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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.
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.
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.