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The Lancet Infect Dis. 5 year efficacy of a bivalent killed whole-cell oral cholera vaccine in Kolkata, India: a cluster-randomised, double-blind, placebo-controlled trial
[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]
The Lancet Infectious Diseases, Early Online Publication, 18 October 2013
doi:10.1016/S1473-3099(13)70273-1
Copyright ? 2013 Elsevier Ltd All rights reserved.
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, 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 PhDg, 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.
Funding
Bill & Melinda Gates Foundation.
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a National Institute of Cholera and Enteric Diseases, Kolkata, India; b Indian Council of Medical Research, New Delhi, India; c International Vaccine Institute, Seoul, South Korea; d Menzies School of Health Research, Casuarina, NT, Australia; e University of Gothenburg, Gothenburg, Sweden; f Shantha Biotechnics, Hyderabad, India; g University of Western Ontario, London, Ontario, Canada; h University of the Philippines Manila, National Institutes of Health, Manila, Philippines; i UCLA School of Public Health, University of California, Los Angeles, CA, USA; j icddr,b, Dhaka, Bangladesh
Correspondence to: Dr Mohammad Ali, International Vaccine Institute, SNU Research Park, San 4-8 Nakseongdae-dong, Gwanak-gu, Seoul 151-919, South Korea
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The Lancet Infectious Diseases, Early Online Publication, 18 October 2013
doi:10.1016/S1473-3099(13)70273-1
Copyright ? 2013 Elsevier Ltd All rights reserved.
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, 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 PhDg, 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.
Funding
Bill & Melinda Gates Foundation.
________
a National Institute of Cholera and Enteric Diseases, Kolkata, India; b Indian Council of Medical Research, New Delhi, India; c International Vaccine Institute, Seoul, South Korea; d Menzies School of Health Research, Casuarina, NT, Australia; e University of Gothenburg, Gothenburg, Sweden; f Shantha Biotechnics, Hyderabad, India; g University of Western Ontario, London, Ontario, Canada; h University of the Philippines Manila, National Institutes of Health, Manila, Philippines; i UCLA School of Public Health, University of California, Los Angeles, CA, USA; j icddr,b, Dhaka, Bangladesh
Correspondence to: Dr Mohammad Ali, International Vaccine Institute, SNU Research Park, San 4-8 Nakseongdae-dong, Gwanak-gu, Seoul 151-919, South Korea
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