Applied Evidence

Travelers' diarrhea: Prevention, treatment, and post-trip evaluation

J Fam Pract. 2013 July;62(7):356-361

References

1. Hill DR. Occurrence and self-treatment of diarrhea in a large cohort of Americans traveling to developing countries. Am J Trop Med Hyg. 2000;62:585–589.

2. Greenwood Z, Black J, Weld L, et al. for the GeoSentinel Surveillance Network. Gastrointestinal infection among international travelers globally. J Travel Med. 2008;15:221–228.

3. DuPont HL. Systematic review: the epidemiology and clinical features of travellers’ diarrhoea. Aliment Pharmacol Ther. 2009;30:187–196.

4. Steffen R, Tornieporth N, Clemens SA, et al. Epidemiology of travelers’ diarrhea: details of a global survey. J Travel Med. 2004;11:231–237.

5. de la Cabada Bauche J, DuPont HL. New developments in traveler’s diarrhea. Gastroenterol Hepatol. 2011;7:88–95.

6. Cabada MM, White AC. Travelers’ diarrhea: an update on susceptibility, prevention, and treatment. Curr Gastroenterol Rep. 2008;10:473–479.

7. Ericsson CD. Travellers with pre-existing medical conditions. Int J Antimicrob Agents. 2003;21:181–188.

8. Cabada MM, Maldonado F, Quispe W, et al. Risk factors associated with diarrhea among international visitors to Cuzco, Peru. Am J Trop Med Hyg. 2006;75:968–972.

9. Mackell S. Traveler’s diarrhea in the pediatric population: etiology and impact. Clin Infect Dis. 2005;41(suppl 8):S547–S552.

10. Hill DR, Ericsson CD, Pearson RD, et al. The practice of travel medicine: guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1499–1539.

11. Connor BA. Travelers’ diarrhea. Available at:http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-2-the-pre-travel-consultation/travelers-diarrhea.htm. Accessed August 20, 2012.

12. Advice for travelers. Treat Guidel Med Lett. 2012;10:45–56.

13. Shlim DR. Looking for evidence that personal hygiene precautions prevent travelers’ diarrhea. Clin Infect Dis. 2005;41(suppl 8):S531–S535.

14. Laverone E, Boccalini S, Bechini A, et al. Travelers’ compliance to prophylactic measures and behavior during stay abroad: results of a retrospective study of subjects returning to a travel medicine center in Italy. J Travel Med. 2006;13:338–344.

15. Ashley DV, Walters C, Dockery-Brown C, et al. Interventions to prevent and control food-borne diseases associated with a reduction in traveler’s diarrhea in tourists to Jamaica. J Travel Med. 2004;11:364–367.

16. Shah N, DuPont HL, Ramsey DJ. Global etiology of travelers’ diarrhea: systematic review from 1973 to the present. Am J Trop Med Hyg. 2009;80:609–614.

17. Riddle MS, Sanders JW, Putnam SD, et al. Incidence, etiology, and impact of diarrhea among long-term travelers (US military and similar populations): a systematic review. Am J Trop Med Hyg. 2006;74:891–900.

18. Koo HL, Ajami NJ, Jiang ZD, et al. Noroviruses as a cause of diarrhea in travelers to Guatemala, India, and Mexico. J Clin Microbiol. 2010;48:1673–1676.

19. Hill DR, Ryan ET. Management of travellers’ diarrhoea. BMJ. 2008;337:863–867.

20. Rendi-Wagner P, Kollaritsch H. Drug prophylaxis for travelers’ diarrhea. Clin Infect Dis. 2002;34:628–633.

21. Pimentel M, Riddle MS. Prevention of traveler’s diarrhea: a call to reconvene. Clin Infect Dis. 2008;46:151–152.

22. DuPont HL. Systematic review: prevention of travellers’ diarrhoea. Aliment Pharmacol Ther. 2008;27:741–751.

23. Wang M, Szucs TD, Steffen R. Economic aspects of travelers’ diarrhea. J Travel Med. 2008;15:110–118.

24. Neal KR, Barker L, Spiller RC. Prognosis in post-infective irritable bowel syndrome: a six year follow up study. Gut. 2002;51:410–413.

25. Tornblom H, Holmvall P, Svenungsson B, et al. Gastrointestinal symptoms after infectious diarrhea: a five-year follow-up in a Swedish cohort of adults. Clin Gastroenterol Hepatol. 2007;5:461–464.

26. DuPont HL, Jiang ZD, Okhuysen PC, et al. A randomized, double-blind, placebo-controlled trial of rifaximin to prevent travelers’ diarrhea. Ann Intern Med. 2005;142:805–812.

27. Taylor DN, McKenzie R, Durbin A, et al. Rifaximin, a nonabsorbed oral antibiotic, prevents shigellosis after experimental challenge. Clin Infect Dis. 2006;42:1283–1288.

28. Sazawal S, Hiremath G, Dhingra U, et al. Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials. Lancet Infect Dis. 2006;6:374–382.

29. Bri V, Buffet P, Genty S, et al. Absence of efficacy of nonviable Lactobacillus acidophilus for the prevention of traveler’s diarrhea: a randomized, double-blind, controlled study. Clin Infect Dis. 2006;43:1170–1175.

30. Hill DR, Ford L, Lalloo DG. Oral cholera vaccines—use in clinical practice. Lancet Infect Dis. 2006;6:361–373.

31. Taylor DN, Bourgeois AL, Ericsson CD, et al. A randomized double-blind, multicenter study of rifaximin compared with placebo and with ciprofloxacin in the treatment of travelers’ diarrhea. Am J Trop Med Hyg. 2006;74:1060–1066.

32. DuPont HL, Ericsson CD, Farthing MJG, et al. Expert review of the evidence base for self-therapy of travelers’ diarrhea. J Travel Med. 2009;16:161–171.

33. Tribble DR, Sanders JW, Pang LW, et al. Traveler’s diarrhea in Thailand: randomized, double-blind trial comparing single-dose and 3-day azithromycin-based regimens with a 3-day levofloxacin regimen. Clin Infect Dis. 2007;44:338–346.

34. Riddle MS, Arnold S, Tribble DR. Effect of adjunctive loperamide in combination with antibiotics on treatment outcomes in travelers’ diarrhea: a systematic review and meta-analysis. Clin Infect Dis. 2008;47:1007–1014.

35. Steffen R. Worldwide efficacy of bismuth subsalicylate in the treatment of travelers’ diarrhea. Rev Infect Dis. 1990;12(suppl 1):S80–S86.

36. Connor BA. Persistent travelers’ diarrhea. Available at:http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-5-post-travel-evaluation/persistent-travelers-diarrhea.htm. Accessed August 20, 2012.

37.Landzberg BR, Connor BA. Persistent diarrhea in the returning traveler: think beyond persistent infection. Scand J Gastroenterol. 2005;40:112–114.

Treating TD and associated symptoms

Antibiotic treatment
Given that most cases of TD are caused by bacterial pathogens, antibiotics are considered the mainstay of treatment. Concerns about the ill effects of antibiotic use in the case of enterohemorrhagic E coli(EHEC O157:H7) can be allayed because this strain is rarely a cause of TD.⁹Patient factors that increase vulnerability to TD are immunodeficiency, achlorhydric states such as atrophic gastritis, and chronic use of proton pump inhibitors.

Consider local resistance patterns and risk of invasive infection. Which antibiotic to recommend is governed by the antibiotic resistance patterns prevalent in the travel destinations and by the risk of infection by invasive pathogens. Invasive TD is generally caused by Campylobacter, Shigella, or Salmonella and manifests clinically with bloody diarrhea, fever, or both. Rifaximin at a dose of 200 mg orally 3 times daily is effective for noninvasive TD.^31,32 However, travelers who develop invasive TD need an alternative to rifaximin. (Those who advocate reserving antibiotic treatment only for invasive diarrhea will not see a role for rifaximin in the first place.) In most invasive cases, a fluoroquinolone will suffice.^10-12,19,32 However, increasing prevalence of fluoroquinolone-resistantCampylobacter species has been reported in South and Southeast Asia. In those locations, azithromycin is an effective alternative, albeit with risk of nausea.³³TABLE 2¹² provides details of recommended antibiotic dosages for adults and children. The duration of treatment is generally 1 day unless symptoms persist, in which case a 3-day course is recommended.^10-12,19,32 If the traveler experiences persistent, new, or worsening symptoms beyond this point, immediate evaluation by a physician is required.

Non-antibiotic treatment
The antimotility agent loperamide is a well-established antidiarrheal agent. Its effective and safe use as an adjunct to antibiotics in the treatment of TD has been demonstrated in several studies.^{10-12,19,32,34} It is generally not used to treat children with TD⁹

No other non-antibiotic treatment for TD has significant guideline or clinical trial support. Bismuth subsalicylate can be helpful as an antidiarrheal agent,³⁵ but is not often recommended because the regimen makes adherence difficult and because antibiotics and loperamide are effective.

Oral rehydration is usually a mainstay of treating gastrointestinal disease among infants and children. However, it, too, has a limited role in cases of TD because dehydration is not usually a significant part of the clinical presentation, perhaps because vomiting is not often prominent.

CASE Advice regarding safe food and beverage choices is essential for the patient and her children. Despite the increased risk for TD due to her history and her use of the immunosuppressant methotrexate, she decides not to pursue antibiotic prophylaxis. Bismuth is also contraindicated because of the methotrexate. Her teenage daughter declines bismuth prophylaxis, and her toddler is too young for it.

The patient does accept a prescription for azithromycin for her and her daughters in case they experience TD. This choice is appropriate given the destination of India and concern about Campylobacterresistance to fluoroquinolones. You also recommend loperamide for use by the mother and older child, in conjunction with the antibiotic.

Two weeks after their trip abroad, the travelers return for an office visit. On the trip, the mother and toddler suffered diarrhea, which responded well to your recommended management. The older child was well during the trip, but she developed diarrhea, abdominal pain, and anorexia one week after returning to the United States. These symptoms have persisted despite a 3-day course of azithromycin and loperamide.

Post-travel evaluation

TD generally occurs within one to 2 weeks of arrival at the travel destination and usually lasts no longer than 4 to 5 days.¹⁹ This scenario is typical of a bacterial infection. When it occurs later or lasts longer, or both, consider several alternative possibilities.^19,36 First, the likelihood of a protozoal parasitic infection is increased. Although giardiasis is most likely, other protozoa such as Entamoeba, Cyclospora, Isospora, and Cryptosporidium are also possibilities. Second, if diarrhea persists, it might be due, not to continued infection, but to a self-limited post-infectious enteropathy or to PI-IBS. Third, TD is known to precipitate the clinical manifestation of underlying gastrointestinal disorders such as inflammatory bowel disease (IBD), celiac disease, or even cancer.³⁷

With an atypical disease course, it’s advisable to send 3 stool samples for laboratory evaluation for ova and parasites and for antigen assays for Giardia. If results of these tests are negative, given the difficulty inherent in diagnosing Giardia, consider empiric treatment with metronidazole in lieu of duodenal sampling.³⁶ If the diarrhea persists, investigate serologic markers for celiac disease and IBD. If these are not revealing, referral for colonoscopy is prudent.

CASE The teenager’s 3 stool samples were negative for ova and parasites and for Giardia antigen. Following empirical treatment with oral metronidazole 250 mg, 3 times daily for 7 days, the diarrhea resolved.