Tuesday, August 27, 2013

Anthrax


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 not be covered here as this does not fall within the purview of Infection Landscapes.

The Pathogen: Anthrax is caused by the gram-positive bacterium, Bacillus anthracis. As indicated by the genus name, this is a bacillary, or rod-shaped, bacterium:

Bacillus anthracis rods

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. B. anthracis initially targets macrophages in the host. Pathogenicity and virulence are driven specifically by the presence the bacterium's capsule and its production of endotoxins. 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: edema factor mediates an increase in intracellular cAMP, which leads to severe edema in tissues, while lethal factor leads to tissue necrosis. Subsequently, the bacilli can be disseminated by way of the blood and lymph circulation.


The Disease. Anthrax typically falls into one of three distinct categories of clinical presentation: cutaneous, pulmonary, and gastrointestinal.

Cutaneous anthrax is the most common presentation in humans. Cutaneous anthrax typically presents with an abscess on the skin, which quickly progresses to a black eschar of necrotized tissue:



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.

Pulmonary anthrax is a much more severe form of disease. 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).

Gastrointestinal anthrax is the least common disease form, but is also quite severe. 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 B. anthracis. 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.

The Epidemiology and the Landscape. There are three primary modes of transmission for B. anthracis 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.

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:


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.

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):


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. 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.

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.

Control and Prevention. 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 B. anthracis, 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 B. anthracis 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.

Human vaccines are also available in the United States, Europe, and China, but these are primarily used in military personnel among whom exposure to B. anthracis 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.

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 B. anthracis and prevent any further spread of the bacteria are critical interventions.

 
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.

19 comments:

  1. I would think that a big portion of the problem is related to the fact that it is indeed difficult to get rid of the carcasses of infected dead animals. In areas where people have limited resources, a simple solution would be to leave the animals where they fall or congregate the carcasses in an area where other creatures can get to them. On the other hand, you have others who probably believe that the best solution is the bury them, but they would have to be aware of the fact that the bacteria can survive for years in unfavorable conditions only to resurface years down the line. They might believe that they successfully solved the problem when in fact they are simply keeping it at bay. People who live in endemic areas where the problem is mostly linked to infected animals would ideally need to be education on the proper methods of disposal. The next plausible solution would be to increase surveillance in order to see where there is a great need for animal vaccines.

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    1. The national bio security resource center suggests that incineration and composting are the best options for disposing carcasses while avoiding the spread of pathogens to humans. With education farmers can apply these methods and reduce the risk of spreading viruses. I agree that surveillance is needed to determine what areas are in need of intervention and are at a greater risk of exposure.

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  2. I think a significant problem is educating those who have to handle livestock. Here in the U.S., for those who work in a health-related field, we are highly aware of the threat of anthrax and possible ways to avoid it, so there are only sporadic episodes. But in these endemic regions, the resources to educate "farmers" may be lacking and they may be at risk without their knowledge. Not only that but it also is related with probability; since it is endemic in those areas, the threat of vulnerability is most likely less than if it were an epidemic. If the perceived threat is low, "farmers" may underestimate their actual risk.

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    1. Marc I agree with your point about educating those at greatest risk for anthrax infection. I would just add that it would be important to combine education about infection with the tools and supplies necessary to prevent exposure and infection. For example, appropriate protective gear such as gloves for those handling animal products or masks for people who work processing wool and are at risk of inhaling spores. We often focus on awareness and education, which is usually important but often not sufficient to reduce the problem.

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  3. Given the many modes of transmission, direct contact, air-borne transmission and food-borne transmission, it seems as though surveillance of anthrax should be of top priority. However, in endemic areas there is a lack of surveillance. These endemic areas are interacting with livestock in different ways and there needs to be more education to help those dealing with infected livestock in order for them to protect themselves from the threat of anthrax.

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    1. I don't necessarily agree. While you do raise a good point (as many of the other commentators have) that education is key in reducing endemicity, I do not think constant surveillance should be a top priority. Compared to many of the other infections around the world, anthrax seems to be less of an issue. Those resources could be put to better use elsewhere.

      As a side note, education and vaccination are probably the two most effective methods, but looking at the map I feel it would be hard to reach the more secluded endemic areas. This is also probably a major issue contributing to the burden of disease.

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  4. In countries such as India where livestock interact with humans regularly and without any boundaries, the risk of transmitting pathogens and developing infections is greater than in 1st world countries. Since it may be difficult and expensive to build irrigation systems, develop higher food safety standards, etc the best way to prevent the transmission of anthrax would be to educate farmers and livestock handlers about the dangers of handling contaminated soil and anthrax infected animals. Through education and general awareness of the problem, we can significantly reduce the spread of anthrax in developing countries.

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  5. I think that the general education on anthrax to the public remains the key, as the hyper-endemic/epidemic and endemic areas shown in the map above are mostly developing countries where health education is generally limited. The education on the lethality of anthrax and the modes of transmission would better help people protect themselves from the disease. On the other hand, the government agency plays an important role in monitoring the proper handling of the infected livestock, as some farmers without much knowledge simply want to get rid of the infected dead animals by disposing carcasses in the open area away from them—they do not even realize the fact that “the undestroyed spores are viable in the environment for years”. This would pose a serious problem and could cause another outbreak in the future.

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    1. I agree with you completely Wen D. People who don't want to deal with the Anthrax infested carcasses will just dump the animal as long as it is out of there hands not realizing that the spores can come back to infect later. This is why the general education of the public with Anthrax is so important and why the governments role is so important when it comes to education and not just the monitoring and handling of infected dead animals. Farmers need to know how and why to properly dispose of the carcasses and the government should let them be aware that if the animal is infected that federal funds will be set aside for the cost of proper disposal so that farmers do not feel that the burden of expense is on their backs.

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  6. As acknowledged above, the risk of anthrax infection is not limited to direct contact with infected livestock, but rather extends to those processing animal products, potentially at a distance, as well. This type of risk, for anthrax as well as other similar diseases, is important to recognize and address because it is not the immediately obvious concern. The less expected risks could potentially be more dangerous than the obvious ones since they might be more likely to go unrecognized, allowing infections to continue to spread.

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    1. I do agree with your point Rachel, I do know of a Nigerian drummer who works in Manhattan, he contracted Anthrax through untreated rawhide that he purchased in Nigeria. Fortunately, he did recover from it but he had a long road to recovery. I believe he was visiting Nigeria at the time and purchased it there but it goes to show that animal products are significant vessels for possible infection. The ultimate question is then, for these rawhides that are being sold to whomever needs them, are these hides coming from livestock who have died from anthrax with the carcasses laying around for how ever long or are these hides coming from animals being coincidentally butchered for their meat? In other words, the demand for animal products rather than animal meat may exacerbate the spread of anthrax.

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  7. I would like to know the epidemiology of anthrax in humans in South-East Asian regions. Kindly give references of the articles. I also would like to map of SE Asian countries with anthrax. My Email ID is -promila_r@rediffmail.com

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  8. Alexandr PinkhasovJune 18, 2014 at 3:56 PM

    Understanding the mode of transmission is essential to addressing concerns pertaining to anthrax related illnesses. Because the causative agent is a spore forming gram positive bacteria the disease is extremely hard to treat (the bacterium has the ability to evade the host immune system). The 95% case fatality rate suggests the importance of prevention of disease before a host becomes infected. People living in hyperendemic and epidemic regions should be taught methods of quick and safe-handling of carcass of those who died of the disease in order to prevent transmission. The fact that animal carcasses serve as a food source for scavengers, and a potential mode of transmission to other animals, raises concern because scavengers can move on to spread the bacteria over a wider regions within the environment.

    Although the article did not discuss using anthrax as a biologic weapon, Im interested to know how terrorists are able to harvest and disseminate the bacteria.

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    1. You make some very good points, Alex. As the article said, burning is highly fuel intensive, burying is potentially dangerous, due to the risk of exposure after erosion e.t.c. So, I wonder how widely the vaccine is employed in these endemic areas, both among human, sylvan, and other animal populations. As the safe disposal of carcasses that are infected is such a complicated matter, I wonder what means of prevention methods, if any, have been successful in endemic areas.

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  9. Modes of transmissions are very important for farmers to understand in livestock especially as it pertains to animal carcasses. It's understandable that it takes a long time to burn the animal completely, but I feel this is a necessity being that the a buried infected carcass that still cause infection for years. I also worry that there may be a possibility of the carcass affecting the ground water which may be used on farms and increase the oral transmission of anthrax. I myself was unaware of the 95% fatality rate of inhalation anthrax which can happen if not treated early. It concerns me that many people may confuse anthrax for flu based upon the symptoms that may present as well as doctors brushing these symptoms off as the flu since the flu can happen year round.

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  10. Anthrax commonly presents with flu-like symptoms as its initial presentation, which mays makes it difficult for a physician to identify as part of the differential diagnosis.
    A possible solution for your concern would be to implement biodegradable bags. When disposing of a carcass known to be infected with anthrax, a biodegradable bag will allow for the natural decomposition of the buried contents in a contained field, so that possible contaminants or sources of infection do not pollute the environment.

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  11. Stephen Budhu


    Epidemiology Comment 3


    Anthrax was of a particular interest of mine especially with 9/11 just passing, it reminds me of the post outbreaks. Anthrax stems from the bacterial group Bacillus anthracis, and it is a toxin that these rod shaped bacteria produce. With the target organism being the white blood cells, one can easily become immuno-compromised. The disease effects one of three regions: Pulmonary, GI tract, and skin. In all forms lesions are formed, which I would believe leads to other opportunistic infections. Most times anthrax infections are life threatening.

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    1. I remember post 9/11 how a person was busted in trying to send anthrax in the mail and how it took a while before he got caught. It's actually frightening that nowadays wars are being fought through chemical means. This means more than likely that other biochemical agents can be launched against a population.

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  12. I was wondering if there are any standard safety measures provided by the WHO or any public health agencies in properly handling the carcasses of animals killed by anthrax.

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