Current Gastroenterology Reports

, Volume 10, Issue 5, pp 473–479 | Cite as

Travelers’ diarrhea: An update on susceptibility, prevention, and treatment



Traditional risk factors do not explain the individual differences in susceptibility to travelers’ diarrhea (TD) among the increasing number of travelers to the developing world. Single-nucleotide polymorphisms of the genes encoding for lactoferrin and interleukin 8 (IL-8) have been linked to susceptibility to TD. Subjects with mutations of the FUT2 gene are immune to norovirus infection. The recognition of individual variations in susceptibility to TD will aid in risk stratification of travelers to the developing world. Diagnosis is usually syndromic, but improved diagnostic methods are in development. Quinolones have been the mainstay of antibiotic treatment, but azithromycin (for resistant organisms) and rifaximin (for noninvasive organisms) may provide advantages. Transcutaneous vaccines for the major Escherichia coli enteropathogens are in development. In the future, travel advice, prophylactic medication regimens, and standby treatment for TD will be better tailored to each patient’s specific risk factors.


Azithromycin Loperamide Rifaximin Acid Tolerance Response Copy Number Polymorphism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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References and Recommended Reading

  1. 1.
    United Nations World Tourism Organization: World tourist arrivals: from 800 million to 900 million in two years. UNWTO World Tourism Barometer 2008, 5:1,3–4. Available at Accessed March 30, 2008.Google Scholar
  2. 2.
    World Trade Organization: International Trade Statistics 2007. Geneva, Switzerland: World Trade Organization; 2007. Available at Accessed April 9, 2008.Google Scholar
  3. 3.
    Steffen R, van der Linde F, Gyr K, Schar M: Epidemiology of diarrhea in travelers. JAMA 1983, 249:1176–1180.PubMedCrossRefGoogle Scholar
  4. 4.
    Jiang ZD, Lowe B, Verenkar MP, et al.: Prevalence of enteric pathogens among international travelers with diarrhea acquired in Kenya (Mombasa), India (Goa), or Jamaica (Montego Bay). J Infect Dis 2002, 185:497–502.PubMedCrossRefGoogle Scholar
  5. 5.
    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.PubMedCrossRefGoogle Scholar
  6. 6.
    Chapin AR, Carpenter CM, Dudley WC, et al.: Prevalence of norovirus among visitors from the United States to Mexico and Guatemala who experienced travelers’ diarrhea. J Clin Microbiol 2005, 43:1112–1117.PubMedCrossRefGoogle Scholar
  7. 7.
    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.PubMedGoogle Scholar
  8. 8.
    ten Hove R, Schuurman T, Kooistra M, et al.: Detection of diarrhoea-causing protozoa in general practice patients in The Netherlands by multiplex real-time PCR. Clin Microbiol Infect 2007, 13:1001–1007.PubMedCrossRefGoogle Scholar
  9. 9.
    Sjöling A, Wiklund G, Savarino SJ, et al.: Comparative analyses of phenotypic and genotypic methods for detection of enterotoxigenic Escherichia coli toxins and colonization factors. J Clin Microbiol 2007, 45:3295–3301.PubMedCrossRefGoogle Scholar
  10. 10.
    Yang JR, Wu FT, Tsai JL, et al.: Comparison between O serotyping method and multiplex real-time PCR to identify diarrheagenic Escherichia coli in Taiwan. J Clin Microbiol 2007, 45:3620–3625.PubMedCrossRefGoogle Scholar
  11. 11.
    Guion CE, Ochoa TJ, Walker CM, et al.: Detection of diarrheagenic Escherichia coli by use of melting-curve analysis and real-time multiplex PCR. J Clin Microbiol 2008, 46:1752–1757.PubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedGoogle Scholar
  13. 13.
    Steffen R, Tornieporth N, Clemens SA, et al.: Epidemiology of travelers’ diarrhea: details of a global survey. J Travel Med 2004, 11:231–237.PubMedCrossRefGoogle Scholar
  14. 14.
    Shlim R. Looking for evidence that personal hygiene precautions prevent traveler’s diarrhea. Clin Infect Dis 2005, 41(suppl 8):S531–S535.PubMedCrossRefGoogle Scholar
  15. 15.
    Zhu H, Hart CA, Sales D, Roberts NB: Bacterial killing in gastric juice—effect of pH and pepsin on Escherichia coli and Helicobacter pylori. J Med Microbiol 2006, 55:1265–1270.PubMedCrossRefGoogle Scholar
  16. 16.
    Martinsen TC, Bergh K, Waldum HL: Gastric juice: a barrier against infectious diseases. Basic Clin Pharmacol Toxicol 2005, 96:94–102.PubMedCrossRefGoogle Scholar
  17. 17.
    Tennant SM, Hartland EL, Phumoonna T, et al.: Influence of gastric acid on susceptibility to infection with ingested bacterial pathogens. Infect Immun 2008, 76:639–645.PubMedCrossRefGoogle Scholar
  18. 18.
    Neal RK, Scott HM, Slack RCB, Logan RFA: Omeprazole as a risk factor for Campylobacter gastroenteritis: case-control study. BMJ 1996, 312:414–415.PubMedGoogle Scholar
  19. 19.
    Neal RK, Brij OS, Slack BCR, et al.: Recent treatment with H2 antagonists and antibiotics and gastric surgery as risk factors for salmonella infection. BMJ 1994, 308:176.PubMedGoogle Scholar
  20. 20.
    Bourret TJ, Porwollik S, McClelland M, et al.: Nitric oxide antagonizes the acid tolerance response that protects Salmonella against innate gastric defenses. PLoS ONE 2008, 3:e1833.PubMedCrossRefGoogle Scholar
  21. 21.
    Benjamin N, O’Driscoll F, Dougall H, et al.: Stomach NO synthesis. Nature 1994, 368:502.PubMedCrossRefGoogle Scholar
  22. 22.
    Lin PW, Simon PO Jr, Gewirtz AT, et al.: Paneth cell cryptdins act in vitro as apical paracrine regulators of the innate inflammatory response. J Biol Chem 2004, 279:19902–19907.PubMedCrossRefGoogle Scholar
  23. 23.
    Aldred PMR, Hollox EJ, Armour JAL: Copy number polymorphism and expression level variation of the human-defensin genes DEFA1 and DEFA3. Hum Mol Genet 2005, 14:2045–2052.PubMedCrossRefGoogle Scholar
  24. 24.
    Hollox EJ, Armour JAL, Barber JCK: Extensive normal copy number variation of a b-defensin antimicrobial-gene cluster. Am J Hum Genet 2003, 73:591–600.PubMedCrossRefGoogle Scholar
  25. 25.
    Legrand D, Elass E, Pierce A, Mazurier J: Lactoferrin and host defence: an overview of its immuno-modulating and anti-inflammatory properties. Biometals 2004, 17:225–229.PubMedCrossRefGoogle Scholar
  26. 26.
    Togawa J, Nagase H, Tanaka K, et al.: Oral administration of lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance. J Gastroenterol Hepatol 2002, 17:1291–1298.PubMedCrossRefGoogle Scholar
  27. 27.
    Gomez HF, Ochoa TJ, Carlin LG, Cleary TG: Human lactoferrin impairs virulence of Shigella flexneri. J Infect Dis 2003, 187:87–95.PubMedCrossRefGoogle Scholar
  28. 28.
    Orsi N: The antimicrobial activity of lactoferrin: current status and perspectives. Biometals 2004, 17:189–196.PubMedCrossRefGoogle Scholar
  29. 29.
    Ochoa TJ, Chea-Woo E, Campos M, et al.: Impact of lactoferrin supplementation on growth and prevalence of Giardia colonization in children. Clin Infect Dis 2008, 46:1881–1883.PubMedCrossRefGoogle Scholar
  30. 30.
    Greenberg DE, Jiang, ZD, Steffen R, et al.: Markers of inflammation in bacterial diarrhea among travelers, with a focus on enteroaggregative Escherichia coli pathogenicity. J Infect Dis 2002, 185:944–949.PubMedCrossRefGoogle Scholar
  31. 31.
    Bouckenooghe AR, Dupont HL, Jiang ZD, et al.: Markers of enteric inflammation in enteroaggregative Escherichia coli diarrhea in travelers. Am J Trop Med Hyg 2000, 62:711–713.PubMedGoogle Scholar
  32. 32.
    Mohamed JA, DuPont HL, Jiang ZD, et al.: A novel single-nucleotide polymorphism in the lactoferrin gene is associated with susceptibility to diarrhea in North American travelers to Mexico. Clin Infect Dis 2007, 44:945–952.PubMedCrossRefGoogle Scholar
  33. 33.
    Allen SJ, Crown SE, Handel TM: Chemokine: receptor structure, interactions, and antagonism. Annu Rev Immunol 2007, 25:787–820.PubMedCrossRefGoogle Scholar
  34. 34.
    Charo IF, Ransohoff RM: The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 2006, 354:610–621.PubMedCrossRefGoogle Scholar
  35. 35.
    Sansonetti PJ, Arondel J, Huerre M, et al.: Interleukin-8 controls bacterial transepithelial translocation at the cost of epithelial destruction in experimental Shigellosis. Infect Immun 1999, 67:1471–1480.PubMedGoogle Scholar
  36. 36.
    Jiang ZD, Okhuysen P, Guo DC, et al.: Genetic susceptibility to enteroaggregative Escherichia coli diarrhea: polymorphism in the interleukin-8 promotor region. J Infect Dis 2003, 188:506–511.PubMedCrossRefGoogle Scholar
  37. 37.
    Jiang ZD, DuPont HL, Garey K, et al.: A common polymorphism in the interleukin 8 gene promoter is associated with Clostridium difficile diarrhea. Am J Gastroenterol 2006, 101:1112–1116.PubMedCrossRefGoogle Scholar
  38. 38.
    Jiang ZD, Garey KW, Price M, et al.: Association of interleukin-8 polymorphism and immunoglobulin G anti-toxin A in patients with Clostridium difficile-associated diarrhea. Clin Gastroenterol Hepatol 2007, 5:964–968.PubMedCrossRefGoogle Scholar
  39. 39.
    Marionneau S, Ruvoen N, Le Moullac-Vaidye B, et al.: Norwalk virus binds to histo-blood group antigens present on gastro-duodenal epithelial cells of secretor individuals. Gastroenterology 2002, 122:1967–1977.PubMedCrossRefGoogle Scholar
  40. 40.
    Lindesmith L, Moe C, Marionneau S, et al.: Human susceptibility and resistance to Norwalk virus infection. Nat Med 2003, 9:548–553.PubMedCrossRefGoogle Scholar
  41. 41.
    Kirkpatrick BD, Haque R, Duggal P, et al.: Association between Cryptosporidium infection and human leukocyte antigen class I and class II alleles. J Infect Dis 2008, 197:474–478.PubMedCrossRefGoogle Scholar
  42. 42.
    Duggal P, Haque R, Roy S, et al.: Influence of human leukocyte antigen class II alleles on susceptibility to Entamoeba histolytica infection in Bangladeshi children. J Infect Dis 2004, 189:520–526.PubMedCrossRefGoogle Scholar
  43. 43.
    Petri WA, Miller M, Binder HJ, et al.: Enteric infections, diarrhea, and their impact on function and development. J Clin Invest 2008, 118:1277–1290.PubMedCrossRefGoogle Scholar
  44. 44.
    Adachi JA, Ericsson CD, Jiang ZD, et al.: Azithromycin found to be comparable to levofloxacin for the treatment of US travelers with acute diarrhea acquired in Mexico. Clin Infect Dis 2003, 37:1165–1171.PubMedCrossRefGoogle Scholar
  45. 45.
    Ericsson CD, DuPont HL, Okhuysen PC, et al.: Loperamide plus azithromycin more effectively treats TD in Mexico than azithromycin alone. J Travel Med 2007, 14:312–319.PubMedCrossRefGoogle Scholar
  46. 46.
    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.PubMedGoogle Scholar
  47. 47.
    Dupont HL, Jiang ZD, Belkind-Gerson J, et al.: Treatment of travelers’ diarrhea: randomized trial comparing rifaximin, rifaximin plus loperamide, and loperamide alone. Clin Gastroenterol Hepatol 2007, 5:451–456.PubMedCrossRefGoogle Scholar
  48. 48.
    Glenn GM, Villar CP, Flyer DC, et al.: Safety and immunogenicity of an enterotoxigenic Escherichia coli vaccine patch containing heat-labile toxin: use of skin pretreatment to disrupt the stratum corneum. Infect Immun 2007, 75:2163–2170.PubMedCrossRefGoogle Scholar
  49. 49.
    McKenzie R, Bourgeois AL, Frech SA, et al.: Transcutaneous immunization with the heat-labile toxin (LT) of enterotoxigenic Escherichia coli (ETEC): protective efficacy in a double-blind, placebo-controlled challenge study. Vaccine 2007, 25:3684–3691.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Infectious Disease Division, Department of Internal MedicineUniversity of Texas Medical BranchGalvestonUSA

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