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. Wierzba; John D Clemens

doi:10.1016/S1473-3099(13)70273-1

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

Global and Tropical Health

Research output: Contribution to journal › Article › peer-review

187 Citations (Scopus)

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 language	English
Pages (from-to)	1050-1056
Number of pages	7
Journal	Lancet Infectious Diseases
Volume	13
Issue number	12
DOIs	https://doi.org/10.1016/S1473-3099(13)70273-1
Publication status	Published - Dec 2013

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10.1016/S1473-3099(13)70273-1

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Bhattacharya, S. K., Sur, D., Ali, M., Kanungo, S., You, Y. A., Manna, B., Sah, B., Niyogi, S. K., Park, J. K., Sarkar, B., Puri, M. K., Kim, D. R., Deen, J. L., Holmgren, J., Carbis, R., Dhingra, M. S., Donner, A., Nair, G. B., Lopez, A. L., ... Clemens, J. D. (2013). 5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: A cluster-randomised, double-blind, placebo-controlled trial. Lancet Infectious Diseases, 13(12), 1050-1056. https://doi.org/10.1016/S1473-3099(13)70273-1

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

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. ",

keywords = "bivalent killed whole cell oral cholera vaccine, cholera vaccine, inactivated vaccine, placebo, shanchol, unclassified drug, adolescent, article, child, cholera, controlled study, double blind procedure, drug efficacy, Escherichia coli K 12, follow up, human, incidence, India, infant, infection rate, infectious diarrhea, major clinical study, outcome assessment, preschool child, priority journal, randomized controlled trial, school child, vaccination, Administration, Oral, Adolescent, Child, Child, Preschool, Cholera, Cholera Vaccines, Cluster Analysis, Diarrhea, Double-Blind Method, Humans, Infant, Placebos, Vaccination, Vaccines, Inactivated, Vibrio cholerae O1",

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

year = "2013",

month = dec,

doi = "10.1016/S1473-3099(13)70273-1",

language = "English",

volume = "13",

pages = "1050--1056",

journal = "Lancet Infectious Diseases",

issn = "1473-3099",

publisher = "The Lancet Publishing Group",

number = "12",

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Bhattacharya, SK, Sur, D, Ali, M, Kanungo, S, You, YA, Manna, B, Sah, B, Niyogi, SK, Park, JK, Sarkar, B, Puri, MK, Kim, DR, Deen, JL, Holmgren, J, Carbis, R, Dhingra, MS, Donner, A, Nair, GB, Lopez, AL, Wierzba, TF & Clemens, JD 2013, '5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: A cluster-randomised, double-blind, placebo-controlled trial', Lancet Infectious Diseases, vol. 13, no. 12, pp. 1050-1056. https://doi.org/10.1016/S1473-3099(13)70273-1

TY - JOUR

T1 - 5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India

T2 - A cluster-randomised, double-blind, placebo-controlled trial

AU - Bhattacharya, Sujit K.

AU - Sur, Dipika

AU - Ali, Mohammad

AU - Kanungo, Suman

AU - You, Young Ae

AU - Manna, Byomkesh

AU - Sah, Binod

AU - Niyogi, Swapan K.

AU - Park, Jin Kyung

AU - Sarkar, Banwarilal

AU - Puri, Mahesh K

AU - Kim, Deok Ryun

AU - Deen, Jacqueline L.

AU - Holmgren, Jan

AU - Carbis, Rodney

AU - Dhingra, Mandeep Singh

AU - Donner, Allan

AU - Nair, G Balakrish

AU - Lopez, Anna Lena

AU - Wierzba, Thomas F.

AU - Clemens, John D

PY - 2013/12

Y1 - 2013/12

N2 - 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.

AB - 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.

KW - bivalent killed whole cell oral cholera vaccine

KW - cholera vaccine

KW - inactivated vaccine

KW - placebo

KW - shanchol

KW - unclassified drug

KW - adolescent

KW - article

KW - child

KW - cholera

KW - controlled study

KW - double blind procedure

KW - drug efficacy

KW - Escherichia coli K 12

KW - follow up

KW - human

KW - incidence

KW - India

KW - infant

KW - infection rate

KW - infectious diarrhea

KW - major clinical study

KW - outcome assessment

KW - preschool child

KW - priority journal

KW - randomized controlled trial

KW - school child

KW - vaccination

KW - Administration, Oral

KW - Adolescent

KW - Child

KW - Child, Preschool

KW - Cholera

KW - Cholera Vaccines

KW - Cluster Analysis

KW - Diarrhea

KW - Double-Blind Method

KW - Humans

KW - Infant

KW - Placebos

KW - Vaccination

KW - Vaccines, Inactivated

KW - Vibrio cholerae O1

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U2 - 10.1016/S1473-3099(13)70273-1

DO - 10.1016/S1473-3099(13)70273-1

M3 - Article

C2 - 24140390

SN - 1473-3099

VL - 13

SP - 1050

EP - 1056

JO - Lancet Infectious Diseases

JF - Lancet Infectious Diseases

IS - 12

ER -

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

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