The whole cell cholera and travellers’ diarrhea vaccine – Looking for evidence in the prevention of travellers’ diarrhea

Susan Hollenberg, B.Sc., M.D., MCFP (biography and disclosures)

What I did before

Travellers’ diarrhea (TD) is by far the most common cause of morbidity in persons travelling abroad.  Incidence rates range from 30-70%¹ on a 2-week vacation in a developing country, depending on the destination.  Unlike in Canada, where the majority of gastroenteritis is of viral etiology, the majority of diarrhea in a developing country is caused by bacterial pathogens; noteably E. Coli, Camplylobacter, Shigella and Salmonella, followed by viral and parasitic causes. The morbidity is significant in terms of time lost to leisure or business activities, and, although, most people recover spontaneously 3 to 5 days, some may have a considerably prolonged course.

After working in the field of Travel Medicine for nearly 20 years, I realize I spend a lot of time counselling travellers about recommended and required vaccines and malaria preventive medications.  Rarely do travellers encounter morbidity or mortality from these particular infectious diseases.  This caused me to evaluate the evidence for prevention of TD, to see if there was some advice that I could give in the pre-travel consult that would, indeed, improve the health of the majority of the travelling public.

My focus traditionally had been placed on food and water precautions, hand washing and food selection, along with some discussion around the use of bismuth subsalicylate² and probiotics in prevention of diarrhea, before entering into the larger discussion about oral rehydration, over the counter and antibiotic treatments for the same.³

What changed my practice

The approval of the oral whole cell cholera and traveller’s diarrhea vaccine (WC/rBS) (Dukoral™) in Canada in 2003 promised a novel approach to the prevention of TD.  Certainly the advertising was compelling!  This vaccine works by developing antibodies in the gut mucosa to cholera toxin.  The B-subunit of cholera toxin is immunologically similar to heat labile toxin produced by Enterotoxigenic E.coli (ETEC).  ETEC produces both heat labile and heat stable toxin.

In people who acquire TD in the developing world, approximately 50% is due to ETEC, of which 50% is heat labile toxin.  After ingestion of the WC/rBS vaccine, there is some short lived cross reactivity to the ETEC heat labile toxin that lasts about 3 months.  The efficacy of this vaccine is about 67% for ETEC.⁴’ ¹¹ This results in an overall theoretical absolute risk reduction of 0.5×0.5×0.67=16.75% for all cases of TD.

There are various ways to evaluate effectiveness of the vaccine:

1. In a study of Spanish travellers who presented to a travel clinic prior to their journey, the incidence of TD was 23% in people who took the WC/rBS vaccine, and 40% in those who had not, for all travel destinations visited.  This is equal to a 17% absolute risk reduction.  However, this can also be reported as a 43% relative risk reduction in occurrence of TD.⁵   Another way of looking at the data in this study concluded that the number needed to treat to prevent one traveller from suffering from an episode of TD was 5.8, which might seem worthwhile compared to many of our other medical interventions.  Statistics can say many things depending on how they are presented.
2. A study of Finnish tourists to Morocco showed a decrease in overall incidence of TD by 23% in those who had taken the WC/rBS vaccine.  Specifically, this study found the vaccine to be 52% protective against ETEC strains.  More interestingly, this study found this vaccine to have a protective efficacy of 71% against the combination of ETEC and any other bacterial pathogen.  The authors surmised that protection against one component of a mixed infection enables the immune system to defend more effectively against other pathogens. ⁶

A significant variable is that ETEC accounts for different proportions of TD in different countries and in different seasons, and this is continually changing with time.  Therefore the effectiveness of this vaccine varies considerably based on destination and type of travel, making it difficult to know how to interpret these studies when one is discussing the topic with the travelling public!

What I do now

In my practice, I always talk about this vaccine with persons travelling to less developed countries in conjunction with the other diarrhea preventive advice.  Other TD prevention strategies might give better protection against all-cause diarrhea illness, rather than targeting a specific organism.

I clarify that the use of this vaccine does not give the traveller free reign to safely indulge in risky type food ingestion.

I more strongly recommend it to certain populations who are more prone to TD, or who might be more at risk of serious consequences from TD.⁷   These include people on proton pump inhibitors with gastric hypochlorhydria, the young and the elderly, those with chronic illness, people with inflammatory bowel disease, the immune- compromised, and those who have a history of repeated severe TD. A recent analysis of the use of this vaccine for leisure travellers demonstrated that if the rates of ETEC caused TD in the country visited exceeded 13%, it would be a cost effective measure.  However, the ‘perceived value’ of the trip for an individual traveller ultimately decides if this vaccination provides good value for money.⁸

I do continue to discuss hand washing, food choice and water hygiene as preventive measure for TD with the travelling public, as these measures intuitively make sense, although, admittedly with less evidence base than I would have thought backing me up!⁹

References and additional reading: (Note: Article requests might require a login ID with the BC College of Physicians website or UBC)

1. Arguin P, Kozarsky P, Navin A., ed.  Health Information for International Travel. U.S. Department of Health and Human Services Centers for Disease Control and Prevention. 2012; Chapter 2, Travellers’ Diarrhea (View article)
2. DuPont, H et al. Prevention of Travellers’ Diarrhea by the Tablet Formulation of Bismuth Subsalicylate.  JAMA. 1987; 257:1347-50. (View article with CPSBC or UBC)
3. DuPont et al. Expert Review of the Evidence Base for Prevention of Travelers’ Diarrhea.  Journal of Travel Medicine 2009 May/June; 16(3):149-60. (View article with CPSBC or UBC)
4. Clemens, J.D., et al.  Field Trial of oral cholera vaccines in Bangladesh: results from three year follow up.  Lancet 1990;335(8684):270-73 (View article with CPSBC or UBC)
5. Lopez-Gigosos R. et al.  Effectiveness in prevention of Travellers’ Diarrhoea by an oral cholera vaccine WC/rBS.  Travel Med Infect Dis. 2007 Nov; 5(6):380-4. (View article with CPSBC or UBC)
6. Peltola H, Siitonen A, Kyronseppa H, et al. Prevention of Travellers’ Diarrhea by oral B-subunit/whole cell cholera vaccine.  Lancet 1991; 338(8778):1285-9. (View article with CPSBC or UBC)
7. Canadian Immunization Guide, 7^th edition.  Public Health Agency of Canada. 2006; 158-165 (View article)
8. Lundkvist, J., Steffen, R., et al. Cost-Benefit of WC/rBS Oral Cholera Vaccine for Vaccination Against ETEC-Caused Travelers’ Diarrhea.  Journal of Travel Medicine2009 Jan/Feb; 16(1):28-34 (View article with CPSBC or UBC)
9.  Kozicki M, Steffen R, Schar M. ‘Boil it, cook it, peel it or forget it’: does this rule prevent travellers’ diarrhea?  Int J Epidemiol 1985: 14:169-172. (View article with CPSBC or UBC)
10. Committee to Advise on Tropical Medicine and Travel (CATMAT).  Statement on travellers’ diarrhea.  Canada Communicable Disease Report 2001; 27(ACS3):1-12. (View article)
11. Committee to Advise on Tropical Medicine and Travel (CATMAT).  Statement on new oral cholera and travellers’ diarrhea vaccination.  Canada communicable Disease Report 2005; 31(ACS7):1-12. (View article)
12. BC Guidelines link to Infectious Diarrhea: http://www.bcguidelines.ca/guideline_diarrhea.html

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The whole cell cholera and travellers’ diarrhea vaccine – Looking for evidence in the prevention of travellers’ diarrhea

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