Correspondence

Lactobacilli to Prevent Traveler's Diarrhea?

N Engl J Med 1995; 333:1360-1361November 16, 1995

Article

To the Editor:

Acute diarrhea is the most common illness in travelers to high-risk areas, with up to half of those engaged in short-term travel affected.1 Although most episodes are mild and self-limiting, there is considerable morbidity and disruption to travel. Effective prophylaxis against traveler's diarrhea is therefore desirable. Antibiotics are efficacious but are not recommended for widespread use.1,2 The efficacy of nonpathogenic bacteria such as lactobacilli has been reported, although confirmatory data are lacking.3 Such bacteria may interfere with the colonization and invasion of the gut by enteropathogenic bacteria, as has been demonstrated in vitro.4 We therefore conducted a randomized, double-blind, placebo-controlled trial of two species of lactobacilli as prophylaxis against traveler's diarrhea.

British soldiers deployed to Belize were randomly assigned to receive two capsules containing Lactobacillus fermentum strain KLD (LF-KLD), L. acidophilus (LA), or placebo daily for three weeks or until diarrhea occurred. There were 10¹¹ colony-forming units of bacteria in each capsule of lactobacilli. LF-KLD, which is isolated from humans, has shown adhesion to human intestine, inhibition of intestinal pathogens, resistance to the toxic effects of bile acid, and survival at low pH in vitro (Department of General and Marine Microbiology, University of Göteborg, Göteborg, Sweden: unpublished data). Prophylaxis began the day before the soldiers' departure, and episodes of diarrhea were recorded for up to four weeks after their arrival. Diarrhea was defined as the passage of three or more unformed stools in a 24-hour period or any number of loose stools in association with blood, fever, abdominal pain, or vomiting.2 Compliance was assessed in all subjects by interviews and capsule counts. Each subject gave informed consent, and ethical approval was obtained from the Army Medical Research Executive.

Among 282 subjects who could be evaluated, the incidence of diarrhea was 24.5 percent after three weeks and 27.7 percent after four weeks. There were no significant differences in the incidence of diarrheal episodes between any groups after three weeks of prophylaxis (incidence with LF-KLD, 23.8 percent among 80 subjects; with LA, 25.7 percent among 101 subjects; with placebo, 23.8 percent among 101 subjects) or one week after the cessation of prophylaxis (LF-KLD, 25.0 percent; LA, 29.7 percent; placebo, 27.7 percent). Among the 214 subjects with better than 90 percent compliance, the attack rate of diarrhea was lower (15.4 percent) than it was among the 68 subjects with poorer compliance (52.9 percent, P<0.001) but the rate did not differ between groups at three weeks (LF-KLD, 16.1 percent among 62 subjects; LA, 15.5 percent among 71 subjects; placebo, 14.8 percent among 81 subjects), suggesting that good compliance was associated with other risk-minimizing behavior. No adverse effects of prophylaxis were reported. The viability of the encapsulated lactobacilli at the end of the trial was confirmed by culture. No protection from traveler's diarrhea was evident with either species of lactobacilli in this location. The concept of protection from traveler's diarrhea mediated by nonpathogenic bacteria remains appealing, but it is not supported by this study.

Peter H. Katelaris, M.D.
Concord Hospital, Sydney 2139, Australia

Imroz Salam, M.B., B.S.
Michael J.G. Farthing, M.D.
St. Bartholomew's Hospital, London EC1M 6BQ, United Kingdom

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