Etiology of Acute Diarrhea among United States Military Personnel Deployed to South America and West Africa

Bourgeois, A. Louis; Gardiner, C. H.; Thornton, Scott A.; Batchelor, Roger A.; Burr, Donald H.; Escamilla, Joel; Echeverria, Peter; Blacklow, Neil R.; Herrmann, John E.; Hyams, Kenneth C.

doi:10.4269/ajtmh.1993.48.243

Cited by 50 publications

(23 citation statements)

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“…Infections caused by this heterogeneous group of pathogens remain major causes of diarrheal morbidity and infant mortality in developing countries (11,33,61), are perennially associated with disease in travelers (4,7,43) and in soldiers deployed to developing countries (8,32), and have recently been associated with large outbreaks in developed countries, including the United States (1,13).…”

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confidence: 99%

Importance of Heat-Labile Enterotoxin in Colonization of the Adult Mouse Small Intestine by Human EnterotoxigenicEscherichia coliStrains

Allen¹,

Randolph²,

2006

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Enterotoxigenic Escherichia coli (ETEC) infections are a significant cause of diarrheal disease and infant mortality in developing countries. Studies of ETEC pathogenesis relevant to vaccine development have been greatly hampered by the lack of a suitable small-animal model of infection with human ETEC strains. Here, we demonstrate that adult immunocompetent outbred mice can be effectively colonized with the prototypical human ETEC H10407 strain (colonization factor antigen I; heat-labile and heat-stable enterotoxin positive) and that production of heat-labile holotoxin provides a significant advantage in colonization of the small intestine in this model.Enterotoxigenic Escherichia coli (ETEC) infections are a significant cause of diarrheal disease worldwide. Infections caused by this heterogeneous group of pathogens remain major causes of diarrheal morbidity and infant mortality in developing countries (11,33,61), are perennially associated with disease in travelers (4, 7, 43) and in soldiers deployed to developing countries (8, 32), and have recently been associated with large outbreaks in developed countries, including the United States (1, 13).In the presently accepted paradigm for ETEC pathogenesis, fimbrial (or fibrillar) colonization factors (CFs) (10,22,27) mediate colonization of the small intestine, where organisms elaborate heat-labile enterotoxin (LT) and/or heat-stable enterotoxin (ST) (21, 68). Vaccine development has largely focused on the CFs; however, development of a broadly protective ETEC vaccine has been hampered due to the considerable heterogeneity of the known CFs (6,52,58,62).While a number of other surface antigens of ETEC have been described (20,25,51), their utility as potential vaccine candidates has not been effectively explored, largely due to the lack of a suitable animal model for testing. Animal models that have been used in previous studies of ETEC include infant (3, 16-18, 28, 47) and adult (9) mice, rats (34, 35), and rabbits (19,46,51). All of these models have inherent difficulties in utilization or require anesthesia and/or significant surgical manipulation. Some of the models have not been thoroughly evaluated.We sought to develop a murine model of small-intestinal colonization with human ETEC isolates using adult immunocompetent mice. Here, we report our initial use of this model using the prototypical human ETEC H10407 strain. Furthermore, similar to recent studies of porcine ETEC infection of gnotobiotic piglets (2), we demonstrate that elaboration of the heat-labile toxin provides a distinct advantage to the organism in establishing early colonization of the small-intestinal mucosa.

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Importance of Heat-Labile Enterotoxin in Colonization of the Adult Mouse Small Intestine by Human EnterotoxigenicEscherichia coliStrains

Allen¹,

Randolph²,

2006

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“…Collectively, these organisms are thought to account for hundreds of millions of cases of diarrheal illness and as many as 500,000 deaths annually in young children (43). Perennially the most common causes of diarrheal illness in travelers (27,38) and soldiers deployed to developing countries (7,25), ETEC strain have also emerged in several recent large-scale outbreaks in the United States (2,13).…”

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The EtpA Exoprotein of Enterotoxigenic Escherichia coli Promotes Intestinal Colonization and Is a Protective Antigen in an Experimental Model of Murine Infection

Roy

Hamilton²,

Allen³

et al. 2008

Infect Immun

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The enterotoxigenic Escherichia coli (ETEC) strains are major causes of morbidity and mortality due to diarrheal illness in developing countries. At present, there is no broadly protective vaccine for this diverse group of pathogens. The EtpA protein, identified in ETEC H10407 in a recent search for candidate immunogens, is a large glycosylated exoprotein secreted via two-partner secretion (TPS). Similar to structurally related molecules, EtpA functions in vitro as an adhesin. The studies reported here use a recently developed murine model of ETEC intestinal colonization to examine the immunogenicity and protective efficacy of EtpA. We report that mice repeatedly exposed to ETEC are protected from subsequent colonization and that they mount immune responses to both EtpA and its presumed two-partner secretion transporter (EtpB) during the course of experimental infection. Furthermore, isogenic etpA deletion mutants were impaired in the colonization of mice, and intranasal immunization of mice with recombinant EtpA conferred protection against ETEC H10407 in this model. Together, these data suggest that EtpA is required for optimal colonization of the intestine, findings paralleling those of previous in vitro studies demonstrating its role in adherence. EtpA and other TPS proteins may be viable targets for ETEC vaccine development.

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“…Ciprofloxacin generally diminished or stopped symptoms and shedding by the second day of antibiotic treatment, but four subjects shed for one to four additional days. The immune responses to colonization factors CS6 and colonization factor antigen I (CFA/I) and to heat-labile toxin ( Enterotoxigenic Escherichia coli (ETEC)-induced diarrhea is recognized frequently in individuals who travel in developing countries around the world (4,7,8,26,29,47) and is a major medical problem for military personnel deployed in these countries (26,44,45). Since strict personal hygiene and avoidance of local water and fresh and undercooked foods are recommendations with which travelers have difficulty complying, other means to reduce the ETEC attack rate must be considered.…”

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Immune Response, Ciprofloxacin Activity, and Gender Differences after Human Experimental Challenge by Two Strains of Enterotoxigenic Escherichia coli

et al. 2007

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In order to test vaccines against enterotoxigenic Escherichia coli (ETEC)-10 CFU B7A or either dose of H10407. B7A had a shorter incubation period than H10407 (P ‫؍‬ 0.001) and caused milder illness; the mean diarrheal output after H10407 challenge was nearly twice that after B7A challenge (P ‫؍‬ 0.01). Females had more abdominal complaints, and males had a higher incidence of fever. Ciprofloxacin generally diminished or stopped symptoms and shedding by the second day of antibiotic treatment, but four subjects shed for one to four additional days. The immune responses to colonization factors CS6 and colonization factor antigen I (CFA/I) and to heat-labile toxin ( Enterotoxigenic Escherichia coli (ETEC)-induced diarrhea is recognized frequently in individuals who travel in developing countries around the world (4,7,8,26,29,47) and is a major medical problem for military personnel deployed in these countries (26,44,45). Since strict personal hygiene and avoidance of local water and fresh and undercooked foods are recommendations with which travelers have difficulty complying, other means to reduce the ETEC attack rate must be considered. The use of short-term chemoprophylaxis and self-treatment for diarrhea are effective for travelers who are unwilling to accept even a short period of illness because of the serious impact it would have on their overall mission. However, the routine use of antimicrobial prophylaxis for the general traveler is not recommended because of the potential for associated adverse drug reactions and the potential to worsen the problem of antibiotic resistance of enteric bacteria (8,25,29,43,47). These factors make development of vaccines against ETEC a priority.

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Etiology of Acute Diarrhea among United States Military Personnel Deployed to South America and West Africa

Cited by 50 publications

References 0 publications

Importance of Heat-Labile Enterotoxin in Colonization of the Adult Mouse Small Intestine by Human EnterotoxigenicEscherichia coliStrains

Importance of Heat-Labile Enterotoxin in Colonization of the Adult Mouse Small Intestine by Human EnterotoxigenicEscherichia coliStrains

The EtpA Exoprotein of Enterotoxigenic Escherichia coli Promotes Intestinal Colonization and Is a Protective Antigen in an Experimental Model of Murine Infection

Immune Response, Ciprofloxacin Activity, and Gender Differences after Human Experimental Challenge by Two Strains of Enterotoxigenic Escherichia coli

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