Competitive Exclusion of Salmonella enteritidis
Competitive Exclusion of Salmonella enteritidis
Salmonella Enteritidis emerged as a major egg-associated pathogen in the late 20th century. Epidemiologic data from England, Wales, and the United States indicate that S. Enteritidis filled the ecologic niche vacated by eradication of S. Gallinarum from poultry, leading to an epidemic increase in human infections. We tested this hypothesis by retrospective analysis of epidemiologic surveys in Germany and demonstrated that the number of human S. Enteritidis cases is inversely related to the prevalence of S. Gallinarum in poultry. Mathematical models combining epidemiology with population biology suggest that S. Gallinarum competitively excluded S. Enteritidis from poultry flocks early in the 20th century.
The avian-adapted serovar Salmonella Gallinarum, which includes two biovars, Gallinarum and Pullorum, was endemic in poultry flocks in Europe and the Americas in the early 20th century. To reduce economic losses to the poultry industry, national surveillance programs were established in the United States (National Poultry Improvement Plan, 1935) and England and Wales (Poultry Stock Improvement Plan, 1939). Since S. Gallinarum (antigen formula O9,12:-:-) has no animal reservoir other than domestic and aquatic fowl, the test-and-slaughter method of disease control under these surveillance programs led to its eradication from commercial poultry flocks in the United States, England, and Wales by the 1970s. At that time, the number of human cases of infection with serovar S. Enteritidis (antigen formula O9,12:g,m:1,7) began to increase in these countries. By the 1980s, S. Enteritidis had emerged as a major concern for food safety in Europe and the Americas; by 1990 it was the most frequently reported Salmonella serovar in the United States. Most S. Enteritidis outbreaks in Europe and the United States are associated with foods containing undercooked eggs. Eggs can become contaminated with S. Enteritidis through cracks in the shell after contact with chicken feces or by transovarian infection. Thus, laying hens were the likely source of the S. Enteritidis epidemic in Europe and the Americas.
The inverse relationship between the incidence of S. Gallinarum infection in chickens and egg-associated S. Enteritidis infections in humans prompted the hypothesis that S. Enteritidis filled the ecologic niche vacated by eradication of S. Gallinarum from domestic fowl. The hypothesis suggests that the epidemic increase in human S. Enteritidis cases in several geographic areas can be traced to the same origin, accounting for the simultaneous emergence of S. Enteritidis as a major egg-associated pathogen on three continents. A connection between the epidemics in Western Europe and the United States was not apparent from analysis of epidemic isolates. Although most human cases from England and Wales result from infection with S. Enteritidis phage type 4 (PT4), most cases in the United States are due to infections with PT8 and PT13a. The PT4 clone is genetically distinct from PT8 and 13a, as shown by IS200 profiling, ribotyping, and restriction length polymorphism of genomic DNA fragments separated by pulsed field gel electrophoresis. The reasons for the differing clonal isolates in the United States and Western Europe are unknown. S. Enteritidis was likely introduced into poultry flocks from its rodent reservoir. The geographic differences in predominant phage types may reflect the fact that at the time of introduction into poultry flocks, different S. Enteritidis strains were endemic in rodent populations in Europe and the United States. Subsequently, S. Enteritidis strains with the highest transmissibility may have become predominant in poultry flocks on each continent. An alternative explanation for the predominance of PT4 in England and Wales is its introduction into poultry breeding lines in the early 1980s, which may have accelerated the epidemic spread of PT4 in laying hens and resulted in its dominance in human isolates from England and Wales. However, factors responsible for the beginning of the S. Enteritidis epidemic should be considered separately from those important for its subsequent spread within the poultry industry. These factors were not specific to PT4 but rather allowed different phage types to emerge as egg-associated pathogens on different continents at the same time.
One such factor could be the eradication of S. Gallinarum from poultry, which would facilitate circulation of S. Enteritidis strains within this animal reservoir regardless of phage type. Experimental evidence indicates that immunization with one Salmonella serovar can generate cross-immunity against a second serovar if both organisms have the same immunodominant O-antigen on their cell surface. The immunodominant epitope of the lipopolysaccharide of S. Gallinarum and S. Enteritidis is the O9-antigen, a tyvelose residue of the O-antigen repeat. Immunization of chickens with S. Gallinarum protects against colonization with S. Enteritidis but not S. Typhimurium, a serovar expressing a different immunodominant determinant, the O4-antigen. Theory indicates that coexistence of S. Gallinarum and S. Enteritidis in an animal population prompts competition as a result of the shared immunodominant O9-antigen, which generates cross-immunity. Mathematical models predict that the most likely outcome of this competition between serovars is that the serovar with the higher transmission success will competitively exclude the other from the host population. S. Gallinarum may have generated populationwide immunity (flock immunity) against the O9-antigen at the beginning of the 20th century, thereby excluding S. Enteritidis strains from circulation in poultry flocks. This proposal is based on analysis of epidemiologic data from the United States, England, and Wales. To formally test this hypothesis, we analyzed epidemiologic data from Germany to determine whether the numbers of human S. Enteritidis cases are inversely related to those of S. Gallinarum cases reported in poultry. We used mathematical models to determine whether our hypothesis is consistent with theoretical considerations regarding transmissibility and flock immunity.
Salmonella Enteritidis emerged as a major egg-associated pathogen in the late 20th century. Epidemiologic data from England, Wales, and the United States indicate that S. Enteritidis filled the ecologic niche vacated by eradication of S. Gallinarum from poultry, leading to an epidemic increase in human infections. We tested this hypothesis by retrospective analysis of epidemiologic surveys in Germany and demonstrated that the number of human S. Enteritidis cases is inversely related to the prevalence of S. Gallinarum in poultry. Mathematical models combining epidemiology with population biology suggest that S. Gallinarum competitively excluded S. Enteritidis from poultry flocks early in the 20th century.
The avian-adapted serovar Salmonella Gallinarum, which includes two biovars, Gallinarum and Pullorum, was endemic in poultry flocks in Europe and the Americas in the early 20th century. To reduce economic losses to the poultry industry, national surveillance programs were established in the United States (National Poultry Improvement Plan, 1935) and England and Wales (Poultry Stock Improvement Plan, 1939). Since S. Gallinarum (antigen formula O9,12:-:-) has no animal reservoir other than domestic and aquatic fowl, the test-and-slaughter method of disease control under these surveillance programs led to its eradication from commercial poultry flocks in the United States, England, and Wales by the 1970s. At that time, the number of human cases of infection with serovar S. Enteritidis (antigen formula O9,12:g,m:1,7) began to increase in these countries. By the 1980s, S. Enteritidis had emerged as a major concern for food safety in Europe and the Americas; by 1990 it was the most frequently reported Salmonella serovar in the United States. Most S. Enteritidis outbreaks in Europe and the United States are associated with foods containing undercooked eggs. Eggs can become contaminated with S. Enteritidis through cracks in the shell after contact with chicken feces or by transovarian infection. Thus, laying hens were the likely source of the S. Enteritidis epidemic in Europe and the Americas.
The inverse relationship between the incidence of S. Gallinarum infection in chickens and egg-associated S. Enteritidis infections in humans prompted the hypothesis that S. Enteritidis filled the ecologic niche vacated by eradication of S. Gallinarum from domestic fowl. The hypothesis suggests that the epidemic increase in human S. Enteritidis cases in several geographic areas can be traced to the same origin, accounting for the simultaneous emergence of S. Enteritidis as a major egg-associated pathogen on three continents. A connection between the epidemics in Western Europe and the United States was not apparent from analysis of epidemic isolates. Although most human cases from England and Wales result from infection with S. Enteritidis phage type 4 (PT4), most cases in the United States are due to infections with PT8 and PT13a. The PT4 clone is genetically distinct from PT8 and 13a, as shown by IS200 profiling, ribotyping, and restriction length polymorphism of genomic DNA fragments separated by pulsed field gel electrophoresis. The reasons for the differing clonal isolates in the United States and Western Europe are unknown. S. Enteritidis was likely introduced into poultry flocks from its rodent reservoir. The geographic differences in predominant phage types may reflect the fact that at the time of introduction into poultry flocks, different S. Enteritidis strains were endemic in rodent populations in Europe and the United States. Subsequently, S. Enteritidis strains with the highest transmissibility may have become predominant in poultry flocks on each continent. An alternative explanation for the predominance of PT4 in England and Wales is its introduction into poultry breeding lines in the early 1980s, which may have accelerated the epidemic spread of PT4 in laying hens and resulted in its dominance in human isolates from England and Wales. However, factors responsible for the beginning of the S. Enteritidis epidemic should be considered separately from those important for its subsequent spread within the poultry industry. These factors were not specific to PT4 but rather allowed different phage types to emerge as egg-associated pathogens on different continents at the same time.
One such factor could be the eradication of S. Gallinarum from poultry, which would facilitate circulation of S. Enteritidis strains within this animal reservoir regardless of phage type. Experimental evidence indicates that immunization with one Salmonella serovar can generate cross-immunity against a second serovar if both organisms have the same immunodominant O-antigen on their cell surface. The immunodominant epitope of the lipopolysaccharide of S. Gallinarum and S. Enteritidis is the O9-antigen, a tyvelose residue of the O-antigen repeat. Immunization of chickens with S. Gallinarum protects against colonization with S. Enteritidis but not S. Typhimurium, a serovar expressing a different immunodominant determinant, the O4-antigen. Theory indicates that coexistence of S. Gallinarum and S. Enteritidis in an animal population prompts competition as a result of the shared immunodominant O9-antigen, which generates cross-immunity. Mathematical models predict that the most likely outcome of this competition between serovars is that the serovar with the higher transmission success will competitively exclude the other from the host population. S. Gallinarum may have generated populationwide immunity (flock immunity) against the O9-antigen at the beginning of the 20th century, thereby excluding S. Enteritidis strains from circulation in poultry flocks. This proposal is based on analysis of epidemiologic data from the United States, England, and Wales. To formally test this hypothesis, we analyzed epidemiologic data from Germany to determine whether the numbers of human S. Enteritidis cases are inversely related to those of S. Gallinarum cases reported in poultry. We used mathematical models to determine whether our hypothesis is consistent with theoretical considerations regarding transmissibility and flock immunity.
