在一项群组随机试验中揭示口服霍乱疫苗的群体保护作用。
Unmasking herd protection by an oral cholera vaccine in a cluster-randomized trial.
机构信息
International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
出版信息
Int J Epidemiol. 2019 Aug 1;48(4):1252-1261. doi: 10.1093/ije/dyz060.
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.
背景
多项研究表明，灭活全细胞口服霍乱疫苗（OCV）不仅能为接种者提供直接保护，还能为人群提供群体保护。由于我们之前在孟加拉国城市进行的一项基于群组的随机对照有效性试验（CRT）未能检测到 OCV 的群体保护作用，因此我们重新分析了该试验，以评估在我们最初的分析中是否掩盖了群体效应。
方法
共有 267270 人被随机分为 90 个大致相等的群组。在 60 个群组中，年龄在 1 岁及以上的人有资格接种 OCV，而在 30 个群组中，人们未接受干预，作为对照组。我们分析了整个群组以及由最内圈家庭组成的子群组中 OCV 对严重脱水性霍乱的保护作用。我们假设，如果在这种人口密集的环境中，OCV 的群体保护作用因霍乱从外部传播到群组中而减弱，那么群体保护作用在最内圈家庭中最为明显。
结果
在所有群组居民随访的 2 年期间，总保护（OCV 接种者相对于对照组居民的保护）为 58%（95%置信区间：43%，70%；P<0.0001），间接保护（OCV 群组中非 OCV 接种者相对于对照组参与者的保护）为 16%（95%置信区间：-20%，41%；P=0.35），总体 OCV 保护（OCV 群组中所有居民相对于对照组居民的保护）为 46%（95%置信区间：30%，59%；P<0.0001）。对群组内 75%和 50%家庭的分析得出了类似的结果。然而，最内圈 25%家庭的总保护率为 75%（95%置信区间：50%，87%；P<0.0001），间接保护率为 52%（95%置信区间：-9%，79%；P=0.08），总体保护率为 72%（95%置信区间：49%，84%；P<0.0001）。
结论
与过去的研究一致，我们发现了大量的 OCV 群体保护作用，但只有通过分析群组的最内圈家庭才能揭示这些作用。在 CRT 中分析疫苗群体效应时，需要谨慎定义群组。
Zotero 插件