Monday, August 15, 2011

Gut Infections


This week at Infection Landscapes, I will begin an extend series on infections of the gut tract and associated diarrheal disease. This series will be extensive, covering standard diseases transmitted by the fecal-oral route, as well as those involving specific foodborne or waterborne transmission. We will also cover fantastically varied organisms, comprising bacteria, viruses, and parasites.


Before beginning a detailed discussion of any specific disease, this week's post will provide a generalized introduction to gut infections.

At the most fundamental level of transmission, all of the infections we will cover in this series are fecal-oral in nature. Not all infections of the gut follow this route, for example there are several helminth infections that infect the human gut tract but do not require ingestion of feces for infection in the human host. Nevertheless, for this series, which will primarily cover diarrheal diseases, I focus on those pathogens that require fecal-oral transmission at some level. While several pathogens may cause substantial, or most, of their infections by way of a foodborne or waterborne vehicle, fundamentally they are all fecal-oral. At some point in the chain of transmission that food source or water source had to have been contaminated with pathogen-laden human (or other animal) feces, which then could subsequently be ingested by a susceptible human host.

Crucial to the understanding of the burden of diarrheal diseases, as they occur in most places in the world, is their locus in very specific spatial context. Gut infections, perhaps more than any other infections, are starkly delineated by social and economic landscapes. The key feature of these landscapes is, of course, poverty. Poverty at the municipal scale corresponds to poor sanitation and water infrastructure.


The combination of first, limited access to water, and second, easy and frequent contamination of the water that is available due to lack of a sewage system, define infrastructural problems that plague the developing world and create a constant source of morbidity and mortality, especially in children. Limited access to clean water also typically promotes poorer personal hygiene at the level of the individual household. When resources are limited, water use is prioritized to meet the fundamental needs: drinking and cooking. So, both the superstructure and the substructure of the social and economic landscape directly contribute to gut infections that can result in high morbidity and mortality among the youngest of the population:




While diarrheal disease is predominantly defined by poverty in the developing world, which is where the greatest burden of disease lies, a distinctly different phenomenon effects the occurrence of disease in the developed world. This phenomenon is the industrialization of agriculture:


The large-scale processing of animals for mass consumption has the potential to introduce cross-contamination of the microbiomes of various domestic animal species with the actual product for consumption. This cross-contamination often results from the animal processing itself, with the spread of the dangerous E. coli O157:H7 in ground beef being a prime example. We will cover these transmission sources more specifically when discussing the relevant pathogens in this series.

What is diarrhea? This may seem obvious given that almost everyone has experienced some form of diarrhea at some point in their lives. Nevertheless, from the epidemiologist's perspective, we need to define diarrhea more precisely for the purposes of developing surveillance systems and investigating outbreaks. Fundamentally diarrhea is a symptom complex that is characterized by stools of decreased consistency and increased number. Most studies and surveillance programs define diarrhea as 3 or more liquid stools in a 24 hour period. Conversely, diarrhea episodes in progress require at least 2 days free of liquid stools in order for the episode to be classified as terminated.  Dysentery is also a diarrheal disease, but it is diarrhea that presents with blood in the loose or liquid stool. Persistent diarrhea is an episode of diarrhea that lasts for 14 days or more.

The burden of diarrheal disease. Studies on diarrhea occurrence come from three main sources: surveillance programs, outbreak investigations, and observational studies. The latter group are comprised of community-based surveys, outpatient clinic visits, and hospitalizations. This group of three classes of observational study provides better global data on the occurrence of diarrhea than either 1) surveillance systems, which tend to be poor in geographical areas where diarrhea is most problematic, or 2) outbreak investigations, which are typically very limited in scope.

Community-based studies provide the best measure of incidence because they do not rely on health-seeking behavior. Furthermore, they can identify those organisms that cause the greatest total number of diarrhea episodes. Based on data from community-based studies, enterotoxigenic Escherichia coli (ETEC), a bacterium, causes the greatest annual incidence of diarrhea in the world at 14%.  In second place is Giardia lamblia, a parasite, which accounts for approximately 10% of diarrhea episodes. Finally, Campylobacter bacteria species, enteropathogenic E. coli (EPEC) and rotavirus are identified in about 7%-8% of diarrhea episodes each year. While these organisms are responsible for the largest proportions of diarrhea episodes in children in the developing world, they do not necessarily represent the most severe disease.

Clinical-based studies, while not representative of the typical occurrence of diarrhea in the general population, do provide valuable data on those organisms that are associated with the greatest morbidity and mortality. Rotavirus accounts for anywhere between 20% and 40% of all diarrhea episodes that require hospitalization in children in the developing world, whereas ETEC infection is number 2 in causing hospitalizations. So, based on these different study types, we can see that ETEC probably causes the greatest number of overall diarrhea episodes, while rotavirus probably causes the greatest number of severe diarrhea episodes. Nevertheless, taken together, rotavirus, ETEC, and Campylobacter species all cause considerable morbidity and mortality among children in much of the world.

Global distribution of rotavirus deaths. Each dot represents 500 deaths. (Glass et al., Nat Med 1997;3:10-1).

Over the last 10 to 15 years many gains have been made by population-wide campaigns to promote oral rehydration therapy. Particularly successful in parts of India, simple oral rehydration therapy has demonstrated success in diminshing the overall burden of diarrheal disease among children under 5 years of age. Nevertheless, approximately 1 to 2 million children still die each year of dehydration due to diarrhea. Obviously there remains much work to be done in community outreach.

Treating Diarrhea. While the consequences of unchecked diarrhea can be dire, especially in young children, the treatment of diarrhea is simple in content and broad in application. Regardless of the infectious organism causing the diarrhea, oral rehydration salts mixed with water provide a universal and highly effective treatment. Moreover, when there is no blood in the stool, oral rehydration therapy in combination with continued normal feeding, is typically sufficient to treat the diarrhea. The goal is to reestablish the electrolyte balance in the person suffering the diarrhea episode. In order to stave off what can develop into deadly dehydration (and in the case of cholera this can happen in a matter of hours), the individual must replace the fluid lost, AND the salts lost. This is precisely the goal of oral rehydration therapy. Packets of oral rehydration salts containing sodium chloride, potassium chloride, citrate and glucose can be obtained from almost any pharmacist or chemist in most areas of the world. These are simply mixed with water and consumed by the diarrhea-afflicted person. In addition, as much as can be tolerated by the ill person, normal nutrition intake should be maintained throughout the diarrhea episode. It may seem as though the food will go right through you, but the body does obtain some nutrients and this helps the immune system fight the infection.

Oral rehydration therapy and continued normal feeding are the cornerstones of treating most diarrhea in the world. These will prevent the overwhelming majority a diarrhea-associated deaths throughout the world. Empiric treatment with antibiotics, especially when there is no blood in the stool (i.e. when the infecting organism is not invasive) is often of limited use and can also be harmful because it can wipe out the gut's natural microbiome, which eliminates the pathogens' competitors and opens up the ecologic niche of the gut.

On the other hand, when the diarrhea is characterized by dysentery, i.e. when blood is present in the stool, additional antibiotic treatment may be required to stop the spread of the organism into surrounding tissue. This is especially relevant for Entomaeba hystolytica and some Salmonella species infections, for example.

Below is a short video on the basic treatment of diarrhea:



Prevention and control of diarrheal disease is usually simple and fundamental. However in those areas where it is most needed, these often remain difficult to achieve. Effective sanitation infrastructure is the cornerstone of a good public health system. Following the implementation of the efficient removal of waste, and the procurement and protection of clean water, the endemicity of diarrheal disease drops rapidly irrespective of climate and geography. Unfortunately, good sanitation is not cheap and requires broad infrastructural resources and maintenance capacity to achieve, which can be extraordinarily difficult for poor countries. And, these are the same countries that suffer the largest burden of disease from diarrhea.

Second to sanitation is personal hygiene. Washing hands following defecation is critical to stopping the chain of transmission of diarrheal disease. Treating water at the level of the household (e.g. boiling water) can also be an important and very useful strategy to reduce gut infections. But any household initiative, whether it be vigilant hand washing or the treatment of water, or both, first requires adequate supply of that all important resource: water. While the specific tactics used to prevent diarrheal disease may indeed be independent of geography, the availability of water is most certainly not. Once again the landscape determines disease.

As we progress through this series I will cover several different types of infection by different organisms, all of which present substantive public health burdens in both the developing and developed worlds.

Next time at Infection Landscapes, I will cover the first of these. It is one which is among the most feared diseases of the last 200 years, responsible for many millions of deaths across the world. It is also responsible for the development of the science of epidemiology, and was a major contributor to the development of the germ theory of disease. I am talking, of course, about none other than cholera.

24 comments:

  1. Even if we have the medical knowledge about gut infections, how do we make sure that the social and economic landscapes of our population of interest are up to par? If sanitation and clean water are the key to preventing gut infections from happening, how can we increase the presence of these two factors?

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  2. Christopher DonnellySeptember 18, 2011 at 9:59 AM

    I think the best way to go about this is through education. Educating those areas where these social and economic barriers exist as well as educating others to the risks presented by these infections. It would take so little, in both money and resources, to help mitigate these problems around the world and it is a matter of making a concerted effort towards ending the spread of these easily preventable diseases. Of course, outbreaks of such diseases are inevitable due to the nature of things, but we could greatly reduce the number of deaths and infections worldwide by just bringing awareness to communities worldwide.

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  3. It is amazing that when speaking about diarrheal diseases they are diseases that can be avoided by putting in place the basics that every country should have. If in a perfect world, every country had good sanitation, a proper sewage system, and was educated on proper personal hygiene diarrheal diseases would not be such a burden. It is very interesting that it is still a major problem in the developed world within the mass production of food and animals. Since this is still a problem both in the developed and undeveloped world, it is very important to educate every country on the importance of a good sanitation and sewage system, and if needed, how to create one. When all the countries can work together to strive towards that goal, there will potentially be a drastic decrease in the amount of infectious diarrheal cases around the world.

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  4. Education obviously plays an important role in prevention of diarrheal disease. However, it needs to be accompanied with action. If there is no action taken by those who can make the situation better then all the education concerning the importance of clean water are a waste of time and money. As a global community there needs to be greater action taken to ensure the availability of clean water for all.

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  5. In response to Dov, he is definitely right that without action there will be no change in a community. However, with more education people become more empowered, more inclined to change, and willing to do more for the betterment of themselves and their community. In the affected communities there definitely needs to be more action, but I believe that it will automatically come with continued education and understanding of what is being taught, and knowing the consequences of not heeding to the education given to them.

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  6. Education is good and action would be nice but without a significant investment by the international community I do not think that clean water, a thing we take for granted, will be enjoyed by all.
    I recently read about a village in the Congo where everyone was dying from diarrhea infections. It was an astronomical spike. After investigation by the UN they found that it was due to the local lake. Local custom had the residents use the lake as the water supply as well as bathroom. Which was fine until refugees brought the population so high that the lake could no longer handle the human waste and everyone got sick with dysentery. Education helped but funds for a sewage system never materialized. The point being that there is just not enough resources going to the places that need it most. It is only through a few select groups, like the Gates foundation and doctors without borders that any real help is given directly to the people of the poorest countries. Which is unfortunate because if we could lower the number of diarrhea infections we could decrease the child mortality rate, which would be a nice bonus.

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    1. I agree with Stan. Without adequate funds, goals of improving education aren't likely to be achieved. And to get and maintain funds, there must be political and/or societal will to do so. This is an especially unfortunate aspect of the process for disenfranchised communities - if the policy makers, as well as philanthropists, of the world are not prioritizing an issue, regardless of how devastating the effects or relatively simple the solution, it is just that much harder to do.
      However, in a way, this could also argue in favor of more education, but specifically for the leaders of communities, nations or foundations: if those who participating in decision making are better informed, the funds could actually come as a result of that education after all.

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  7. To andrianne:
    Improving decrepit water systems requires priority decision making on the part of national governments. Many parts of the world are without infrastructure that will allow for proper waste drainage. When not dealing with natural disasters, I find that NGOs can play a major role in bringing vulnerable, extremely underdeveloped places to the attention of government and aid organizations.
    Enteric diseases are not "sexy", as compared to other major global health issues such as HIV or TB. The financing mechanisms to promote clean water systems are no where near the magnitude of the "sexy" diseases.

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  8. In response to Andrianne's post, I believe that much of the efforts to getting our societies up to par, in terms of sanitation, can follow other public health efforts in the push for education. The efforts of the WHO in reaching the under served populations of the world can be used as an example. As George also pointed out, it seems that financing efforts on the less "sexy" diseases is often difficult and public health officials need to be aware of this. If the money is not available, the next best thing would be education to make the at risk populations aware of the risks and help to contain any outbreaks.

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  9. From reading this post I am curious to know how much research and surveillance is being conducted on nosocomial “Gut Infections” in developed nations, such as the United States. Gut Infections causing Diarrhea and eventually leading Dehydration can potentially be deadly for the immunocompromised that go to health care facilities to have other ailments treated. I interested to find out how many health professionals are aware that using antibiotics to treat these types of infections may not always be the correct action, and if oral hydration therapy is used in many of these settings?? If so how often??? My final thought is, if the main transmission for gut infections is fecal to oral, then the sanitary steps for health care employees may need to be reevaluated to figure out what loop-holes exist that prevent or limit proper hygienic practices in these settings.

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    1. As an aspiring health care professional, I know for a fact that all medical candidates are aware of diarrheal diseases and how they are treated. While not all diarrheal diseases are bacterial, the majority of deadly ones are. Nosocomial infections of concern like Clostridium difficile although ironically caused by antibiotic use are treated with vancomycin (another antibiotic). There are cases of gastroenteritis and dysentery that are prolonged by antibiotics, such is the case with salmonella. There are many types of diarrhea: non-inflammatory, inflammatory and invasive diarrhea. Ones requiring oral rehydration like that caused by vibrio cholera are non-inflammatory diarrhea, and oral rehydration solution are a mainstay for treatment for this specific case. Rotavirus causes an equivalent disease in children. However, rotavirus is a virus so clearly antibiotics are never going to be an effective form of treatment. In these case vaccines like Rotarix are preventive measures, while oral rehydration is the treatment. Lastly, fecal-oral transmission from health care employees is a worry, more so because they are in contact with so many patients and can be a medium for transmission. Beyond washing hands and changing gowns, what else could professional really do?

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    2. Alexandr PinkhasovJuly 11, 2014 at 2:29 PM

      Dean, you raised a very interesting point about the various types of diarrhea. I feel like this is something that could be expanded on because they do differ in symptoms and severity of diseases. Furthermore, as you mentioned the different types of diarrhea may require different methods of prevention/treatment depending on the causative nature of the disease. The article does prevent a valid point, which you underlined as well, is that the best method of treatment is oral rehydration and nutrition. From personal experience, this sometimes a difficult task to accomplish with kids because they don't understand (or may be to cranky) how to alleviate the disease. I think professionals should focus more on educating how to maintain proper hygiene to prevent infection. As rudimentary as it may seem, a lot of people do not know how to effectively wash their hands.

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  10. Education and improved infrastructure are important to alleviating this problem but it would still be difficult to resolve this issue in regions that lack natural resources and are generally neglected. Trying to improve sanitation and personal hygiene would be tricky in areas where water is scarce and proper waste management systems are absent. In some villages in South Asia there are local ponds that are used for everything, by everyone in the nearby community. These water sources are used for recreation, bathing, feeding cattle, washing clothes etc. It sometimes becomes difficult to separate a water source for one use over another because there aren’t very many options available. It seems as though gut infections are simple in nature but there are so many external factors – social, economical, environmental, cultural etc. – that affect populations. Trying to prevent gut infections from occurring at all is somewhat naïve but trying to reduce mortality through increasing public awareness, improving sanitation systems and utilizing effective treatment and therapies would be the best way to tackle such an issue.

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    1. Rukshana makes an important point about the social, economic and environmental blockades to seemingly simple solutions to public health issues such as the prevalence of gut infections in poor regions. But I always emphasize the political component, which, arguably, backs each of the three aforementioned components. The engineering department at my college, for example, seemed to run into the implacable realm of politics when it was able to develop a water purification and distribution system that (as advertised) could bring clean water to a rather large number of people in a few towns somewhere in Africa (I forget the exact nation). This department was able to present the system to the WHO, because of its nascent success, but the WHO ultimately turned down the system as an option for the targeted region (even though the price of the system was shown not to be an issue). This disappointing result was difficult to reason through, and many of the engineering students (and faculty) behind this project projected ideas such as population control in order to explain the almost ridiculous rejection. Even if these speculations are incorrect, politics is still, and always will be, a wall to hit when dealing with issues such as sanitation in poor regions for the prevention of gut infections.

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  11. Nicole MastrogiovanniJune 18, 2014 at 7:46 AM

    Since diarrhea happens in both developed and underdeveloped countries, there are various way to go about solving the issue. Education would work for both situations where workers that produce foods such as meat have to go through a rigorous course on personal hygiene as well as sessions on protecting the edible food part of the animal from the other, non edible sections, where the cross contaimination can be prevented. As for developing countries education has to be a huge role in showing people how to boil water or showing how to properly wash their hands. We can't expect them to protect themselves if they do not know how to. However with education comes the issue of the public actually putting their knowledge into play. You can teach someone a million times how to wash their hands but if they do not actively practice this method on their own, then we cannot solve the problem. Therefore, we must not only educate but motivate everyone to always participate in boiling water and washing hand practices. This motivation can also be applied to food workers, they have to take care of themselves and take pride in their work in order to do it properly and healthy for the rest of us.

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  12. Racquel BreretonJuly 2, 2014 at 3:37 PM

    Water is central to diarrheal transmission. While education is key, lack of clean water remains the driver of infection and disease spread. Developing countries with poor sanitation lacking standard infrastructure are vulnerable to spread of diarrheal disease. Implanting organized sewage systems are often costly, large scale projects. Smaller measures such as frequent hand-washing prove to reduce transmission and spread. However, the issue of clean water inaccessibility remains. Smaller scale projects to create clean water such as boiling and individual use water filtration devices prove effective in providing developing countries with clean water. These methods can substitute temporarily until entire sewage system implementation becomes available.

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    1. Water is central to diarrheal transmission. While education is key, lack of clean water remains the driver of infection and disease spread. Developing countries with poor sanitation lacking standard infrastructure are vulnerable to spread of diarrheal disease. Implanting organized sewage systems are costly large-scale projects. Smaller measures such as frequent hand washing prove to reduce transmission and spread. However, the issue of clean water inaccessibility remains. Smaller scale projects to create clean water such as boiling and individual use water filtration devices prove effective in providing developing countries with clean water. These methods can substitute temporarily until entire sewage system implementation becomes available. Large-scale projects such as sewer system implementation tend to be very costly and could take decades to complete. Many of the developing countries in need of such systems do not have the financial means by which to even begin the process. Additionally some degree of civil unrest or political strife usually exist that can further complicate matters. Add to that any cultural ideologies that can shape human thinking or behavior and you have the recipe for no progress in the implementation of a much needed sanitation infrastructure. Resources for boiling water and filtration devices may also be difficult or next to impossible to deliver to these areas because of the prior-mentioned reasons.

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  13. Alexandr PinkhasovJuly 11, 2014 at 2:18 PM

    Having overcome gastritis recently, I took particular interest in learning more about gut infections. This article does a very good job at describing the driving forces of diarrheal disease, and how they can vary by different regions in the world. The endemic nature of this disease in developed countries such as the United States indicates one of two methods of infection as outlined by the passage: 1) ineffective sanitation, 2) poor personal hygiene. These points could be improved on to lower the incidence of diarrheal diseases. The first, ineffective sanitation could be improved by stricter regulation of any food processing plant, and food service locations. As mentioned in the passage, the higher turnover rate required to meet consumer demands, increases the likelihood of cross contamination. Regulations imposed by the government should provide incentives to food-processing companies to enforce better methods of sanitation, thus decreasing the likelihood of cross contamination, and hence lowering the incidence of disease. The second intervention to address gut infection caused by lack of personal hygiene could be addressed through education. Although it seems simple enough, most young children don’t know proper hand washing techniques.
    Being bed-ridden with body aches for the past few days has led me to relook some of my personal hygiene habits, as well as made me more vigilant when eating somewhere else. Of course it is always better to learn about preventing a disease, then getting a diseases and then learning of it after.

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  14. It amazing that was is so simple to be a solution is the most difficult to obtain. I know most interventions have issues being implemented due to the politics but something so simple as to obtaining clean water, is the underlying factor that can aid most developing countries in their combat of certain infectious diseases. This is why I can appreciate the clean water organizations that make efforts to raise funding for clean water in certain areas of the world. WIth that being said how much of the proceeds do indeed go to the funding of these efforts.

    Pertaining to the hygiene, we the water to be contaminated with the fecal matter, I would think it to be hard to get a proper cleanse when you are washing with dirty water. Either way the bacteria has route to infect. Even if people were to be educated on proper hand washing or overall cleanliness, how much a difference would it make if the very same water they are using to be clean is dirty?

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    1. I agree with Ashley, it is amazing that a simple solution can be so difficult to obtain. Many people on this blog have spoken about education; as always knowledge is power, but I believe that, as in many cases that have been discussed here, when the population to natural resource balance is tipped too far; it's the culture and practice of hygiene and water collection that need to evolve. Sustaining a healthy population means keeping the poop separate from the drinking water. This means innovation and infrastructure. There are many creative people out there that have devised toilets for all types of situations, made to be durable and self sustaining, even solar. Ultimately, the responsibility for building a system for sanitation falls (or should fall) on the local public health systems and civic leadership aka governments. Decreasing disease could be so easy, as Ashley states, and it should be so easy. It's not easy, though, to do it alone as an individual, because it takes engineering. How can we encourage governments to invest in this task? Are there hygiene practices that are low tech that can help in the mean time? As stated in this article, "Following the implementation of the efficient removal of waste, and the procurement and protection of clean water, the endemicity of diarrheal disease drops rapidly irrespective of climate and geography." This says it all.

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  15. Do repeated gut-infection lead to any long-term negative health outcome? I'm curious since poor hygiene is prevalent in many of the developing countries that have the greatest morbidity and mortality from diarrhea and some percent of the population are more likely to get infected with the gut-infection if not from the same parasite but definitely from a different one.

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  16. Hi Tsering! I think you've moved on and graduated already but I thought your question was an interesting one so I did a bit of research. I found a paper published back in 2008 in Nutr Rev that looked at the long term effects of enteric diseases (in the context of malnutrition) on child development. The authors made an interesting argument that malnutrition should be viewed as an infectious disease, reasoning that that gut infections lead to malnutrition and consequently malnutrition worsens the infections. Anyway, they did note that children with repeated gut infections experienced reduced weight gains (obviously), but also stunted long-term growth. Specifically, that "diarrheal illnesses in the first 1–2 years of life may account for a persisting 4–5 cm (∼8.2 cm) shortfall of growth".

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  17. I thought the point raised about studying something like diarrheal disease - that "community-based studies provide the best measure of incidence because they do not rely on health-seeking behavior" - was especially interesting. I always wondered about the validity of studies for which people may not seek medical attention and if they fact is taken into account. Even in areas that are not resource-poor, cultures that do not accept people taking off work to go to the doctor, such as America, can impact surveillance data.

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  18. Given that the vast bulk of the disease burden lies on the developing world, it seems that clean water sources are the goal for both prevention and treatment of these diarrheal diseases. As population densities increase in cities of the developing world, clean water provision is going to become even more difficult than it currently is. Rough predictions of the future effects of a warming planet on rainfall patterns are that we will experience less frequent episodes of more intense precipitation on average. This does not portend well as it is likely to create flooding but not replenish water tables and reservoirs as efficiently. Overall this will contribute to conditions of both contaminated water outside of a regulated system and less water within them.

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