PerspectiveEpidemiology

Tracing the Origins of Salmonella Outbreaks

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Science  07 Jan 2000:
Vol. 287, Issue 5450, pp. 50-52
DOI: 10.1126/science.287.5450.50

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In the 1980s, health officials in Europe and the Americas noted a considerable increase in human food-borne illness [HN1] caused by Salmonella enteritidis[HN2], a pathogen found in chicken carcasses, eggs, and egg products (1). It has been suggested that the emergence of S. enteritidis as a public health problem may be the result of modern poultry farming practices and of a decline in the genetic diversity of domestic fowl (2). But this hypothesis does not explain why the number of humans infected with other Salmonella serotypes, such as S. typhimurium, has not increased (3, 4). For example, the incidence of human infection with S. enteritidis has steadily increased since the 1960s, whereas the incidence of S. typhimurium[HN3] infection has remained relatively constant (see figure, below). It has been proposed that the S. enteritidis epidemic could be caused by clonal expansion of a single, more virulent S. enteritidis isolate. However, the observation that human Salmonellacases in Europe and the United States are associated with different S. enteritidis isolates does not support this notion.

Secrets ofSalmonellaserotypes. Prevalence of Salmonellaserotypes in humans and poultry in the United States (A) and in England and Wales (B). Circles show the percentage (A) or incidence (B) of domestic poultry infected with S. pullorum (17, 18). Squares and diamonds show the numbers of human cases of food-borne illness caused by S. typhimurium or S. enteritidis, respectively (3, 8, 9, 19).

Through a retrospective analysis of epidemiological surveys, we now put forward the hypothesis that the epidemic of salmonellosis [HN4] in humans due to S. enteritidis was triggered by this Salmonella serotype filling the ecological niche vacated by the avian Salmonella pathogens S. pullorumand S. gallinarum [HN5]. Retrospective analysis revealed that S. enteritidis became established in poultry flocks in the 1960s, which coincided with the eradication of the avian Salmonella pathogens from domestic fowl. As these three pathogens share a common immunodominant surface antigen (O9) [HN6], we postulate that the flock immunity generated by the two avian Salmonella biotypes prevented S. enteritidis from circulating in poultry flocks in the first half of this century.

Records documenting the prevalence of Salmonella serotypes among poultry in Britain and North America date back to 1930. At this time, an illness called “bacillary white diarrhea” (pullorum disease), caused by S. pullorum, posed a serious economic threat to the poultry industry (5). A test tube agglutination assay revealed that 10 to 20% of chicks possessed high titers of antibody against S. pullorum (6). A National Poultry Improvement Plan [HN7], designed to reduce the level of S. pullorum infection in the United States, was adopted in 1935 and included large-scale voluntary testing of poultry flocks using a whole-blood test for agglutination of stained antigen. Similar S. pullorum control programs were implemented in some European countries. In 1954, the National Poultry Improvement Plan was revised to recognize fowl typhoid, an illness caused by S. gallinarum(5). As both biotypes belong to the same Salmonella (O9) serotype, blood testing for pullorum disease effectively lowered the incidence of fowl typhoid as seropositive birds were culled. Thus, by the mid-1970s, S. pullorum and S. gallinarum were eliminated from commercial poultry flocks in Britain and the United States (see figure, above).

In the early 1900s, human S. enteritidis infections were not associated with poultry, but rather with rodents, the only known animal reservoir for this pathogen (7). This situation changed in the second half of this century. The incidence of S. enteritidisinfection in the British population remained almost constant between 1949 and 1963, but the increased frequency of S. enteritidis infection of chickens (which began in 1967) resulted in a doubling of human cases reported in 1968 and 1969 and a continued increase thereafter (8, 9) (see figure, above). Similarly, the first 5-year report on human salmonellosis in the United States revealed that S. enteritidis increased in frequency from being the sixth most common causative serotype in 1963 to the third most common in 1967 (3). When these data are plotted on a linear scale, the beginning of the epidemic is not apparent because the exponential increase in S. enteritidis cases produces a sigmoid curve. However, logarithmic conversion of the data shows that the number of human cases has increased at an almost constant rate since the 1960s (see figure, above). Thus, it seems possible that the current S. enteritidis epidemic started in the late 1960s—much earlier than previously thought (1).

It is likely that S. enteritidis was initially introduced into poultry flocks through its rodent animal reservoir because mice and rats captured in hen-houses frequently carried this organism (10). But, as S. enteritidis was present in rodents when monitoring began in the 1930s (7), it is not obvious why it did not spread to domestic fowl until much later. An important event coinciding with the increase in human S. enteritidis cases in Britain and the United States in the 1960s, was the remarkable decline in domestic poultry that tested seropositive for S. pullorum. We suggest that the elimination of S. pullorum “reactors” may have increased the ability of S. enteritidis to gain a foothold in poultry flocks. The O antigen of S. enteritidis, S. pullorum, and S. gallinarum consists of the O12 antigen (a sugar backbone composed of O-polysaccharide repeating units) and the O9 antigen (a tyvelose sugar chain) (see figure, below). Chickens infected with S. gallinarumor S. pullorum develop O9 antibody titers that are >10-fold higher than O12 antibody titers (11), suggesting that the O9 antigen is immunodominant. Consistent with the induction of protective immunity by O9 antigen, vaccination with live S. gallinarum (O9,12) protects mice against subsequent challenge with S. enteritidis (O9,12) but not against challenge with virulent S. typhimurium (O4,5,12) (12). Furthermore, vaccination of mice with an S. enteritidis aroA mutant (O9,12) elicits protection against subsequent challenge with a virulent S. typhimurium strain genetically engineered to express the O9,12 antigen but not against wild-type S. typhimurium (O4,5,12) (13). Thus, cross-immunity is, at least in part, caused by an immune response directed against the immunodominant O9 antigen. We propose that seropositive S. pullorum poultry had increased immunity that protected them against infection with S. enteritidis; this could have reduced the transmission of this biotype by reducing the number of susceptible hosts (14). So, flock immunity against the O9 antigen generated by the avian Salmonellabiotypes could have prevented S. enteritidis from circulating in the avian host population. After elimination of seropositive birds from European and U.S. commercial poultry flocks in the 1960s, S. enteritidis would then have readily been able to circulate among domestic fowl. The increased incidence of salmonellosis in humans may have been caused by S. enteritidis filling the ecological niche vacated by eradication of the avian pathogens. The number of S. typhimurium cases, on the other hand, would not be expected to increase because this serotype lacks the O9 antigen and therefore would be unaffected by this elimination [HN8].

Sugary coat of an evil pathogen. Chemical composition of the O antigen of different Salmonella serotypes. (A) The O antigen of S. enteritidis, S. gallinarum, and S. pullorum consists of an O12 backbone of sugar repeats and O9 (a tyvelose branching sugar). (B) The O antigen of S. typhimurium has the same O12 backbone but different (O4,5) branching sugar chains.

Although S. enteritidis possesses the O9 antigen, its establishment in poultry flocks was not detected or prevented by S. pullorum surveillance programs. Because S. enteritidis colonizes chickens without causing overt signs of disease (and hence without eliciting high anti-O9 titers), it escapes detection by the relatively insensitive whole-blood agglutination test (15). The lack of simple and inexpensive methods for detecting S. enteritidis in poultry has been a major impediment to implementing effective control measures (16). However, even with a good test in place, it is unlikely that the current epidemic could be controlled, because unlike avian Salmonella pathogens, S. enteritidis has a rodent animal reservoir. Therefore, culling infected birds, which proved so successful during the eradication of S. gallinarum and S. pullorum, has a much smaller chance of success in reducing the incidence of S. enteritidis in poultry. Instead, a more effective strategy might be to reestablish flock immunity through vaccination.

HyperNotes Related Resources on the World Wide Web

General Hypernotes

The Biology Links Internet resource guide is maintained by the Department of Molecular and Cellular Biology, Harvard University.

The WWW Virtual Library: Microbiology and Virology is provided by the Microbiology Network.

The WWW Virtual Library of Epidemiology is maintained by the Department of Epidemiology and Biostatistics at the University of California, San Francisco.

The library of the Karolinska Institutet, Stockholm, Sweden, provides a collection of links to biomedical information on the Web; a section on epidemiology and biostatistics is included.

BMJ (British Medical Journal) presents Epidemiology for the Uninitiated by D. Coggon, G. Rose, and D. Barker.

Lecture notes by J.-D. Wang titled “Basic principles and practical applications of epidemiologic research” are made available on the Web site of the World Health Organization's course on health, environment, and sustainable development.

R. LaPorte, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, provides lecture notes and Web links for a course titled “Epidemiology, the Internet, and global health.”

P. Bugl, Department of Mathematics, University of Hartford, CT, presents lecture notes on epidemiology for a course on epidemics and AIDS.

The “Bad Bug Book” provided by the Center for Food Safety and Applied Nutrition of the U.S. Food and Drug Administration provides an information page about Salmonella.

Medical Microbiology, an online textbook edited by S. Baron, Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, has a chapter on Salmonella by R. Giannella. The chapter by S. Gorbach on the microbiology of the gastrointestinal tract discusses Salmonella food poisoning.

The Division of Bacterial and Mycotic Diseases of the U.S. Centers for Disease Control and Prevention (CDC) offers information about salmonellosis and Salmonella enteritidis infection. The CDC Prevention Guidelines Database includes links to articles and reports about Salmonella infections.

The UK Public Health Laboratory Service information page on Salmonella infections.

The UK Institute for Animal Health offers a presentation about possible solutions to the problem of Salmonella food poisoning and reports on its current and previous research on Salmonella .

The United States Animal Health Association (USAHA) provides the 1999 Report of the Committee on Salmonella; links to previous Salmonella reports are included. The proceedings of the 1998 USAHA annual meeting included a paper by A. Sneed titled “The impact of Salmonella enteritidis on public health and environmental quality.”

The 20 July 1998 issue of The Scientist had an article by S. Hoffert titled “Researchers take strides against Salmonella .”

Numbered Hypernotes

1. The World Health Organization issued a press release on 13 August 1997 titled “Foodborne diseases: Possibly 350 times more frequent than reported.” The September-October 1999 issue of Emerging Infectious Diseases, a journal from the CDC's National Center for Infectious Diseases, had an article by Paul S. Mead et al . titled “Food-related illness and death in the United States”; the October-December 1997 issue was a special issue on food-borne disease and had an article by R. Tauxe “Emerging foodborne diseases: An evolving public health challenge.” R. Hurlbert, Washington State University, provides lecture notes on food borne diseases in the food microbiology section of his Web microbiology course. The 25 May 1996 issue of Science News had an article by J. Raloff titled “Tracking and tackling foodborne germs”; the 27 July 1996 issue had a “Food for Thought” column by Raloff titled “Lessons from a case of toxic ice cream”; and the 20 November 1999 issue had a column titled “Sickening food.” The 24 November 1997 issue of U.S. News had an article by A. Spake titled “O is for outbreak” about food-borne illness.

2. Microbionet, presented by the Sciencenet Multimedia Publishing House, Victoria, Australia, provides a profile of Salmonella. J. Lindquist, Department of Bacteriology, University of Wisconsin, presents an overview of Salmonella and Salmonella nomenclature for a laboratory course on bacteriology and food science. Lecture notes on Salmonella by J. Clements are included on the Microbiology Lecture Pages presented by the Tulane University Medical School. D. Fix, Department of Microbiology, Southern Illinois University, provides an introduction to Salmonella for a medical microbiology course. The Food Safety and Inspection Service of the U.S. Department of Agriculture (USDA) provides information on the Salmonella serotypes isolated from raw meat and poultry from 26 January 1998 to 25 January 1999; the report “HACCP implementation: First year Salmonella test results” is also available.

3. The Microbial Genomics resource page from the National Center for Genome Resources provides information about Salmonellatyphimurium. The World Health Organization presents a fact sheet titled “Multi-drug resistant Salmonella typhimurium .” The USDA Food Safety and Inspection Service presents a report on Salmonella typhimurium DT104 The USDA Animal and Plant Health Inspection Service provides an article by D. Dargatz et al . titled “The veterinarian's role in diagnosis, treatment, and prevention of multidrug resistant Salmonella typhimurium .” The UK Institute of Food Science and Technology offers a report on Salmonella typhimurium DT 104.

4. Britannica.com offers Encyclopædia Britannica articles on salmonellosis and Salmonella. The 14 July 1998 issue of the Canadian Medical Association Journal had an article by P. Buck and D. Werker titled “Salmonellosis: No longer just a chicken and egg story.” The Manual of Standards for Diagnostic Tests and Vaccines, provided online by the Office International des …pizooties, Paris, includes a chapter on salmonellosis. The Merck Manual of Diagnosis and Therapy includes a section on Salmonella infections in the chapter on Enterobacteriaceae infections. The Food Safety Briefing Room Web page of the USDA Economic Research Service provides a graph of reported cases of salmonellosis in the U.S., 1967-1996. The collection of science education articles provided by the Department of Bacteriology, University of Wisconsin, Madison, includes an article titled “The resurgence of Salmonella ” by L. Garcia The GI Focus - Clinical Updates Web page from the American College of Gastroenterology presents a summary of the epidemiology of Salmonella enteritidis infections in the United States. The SafeFood Rapid Response Network of the Colorado State University Cooperative Extension provides a background article about outbreaks of Salmonella enteritidis infection associated with consumption of raw eggs.

5. Surface antigens of Salmonella are discussed in lecture notes on bacterial endotoxins by K. Todar, Department of Bacteriology, University of Wisconsin. S. Hammonds, Department of Life Sciences, Nottingham Trent University, UK, discusses Salmonella antigens in lecture notes on sub-specific typing of bacteria for a medical microbiology course.

6. The Foreign Animal Diseases resource guide from the Emergency Preparedness Information Exchange at the Centre for Policy Research on Science and Technology, Simon Fraser University, offers information about pullorum disease (Salmonella pullorum) and fowl typhoid (Salmonella gallinarum). The Manual of Standards for Diagnostic Tests and Vaccines contains a section on pullorum disease and fowl typhoid. The Poultry Science Home Page at the College of Agriculture and Life Sciences, Mississippi State University, provides information about pullorum disease and fowl typhoid in a presentation on bacterial diseases in poultry. The Handbook on Poultry Diseases, provided by the American Soybean Association, includes information on pullorum disease and fowl typhoid. A Manual on Poultry Diseases from the Department of Poultry Science, Texas A&M University, has a section on pullorum and fowl typhoid. The USDA Agricultural Research Service issued a news release on 25 February 1999 about research on Salmonella pullorum titled “Hot on the tail of poultry killer.”

7. A brief history of the eradication of pullorum disease in the U.S. is included in the Web page of the National Poultry Improvement Plan, provided by the USDA Animal and Plant Health Inspection Service. A history of the United States Animal Health Association titled Animal Health: A Century of Progress by N. Black includes a discussion of pullorum disease eradication in the chapter on poultry diseases.

8. Access Excellence offers a science update article by S. Henahan titled “Salmonella vaccine.” The November 1999 issue of Applied and Environmental Microbiology had an article by M. Pascual et al . titled “Lactobacillus salivarius CTC2197 prevents Salmonella enteritidis colonization in chickens.”

9. A. J. Bäumler is in the Department of Medical Microbiology and Immunology, College of Medicine, Texas A&M University.

10. B. M. Hargis and R. M. Tsolis are in the Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University.

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