Oral Cholera Vaccine Safe, Effective in First Real-life Trial

Laurie Barclay, MD

July 09, 2015

An inexpensive, oral, killed whole-cell cholera vaccine (Shanchol, Shantha) delivered through routine government services safely protected poor urban populations in Bangladesh from endemic cholera, according to a new study. The results from the first real-life, cluster-randomized open-label trial of the vaccine were published online July 8 in the Lancet.

"Our findings show that a routine oral cholera vaccination programme in cholera-endemic countries could substantially reduce the burden of disease and greatly contribute to cholera control efforts," lead author Firdausi Qadri, PhD, from the International Centre for Diarrhoeal Disease Research Bangladesh in Dhaka, said in a journal news release. "The vaccine is cheap, two doses cost US$3.7, around a third of the price of the other licensed vaccine Dukoral [SBL Vaccines/Crucell]."

Participants in the Introduction of Cholera Vaccine in Bangladesh feasibility study were aged 1 year and older and living in the urban slums of Mirpur in Dhaka, where overcrowding and poor sanitation increase the risk for cholera infection.

The investigators randomly assigned 90 clusters (1:1:1) to vaccination only (n = 94,675), to vaccination and behavioral change intended to encourage safe drinking water and hand washing (n = 92,539), or to no intervention (n = 80,056).

Routine government health services delivered the vaccine, given in two doses 14 days apart. Even though the population is highly mobile, the rate of vaccine coverage with both doses was 65% in the vaccination-only group and 66% in the vaccination and behavioral change group, reflecting good acceptance of the vaccination campaign by the local community.

Overall protective effectiveness, determined from the risk for severely dehydrating cholera for 2 years after vaccination for all persons present at time of the second dose, was 37% (95% confidence interval [CI] lower bound, 18%; P = .0024) in the vaccination group and 45% (95% CI lower bound, 24%; P = .0011) in the vaccination and behavioral change group.

For participants who received two doses of the vaccine, total effectiveness was 53% (95% CI lower bound, 34%; P = .0001) in the vaccination group and 58% (95% CI lower bound, 41%; P < .0001) in the vaccination and behavioral change group.

Even with moderate vaccination coverage, cases of severe, life-threatening cholera went down by nearly 40%, including among children aged 5 years and younger, who are particularly susceptible to severe cholera. Surprisingly, the behavioral intervention offered little additional protection.

"Ultimately, the key to controlling cholera is clean water and adequate sanitation, which half the developing world (around 2.5 billion people) lack, but this remains a rather difficult reality for the world's poorest nations as well as those affected by climate change, war, and natural disasters," Dr Qadri said in the news release.

There were no reported vaccine-related serious adverse events. Most adverse events were mild or moderate, and the most common were acute watery diarrhea, vomiting, abdominal pain, and fever.

Comprehensive Program Needed to Control Cholera

In an accompanying comment, Maureen O'Leary, MSc, from the London School of Hygiene & Tropical Medicine in the United Kingdom, and Kim Mulholland, MBBS, FRACP, MD, from the London School of Hygiene & Tropical Medicine in the United Kingdom and Royal Children’s Hospital, in Melbourne, Victoria, Australia, note estimates of more than 1 billion people at risk for cholera in more than 50 countries where it is endemic, with approximately 2.5 million cases and 95,000 deaths each year in endemic regions.

They refer to this trial as a "welcome step towards vaccine deployment in endemic settings," although they point out that the open-label design might have biased estimates of effectiveness. Moreover, the vaccine used has sustained efficacy for up to 5 years, but efficacy beyond that time is still undetermined.

"Ongoing monitoring to assess the duration of protection should be an essential component of any mass vaccination programme, to inform the need for booster doses and to evaluate intervention cost-effectiveness," the commentators write.

"Furthermore, oral cholera vaccine is only one part of the larger programme needed to control cholera. It should not supersede efforts to reduce risky behaviours, and to improve sanitation and provide safe drinking water to people living in cholera-endemic areas."

The Bill & Melinda Gates Foundation funded this study. The authors and commentators have disclosed no relevant financial relationships.

Lancet. Published online July 8, 2015.

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