Efficacy of a low-cost, inactivated whole-cell oral cholera vaccine: results from 3 years of follow-up of a randomized, controlled trial.
BACKGROUND
Killed oral cholera vaccines (OCVs) have been licensed for use in developing countries, but protection conferred by licensed OCVs beyond two years of follow-up has not been demonstrated in randomized, clinical trials.


RESULTS
We conducted a cluster-randomized, placebo-controlled trial of a two-dose regimen of a low-cost killed whole cell OCV in residents 1 year of age and older living in 3,933 clusters in Kolkata, India. The primary endpoint was culture-proven Vibrio cholerae O1 diarrhea episodes severe enough to require treatment in a health care facility. Of the 66,900 fully dosed individuals (31,932 vaccinees and 34,968 placebo recipients), 38 vaccinees and 128 placebo-recipients developed cholera during three years of follow-up (protective efficacy 66%; one-sided 95%CI lower bound = 53%, p<0.001). Vaccine protection during the third year of follow-up was 65% (one-sided 95%CI lower bound = 44%, p<0.001). Significant protection was evident in the second year of follow-up in children vaccinated at ages 1-4 years and in the third year in older age groups.


CONCLUSIONS
The killed whole-cell OCV conferred significant protection that was evident in the second year of follow-up in young children and was sustained for at least three years in older age groups. Continued follow-up will be important to establish the vaccine's duration of protection.


BACKGROUND
ClinicalTrials.gov NCT00289224.
National Institute of Cholera and Enteric Diseases, Kolkata, India.
Dipika
D
Sur
Suman
S
Kanungo
Binod
B
Sah
Byomkesh
B
Manna
Mohammad
M
Ali
Allison M
AM
Paisley
Swapan K
SK
Niyogi
Jin Kyung
JK
Park
Banawarilal
B
Sarkar
Mahesh K
MK
Puri
Deok Ryun
DR
Kim
Jacqueline L
JL
Deen
Jan
J
Holmgren
Rodney
R
Carbis
Raman
R
Rao
Thu Van
TV
Nguyen
Seung Hyun
SH
Han
Stephen
S
Attridge
Allan
A
Donner
Nirmal K
NK
Ganguly
Sujit K
SK
Bhattacharya
G Balakrish
GB
Nair
John D
JD
Clemens
Anna Lena
AL
Lopez
D000284:Administration, Oral; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002771:Cholera / Q000382:microbiology / Q000517:prevention & control*; D022121:Cholera Vaccines / Q000008:administration & dosage / Q000191:economics / Q000276:immunology*; D003967:Diarrhea / Q000382:microbiology / Q000517:prevention & control; D005500:Follow-Up Studies; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007194:India; D007223:Infant; D010919:Placebos / Q000008:administration & dosage; D013997:Time Factors; D014611:Vaccination / Q000379:methods; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000191:economics / Q000276:immunology; D041241:Vibrio cholerae O1 / Q000302:isolation & purification
D022121:Cholera Vaccines; D010919:Placebos; D015164:Vaccines, Inactivated