TY - JOUR
T1 - Unmasking herd protection by an oral cholera vaccine in a cluster-randomized trial
AU - Ali, Mohammad
AU - Qadri, Firdausi
AU - Kim, Deok Ryun
AU - Islam, Taufiqul
AU - Im, Justin
AU - Ahmmed, Faisal
AU - Chon, Yun
AU - Islam Khan, Ashraful
AU - Zaman, Khalequ
AU - Marks, Florian
AU - Clemens, John D.
N1 - Funding Information:
The work was supported by the Bill & Melinda Gates Foundation (OPP1171432). The study was also supported by core grants to the icddr, b from the Governments of Bangladesh, Canada, Sweden, and the UK. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Funding Information:
The study was funded by the Bill and Melinda Gates Foundation (OPP1171432). The funder had no role in data analysis, data interpretation or writing of this manuscript.
Publisher Copyright:
© 2019 The Author(s).
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Background: Several studies have shown that inactivated, whole-cell oral cholera vaccines (OCVs) confer both direct protection on vaccinees and herd protection on populations. Because our earlier cluster-randomized effectiveness trial (CRT) in urban Bangladesh failed to detect OCV herd protection, we reanalysed the trial to assess whether herd effects were masked in our original analysis. Methods: A total of 267 270 persons were randomized to 90 approximately equal-sized clusters. In 60 clusters persons aged 1 year and older were eligible to receive OCV and in 30 clusters persons received no intervention and served as controls. We analysed OCV protection against severely dehydrating cholera for the entire clusters, as in our original analysis, and for subclusters consisting of residents of innermost households. We hypothesized that if OCV herd protection was attenuated by cholera transmission into the clusters from the outside in this densely populated setting, herd protection would be most evident in the innermost households. Results: During 2 years of follow-up of all residents of the clusters, total protection (protection of OCV recipients relative to control residents) was 58% [95% confidence interval (CI): 43%, 70%; P<0.0001], indirect protection (protection of non-OCV recipients in OCV clusters relative to control participants) was 16% (95% CI: -20%, 41%; P=0.35) and overall OCV protection (protection of all residents in the OCV clusters relative to control residents) was 46% (95% CI: 30%, 59%; P<0.0001). Analyses of the inner 75% and 50% households of the clusters showed similar findings. However, total protection was 75% (95% CI: 50%, 87%, P<0.0001), indirect protection 52% (95% CI: -9%, 79%; P=0.08) and overall protection 72% (95% CI: 49%, 84%; P<0.0001) for the innermost 25% households. Conclusion: Consistent with past studies, substantial OCV herd protective effects were identified, but were unmasked only by analysing innermost households of the clusters. Caution is needed in defining clusters for analysis of vaccine herd effects in CRTs of vaccines.
AB - Background: Several studies have shown that inactivated, whole-cell oral cholera vaccines (OCVs) confer both direct protection on vaccinees and herd protection on populations. Because our earlier cluster-randomized effectiveness trial (CRT) in urban Bangladesh failed to detect OCV herd protection, we reanalysed the trial to assess whether herd effects were masked in our original analysis. Methods: A total of 267 270 persons were randomized to 90 approximately equal-sized clusters. In 60 clusters persons aged 1 year and older were eligible to receive OCV and in 30 clusters persons received no intervention and served as controls. We analysed OCV protection against severely dehydrating cholera for the entire clusters, as in our original analysis, and for subclusters consisting of residents of innermost households. We hypothesized that if OCV herd protection was attenuated by cholera transmission into the clusters from the outside in this densely populated setting, herd protection would be most evident in the innermost households. Results: During 2 years of follow-up of all residents of the clusters, total protection (protection of OCV recipients relative to control residents) was 58% [95% confidence interval (CI): 43%, 70%; P<0.0001], indirect protection (protection of non-OCV recipients in OCV clusters relative to control participants) was 16% (95% CI: -20%, 41%; P=0.35) and overall OCV protection (protection of all residents in the OCV clusters relative to control residents) was 46% (95% CI: 30%, 59%; P<0.0001). Analyses of the inner 75% and 50% households of the clusters showed similar findings. However, total protection was 75% (95% CI: 50%, 87%, P<0.0001), indirect protection 52% (95% CI: -9%, 79%; P=0.08) and overall protection 72% (95% CI: 49%, 84%; P<0.0001) for the innermost 25% households. Conclusion: Consistent with past studies, substantial OCV herd protective effects were identified, but were unmasked only by analysing innermost households of the clusters. Caution is needed in defining clusters for analysis of vaccine herd effects in CRTs of vaccines.
KW - Cholera
KW - cluster-randomized trial
KW - fried-egg design
KW - vaccine effectiveness
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U2 - 10.1093/ije/dyz060
DO - 10.1093/ije/dyz060
M3 - Article
C2 - 30968110
AN - SCOPUS:85070813724
SN - 0300-5771
VL - 48
SP - 1252
EP - 1261
JO - International journal of epidemiology
JF - International journal of epidemiology
IS - 4
M1 - dyz060
ER -