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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Bill & Melinda Gates Foundation and the governments of South Korea and Sweden.
authors.affiliation: National Institute of Cholera and Enteric Diseases, Kolkata, India; Indian Council of Medical Research, New Delhi, India.
authors.forename: Sujit K
authors.initials: SK
authors.lastname: Bhattacharya
authors.forename: Dipika
authors.initials: D
authors.lastname: Sur
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ali
authors.forename: Suman
authors.initials: S
authors.lastname: Kanungo
authors.forename: Young Ae
authors.initials: YA
authors.lastname: You
authors.forename: Byomkesh
authors.initials: B
authors.lastname: Manna
authors.forename: Binod
authors.initials: B
authors.lastname: Sah
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Niyogi
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Park
authors.forename: Banwarilal
authors.initials: B
authors.lastname: Sarkar
authors.forename: Mahesh K
authors.initials: MK
authors.lastname: Puri
authors.forename: Deok Ryun
authors.initials: DR
authors.lastname: Kim
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Deen
authors.forename: Jan
authors.initials: J
authors.lastname: Holmgren
authors.forename: Rodney
authors.initials: R
authors.lastname: Carbis
authors.forename: Mandeep Singh
authors.initials: MS
authors.lastname: Dhingra
authors.forename: Allan
authors.initials: A
authors.lastname: Donner
authors.forename: G Balakrish
authors.initials: GB
authors.lastname: Nair
authors.forename: Anna Lena
authors.initials: AL
authors.lastname: Lopez
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wierzba
authors.forename: John D
authors.initials: JD
authors.lastname: Clemens
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002771:Cholera / Q000453:epidemiology / Q000382:microbiology / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000008:administration & dosage*; D016000:Cluster Analysis; D003967:Diarrhea / Q000382:microbiology / Q000517:prevention & control; D004311:Double-Blind Method; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D010919:Placebos; D014611:Vaccination / Q000379:methods; D015164:Vaccines, Inactivated / Q000008:administration & dosage; D041241:Vibrio cholerae O1 / Q000276:immunology
chemical_list: D022121:Cholera Vaccines; D010919:Placebos; D015164:Vaccines, Inactivated