Meta-analysis of probiotics for the prevention of traveler's diarrhea☆
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
References (51)
Diarrhoeagenic Escherichia coli—an emerging problem?
Diagn Microbiol Infect Dis
(2001)- et al.
Improving the quality of reports of meta-analyses of randomized controlled trials: the QUOROM statement. Quality of reporting of meta-analysis
Lancet
(1999) - et al.
Current methods of the US preventive services task force: a review of the process
Am J Prev Med
(2001) - et al.
Meta-analysis in clinical trials
Control Clin Trials
(1986) - et al.
Post-traveler's diarrhea irritable bowel syndrome: a prospective study
Am J Gastroenterol
(2003) - et al.
Update on traveler's diarrhea
Curr Infect Dis Rep
(2002) Occurrence and self-treatment of diarrhea in a large cohort of Americans traveling to developing countries
Am J Trop Med Hyg
(2000)- et al.
Traveler's diarrhea: epidemiology and impact on visitors to Fortaleza, Brazil
Rev Panam Salud Publica
(2002) - et al.
Drug prophylaxis for travelers’ diarrhea
Clin Infect Dis
(2002) Traveler's diarrhea
Am Fam Physician
(2005)
Rifaximin versus ciprofloxacin for the treatment of traveler's diarrhea: a randomized, double-blind clinical trial
Clin Infect Dis
Persistent traveler's diarrhea
Infect Med
Persistent diarrhea in travelers
Clin Infec Dis
Centers for Disease Control and Prevention C. Outbreaks of gastroenteritis associated with noroviruses on cruise ships-United States 2002
Morbidity and Mortality Weekly Report
Infectious diseases on cruise ships
Clin Infect Dis
Traveler's diarrhea at sea: three outbreaks of waterborne enterotoxigenic Escherichia coli on cruise ships
J Infect Dis
Chronic diarrhoeal illness in US Peace Corps volunteers
Int J Epidemiol
Diarrheal disease incidence and morbidity among United States military personnel during short-term missions overseas
Am J Trop Med Hyg
An observational clinic-based study of diarrheal illness in deployed United States military personnel in Thailand: presentation and outcome of Campylobacter infection
Am J Trop Med Hyg
Azithromycin found to be comparable to levofloxacin for the treatment of US travelers with acute diarrhea acquired in Mexico
Clin Infect Dis
A review of the evidence of health claims for biotherapeutic agents
Microb Ecol Health Dis
Normal flora: diversity and functions
Microb Ecol Health Dis
Properties of evidence-based probiotics for human health
Biotherapeutic agents for Clostridium difficile-associated disease
Cited by (0)
- ☆
This paper was presented at the 1st International Conference of the Journal of Travel Medicine and Infectious Diseases, London UK, November 10–11, 2005.