Dr. Alissa Wright (biography and disclosures)
What I did before
Traveller’s diarrhea can affect 20- 60% of travellers to tropical or developing areas, making it one of the most common illnesses to occur during travel.(1, 2) The most commonly used definition of diarrhea is 3 or more loose stools in a 24 hour period accompanied by one or more of abdominal cramping, bloody stool, fever, nausea or vomiting. This can be either acute (lasting <14 days) or persistent (>14 days). Enterotoxigenic Escherichia coli (ETEC) is the number one cause of acute traveller’s diarrhea, although other enteric bacteria including enteroaggregative E. coli (EAEC), Campylobacter spp., Shigella spp., and Salmonella spp. can also be responsible. The majority of travellers will have spontaneous resolution of their symptoms over a 5 day period, but up to one-quarter may change their plans as a result.(1) Consequently, a common question in patients who seek pre-travel advice is how to avoid or manage this condition.
What changed my practice?
Although there are several strategies for dealing with traveller’s diarrhea – including specific food and water avoidance strategies and/or vaccination against select pathogens – the more common discussion revolves around antibiotics or over-the-counter medications such as bismuth subsalicylate. Antibiotics may either be given as chemoprophylaxis for the entire duration of the trip in short-term travellers (<4 weeks) or as a prescription for self-treatment if symptoms occur in both short and long-term travellers. The latter is generally preferred as it is efficacious and reduces overall antibiotic exposure. This also reduces the chance that the traveller will develop allergic reactions or acquire Clostridium difficile or other drug-resistant pathogens as a consequence of therapy.
Quinolones have traditionally been the drug of choice for prophylaxis or treatment of traveller’s diarrhea. However, quinolone resistance has been rising in certain areas of the world, particularly for Campylobacter jejuni and C. coli. A recent study of isolates recovered in travellers attending an outpatient travel clinic between 1994 and 2006 found that overall resistance for norfloxacin was 35.1%.(3) Norfloxacin resistance increased over time and was particularly prominent in isolates from India (78.8%) and East Asia (70.5%).
Moreover, not all travellers may need or want antibiotic therapy and this necessitates a trip to the travel clinic as pre-travel advice is not covered under MSP. A recent European study found that most travellers who experience traveller’s diarrhea did not find it as important in retrospect as they had thought before they travelled.(4) In that study, 41% of a cohort of healthy travellers experienced traveller’s diarrhea. Individuals with diarrhea judged their symptoms as mild in one-third of cases and two-thirds of individuals had no change in their plans as a result. In this series, only 9% of those travellers with diarrhea used antibiotics. The majority – 34% of those experiencing diarrhea – chose an antimotility agent instead.
What I do now
Given the rise in resistance, several measures can be employed for prevention or treatment of traveller’s diarrhea. Travellers who seek pre-travel advice should still be counselled regarding safe food and water practices. However, they should recognize that even complete adherence to these measures may not reduce the risk of acquiring traveller’s diarrhea.(2) Travellers should also be offered vaccination if either the risk of acquiring traveller’s diarrhea is high or the individual places significant value on avoiding traveller’s diarrhea. WC/rBS oral cholera vaccine (Dukoral®) contains both killed Vibrio cholerae and a recombinant form of the cholera toxin B-subunit. As the heat-labile toxin of ETEC shares ~80% homology with the cholera toxin, WC/rBS oral cholera vaccine also provides moderate, short-term protection against ETEC (67% over 3 months).(5) Side-effects are minimal and the vaccine is cost-effective if the incidence of ETEC-associated traveller’s diarrhea is above 13% for leisure travellers or 9% for business travellers.(6) For continued protection, a booster dose can be given after two years for adults and children over six years, and after six months for children aged two to six years. Vaccination against Salmonella typhi is not recommended for typical business or short-term (<4 weeks) traveller.(5)
Travellers should next be carefully assessed for their ability to tolerate diarrhea given their age and comorbid conditions (e.g. underlying renal disease or colostomy). All travellers should understand the usual self-limited nature of traveller’s diarrhea and the importance of supportive care measures such as maintaining fluid and electrolyte intake. Antimotility treatment with loperamide may be used as long as the stool is non-bloody and the patient is not febrile (4 mg after first loose stool with 2 mg after each subsequent up to 8 mg/d with medical attention sought if diarrhea does not improve in next one to two days). For travellers who are otherwise healthy, bismuth subsalicylate preparations (e.g. Pepto-Bismol 30 mL po every 30 min for 8 doses) is one alternative treatment for mild traveller’s diarrhea as it has been found to reduce stool frequency by 50%.(1) It should not be used in patients on doxycycline (e.g. for malaria prophylaxis) because reduces the absorption of all tetracyclines. It should also not be used in children with viral infections because it contains salicylate and has the potential to cause Reye’s syndrome. Bismuth subsalicylate has also been shown to be effective for prophylaxis (e.g. Pepto-Bismol 30 mL po QID); however the same cautions listed above apply and travellers may find this regimen inconvenient.
If an antibiotic prescription is given because of the nature of the trip – such as a business meeting that cannot be rescheduled – or comorbid conditions, quinolones may still be used. A typical prescription would be for ciprofloxacin 500 mg po bid for 1-3 days.(1) However, travellers who are visiting Asia or South East Asia should be offered an alternative antibiotic given the resistance rates. Azithromycin 1000 mg po once has been found to be effective in treating quinolone-resistant Campylobacter.(2) It is also the preferred antibiotic in children and pregnant women. Travellers should be reminded that they must fill the prescription before they leave. Any traveller receiving prescription antibiotics should be carefully counselled that there is still a risk that this treatment may fail given rising rates of antibiotic resistance and that if their symptoms have not rapidly improved within one or more days, they should seek medical attention.
|Trip <4 weeks|
|Prophylaxis:||Bismuth subsalicylate (Pepto-Bismol) 30 mL po QID||Not for children with viral illnesses (Reyes), patients on doxycycline for malaria prophylaxis or warfarin|
|Antibiotics not recommended given risks (e.g. C. difficile) and ease of treating diarrheal episodes|
|Treatment:||Bismuth subsalicylate (Pepto-Bismol) 30 mL q30 minutes||Max 8 doses/day
Not for children with viral illnesses (Reyes), patients on doxycycline for malaria prophylaxis or warfarin
|Loperamide 4 mg after first loose stool with 2 mg after each subsequent stool||Max 8 mg/d
Not for bloody diarrhea or other systemic signs of illness
|Ciprofloxacin 500 mg po BID x 1-3 days|
|Azithromycin 1000 mg po x 1 dose||Preferred in children, pregnant women and if visiting a ciprofloxacin-resistant area such as Asia or South-East Asia|
|Trip >4 weeks|
|Prophylaxis:||Not recommended given risks (e.g. C. difficile) and ease of treating diarrheal episodes|
|Treatment:||Same as above|
References and/or Additional reading:
1. Hill DR, Ericsson CD, Pearson RD, Keystone JS, Freedman DO, Kozarsky PE, et al. The practice of travel medicine: Guidelines by the infectious diseases society of america. Clin Infect Dis. 2006 Dec 15;43(12):1499-539.
2. Hill DR, Ryan ET. Management of travellers’ diarrhoea. BMJ. 2008 Oct 6;337:a1746. (View)
3. Vlieghe ER, Jacobs JA, Van Esbroeck M, Koole O, Van Gompel A. Trends of norfloxacin and erythromycin resistance of campylobacter jejuni/Campylobacter coli isolates recovered from international travelers, 1994 to 2006. J Travel Med. 2008 Nov-Dec;15(6):419-25. (View)
4. Soonawala D, Vlot JA, Visser LG. Inconvenience due to travelers’ diarrhea: A prospective follow-up study. BMC Infect Dis. 2011 Nov 20;11:322. (View)
5. Canada. National Advisory Committee on Immunization, Public Health Agency of Canada. Canadian immunization guide. 7th ed. Ottawa: Public Health Agency of Canada; 2006. (View)
6. Lundkvist J, Steffen R, Jonsson B. Cost-benefit of WC/rBS oral cholera vaccine for vaccination against ETEC-caused travelers’ diarrhea. J Travel Med. 2009 Jan-Feb;16(1):28-34. (View)