TY - JOUR
T1 - Exclusion of clinically atypical or microbiologically mixed diarrhoeal episodes from outcome events in a field trial of oral cholera vaccines
AU - Clemens, John D.
AU - Stanton, Bonita F.
AU - Harris, Jeffrey R.
AU - Chakraborty, J.
AU - Sack, David A.
AU - Rao, Malla R.
AU - Ahmed, Faruque
AU - Ansaruzzaman, M.
AU - Yunus, Md
AU - Svennerholm, Ann Mari
AU - Holmgren, Jan
N1 - Funding Information:
This work was supported by funds from the US Agency for International Development, the government of Japan, the Swedish Agency for Research Cooperation with Developing Countries, and the World Health Organization.
PY - 1989/6
Y1 - 1989/6
N2 - Clemens J D (International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh), Stanton B F, Harris J R, Chakraborty J, Sack D A, Rao M R, Ahmed F, Ansaruzzaman M, Yunus M, Svennerholm A M and Holmgren J. Exclusion of clinically atypical or microbiologically mixed diarrhoeal episodes from outcome events in a field trial of oral cholera vaccines. International Journal of Epidemiology 1989, 18: 441-445.We investigated whether alternative clinical and microbiological criteria for outcome events affected estimates of vaccine efficacy in a randomized, double-blind field trial of B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) oral cholera vaccines among 62285 rural Bangladeshi participants. At one year of follow-up estimates of vaccine protective efficacy (PE = 60%, P<0.0001 for BS-WC; PE = 54%, P<0.0001 for WC) against all treated diarrhoeal episodes associated with V. cholerae 01 were similar to estimates of efficacy against only those episodes which were clinically typical and unassociated with additional enteric pathogens (PE = 62%, P<0.0001 for BS-WC; PE = 52%, P<0.0001 for WC). In contrast, estimates of vaccine cross-protection against episodes associated with each of several agents antigenically related to V. cholerae 01 (LT-ETEC, non-cholera Vibrio sp, Aeromonas sp) were substantially reduced when mixed infections with V. cholerae 01 were excluded. We conclude that restrictive criteria intended to improve the specificity of the definition of cholera did not increase the detectability of vaccine efficacy against V. cholerae 01, but that exclusion of mixed infections with V. cholerae 01 was necessary to avoid false-positive conclusions about vaccine cross-protection against other potential target pathogens.
AB - Clemens J D (International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh), Stanton B F, Harris J R, Chakraborty J, Sack D A, Rao M R, Ahmed F, Ansaruzzaman M, Yunus M, Svennerholm A M and Holmgren J. Exclusion of clinically atypical or microbiologically mixed diarrhoeal episodes from outcome events in a field trial of oral cholera vaccines. International Journal of Epidemiology 1989, 18: 441-445.We investigated whether alternative clinical and microbiological criteria for outcome events affected estimates of vaccine efficacy in a randomized, double-blind field trial of B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) oral cholera vaccines among 62285 rural Bangladeshi participants. At one year of follow-up estimates of vaccine protective efficacy (PE = 60%, P<0.0001 for BS-WC; PE = 54%, P<0.0001 for WC) against all treated diarrhoeal episodes associated with V. cholerae 01 were similar to estimates of efficacy against only those episodes which were clinically typical and unassociated with additional enteric pathogens (PE = 62%, P<0.0001 for BS-WC; PE = 52%, P<0.0001 for WC). In contrast, estimates of vaccine cross-protection against episodes associated with each of several agents antigenically related to V. cholerae 01 (LT-ETEC, non-cholera Vibrio sp, Aeromonas sp) were substantially reduced when mixed infections with V. cholerae 01 were excluded. We conclude that restrictive criteria intended to improve the specificity of the definition of cholera did not increase the detectability of vaccine efficacy against V. cholerae 01, but that exclusion of mixed infections with V. cholerae 01 was necessary to avoid false-positive conclusions about vaccine cross-protection against other potential target pathogens.
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U2 - 10.1093/ije/18.2.440
DO - 10.1093/ije/18.2.440
M3 - Article
C2 - 2767860
AN - SCOPUS:0024382392
SN - 0300-5771
VL - 18
SP - 440
EP - 445
JO - International journal of epidemiology
JF - International journal of epidemiology
IS - 2
ER -