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This week at Infection Landscapes, we continue our series on gut infections by considering a parasite: Giardia lamblia. This is the most significant parasitic cause of diarrhea in the world, and perhaps the third most important contributor to diarrheal disease overall.
The Pathogen. Giardia lamblia (also known as Giardia intestinalis) is a flagellated protozoan parasite. It can infect many different types of animals, including domestic livestock, rodents, household domestic animals like dogs and cats, as well as many sylvan mammals, fish, birds, reptiles and, of course, humans. The parasite has two main forms during the course of its life cycle: the cyst, which is the dormant, yet infectious, stage:
and the trophozoite, which is the motile, feeding, albeit non-infectious, form that inhabits the gut of its host:
The trophozoite targets the villi of the epithelial cells of the small intestine, directly adhering to the epithelium. The parasites attach to the surface of the villi but do not penetrate the cells. During infections with large numbers of organisms, this attachment pattern results in the fusion and flattening of the microvilli, which subsequently results in malabsorption.
The overall life cycle is nicely depicted in this graph by the Centers for Disease Control and Prevention:
As well as in this graph by Mariana Ruiz Villarreal:
Infection is initiated when the cysts are ingested and subsequently excyst in response to environmental stimuli within the host gut tract. The low pH of the stomach is one such important cue. From each quadranucleate cyst, two binucleate trophozoites will emerge during the process of excystation. These trophozoites are morphologically specialized with a concave ventral surface and a ventral disc-shaped organelle to adhere to the epithelial surface of the small intestine. Once emerged, the trophozoites replicate by binary fission. Because an adaptive immune response in the host follows and will eventually clear the parasite, the trophozoites must transform into cysts (encystation) and exit the host in order to survive. These cysts can survive free-living in the environment for long periods of time as long as they do not dry out or freeze. The encysted parasites are also resistant to moderate levels of chlorination. These cysts are highly infectious, demonstrating an infectious dose of only a couple dozen organisms. Given that tens of thousands of cysts are typically present per liter of untreated sewage in the US, and hundreds of thousands to millions of cysts can be present in untreated sewage in the developing world, the importance of good sanitation and water infrastructure for blocking infection is obvious.
The Disease. Up to 50% of infections are asymptomatic. Among those that do experience clinical disease the most common manifestation is diarrhea, with some distinction from that which has been covered in other gut infections at Infection Landscapes. As described above, the adherence of the parasite to the villi of the epithelium disrupts nutrient absorption in the gut. One of the nutrients drastically affected is fat. During active infection fats are not taken up appropriately by the host and are instead digested in part by the natural gut flora of the colon. The excess of fats combined with the excited metabolic state of the gut bacteria and their subsequent metabolic biproducts results in an extraordinarily foul smelling and greasy steatorrhea (high fat content in the stool), in addition to the typical watery diarrhea associated with most of the common gut pathogens. Bloating and excess flatulence are quite common. Frank dysentery can present in clinically apparent giardiasis, but this is rare. With large volume diarrhea, dehydration can also present in acute infections so fluid loss must be monitored. Abdominal pain and fatigue are also common, and weight loss can accompany both acute and chronic infections. Weight loss can be particularly important since it is observed in up to half of the cases. Vomiting can occur in some cases, though this is less common. While diarrhea and steatorrhea are generally transient, repeated or chronic infections with G. lamblia can cause important disruption in growth and development in children because of the malabsorption induced by the parasites in the small intestine. While not typically a killer, because of its high prevalence in children in the developing world, it certainly can be considered a neglected infectious disease and, therefore, an important impediment to children's ability to thrive in geographic regions of poverty.
The Epidemiology and the Landscape. As described above the infectious stage of the parasite is the cyst. These cysts are transmitted fecal-orally, with waterborne transmission probably the most important route followed closely by foodborne transmission. In addition, direct person to person transmission may also constitute a significant route of transmission, though not as substantial at the population level as the common vehicles of water and food.
The occurrence of giardiasis is quite different between the developing and developed worlds so we will consider these separately as two distinct geographies.
In the developing world, community-based surveys show that greater than 10% of all diarrhea episodes in children may be due to G. lamblia, and approximately one quarter of the people in this part of the world are infected at any given time. In this setting, infection with G. lamblia is associated with the classic risk profile for gut infections in general, i.e. poor sanitation and water infrastructure. These structural deficiencies are the primary reason for the widespread infection with this parasite in resource poor areas. And, while high child mortality doesn't typically attend this infection (unless one is immunocompromised, which is not uncommon in measles-endemic areas), this infection is attended by a fairly high degree of childhood developmental delay due to the extended malabsorption in repeated or chronic disease. So the social cost, while comprising less death, is still high in the developing world. We do not have good country-specific estimates of giardiasis for the whole world. However, based on a wide geographic spectrum of community-based studies and some national surveillance programs, we do know that giardiasis infection is very similar in global distribution to diarrheal disease in general. Moreover, the substantive burden of diarrheal disease as measured by the disability-adjusted life years (DALY) can be applied to giardiasis. The World Health Organization map below depicts the diarrhea-associated global distribution of DALYs. While the specific numbers do not reflect the DALYs directly attributable to giardiasis, they are proportional and therefore the disparities in the map reflect very similar disparities in giardiasis occurrence and its associated morbidity:
In the developed world, the landscape of infection is distinctly different because of the presence of better sanitation and water infrastructure. Rather than the general population of children being at high risk as is the case in the developing world, in the developed world those at greatest risk are specific subgroups that constitute either 1) potentially high transmission networks due to specific behavior and social contacts, such as settings that aggregate small children (e.g., daycare centers) and 2) rural communities whose water sources draw from small surface water with hydrogeographic features that are easily contaminated by either domesticated livestock or sylvan animal reservoirs. Periods of heavy rain can be particularly important in contamination as runoff carries fecal matter into these water sources as it drains the landscape. In addition, individuals who spend significant time in the outdoors due to occupation or recreation may also be at increased risk because of contact with potentially infected water sources. However, while this is often purported, there is very little evidence to support such risk in general, and may be limited to specific bodies of water or to very specific animal-human-water vehicle transmission nidi, for example areas proximal to beaver habitat.
Control and Prevention. Control and prevention of giardiasis begins by following the usual guidelines: improving sanitation in resource poor areas and maintaining vigilance in personal hygiene. In most settings in the world where giardiasis is a significant contributor to diarrheal illness, improved infrastructure that can maintain adequate water resources is a first priority in its prevention.
Secondarily, personal hygiene at the individual level, especially in the context of food preparation, can also be very important in preventing the spread of giardiasis: consistent hand washing, boiling water, and thoroughly cooking food are all important in stopping the chain of transmission. Most importantly, since giardiasis is probably the biggest parasitic contributor to global diarrhea overall, and an important contributor to malnutrition, the implementation of these strategies would be an important component to eliminating the global burden of diarrhea as well as delayed development in young children in much of the world.
This week at Infection Landscapes, we continue our series on gut infections by considering a parasite: Giardia lamblia. This is the most significant parasitic cause of diarrhea in the world, and perhaps the third most important contributor to diarrheal disease overall.
The Pathogen. Giardia lamblia (also known as Giardia intestinalis) is a flagellated protozoan parasite. It can infect many different types of animals, including domestic livestock, rodents, household domestic animals like dogs and cats, as well as many sylvan mammals, fish, birds, reptiles and, of course, humans. The parasite has two main forms during the course of its life cycle: the cyst, which is the dormant, yet infectious, stage:
and the trophozoite, which is the motile, feeding, albeit non-infectious, form that inhabits the gut of its host:
The trophozoite targets the villi of the epithelial cells of the small intestine, directly adhering to the epithelium. The parasites attach to the surface of the villi but do not penetrate the cells. During infections with large numbers of organisms, this attachment pattern results in the fusion and flattening of the microvilli, which subsequently results in malabsorption.
The overall life cycle is nicely depicted in this graph by the Centers for Disease Control and Prevention:
As well as in this graph by Mariana Ruiz Villarreal:
Infection is initiated when the cysts are ingested and subsequently excyst in response to environmental stimuli within the host gut tract. The low pH of the stomach is one such important cue. From each quadranucleate cyst, two binucleate trophozoites will emerge during the process of excystation. These trophozoites are morphologically specialized with a concave ventral surface and a ventral disc-shaped organelle to adhere to the epithelial surface of the small intestine. Once emerged, the trophozoites replicate by binary fission. Because an adaptive immune response in the host follows and will eventually clear the parasite, the trophozoites must transform into cysts (encystation) and exit the host in order to survive. These cysts can survive free-living in the environment for long periods of time as long as they do not dry out or freeze. The encysted parasites are also resistant to moderate levels of chlorination. These cysts are highly infectious, demonstrating an infectious dose of only a couple dozen organisms. Given that tens of thousands of cysts are typically present per liter of untreated sewage in the US, and hundreds of thousands to millions of cysts can be present in untreated sewage in the developing world, the importance of good sanitation and water infrastructure for blocking infection is obvious.
The Disease. Up to 50% of infections are asymptomatic. Among those that do experience clinical disease the most common manifestation is diarrhea, with some distinction from that which has been covered in other gut infections at Infection Landscapes. As described above, the adherence of the parasite to the villi of the epithelium disrupts nutrient absorption in the gut. One of the nutrients drastically affected is fat. During active infection fats are not taken up appropriately by the host and are instead digested in part by the natural gut flora of the colon. The excess of fats combined with the excited metabolic state of the gut bacteria and their subsequent metabolic biproducts results in an extraordinarily foul smelling and greasy steatorrhea (high fat content in the stool), in addition to the typical watery diarrhea associated with most of the common gut pathogens. Bloating and excess flatulence are quite common. Frank dysentery can present in clinically apparent giardiasis, but this is rare. With large volume diarrhea, dehydration can also present in acute infections so fluid loss must be monitored. Abdominal pain and fatigue are also common, and weight loss can accompany both acute and chronic infections. Weight loss can be particularly important since it is observed in up to half of the cases. Vomiting can occur in some cases, though this is less common. While diarrhea and steatorrhea are generally transient, repeated or chronic infections with G. lamblia can cause important disruption in growth and development in children because of the malabsorption induced by the parasites in the small intestine. While not typically a killer, because of its high prevalence in children in the developing world, it certainly can be considered a neglected infectious disease and, therefore, an important impediment to children's ability to thrive in geographic regions of poverty.
The Epidemiology and the Landscape. As described above the infectious stage of the parasite is the cyst. These cysts are transmitted fecal-orally, with waterborne transmission probably the most important route followed closely by foodborne transmission. In addition, direct person to person transmission may also constitute a significant route of transmission, though not as substantial at the population level as the common vehicles of water and food.
The occurrence of giardiasis is quite different between the developing and developed worlds so we will consider these separately as two distinct geographies.
In the developing world, community-based surveys show that greater than 10% of all diarrhea episodes in children may be due to G. lamblia, and approximately one quarter of the people in this part of the world are infected at any given time. In this setting, infection with G. lamblia is associated with the classic risk profile for gut infections in general, i.e. poor sanitation and water infrastructure. These structural deficiencies are the primary reason for the widespread infection with this parasite in resource poor areas. And, while high child mortality doesn't typically attend this infection (unless one is immunocompromised, which is not uncommon in measles-endemic areas), this infection is attended by a fairly high degree of childhood developmental delay due to the extended malabsorption in repeated or chronic disease. So the social cost, while comprising less death, is still high in the developing world. We do not have good country-specific estimates of giardiasis for the whole world. However, based on a wide geographic spectrum of community-based studies and some national surveillance programs, we do know that giardiasis infection is very similar in global distribution to diarrheal disease in general. Moreover, the substantive burden of diarrheal disease as measured by the disability-adjusted life years (DALY) can be applied to giardiasis. The World Health Organization map below depicts the diarrhea-associated global distribution of DALYs. While the specific numbers do not reflect the DALYs directly attributable to giardiasis, they are proportional and therefore the disparities in the map reflect very similar disparities in giardiasis occurrence and its associated morbidity:
Age-standardised disability-adjusted life year (DALY) rates from diarrheal diseases by country (per 100,000 inhabitants).
no data
less than 500
500-1000
1000-1500
1500-2000
2000-2500
2500-3000
3000-3500
3500-4000
4000-4500
4500-5000
5000-6000
more than 6000
In the developed world, the landscape of infection is distinctly different because of the presence of better sanitation and water infrastructure. Rather than the general population of children being at high risk as is the case in the developing world, in the developed world those at greatest risk are specific subgroups that constitute either 1) potentially high transmission networks due to specific behavior and social contacts, such as settings that aggregate small children (e.g., daycare centers) and 2) rural communities whose water sources draw from small surface water with hydrogeographic features that are easily contaminated by either domesticated livestock or sylvan animal reservoirs. Periods of heavy rain can be particularly important in contamination as runoff carries fecal matter into these water sources as it drains the landscape. In addition, individuals who spend significant time in the outdoors due to occupation or recreation may also be at increased risk because of contact with potentially infected water sources. However, while this is often purported, there is very little evidence to support such risk in general, and may be limited to specific bodies of water or to very specific animal-human-water vehicle transmission nidi, for example areas proximal to beaver habitat.
Control and Prevention. Control and prevention of giardiasis begins by following the usual guidelines: improving sanitation in resource poor areas and maintaining vigilance in personal hygiene. In most settings in the world where giardiasis is a significant contributor to diarrheal illness, improved infrastructure that can maintain adequate water resources is a first priority in its prevention.
Secondarily, personal hygiene at the individual level, especially in the context of food preparation, can also be very important in preventing the spread of giardiasis: consistent hand washing, boiling water, and thoroughly cooking food are all important in stopping the chain of transmission. Most importantly, since giardiasis is probably the biggest parasitic contributor to global diarrhea overall, and an important contributor to malnutrition, the implementation of these strategies would be an important component to eliminating the global burden of diarrhea as well as delayed development in young children in much of the world.