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Oral Vaccine Effective Against Severe Travelers' Diarrhea


 

WASHINGTON — An experimental oral vaccine appears safe and effective in reducing the incidence and severity of travelers' diarrhea in adults, A. Louis Bourgeois, Ph.D., reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

Travelers' diarrhea (TD) occurs in more than 30% of people who travel to developing countries. The new vaccine, under development by Sweden-based SBL Vaccines, is designed to protect against both the colonization factors and the two toxins produced by enterotoxigenic Escherichia coli (ETEC), which is responsible for 20%–50% of all TD cases and is also a common cause of morbidity and mortality among children who live in the developing world, said Dr. Bourgeois of Johns Hopkins University, Baltimore.

A total of 1,406 healthy volunteers aged 18 years and older—most of whom were going to study Spanish in either Guatemala or Mexico—were randomly assigned to receive either the oral vaccine or placebo.

Two doses were administered 2 weeks apart by the subject at home, with the second dose taken about 1 week prior to travel. The subjects kept symptom diary cards prior to and during the 2–4 weeks of travel and provided stool samples during twice weekly office visits at the travel site.

Overall, the vaccine did not prevent TD (defined as five or more watery stools plus gastrointestinal symptoms) caused by ETEC that contained only a vaccine antigen; 1.1% of 705 vaccine recipients were affected, versus 0.71% of the 701 placebo subjects. There was a trend toward prevention of cases in which the subject had three or more watery stools per 24 hours plus moderate to severe symptoms that caused a change in daily activity (0.57% vs. 1.43%), although this did not quite reach statistical significance.

However, a major difference in TD rates was seen between the subjects with and without vaccine “takes,” defined as a serum IgA antibody titer of 1,358 or greater to the B-subunit of the cholera enterotoxin component of the vaccine.

Compared with the placebo group, the vaccine recipients who had “takes” had 63% vaccine efficacy against ETEC TD with any degree of gastrointestinal symptoms, 84% efficacy against ETEC TD with GI symptoms plus a change in daily activity, and 100% efficacy against ETEC TD with moderate to severe GI symptoms plus a change in activity. Severity of ETEC illness in vaccine “takes” was reduced, compared with placebo recipients, even when the ETEC strain did not match with the vaccine, Dr. Bourgeois noted.

Future formulations of this vaccine will need to produce better immunity, but “clearly this is a concept that deserves further evaluation,” he said.

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