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

Abstract

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.

Refinement of a Human Challenge Model for Evaluation of Enterotoxigenic Escherichia coli Vaccines

“…Though the mean purging was not as severe as is seen with volunteers challenged with V. cholerae (27), nevertheless, about 20% were given intravenous fluids and 60% were given early antibiotics. In contrast to previous studies using a higher dose, in which the mean incubation periods were typically 25 to 43 h (5,19), the incubation period observed in this study was somewhat longer, generally exceeding 48 h. An extended incubation suggests that the lower-dose inoculum requires more time to colonize the small intestine and reach the high concentrations of bacteria sufficient to cause symptoms. Even though the time to symptom onset was longer in this study, postchallenge ETEC H10407 shedding by naïve subjects was similar in frequency and magnitude to observations in higher-dose challenge studies (3,17,18).…”

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

“…We are intrigued by the observation that H10407 (CFAI LT ϩ ST ϩ ), originally isolated from a Bangladeshi child with severe cholera-like diarrheal illness (18), appears to be significantly more virulent than strain B7A (CS6 LT ϩ ST ϩ ), which lacks etpA and other candidate virulence loci (19,20,34). In human clinical challenge studies of these two organisms, the volume of diarrhea in volunteers that ingested H10407 was nearly twofold that of those who were infected with the same dose of B7A (11). Additional studies that define virulence traits associated with organisms capable of causing more severe illness would be of potential importance in the development of vaccines for deployment to developing countries, where deaths occur after rapid dehydration from voluminous ETEC-induced diarrhea.…”

A Commensal Gone Bad: Complete Genome Sequence of the Prototypical Enterotoxigenic Escherichia coli Strain H10407

“…The ETEC O78:H11:K80 strain H10407 was isolated from an adult with cholera-like symptoms in the course of an epidemiologic study in Dacca, Bangladesh, prior to 1973 (19) and was shown to cause diarrhea in adult volunteers (6,17). The E. coli H10407 isolate that was sequenced was from the Walter Reed Army Institute of Research (WRAIR) cGMP stock manufactured in February 1998 as lot 0519.…”