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This week at Infection Landscapes, I will discuss shigellosis. This is a serious diarrheal disease that accounts for some of the greatest morbidity and mortality of all the diarrheal diseases we will consider. Its greatest burden is experienced by young children in the developing world. Shigellosis poses a pandemic threat, and in fact has caused a widespread pandemic within only the last 40 years.
The Pathogen. Shigellosis is caused by one of four pathogenic species of the genus Shigella. The species are classified according to serogroups and so the species are often referred to as serogroups. Shigella dysenteriae, S. flexneri, S. boydii, and S. Sonnei are the four species that can cause disease in humans, which correspond to the serogroups A, B, C, and D, respectively. Here is the general morphology of the Shigella genus:
The bacteria are gram-negative bacilli and are non-motile. They are able to resist the low pH environment of the stomach, pass through and target the epithelial cells of the colon for infection. Unlike V. cholerae in the small intestine, Shigella spp. actually invade the epithelial cells of the lower intestine, which is facilitated by a lipoprotein antigen in the cell wall of the bacterium and the production of the Shiga toxin. The organisms invade and multiply in the epithelial cells producing ulcers in the epithelium of the colon and subsequent dysentery, for which shigellosis is known. Disseminated Shigella infection is quite rare as the organisms typically remain localized and do not cause bacteremia. Tissue damage in the colon is most pronounced in infections with S. dysenteriae. The mechanism by which the organisms invade the epithelial cells is quite interesting and indirect. Here is a graph published in Nature Reviews Immunology depicting the pathway of infection (Nature Reviews Immunology 4, 953-964 (December 2004)):
The Shigella bacteria cannot invade the epithelial cells of the large intestine directly. Rather, they are taken up by microfold cells (M-cells) and delivered to macrophages. The bacteria are able to lyse the phagosome by which it was taken up in the macrophage. Following apoptosis of the macrophage, the Shigella survive and can now invade the epithelial cell by way way of the Type III secretion system, which acts as a syringe for the infecting bacteria. The bacteria then infect neighboring epithelial cells by way of paracytophagy.
Antibiotic resistance is a serious problem with shigellosis and, in particular, with the type 1 strains of S. dysenteriae. These organisms were highly susceptible to many antibiotics during the 1940s, but after extensive use many are no longer effective. This has presented a substantial public health problem in dealing with epidemics of shigellosis in many parts of the world.
The Disease. Shigellosis is a diarrheal disease characterized by dysentery, that is, loose stool with blood and mucous. High fever and severe abdominal cramps are also common clinical features. This kind of dysentery is not unique to shigellosis, however, making the diagnosis on clinical presentation very difficult in the absence of laboratory or epidemiologic findings. Some other common causes of such dysentery are infections with Salmonella enteritidis, enteroinvasive and enterohemorrhagic Escherichia coli strains, and Campylobacter jejuni, which are all bacteria, and Entamoeba hystolytica, which is a parasite. While shigellosis is a dysentery diarrhea, watery diarrhea can still be present especially during the early stages of disease.
Most shigellosis cases resolve within a week, especially with effective antibiotic therapy. However, infections with S. dysenteriae type 1 can progress to a complicated clinical course. Their are two categories of complications. The first is intestinal and can include intestinal perforation, hemorrhage, rectal prolapse, paralytic ileus, and enteropathy with associated protein malabsorption. The second category is extraintestinal and can include hemolytic uremic syndrome, meningitis, vaginitis, arthritis, rash, hypoglycemia, and high white blood cell count. Such complications are serious and warrant immediate medical attention. The case-fatality for infection with S. dysenteriae type 1 can be between 10% and 20%
If watery diarrhea is present during a Shigella infection, then the standard oral rehydration therapy should be employed. 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, antibiotic therapy is often warranted in severe cases of shigellosis. But due to the high level of antibiotic resistance of the Shigella organisms, assigning the appropriate therapy regimen is complex and very much region specific. The local Shigella strains prevalent in a given geographic area in combination with the epidemiologic characteristics of endemic, epidemic, or sporadic cases must be thoroughly considered by those clinicians with the appropriate experience in treating shigellosis locally. This kind of laboratory- and epidemiology-based clinical decision making is critical to simultaneously prevent morbidity and mortality among the human population (especially young children) and to prevent increased antibiotic resistance among the microbial population.
The Epidemiology and the Landscape. Both sporadic and epidemic occurrence of shigellosis is common. The bacteria can be both waterborne and foodborne, but direct person-to-person fecal-oral transmission is a very important mode of transmission, unlike what we saw for cholera. Humans are the only substantive reservoir, although apes can also be infected. The Shigella bacteria are highly infectious, requiring only a few score organisms to infect in most cases. As such, the person-to-person transmission capacity is greatly enhanced and, thus, this mode of transmission is much more important for shigellosis. Nevertheless, as with most gut infections that constitute a major global burden of disease, conditions of poverty and a lack of sanitation infrastructure delineate those geographic regions that suffer a disproportionate amount of the burden. It's just that the other player in the sanitation/hygiene partnership plays a much bigger role in the transmission of shigellosis because of its extremely high infectivity.
There are no good estimates of the country-specific geographic distribution of shigellosis. However, the global burden of disease is quite significant. between 120 and 165 millions incident cases are believed to occur each year. Furthermore, approximately 1 millions deaths occur annually, with greater than 60% of these experienced by children under 5 years of age.
The distribution of Shigella species varies geographically. In the developing world, under conditions of poor sanitation and overcrowding, S. flexneri is most prevelent, whereas in the developed world S. sonnei is the most common. In the United States, S. sonnei accounts for about 2/3 of shigellosis infections and S. flexneri about 1/3 of infections.
Control and Prevention. Control and prevention of shigellosis begins by following the usual guidelines: improving sanitation in resource poor areas and maintaining vigilance in personal hygiene. The latter is especially important in stopping the secondary transmission of shigellosis at the level of the household, which is a critical modality for this diarrheal disease.
Because of the high infectivity, potentially high case-fatality, and antibiotic resistance, epidemics of type 1 S. dysenteriae require more advanced control measures than the standard generic prevention strategies of providing safe drinking water and maintaining personal hygiene. Outbreaks involving this strain of S. dysenteriae require the identification of the source of each infection. Specific source tracking and elimination add a great deal of labor to shigellosis outbreak investigation, but thorough epidemiologic field investigation can substantially reduce the overall impact of an outbreak.
This week at Infection Landscapes, I will discuss shigellosis. This is a serious diarrheal disease that accounts for some of the greatest morbidity and mortality of all the diarrheal diseases we will consider. Its greatest burden is experienced by young children in the developing world. Shigellosis poses a pandemic threat, and in fact has caused a widespread pandemic within only the last 40 years.
The Pathogen. Shigellosis is caused by one of four pathogenic species of the genus Shigella. The species are classified according to serogroups and so the species are often referred to as serogroups. Shigella dysenteriae, S. flexneri, S. boydii, and S. Sonnei are the four species that can cause disease in humans, which correspond to the serogroups A, B, C, and D, respectively. Here is the general morphology of the Shigella genus:
The bacteria are gram-negative bacilli and are non-motile. They are able to resist the low pH environment of the stomach, pass through and target the epithelial cells of the colon for infection. Unlike V. cholerae in the small intestine, Shigella spp. actually invade the epithelial cells of the lower intestine, which is facilitated by a lipoprotein antigen in the cell wall of the bacterium and the production of the Shiga toxin. The organisms invade and multiply in the epithelial cells producing ulcers in the epithelium of the colon and subsequent dysentery, for which shigellosis is known. Disseminated Shigella infection is quite rare as the organisms typically remain localized and do not cause bacteremia. Tissue damage in the colon is most pronounced in infections with S. dysenteriae. The mechanism by which the organisms invade the epithelial cells is quite interesting and indirect. Here is a graph published in Nature Reviews Immunology depicting the pathway of infection (Nature Reviews Immunology 4, 953-964 (December 2004)):
The Shigella bacteria cannot invade the epithelial cells of the large intestine directly. Rather, they are taken up by microfold cells (M-cells) and delivered to macrophages. The bacteria are able to lyse the phagosome by which it was taken up in the macrophage. Following apoptosis of the macrophage, the Shigella survive and can now invade the epithelial cell by way way of the Type III secretion system, which acts as a syringe for the infecting bacteria. The bacteria then infect neighboring epithelial cells by way of paracytophagy.
Antibiotic resistance is a serious problem with shigellosis and, in particular, with the type 1 strains of S. dysenteriae. These organisms were highly susceptible to many antibiotics during the 1940s, but after extensive use many are no longer effective. This has presented a substantial public health problem in dealing with epidemics of shigellosis in many parts of the world.
The Disease. Shigellosis is a diarrheal disease characterized by dysentery, that is, loose stool with blood and mucous. High fever and severe abdominal cramps are also common clinical features. This kind of dysentery is not unique to shigellosis, however, making the diagnosis on clinical presentation very difficult in the absence of laboratory or epidemiologic findings. Some other common causes of such dysentery are infections with Salmonella enteritidis, enteroinvasive and enterohemorrhagic Escherichia coli strains, and Campylobacter jejuni, which are all bacteria, and Entamoeba hystolytica, which is a parasite. While shigellosis is a dysentery diarrhea, watery diarrhea can still be present especially during the early stages of disease.
Most shigellosis cases resolve within a week, especially with effective antibiotic therapy. However, infections with S. dysenteriae type 1 can progress to a complicated clinical course. Their are two categories of complications. The first is intestinal and can include intestinal perforation, hemorrhage, rectal prolapse, paralytic ileus, and enteropathy with associated protein malabsorption. The second category is extraintestinal and can include hemolytic uremic syndrome, meningitis, vaginitis, arthritis, rash, hypoglycemia, and high white blood cell count. Such complications are serious and warrant immediate medical attention. The case-fatality for infection with S. dysenteriae type 1 can be between 10% and 20%
An example of rectal prolapse
If watery diarrhea is present during a Shigella infection, then the standard oral rehydration therapy should be employed. 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, antibiotic therapy is often warranted in severe cases of shigellosis. But due to the high level of antibiotic resistance of the Shigella organisms, assigning the appropriate therapy regimen is complex and very much region specific. The local Shigella strains prevalent in a given geographic area in combination with the epidemiologic characteristics of endemic, epidemic, or sporadic cases must be thoroughly considered by those clinicians with the appropriate experience in treating shigellosis locally. This kind of laboratory- and epidemiology-based clinical decision making is critical to simultaneously prevent morbidity and mortality among the human population (especially young children) and to prevent increased antibiotic resistance among the microbial population.
The Epidemiology and the Landscape. Both sporadic and epidemic occurrence of shigellosis is common. The bacteria can be both waterborne and foodborne, but direct person-to-person fecal-oral transmission is a very important mode of transmission, unlike what we saw for cholera. Humans are the only substantive reservoir, although apes can also be infected. The Shigella bacteria are highly infectious, requiring only a few score organisms to infect in most cases. As such, the person-to-person transmission capacity is greatly enhanced and, thus, this mode of transmission is much more important for shigellosis. Nevertheless, as with most gut infections that constitute a major global burden of disease, conditions of poverty and a lack of sanitation infrastructure delineate those geographic regions that suffer a disproportionate amount of the burden. It's just that the other player in the sanitation/hygiene partnership plays a much bigger role in the transmission of shigellosis because of its extremely high infectivity.
There are no good estimates of the country-specific geographic distribution of shigellosis. However, the global burden of disease is quite significant. between 120 and 165 millions incident cases are believed to occur each year. Furthermore, approximately 1 millions deaths occur annually, with greater than 60% of these experienced by children under 5 years of age.
The distribution of Shigella species varies geographically. In the developing world, under conditions of poor sanitation and overcrowding, S. flexneri is most prevelent, whereas in the developed world S. sonnei is the most common. In the United States, S. sonnei accounts for about 2/3 of shigellosis infections and S. flexneri about 1/3 of infections.
Control and Prevention. Control and prevention of shigellosis begins by following the usual guidelines: improving sanitation in resource poor areas and maintaining vigilance in personal hygiene. The latter is especially important in stopping the secondary transmission of shigellosis at the level of the household, which is a critical modality for this diarrheal disease.
Because of the high infectivity, potentially high case-fatality, and antibiotic resistance, epidemics of type 1 S. dysenteriae require more advanced control measures than the standard generic prevention strategies of providing safe drinking water and maintaining personal hygiene. Outbreaks involving this strain of S. dysenteriae require the identification of the source of each infection. Specific source tracking and elimination add a great deal of labor to shigellosis outbreak investigation, but thorough epidemiologic field investigation can substantially reduce the overall impact of an outbreak.