViLkyvMzNiOtDmHrmawHxB5txc/s1600/pit+privy.gif" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" height="247" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi_2TieUbkMsR8vh3Cii8co4jCk8M6felns_QU9uOlRN4-M0OyfXx9BW_X3aECOcDMvquxuqcp_IqLcZ8LVCqa4NrKnpDnRoCnpMqdA6Qa4_4RcFEOAVViLkyvMzNiOtDmHrmawHxB5txc/s400/pit+privy.gif" width="400" /></a></div>
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<b>Wearing good shoes without holes while outside in endemic areas is another critical step in the prevention of new hookworm infections</b>. Unfortunately, footwear is often simply not available for those people who need it most, and as such this very simple transmission block cannot be utilized.<br />
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<i><span style="font-size: x-small;"><a href="http://www.flickr.com/photos/matthetube/2436062056/" target="_blank">Photo</a> by Peter Byrne</span></i></div>
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Finally, <b>changing agricultural practices that rely on human feces for fertilization of crops could dramatically help reduce the widespread distribution of hookworm in soils</b> in many agricultural subsistence communities.<br />
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Unfortunately this, too, can be a difficult practice to disengage since human feces serves as a very rich fertilizer and, thus, can form a critical component to subsistence farming in many parts of the world where other fertilizers or farming technologies are cost prohibitive. And, of course, without an affordable substitute refraining from human feces fertilization could very well lead to starvation. The massive scope of the problem presented by soil-transmitted helminths in general, and hookworm in particular, should now be coming into focus.<br />
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<b>De-worming campaigns do offer some hope, since there are safe, effective, and fairly cheap anti-helminthic drugs available</b>. However, as one might expect, there are obstacles to overcome in de-worming. <b>First</b>, these drugs are not free and, while cheap they may be, without adequate funding poor communities will not be able to prioritize the cost, especially since most infections are generally asymptomatic. <b>Second</b>, effective ways to deliver the de-worming medications to communities need to be implemented, which can be logistically challenging particularly in remote communities or during times of the year when travel may be restricted (i.e. during the rainy season). <b>Third</b>, the extensive use, or misuse, of these drugs will likely lead to antihelminthic-resistance in the worms, thus making the drugs ineffective. Nevertheless, if adequate resources can be put behind de-worming campaigns, and if delivery systems can be adapted to <i>actively engage community members in the delivery and monitoring of these de-worming medications</i> to simultaneously circumvent logistical obstacles and reduce the development of resistance, then substantial reductions in hookworm infections may still be possible.</div>Michael Walshhttp://www.blogger.com/profile/05038031388622939797noreply@blogger.com26