The first search resulted in the identification of 38 studies from more than 100 papers and no further papers were included following a comprehensive screening of the references. Several papers9
which described only the results of interim analyses rather than a full review of a study were excluded from this review.16
Similarly, twelve papers which focused on immunogenicity and safety without providing data regarding efficacy were not included.17
Consequently, four clinical trials involving oral whole cell cholera vaccines were reviewed as follows: WC-BS,27
In order to review the optimal evidence base, this review paper was only based on clinical trial data and observational studies were not included.
The study population consisted of indigenous populations of children residing in endemic countries and who were at risk of infection with cholera. Travelers as an at risk group were not considered as part of this review because clinical trials have not been completed in this particular cohort. The four studies included approximately 278,000 people, with approximately 96,000 children aged 1–15 years living throughout Asia and South America (). Each trial included at least 10,000 children living in a non-outbreak area, with the exception of one study by Trach et al.29
These trials provided results for each age group, type of oral cholera vaccine administered as well as for each year of follow-up, although different strata were applied for each clinical trial.
Description of studies included in review
In 1985, Clemens et al27
conducted a randomized double-blind controlled trial including follow-up over a period of 3 years to assess the protective efficacy of three doses of WC-BS or killed whole cell only oral cholera vaccines administered at 6-week intervals against placebo (E. coli
K12) among 62,285 children and women residing in rural Bangladesh. Only 20,705 people received the WC-BS vaccine and 61.8% (n = 12,708) were children aged 2–15 years. Efficacy was defined through different outcomes based on cases of cholera (symptomatic and asymptomatic), deaths of all causes, and cholera deaths in vaccinees who received WC-BS as compared with the placebo group. The data were stratified according to age: 2–5 years of age or older than 5 years; and follow-up was undertaken after the at first, second, and third year.
From 1993 to 1995, Taylor et al28
conducted a randomized double-blind controlled trial with a follow-up of 2 years to assess the protective efficacy of two doses of WC-rBS administered at 2-week intervals followed by a booster 10 months later as compared against placebo (E. coli
K12) among 14,997 children and adults up to 65 years old residing in marginal neighborhoods in Lima, Peru. Only 7594 people received the WC-BS vaccine of which 53.9% (n = 4096) were children aged 2–15 years old. The efficacy of the vaccine was defined by different outcomes based on cases of cholera and level of dehydration according to the World Health Organization definitions. These outcomes were identified through active household or passive surveillance, the latter being completed at health centers. The data were stratified by age: 2–5 years of age or older than 5 years; and follow-up was undertaken after the first and second year.
In 1992, Trach et al29
conducted a nonrandomized open-label trial during an outbreak of El Tor cholera with a follow-up of 1 year to assess the protective efficacy of two doses of vWC administered at 2-week intervals as compared with placebo (E. coli
K12) among 134,453 residents aged 1 year or more in urban Vietnam (Hue). Half of the population (n = 67,395) received the vWC vaccine and 22.6% (n = 15,253) were children aged 2–10 years old. The efficacy was defined by different outcomes based on cases of cholera or diarrhea requiring inpatient care, or deaths from cholera. The data were stratified using the following age groups: 1–5 years, 6–10 years, 11–20 years, 21–40 years, and older than 40 years; no results were reported regarding the follow-up period.
In 2006, Sur et al30
conducted a cluster randomized double-blind controlled trial with a follow-up of 2 years to assess the protective efficacy of two doses of bivalent vaccine (BivWC) administered at 2-week intervals as compared with placebo (E. coli
K12) among 66,900 residents aged 1 year or more in urban India (Kolkata). Only 31,932 people received BivWC of which 28.5% (n = 9,105) were children aged 1–14.9 years old. The efficacy was defined by different outcomes based on cases of cholera (first symptomatic cholera episode confirmed by fecal excretion of V. cholerae
O1 during a nonbloody diarrheal episode) and deaths of all causes in vaccinees as compared with the placebo group. The data were stratified by age group: 1–4.9 years, 5–14.9 years, and 15 years or older. The data obtained with reference to the second year of follow-up were only stratified by the age of the population only and results regarding the first year of follow-up were unpublished and unavailable.