5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: A cluster-randomised, double-blind, placebo-controlled trial

Sujit K. Bhattacharya, Dipika Sur, Mohammad Ali, Suman Kanungo, Young Ae You, Byomkesh Manna, Binod Sah, Swapan K. Niyogi, Jin Kyung Park, Banwarilal Sarkar, Mahesh K Puri, Deok Ryun Kim, Jacqueline L. Deen, Jan Holmgren, Rodney Carbis, Mandeep Singh Dhingra, Allan Donner, G Balakrish Nair, Anna Lena Lopez, Thomas F. WierzbaJohn D Clemens

    Research output: Contribution to journalArticle

    Abstract

    Background: Efficacy and safety of a two-dose regimen of bivalent killed whole-cell oral cholera vaccine (Shantha Biotechnics, Hyderabad, India) to 3 years is established, but long-term efficacy is not. We aimed to assess protective efficacy up to 5 years in a slum area of Kolkata, India. 

    Methods: In our double-blind, cluster-randomised, placebo-controlled trial, we assessed incidence of cholera in non-pregnant individuals older than 1 year residing in 3933 dwellings (clusters) in Kolkata, India. We randomly allocated participants, by dwelling, to receive two oral doses of modified killed bivalent whole-cell cholera vaccine or heat-killed Escherichia coli K12 placebo, 14 days apart. Randomisation was done by use of a computer-generated sequence in blocks of four. The primary endpoint was prevention of episodes of culture-confirmed Vibrio cholerae O1 diarrhoea severe enough for patients to seek treatment in a health-care facility. We identified culture-confirmed cholera cases among participants seeking treatment for diarrhoea at a study clinic or government hospital between 14 days and 1825 days after receipt of the second dose. We assessed vaccine protection in a per-protocol population of participants who had completely ingested two doses of assigned study treatment. 

    Findings: 69 of 31932 recipients of vaccine and 219 of 34968 recipients of placebo developed cholera during 5 year follow-up (incidence 2·2 per 1000 in the vaccine group and 6·3 per 1000 in the placebo group). Cumulative protective efficacy of the vaccine at 5 years was 65% (95% CI 52-74; p<0·0001), and point estimates by year of follow-up suggested no evidence of decline in protective efficacy. 

    Interpretation: Sustained protection for 5 years at the level we reported has not been noted previously with other oral cholera vaccines. Established long-term efficacy of this vaccine could assist policy makers formulate rational vaccination strategies to reduce overall cholera burden in endemic settings. 

    Funding: Bill & Melinda Gates Foundation and the governments of South Korea and Sweden. 

    Original languageEnglish
    Pages (from-to)1050-1056
    Number of pages7
    JournalLancet Infectious Diseases
    Volume13
    Issue number12
    DOIs
    Publication statusPublished - Dec 2013

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