Meta-analysis of probiotics for the prevention of traveler's diarrhea

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Summary

Background

Traveler's diarrhea (TD) is a common health complaint among travelers. Rates of TD can range from 5% to 50%, depending on the destination. The use of probiotics for this disease remains controversial. The objective of this study was to compare the efficacy of probiotics for the prevention of TD based on published randomized, controlled clinical trials.

Methods

PubMed, Google Scholar, metaRegister, NIH registry of clinical trials and Cochrane Central Register of Controlled Trials were searched from 1977 to 2005, unrestricted by language. Secondary searches of reference lists, authors, reviews, commentaries, associated diseases, books and meeting abstracts. Inclusion criteria included: randomization, controlled, blinded, efficacy trials, in humans, peer-reviewed journals. Exclusion criteria were: pre-clinical, safety, phase 1 studies in volunteers, reviews, duplicate reports, trials of unspecified probiotics, trials of prebiotics, and inconsistent outcome measures.

Results

Twelve of 940 screened studies met the inclusion and exclusion criteria. The pooled relative risk indicates that probiotics significantly prevent TD (RR=0.85, 95% CI 0.79,0.91, p<0.001).

Conclusion

Several probiotics (Saccharomyces boulardii and a mixture of Lactobacillus acidophilus and Bifidobacterium bifidum) had significant efficacy. No serious adverse reactions were reported in the 12 trials. Probiotics may offer a safe and effective method to prevent TD.

Introduction

TD is a common health problem among travelers. Every year 12 million cases of TD are reported.1 Rates for TD vary from areas of high incidence (over 50%) such as to northern Africa, Latin America, the Middle East and Southeast Asia to areas of low incidence (5–10%) such as North America, northern Europe, Australia, New Zealand and the United Kingdom.2, 3, 4, 5 However, it is worth noting that TD can strike even “presumed safe” destinations.

TD is acquired by ingestion of fecally contaminated food, water or other liquids. High-risk foods include raw or undercooked meats and seafood, unpeeled raw fruits and vegetables. Tap water, ice, non-pasteurized milk and other diary products also can be of high risk. The riskiest sources of contaminated food are street vendors, farmers markets and small restaurants.6

The incubation period (time from exposure to the contaminated food or liquid to the beginning of symptoms) usually is 2–3 days. The major symptom is diarrhea (4–6 loose, watery or bloody bowel movements/d). The duration of TD usually is 2–6 days, if untreated. Other common symptoms are abdominal cramps and nausea. Vomiting and fever are less common.3, 7 In up to 15% of cases, diarrhea may be prolonged (1 week to 1 month or, rarely, up to one year) and may be associated with repeated bouts of abdominal cramping, malaise, nausea, fever or muscle pain. Traveler's diarrhea may be especially hazardous for children due to severe dehydration and in people who are frail or immunocompromised.6, 8, 9 Other complications of TD include changes in travel plans (35% of 784 surveyed tourists), economic losses to the traveling public (cancelled trips, delays, changed tickets), and economic losses to the host country and its tourist-related industries.2

TD usually is experienced by individual travelers, but outbreaks of TD involving large groups of people also occur. Most at risk are groups visiting developing countries, passengers on cruise ships, Peace Corps or other voluntary health teams.6, 10, 11, 12, 13 Traveler's diarrhea was found to be the common prevalent non-combat medical condition (29%) in military troops on short-term missions.14, 15

Most (80–85%) cases of TD are due to bacterial pathogens (Enterotoxigenic Escherichia coli, Enteroaggregative E. coli, Campylobacter jejuni, Shigella species, Salmonella species, Vibrio parahemolyticus, Plesiomonas shigelloides, Aeromonas hydrophila, Yersinia enterocolitica, Vibrio cholerae). The most common cause of bacterial TD is one of the seven types of diarrheagenic E. coli.16, 17 Other less frequent causes of TD are viruses (Norwalk or Rotavirus) and parasites (Entamoeba histolytica, Giardia lamblia, Cyclospora, Cryptosporidium). Sometimes the cause cannot be determined.

The best strategy to prevent TD is education and avoiding contaminated foods and liquids. As easy as this sounds, most tourists do not follow these guidelines.3 Their focus usually is on their vacation and not food safety. Tourists often engage in riskier behaviors at exotic destinations than at home.

Traditional medications taken to prevent TD include bismuth subsalicylate and prophylactic antibiotics. Bismuth subsalicylate (the active ingredient in Pepto-Bismol) is best when taken with food four times daily. Prolonged use over 3 weeks is not recommended and this medication cannot be taken by everyone. Bismuth subsalicylate frequently is not effective as a preventive agent because of non-compliance. To be effective, travelers must ingest 6–8 tablets/d and many fail to do so. Prophylactic antibiotics are also not recommended for TD as the etiologies of TD varies widely and the concern over antibiotic resistance by overuse of antibiotics overweighs the potential benefits.6

One of the most promising is the use of probiotics for the prevention of various types of diarrhea.18 Use of probiotic microorganisms lowers dependence on antibiotics, is relatively inexpensive and is well tolerated, even for prolonged use.

One of the reasons tourists become susceptible to illness is travel can disrupt the body's normal defense mechanisms against infections. Stress, jet lag, unfamiliar foods and water and disrupted body rhythms can disturb the normally protective bacteria in the intestines. These protective bacteria usually fight off disease-causing bacteria and viruses by “colonization resistance.” Colonization resistance is a barrier effect that prevents attachment and colonization by harmful microorganisms.19 Probiotics are a promising therapeutic strategy for diseases that involve a disruption of normal microflora as they act by inhibiting pathogen attachment, enhancing the immune response and assisting in re-establishing normal microflora.20

Section snippets

Objective

The objective of this meta-analysis is to assess the efficacy and safety of probiotics for the prevention of TD.

Criteria for study selection

Abstracts of all citations and retrieved studies were reviewed and rated for inclusion. Full articles were retrieved if specific treatments were given to either prevent or treat the disease of interest. Inclusion criteria include: randomized, controlled, blinded efficacy trials in humans published in peer-reviewed journals. Exclusion criteria include: pre-clinical studies, safety

Overview of included studies

The literature search yielded 940 citations on probiotics, of which 37 relating to TD were selected from retrieval. Twelve (32%) probiotic treatments from seven of the 37 screened articles met inclusion criteria and provided data on 4709 enrolled subjects (Table 1).31, 32, 33, 34, 35, 36, 37 The number of patients in each of these studies was generally large (median, 310; range 50–832 subjects).

Excluded studies

Of the TD studies, 25 failed to meet one or more of the inclusion criteria. Most were reviews or

Discussion

This meta-analysis found probiotics are safe and effective for the prevention of TD. The pooled risk estimate found that 85% of TD cases were prevented by probiotics. The main advantage of probiotic therapy for this type of disease that is mediated through changes in intestinal microflora in response to exposures incurred during travel is that they are therapeutically active but they do not disrupt the re-establishment of the protective normal microbial flora.

An important consideration when

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    This paper was presented at the 1st International Conference of the Journal of Travel Medicine and Infectious Diseases, London UK, November 10–11, 2005.

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