Tuesday, June 25, 2013

Leptospirosis


This time at Infection Landscapes we will explore one of the most widespread and prevalent zoonotic infections in the world: leptospirosis.

The Pathogen. Leptospirosis in humans is caused by one of five pathogenic bacteria species of the genus Leptospira in the the Leptospiraceae family. Leptospira spp. are spirochetes, displaying the characteristic spiraled cellular structure:


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. Leptospira have two flagella used for motility.

Leptospira 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.

The Disease. Leptospirosis can range from asymptomatic infection to severe life threatening illness. 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.

The Epidemiology and the Landscape. 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 Leptospira. As such, 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. 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.

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, 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. 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:


An important feature of the landscape epidemiology of leptospirosis is the pathogen's ability to occupy two very distinct domains. First, Leptospira can exist as free-living organisms in water and soil (provided the soils stays moist). Second, Leptospira can exist for extended periods of time in the kidneys of some sylvan and domestic hosts. Rodents are the likely primary natural reservoir for these spirochetes. 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 Leptospira 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.

The particular importance of these two features lies distinctly within their spaces of intersection in the landscape. Since the Leptospira 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:


Control and Prevention. 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.


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. 

38 comments:

  1. After reading this post, I am amazed at how mild the Bubbles case study was. All the teens that developed to leptospirosis were mild cases. This disease can lead to liver and kidney failure, and in that case study, there were no complications.

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    1. Colee, I thought the same thing while I was reading this post. It's very interesting that none of the cases from the Bubbles case study had severe leptospirosis (i.e. kidney and/or liver failure). I wonder if this is arbitrary. Maybe it has something to do with the concentration of leptospira in the water?

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    2. @ Kizzi and CBethany, How funny! I was thinking about the same thing as I was reading the post.

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    3. I agree that the lepto outbreak in the Bubbles case seems mild as compared to other worldwide ones. I'd like to suggest that the Bubbles case was different in that those teens had limited contact with the contaminated water ie; afternoon swims for a couple hours. They also came from an environment where the rest of their water was clean, they were well fed and had access to healthcare. Outbreaks in the rest of the world could not boast the same thing, thus exacerbating the exposure to, and ingestion of the pathogen.

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  2. Due to the agent’s free environmental existence, I don’t think its possible to prevent the infection, although agricultural measures to prevent contamination my be helpful in preventing the spread.

    Diagnosis is always an issue with Weil’s disease. New ELISA tests now available are about 80-90% sensitive but MAT is still the gold standard test. Good thing about leptospirosis is that it’s sensitive to most antibiotics. If you don’t know what you are treating and give penicillins you would inadvertently cure the patient.

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    1. I agree that the pathogens existence and natural reservoir state makes it practically impossible to eradicate. An infected mouse can make its way into a corn field and contaminate the whole area. Moreover, as others have mentioned, I am surprised that the Bubbles case from "Outbreak Investigations" was not as severe as it could’ve been given the amount of teenagers infected.

      However, it is important to utilize the testing available. Physicians that over-prescribe antibiotics for any case presenting that may be mildly related to a bacterial infection are contributing a profound problem in our healthcare system. 1) Consistent injection of antibiotics, even more that once a year can lead to significant resistance builds up. At the rate antibiotics are being prescribed this can be applied to many patients who no longer can use standard amoxicillin as a treatment. Additionally, the cost of prescribing useless antibiotics is taxing our healthcare system.

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  3. I wanted to supplement my knowledge on leptospirosis from the Dworkin chapter we read earlier in the semester. I found it interesting the infection's non-specific symptoms leads to frequent misdiagnosis as well as underestimates of infection. I imagine this makes for some very difficult investigation outbreaks. A main takeaway from this post was for these types of non-specific infections, the enviornment of the infection are extremely important tools to discover its source.

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    1. I want to add information about the environment of infection. There was leptospirosis outbreak in Guyana occurred after severe flooding in 2005. Scientists suggest rapid testing for the disease and large-scale interventions are necessary to identify and control infection. People should increase preventive measure and caution on leptospirosis outbreak in some districts this year due to heavy rainfall for example Colorado after flooding.

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  4. The post provides an example that the biological environment can be a crucial factor in the transmission of an infectious disease in addition to the host of a pathogen itself. Particularly, the rapid circulation of contaminated liquid either in the form of running-water or rainfall poses a greater risk in the spread of leptospirosis from distant places. Thus, environmental infection control becomes especially important in surveillance and disease prevention.

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    3. I agree that infection control through cleaner water is a primary goal in decreasing the disease burden from Leptospira. I was interested to learn from a TED talk (http://www.ted.com/talks/michael_pritchard_invents_a_water_filter) that recently there has been technology developed that can actually filter even bacteria from water. It seems to be reasonably cheap and I would wonder how long it could take to get such technology onto the ground, especially in those areas where the disease burden is heaviest (from the map, it looks like Southern Asia). The economies of southern Asia are definitely booming, so I think we could see shifts in disease burden soon, as people learn about and embrace the filtration technology.

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  5. Wen your comment about the spread of leptospirosis to distant places brought me back to the outbreak in 1964 that we looked over in class. The cattle that were deemed to be the source of the pathogen were 300 yards away from the location were people were getting infected!

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  6. I was struck by how much influence access to clean water and having sanitation infrastructure can influence rates of leptospirosis infections. Since symptoms can be mild, it may aid the organism in being passed back into the soil and water supply in regions where toilets and sanitary disposal of waste is not common (or even areas where public urination is a problem). As noted in the text, epidemics of leptospirosis may occur where sanitation and access to clean water are poor. I feel that this highlights the need for public health efforts in increasing clean water access and sanitation infrastructure as was done in the developed world over the past few centuries. It is especially because this article says that there is a thousand-fold increase of infection in less developed countries over more developed countries, which may in part be due to sanitation infrastructure and clean water access. Although I have heard of leptospirosis infections popping up sporadically here in the States, I would wonder which policies specifically have led to the containment of a health threat that seems to be able to move through the water literally. In other words, is it all because we don’t have water buffalo (or more generally vectors/reservoirs of the bacterium) here in NY, or are there specific policies in place to prevent or control the spread of such an infection?

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  7. It is interesting that this spirochete causes a disease that is so much different than other spirochetes like Treponema and Borrelia. Moreover,its primary route through a common vehicle is certainly different from contact (in terms of Treponema) and vector borne (Lyme disease). These spiral-shaped bacteria are difficult to visualize with dark-field microscopy. Moreover, they seem to have proven pretty resilient in the environment as they were able to travel hundreds of yards in the water stream contaminated by infected cattle in the Bubbles case as others have mentioned. What about its genome/ structure allows it to remain infectious and what type of filtering system is required to prevent its transmission into drinking water?

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  8. I find it interesting when there are still places with poor sanitation and no access to clean water. These two routes of transmission are the easiest control methods that can be placed to prevent many bacterial infectious outbreaks.


    Whats interesting about Leptospirosis is that in this post, its symptoms of diarrhea, vomiting, and complications of organs such as the kidneys and liver and can even effect the lungs and heart. However in the case of Bubbles, the cases were not as sever as this and many recovered. What is the difference between these cases and the cases of Bubbles?


    One measure that was mentioned is to not swim in water that is most likely contaminated with urine from livestock however there needs to be polices placed in order to inform the community which places may be contaminated and educational resources to educate the population.

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  9. Nicole MastrogiovanniJuly 16, 2014 at 9:32 PM

    Difaa I definitely agree that both poor sanitation and access to clean water are major contributors to continued outbreaks of Leptospirosis. As for your question concerning why the outbreak reactions in the Bubbles case seemed less severe than the cases described above is likely due to the immediate medical attention many of the children received in the Bubbles case and their easy and quick access to medical care. The majority of people who deal with leptospirosis on a daily basis are those who are unfortunately in underdeveloped countries that as stated do not have the greatest sanitation measures or clean water to drink and prepare food with as well as access to medical attention. Also as you stated, they are most likely not education on the topic of leptospirosis and may not know the proper precautions to take to avoid becoming ill or may not know the warning signs and symptoms of having this infection before it may be too late and extends into serious conditions such as kidney and liver infections. I again agree that education and governmental policies on access to clean water should be put in to place, especially in countries that have higher rates of leptospirosis.

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    1. I certainly agree that policies must be in place to keep water clean and people safe from leptospirosis. I also think that we can take this notion a step further - since people exposed to water, like subsistence farmers, are at a particularly increased risk perhaps these policies should be geared toward those individuals. A Department of Public Health could take regular water samples from farmers to test for the disease. Outside organizations like the WHO could also implement educational programs about the policies in order to gain buy in (compliance) from the target populations.

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  10. Its a shame that many third world countries are ripe for Leptospirosis due to not having access to adequate water supplies. The world map shows that countries with high poverty rates are most likely to exhibit the symptoms of the disease. We hear stories about people in some 3rd world countries travel miles for water only to see that the water they receive is contaminated yet they still drink it because they have no choice. What can be done to combat this as many countries still lag behind in terms of sanitation measures which I'm sure help with the spread of it.

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    1. Yes, some countries still do not have proper sanitation and it should be a priority to fix this issue. Education concerning infectious diseases, hygiene and precautions to take in these conditions are also a problem in these countries. It is possible that the spread of infectious diseases would be lessened if residents of these countries were aware of steps they could take to treat contaminated water (if faced with no choice) such as boiling. Boiling water may not get rid of the chemicals or toxins but can help in destroying infectious organisms.

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    3. I agree that community education is important, especially to reduce the duration of illness and its severity through the early recognition of suspicious symptoms. There is also need for availability of community diagnostic services to carry out leptospiral screening tests for anti-leptospira antibodies. The health department in developing countries can also help combat the disease by regularly checking the environment for leptospires parasites, taking samples of the water and soil for culturing to check for growth of pathogenic leptospires. Also undertaking active disease surveillance and strengthen control measures will help determine the incidence in the community. Are there vaccines for this disease? I would like to know if humans can be protected from this disease by immunization.

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    4. Commercial human vaccines have been produced in France and Cuba, but they are not proven clinically successful. Creating a vaccine is difficult because the vaccine would have to consist of different serovars present in the local communities.

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  11. The fact that rodents are not the only reservoir for Leptospira brings greater challenges in the surveillance and prevention of the disease. Preventive measures cannot only involve extermination of rodents since domestic livestock are also capable of passing on the infection to humans. The wide incidence range between the developed and developing world (less than one case per million persons per year to one case per thousand per year) highlights the need for proper infection control measures and sanitation in developing countries.

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    1. You brought up a good point Desrene. Leptospirosis seems to be a disease that will avoid eradication. Because the disease occurs in two distinct domains, and is sometimes asymptomatic, it is hard to conduct adequate surveillance. Another problem with leptospirosis is that it tends to be prevalent in agricultural regions; these regions may promote transmission of the disease through poor sanitation and limited access to care.

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  12. For many, their only means of bathing are these local bodies of water. For the areas where access to clean water is scarce, they are taking great risks in trying to practice good hygiene where their environment limits them in a way. I can only imagine the efforts of carrying the water and then boiling the water just to take a bath on a daily.

    Its bothersome, for something that has such an easy fix in a way its hard to believe that little progress has been made in improving these conditions.

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  13. When thinking about water-borne diseases that disproportionately affect people in tropical or rainy areas, I tend to think about the effect on the lower income countries of the world and not necessarily about the individuals in those countries who are affected. In other words, I think about diseases as occurring either inside or outside of the US and rarely about the demographics within countries outside the US. It makes perfect sense that the subsistence farmers living in such low-income countries would be at an increased risk. This really pointed out to me that I need to think more globally. Considering countries outside of the US is only the first step; we are all global citizens, some of whom are exposed to these pathogens. The country of India is not necessarily affected - the people living and working around bodies of water in that area are affected.

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  14. Diseases transmitted through common vehicle fascinate me because they highlight big misses in infrastructure, sanitation or personal hygiene. I keep trying to distinguish features of cholera with features of leptospirosis, and while they do manifest differently clinically, they are both dangerous water-borne diseases. Why don’t we hear about leptospirosis more frequently? Especially since the same developing populations are at risk. Are there any places where the risk of one influences the risk of the other? This really highlights that while changing infrastructure in the developing world is easy, that any progress or change made would not be just to combat one disease, but many different ones that might be transmitted in similar ways.

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  15. I'm confused on one point about spirochetes (like Leptospira). They are didermic: which is to say that they have an inner membrane and an outer membrane, but spirochetes are also often able to coat themselves with the lipid bi-membrane of a host cell, which is part of the reason diseases that are caused by some spirochetes can lay dormant for a long time and have a long disease course, think lyme disease (Borrelia) or syphilis (Treponema).

    Is the didermic nature of the bacterial cell and it's ability to coat itself with host membrane distinct phenomena? Are they at all related to one another?

    Are Leptospira unable to coat themselves with host membrane? Otherwise why is the disease course of leptospirosis so much shorter than that of other spirochete diseases?

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  16. I was interested in this article because I recently read about the history and epidemiology of leptospirosis at the Bubbles in Dworkin chapter 2. Reading the entry above informed me of leptospirosis’ structure and about where it binds and travels in the host. I also learned that this pathogen can be present in both water/soil and the kidneys of some hosts. Similar to other comments made, I was unaware about the severity of leptospirosis affecting the lungs and heart. It is unfortunate that diagnostic testing for leptospirosis is difficult and that there are limited indicators of the disease. I am curious to know if there has been progress on finding easier ways to detect leptospirosis.

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    1. Reading this article after reading about the Dwrokin chapter on Leptospirosis at the Bubbles provided much clarity and provided an in-depth look into the the burden of this disease. Considering contaminated water as a common vehicle, it is a severe challenge when the bacteria that cause leptospirosis can stay alive in the water for several days. In reference to your inquiry regarding advancement in diagnostic testing, I found a recent article that highlights improvement in testing. Their diagnostic test used spiked human blood which was at least 100-fold more sensitive than corresponding leptospiral DNA-based quantitative PCR assays. The sensitivity and specificity of their RNA test versus laboratory-confirmed human leptospirosis clinical samples were 64% and 100%, respectively, which was superior then an established DNA detection test. It is good to know that efforts for improvement in testing are being made.


      Reference: http://www.ncbi.nlm.nih.gov/pubmed/26091292

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  17. If one the natural reservoirs for leptospirosis is the rat, and it can be shed through the host's urine, I am surprised there aren't higher incidence rates in big cities in developed countries, like New York or Chicao, where humans often come in to contact with surfaces where rats could have spread the pathogen (i.e. subways and parks). Of course, since symptoms of the disease can come across as "flu-like" or non-threatening (as in The Bubbles case), most people wouldn't think to go to the doctor (even if they go to the doctor at all) and ask if they have leptospirosis.

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    3. Interesting points. According to the American Society for Microbiology, 93% of human and 58% of dog cases in New York City were infected with the type of Leptospirosis commonly carried by rodents. As you mentioned the prevalence could be underreported because people may not go to the doctor for mild to moderate leptospirosis presentations. Another factor to consider is whether those who do go to the doctor presenting with the non-specific symptoms of mild to moderate leptospirosis are diagnosed correctly by their physician or if the physicians assumes they have a more common illness, such as influenza.

      Reference: https://www.asm.org/index.php/asm-newsroom2/press-releases/93606-leptospirosis-in-new-york-city-a-risk-from-rats-to-dogs-and-people

      PS: sorry about the deletions!

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  19. Since outbreaks of leptospirosis are better managed and easily mitigated in advanced countries such as the U.S., novel interventions are much needed in under-resourced countries to curtail the spread of the disease. As mentioned in this case report, domestic livestock play a significant role in the animal-human transmission dynamics. Therefore, at risk populations should be targeted for early detection of symptoms and disease prevention. Fortunately, those diagnosed with the disease can be treated with antibiotics, however, caution must be taken in its usage due to the possibility of antibiotic-resistant strains.

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  20. It is quite interesting how the two features of the landscape epidemiology of leptospirosis intersect and allow for a distinct and continuous pathogen movement through both the domestic and sylvan environment. Further, as mentioned, the spatial range is largely a function of the presence and movement of water, thus it seems that when there is poor infrastructure the movement of leptospirosis will likely be amplified. After reading a number of these infection landscape posts I am astonished (and saddened) by both the impact of poor infrastructure on health and also the lack of focused aid from developed countries in improving water infrastructure and sanitation. Although this would be an expensive feat, clearly a large burden of infectious disease would be alleviated if water infrastructure and sanitation were improved.

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