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Salmonella pathogens are some of the most common causes of foodborne outbreaks in developed regions of the world, and are also the cause of significant morbidity and mortality in quite different settings in the developing world. This time at Infection Landscapes, we will explore the disease salmonellosis as it occurs in both geographic contexts.
The Pathogen. Salmonellosis is caused by bacteria species in the genus Salmonella. Most infections in endothermic animals, such as mammals, are caused by the species Salmonella enterica, subspecies enterica. However, there are several subspecies within S. enterica and some of these other subspecies cause disease in ectothermic animals, such as reptiles, while still others are free living in the environment. Each subspecies has many serotypes (or serovars), which are defined by their unique antigen composition. S. enterica enterica (also referred to as subspecies I) is comprised of many serovars that cause disease in cattle, poultry, swine, and humans. The naming convention typically uses the genus and the serovar only. Some of the most important serovars to infect humans and domestic animals are Salmonella Enteritidis, S. Typhimurium, S. Montevideo, S. Typhi (humans only), S. Paratyphi (humans only), and many others.
Salmonella enterica is a gram-negative bacillus and a facultative anaerobe. It has a flagellum for motility, and fimbriae and adhesins for attachment to host cells. The O and H antigens are present on this organism, antigens you will recall from previous enteric organisms covered at Infection Landscapes. The O antigen is part of the lipopolysaccharide (LPS) molecule and the H antigen is the flagellum.
In general, pathogenic Salmonellae employ their fimbriae and adhesins to attach to the host cells of the small intestine. Subsequently, the Salmonella bacteria utilize a type III secretion system to inject proteins into the host cell, altering the host cell's structure and facilitating the uptake of the bacterium into the host cell, where it can then replicate.
The important virulence factors vary across the different serovars, which leads to host-specific infectivity, and ultimately varied pathogenicity and virulence across different susceptible hosts. Here is a nice animated video by the Institute of Microbiology ETH Zurich demonstrating the infectivity and pathogenicity of Salmonella Typhimurium:
The Disease. As mentioned above, the pathogenicity and virulence of Salmonella infections are complex and typically host-dependent. Some Salmonella serovars are pathogenic only in their natural reservoir hosts, causing little or no disease in other hosts (e.g. S. Typhi, S. Pullorum, and S. Gallinarum). Some serovars, on the other hand, are not pathogenic in their natural reservoir host, but can cause pathogenic infections in animals outside the natural reservoir. S. Enteritidis is a good example of this, where the serovar causes little disease in poultry, but is one of the most important sources of foodborne salmonellosis in humans. Finally, there are some recognized serovars that are pathogenic to their natural reservoir hosts, but develop even more virulent pathogenesis when they infect other hosts. S. Cholerae-suis and S. Dublin can cause severe clinical presentations in humans, with disseminated pathogenesis and high mortality.
Salmonellosis comprises 3 major disease forms in humans: enteric fever, non-typhoid invasive disease, and gastroenteritis.
Enteric fever is caused by S. Typhi and is more commonly known as typhoid fever. This is an important global disease in itself and so will be covered independently in a separate post next time.
Non-typhoid invasive salmonellosis is typically a pyemic infection, meaning abscess-forming and disseminated. The abscesses are often found in the bones and joints, meninges, serosa, and visceral organs. Salmonella Dublin, S. Virchow, and S. Cholerae-suis are the classic non-typhoid serovars that are associated with invasive disease. Nevertheless, serovars that are not usually invasive in humans can cause invasive disease among those who are not immunocompetent, or among those who receive an unusually high infectious dose of the pathogen. Invasive disease is a serious condition and requires directed antibiotic treatment.
Most foodborne salmonellosis results in gastroenteritis with a spectrum of diarrhea from watery to frank dysentery. Nausea, vomiting, and abdominal cramps are also common. This infection is most often self-limited, though distinctly uncomfortable and tiring. The typical disease course notwithstanding, more severe clinical presentation can occur in extremes of age, including children less than 5 years and adults greater than 65 years. There are many serovars that cause sporadic cases of gastroenteritis salmonellosis, however, S. Enteritidis is particularly important in causing foodborne outbreaks in developed countries.
The Epidemiology and the Landscape. There are approximately 3 billion incident cases of salmonellosis each year including all the serovars capable of infecting humans. There is substantial morbidity and mortality associated with typhoid fever, with approximately 22 million incident cases and 200, 000 deaths each year. However, as mentioned above, this posting is focusing on non-typhoid salmonellosis, so we will return to typhoid fever in the next post.
The epidemiology of non-typhoid salmonellosis is geographically distinct between the developed and developing regions of the world.
In the developed world, outbreaks have been driven by the agricultural industry as well as by the improper handling and cooking of food products. In this setting, salmonellosis in humans is essentially a foodborne disease. The Salmonella pathogens are maintained in animal reservoirs, and infection in humans follows ingestion of contaminated animal products or ingestion of produce contaminated with infected animal feces. S. Enteritidis and S. Typhimurium are the most important disease-causing serovars in these regions of the world. Poultry is the reservoir for S. Enteritidis, which has caused the greatest number of cases of gastroenteritis salmonellosis in the United States and Europe.
Because the organism can be transmitted vertically from a hen to her eggs, eggs have thus also been an important source of foodborne infection in humans.
S. Typhimurium has also become an important source of foodborne outbreaks in both Europe and North America. Originally identified in sea gulls in Britain, this serovar subsequently became epidemic in cattle and poultry, and is now a relevant pathogen in beef, chicken and pork products. It has also been identified in infections among those who work closely with the animal sources in this industry, though infection by way of animal contact is far less common than the eating of contaminated foods. Antibiotic resistance has become especially problematic with S. Typhimurium.
It is important to keep in mind that Salmonella contamination is not limited to the animal products themselves, but can also include any product that comes into contact with animal waste containing pathogen laden feces. The pathways of agricultural product movement from farm to markets is such that cross-contamination between animal waste and other non-animal products, especially fruits and vegetables, is readily facilitated. As such, produce often becomes an even more important vehicle for human infection than infected animal products. This is amplified when the flow of food products crosses international boundaries (which is commonplace for modern produce sales), where different governments apply different public health policies in the protection and movement of foods.
There are approximately 150,000 incident cases of salmonellosis in the US each year, and roughly the same number of cases per year in the EU. The annual deaths range from tens to thousands. Somewhere between 15% and 20% of all chickens are infected with Salmonella organisms that are pathogenic to humans.
In the developing world, non-typhoid pathogenic Salmonellae are commonly associated with nosocomial outbreaks, rather than foodborne outbreaks. Indeed, person to person transmission is the norm in this setting, where there is typically a complete absence of a food animal reservoir. Also, the bacteria are often more virulent. In South Asia and the Middle East, S. Typhimurium has been particularly prominent, with the case-fatality as high as 30% in some outbreaks. The strain in this geographic region is considerably more virulent than that found in northern Europe and North America. S. Wien has been more prominent in countries in northern Africa and the Mediterranean, while also appearing in India. The more virulent strains in the geographic regions of poor and middle income are also associated with extensive resistance to antibiotic treatment. This is largely due to the widespread overuse of antibiotics especially in the context of unregulated access to these drugs in the community.
Unfortunately, we do not currently have good surveillance data to estimate the burden of disease attributable to non-typhoid salmonellosis in the developing world.
Control and Prevention. Public health strategies for salmonellosis need to be directed by the unique circumstances found in different parts of the world where Salmonellae comprise significant human pathogens.
In the developed world, as with pathogenic E. coli, salmonellosis control and prevention must focus on the agricultural industry. First, the application and maintenance of rigorous production standards must be applied to the processing of animal products, with special attention to poultry, beef and pork. The use of antibiotics as growth stimulators in these animals is also an important component of the development of antibiotic resistance in organisms that are pathogenic to both humans and animals. Second, rigorous environmental controls are required to prevent cross-contamination between domestic livestock and produce, which is probably a larger source of foodborne outbreaks than, or at least as significant as, the contaminated animal products themselves. Unfortunately, since large-scale agribusiness is now a global phenomenon, produce is distributed far and wide throughout the world. As such, the application of uniform public health standards is often not possible and so a significant proportion of produce reaches local markets contaminated with Salmonella pathogens.
In addition to sources of infection in the agricultural industry, it is also important to focus on sources of infection in the home. First, thorough cooking of all animal products, including eggs, should be standard practice. Second, when preparing animal products, it is critical to segregate food preparation areas and utensils, and to wash all food preparation areas and utensils with soap and water after use to avoid cross-contamination. Third, all produce must always be thoroughly washed. This includes fruits or vegetables with skins that are removed prior to eating. Remember this, cantaloupe are a regular source of Salmonella pathogens. The pathogens reside on the surface, but the act of cutting the melon can easily introduce the bacteria to its flesh and infect us upon eating, even though the rind is not eaten.
In the developing world, most specifically, a new approach to regulating the use of antibiotics is critical to reducing the spread of antibiotic resistance in pathogenic Salmonella as well as other pathogenic organisms. This is especially important for enteric pathogens as these can easily end up in the the water supply since poor sanitation infrastructure is often characteristic of the landscape in such regions.
More generally, since person to person transmission is far more common for Salmonella infections in the developing world, the importance of consistent hand washing after using the toilet and before preparing and eating meals should be emphasized in the home, but also especially in hospital settings since virulent salmonellosis is nosocomially important in these regions.
Salmonella pathogens are some of the most common causes of foodborne outbreaks in developed regions of the world, and are also the cause of significant morbidity and mortality in quite different settings in the developing world. This time at Infection Landscapes, we will explore the disease salmonellosis as it occurs in both geographic contexts.
The Pathogen. Salmonellosis is caused by bacteria species in the genus Salmonella. Most infections in endothermic animals, such as mammals, are caused by the species Salmonella enterica, subspecies enterica. However, there are several subspecies within S. enterica and some of these other subspecies cause disease in ectothermic animals, such as reptiles, while still others are free living in the environment. Each subspecies has many serotypes (or serovars), which are defined by their unique antigen composition. S. enterica enterica (also referred to as subspecies I) is comprised of many serovars that cause disease in cattle, poultry, swine, and humans. The naming convention typically uses the genus and the serovar only. Some of the most important serovars to infect humans and domestic animals are Salmonella Enteritidis, S. Typhimurium, S. Montevideo, S. Typhi (humans only), S. Paratyphi (humans only), and many others.
Salmonella enterica is a gram-negative bacillus and a facultative anaerobe. It has a flagellum for motility, and fimbriae and adhesins for attachment to host cells. The O and H antigens are present on this organism, antigens you will recall from previous enteric organisms covered at Infection Landscapes. The O antigen is part of the lipopolysaccharide (LPS) molecule and the H antigen is the flagellum.
In general, pathogenic Salmonellae employ their fimbriae and adhesins to attach to the host cells of the small intestine. Subsequently, the Salmonella bacteria utilize a type III secretion system to inject proteins into the host cell, altering the host cell's structure and facilitating the uptake of the bacterium into the host cell, where it can then replicate.
The important virulence factors vary across the different serovars, which leads to host-specific infectivity, and ultimately varied pathogenicity and virulence across different susceptible hosts. Here is a nice animated video by the Institute of Microbiology ETH Zurich demonstrating the infectivity and pathogenicity of Salmonella Typhimurium:
The Disease. As mentioned above, the pathogenicity and virulence of Salmonella infections are complex and typically host-dependent. Some Salmonella serovars are pathogenic only in their natural reservoir hosts, causing little or no disease in other hosts (e.g. S. Typhi, S. Pullorum, and S. Gallinarum). Some serovars, on the other hand, are not pathogenic in their natural reservoir host, but can cause pathogenic infections in animals outside the natural reservoir. S. Enteritidis is a good example of this, where the serovar causes little disease in poultry, but is one of the most important sources of foodborne salmonellosis in humans. Finally, there are some recognized serovars that are pathogenic to their natural reservoir hosts, but develop even more virulent pathogenesis when they infect other hosts. S. Cholerae-suis and S. Dublin can cause severe clinical presentations in humans, with disseminated pathogenesis and high mortality.
Salmonellosis comprises 3 major disease forms in humans: enteric fever, non-typhoid invasive disease, and gastroenteritis.
Enteric fever is caused by S. Typhi and is more commonly known as typhoid fever. This is an important global disease in itself and so will be covered independently in a separate post next time.
Non-typhoid invasive salmonellosis is typically a pyemic infection, meaning abscess-forming and disseminated. The abscesses are often found in the bones and joints, meninges, serosa, and visceral organs. Salmonella Dublin, S. Virchow, and S. Cholerae-suis are the classic non-typhoid serovars that are associated with invasive disease. Nevertheless, serovars that are not usually invasive in humans can cause invasive disease among those who are not immunocompetent, or among those who receive an unusually high infectious dose of the pathogen. Invasive disease is a serious condition and requires directed antibiotic treatment.
Most foodborne salmonellosis results in gastroenteritis with a spectrum of diarrhea from watery to frank dysentery. Nausea, vomiting, and abdominal cramps are also common. This infection is most often self-limited, though distinctly uncomfortable and tiring. The typical disease course notwithstanding, more severe clinical presentation can occur in extremes of age, including children less than 5 years and adults greater than 65 years. There are many serovars that cause sporadic cases of gastroenteritis salmonellosis, however, S. Enteritidis is particularly important in causing foodborne outbreaks in developed countries.
The Epidemiology and the Landscape. There are approximately 3 billion incident cases of salmonellosis each year including all the serovars capable of infecting humans. There is substantial morbidity and mortality associated with typhoid fever, with approximately 22 million incident cases and 200, 000 deaths each year. However, as mentioned above, this posting is focusing on non-typhoid salmonellosis, so we will return to typhoid fever in the next post.
The epidemiology of non-typhoid salmonellosis is geographically distinct between the developed and developing regions of the world.
In the developed world, outbreaks have been driven by the agricultural industry as well as by the improper handling and cooking of food products. In this setting, salmonellosis in humans is essentially a foodborne disease. The Salmonella pathogens are maintained in animal reservoirs, and infection in humans follows ingestion of contaminated animal products or ingestion of produce contaminated with infected animal feces. S. Enteritidis and S. Typhimurium are the most important disease-causing serovars in these regions of the world. Poultry is the reservoir for S. Enteritidis, which has caused the greatest number of cases of gastroenteritis salmonellosis in the United States and Europe.
Because the organism can be transmitted vertically from a hen to her eggs, eggs have thus also been an important source of foodborne infection in humans.
S. Typhimurium has also become an important source of foodborne outbreaks in both Europe and North America. Originally identified in sea gulls in Britain, this serovar subsequently became epidemic in cattle and poultry, and is now a relevant pathogen in beef, chicken and pork products. It has also been identified in infections among those who work closely with the animal sources in this industry, though infection by way of animal contact is far less common than the eating of contaminated foods. Antibiotic resistance has become especially problematic with S. Typhimurium.
It is important to keep in mind that Salmonella contamination is not limited to the animal products themselves, but can also include any product that comes into contact with animal waste containing pathogen laden feces. The pathways of agricultural product movement from farm to markets is such that cross-contamination between animal waste and other non-animal products, especially fruits and vegetables, is readily facilitated. As such, produce often becomes an even more important vehicle for human infection than infected animal products. This is amplified when the flow of food products crosses international boundaries (which is commonplace for modern produce sales), where different governments apply different public health policies in the protection and movement of foods.
There are approximately 150,000 incident cases of salmonellosis in the US each year, and roughly the same number of cases per year in the EU. The annual deaths range from tens to thousands. Somewhere between 15% and 20% of all chickens are infected with Salmonella organisms that are pathogenic to humans.
In the developing world, non-typhoid pathogenic Salmonellae are commonly associated with nosocomial outbreaks, rather than foodborne outbreaks. Indeed, person to person transmission is the norm in this setting, where there is typically a complete absence of a food animal reservoir. Also, the bacteria are often more virulent. In South Asia and the Middle East, S. Typhimurium has been particularly prominent, with the case-fatality as high as 30% in some outbreaks. The strain in this geographic region is considerably more virulent than that found in northern Europe and North America. S. Wien has been more prominent in countries in northern Africa and the Mediterranean, while also appearing in India. The more virulent strains in the geographic regions of poor and middle income are also associated with extensive resistance to antibiotic treatment. This is largely due to the widespread overuse of antibiotics especially in the context of unregulated access to these drugs in the community.
Unfortunately, we do not currently have good surveillance data to estimate the burden of disease attributable to non-typhoid salmonellosis in the developing world.
Control and Prevention. Public health strategies for salmonellosis need to be directed by the unique circumstances found in different parts of the world where Salmonellae comprise significant human pathogens.
In the developed world, as with pathogenic E. coli, salmonellosis control and prevention must focus on the agricultural industry. First, the application and maintenance of rigorous production standards must be applied to the processing of animal products, with special attention to poultry, beef and pork. The use of antibiotics as growth stimulators in these animals is also an important component of the development of antibiotic resistance in organisms that are pathogenic to both humans and animals. Second, rigorous environmental controls are required to prevent cross-contamination between domestic livestock and produce, which is probably a larger source of foodborne outbreaks than, or at least as significant as, the contaminated animal products themselves. Unfortunately, since large-scale agribusiness is now a global phenomenon, produce is distributed far and wide throughout the world. As such, the application of uniform public health standards is often not possible and so a significant proportion of produce reaches local markets contaminated with Salmonella pathogens.
In addition to sources of infection in the agricultural industry, it is also important to focus on sources of infection in the home. First, thorough cooking of all animal products, including eggs, should be standard practice. Second, when preparing animal products, it is critical to segregate food preparation areas and utensils, and to wash all food preparation areas and utensils with soap and water after use to avoid cross-contamination. Third, all produce must always be thoroughly washed. This includes fruits or vegetables with skins that are removed prior to eating. Remember this, cantaloupe are a regular source of Salmonella pathogens. The pathogens reside on the surface, but the act of cutting the melon can easily introduce the bacteria to its flesh and infect us upon eating, even though the rind is not eaten.
In the developing world, most specifically, a new approach to regulating the use of antibiotics is critical to reducing the spread of antibiotic resistance in pathogenic Salmonella as well as other pathogenic organisms. This is especially important for enteric pathogens as these can easily end up in the the water supply since poor sanitation infrastructure is often characteristic of the landscape in such regions.
More generally, since person to person transmission is far more common for Salmonella infections in the developing world, the importance of consistent hand washing after using the toilet and before preparing and eating meals should be emphasized in the home, but also especially in hospital settings since virulent salmonellosis is nosocomially important in these regions.