The Lancet Infectious Diseases, Volume 13, Issue 12, Pages 1050 – 1056, December 2013

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 MD a b, Dipika Sur MD a, Dr Mohammad Ali PhD c Corresponding AuthorEmail Address, Suman Kanungo DIH a, Young Ae You MS c, Byomkesh Manna PhD a, Binod Sah MBBS c, Swapan K Niyogi MD a, Jin Kyung Park PhD c, Banwarilal Sarkar PhD a, Mahesh K Puri MSc c, Deok Ryun Kim MS c, Jacqueline L Deen MD d, Jan Holmgren PhD e, Rodney Carbis BSc c, Mandeep Singh Dhingra MD f, Allan Donner PhD g, G Balakrish Nair PhD a, Anna Lena Lopez MD c h, Thomas F Wierzba PhD c, John D Clemens MD c i j
Summary
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 31 932 recipients of vaccine and 219 of 34 968 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.

G Mohan.