Oral Bivalent Whole-Cell Cholera Vaccine Efficacy Over 5 Years

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Efficacy did not appear to wane during the trial among adult vaccines. <i>Photo Credit: CDC.</i>
Efficacy did not appear to wane during the trial among adult vaccines. Photo Credit: CDC.

Oral cholera vaccine (OCV) may be age-dependent, showing a higher efficacy in children age 5 to 15 than in adults or children age <5, according to a study published in BMC Infectious Diseases.

Roughly 100,000 cholera cases of the 3 million that occur each year are fatal. Clean water and sanitation facilities can help disease prevention, but is not feasible in the near future for cholera-endemic regions. The use of OCV is a short-term solution that can provide protection.

Conducted in the urban slum wards of Kolkata, India, a previous trial (ClinicalTrails.gov identifier: NCT00289224) evaluated OCV efficacy in 66,000 people either receiving 2 doses of OCV (n=31,619) or 2 doses of placebo (n=34,596). 

Participants age ≥1, and not pregnant, were included in the study. The first vaccine was administered between July 27 and August 13, 2006; the second between August 27 and September 20, 2006. At the 2-year interim analysis, OCV was found to be safe and effective. The final 5-year analysis confirmed that OCV provided protection over 5 years, at least in older children and adults.

Unfortunately, important questions remained unanswered, including vaccine efficacy (VE) by age or whether protective efficacy waned over time. In cholera-endemic regions, young children have the highest risk for illness, but this risk should decline with age, possibly affecting cholera risk by age and VE estimates. In addition, during the fourth year of the trial, a large outbreak occurred which accounted for approximately 25% of cholera cases reported in the trial. This outbreak could affect analyses since all geographical regions and age groups were not affected equally.

Therefore, this study re-analyzed the trial results to determine OCV efficacy in different age groups and find evidence of waning efficacy over time. The study also compared results, including and excluding events related to the large cholera outbreak. To compare different mechanisms that could indicate age-dependent OCV efficacy, 4 Cox models with different assumptions about a vaccinated or unvaccinated individual's risk for cholera as s/he ages were used. The 4 models only differed in how the age groups were defined for the vaccine effect and natural risk.

Results found definitive evidence supporting age group-dependent VE. VE was found to be higher in children between age 5 and 15(85%), than in younger children (38%; P =.002) or adults (69%; P =.106), with an overall significance of .007. These results were similar to the original 2-year interim follow-up results. In addition, VE in older children was higher when the outbreak data was excluded. This study also found no evidence of waning VE in adults who were vaccinated over the 5 years of follow-up.

Overall, study results may be relevant for future OCV deployment plans in cholera-endemic regions. The study investigators concluded that “OCV could provide 5 years of high-quality protection for those over 5 years old with no evidence of waning among adults, suggesting that they might not need to be re-vaccinated frequently to maintain protection, making mass vaccination more cost-effective in cholera-endemic regions.”

Reference

Fong Y, Halloran ME, Park JK, Marks F, Clemens JD, Chao DL. Efficacy of a bivalent killed whole-cell cholera vaccine over five years: a re-analysis of a cluster-randomized trial. BMC Infect Dis. 2018;18:84.

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