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 ofplacebo 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.
RCT Entities:
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. FUNDING: Bill & Melinda Gates Foundation and the governments of South Korea and Sweden.
Authors: Louise C Ivers; Richelle C Charles; Isabelle J Hilaire; Leslie M Mayo-Smith; Jessica E Teng; J Gregory Jerome; Jenna Rychert; Regina C LaRocque; Peng Xu; Pavol Kovácˇ; Edward T Ryan; Firdausi Qadri; Charles P Almazor; Molly F Franke; Jason B Harris Journal: J Infect Dis Date: 2015-02-26 Impact factor: 5.226
Authors: Lana Childs; Jeannot François; Alina Choudhury; Kathleen Wannemuehler; Amber Dismer; Terri B Hyde; Catherine Y Yen; Kashmira A Date; Stanley Juin; Mark A Katz; Erica Felker Kantor; Janell Routh; Melissa Etheart; Tracie Wright; Paul Adrien; Rania A Tohme Journal: Am J Trop Med Hyg Date: 2016-10-31 Impact factor: 2.345
Authors: Karine Sévère; Vanessa Rouzier; Stravinsky Benedict Anglade; Claudin Bertil; Patrice Joseph; Alexandra Deroncelay; Marie Marcelle Mabou; Peter F Wright; Florence Duperval Guillaume; Jean William Pape Journal: Am J Trop Med Hyg Date: 2016-02-29 Impact factor: 2.345
Authors: Molly F Franke; J Gregory Jerome; Wilfredo R Matias; Ralph Ternier; Isabelle J Hilaire; Jason B Harris; Louise C Ivers Journal: Vaccine Date: 2017-09-12 Impact factor: 3.641