Oral cholera vaccines consisting of killed whole cells have been available for many
years, but they have not been used extensively in populations with endemic disease.
An inexpensive, locally produced oral killed-whole-cell vaccine has been used in high-risk
areas in Vietnam. To expand the use of this vaccine, it was modified to comply with
WHO standards. We assessed the efficacy and safety of this modified vaccine in a population
with endemic cholera.
In this double-blind trial, 107 774 non-pregnant residents of Kolkata, India, aged
1 year or older, were cluster-randomised by dwelling to receive two doses of either
modified killed-whole-cell cholera vaccine (n=52 212; 1966 clusters) or heat-killed
Escherichia coli K12 placebo (n=55 562; 1967 clusters), both delivered orally. Randomisation
was done by computer-generated sequence in blocks of four. The primary endpoint was
prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough
for the patient to seek treatment in a health-care facility. We undertook an interim,
per-protocol analysis at 2 years of follow-up that included individuals who received
two completely ingested doses of vaccine or placebo. We assessed first episodes of
cholera that occurred between 14 days and 730 days after receipt of the second dose.
This study is registered with ClinicalTrials.gov, number NCT00289224.
31 932 participants assigned to vaccine (1721 clusters) and 34 968 assigned to placebo
(1757 clusters) received two doses of study treatment. There were 20 episodes of cholera
in the vaccine group and 68 episodes in the placebo group (protective efficacy 67%;
one-tailed 99% CI, lower bound 35%, p<0.0001). The vaccine protected individuals in
age-groups 1.0-4.9 years, 5.0-14.9 years, and 15 years and older, and protective efficacy
did not differ significantly between age-groups (p=0.28). We recorded no vaccine-related
serious adverse events.
This modified killed-whole-cell oral vaccine, compliant with WHO standards, is safe,
provides protection against clinically significant cholera in an endemic setting,
and can be used in children aged 1.0-4.9 years, who are at highest risk of developing
cholera in endemic settings.
Bill & Melinda Gates Foundation, Swedish International Development Cooperation Agency,
Governments of South Korea, Sweden, and Kuwait.