Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau; OPEN, Odense Patient Data Explorative Network, Institute of Clinical Research, Odense University Hospital/University of Southern Denmark, Odense, Denmark.
Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau; OPEN, Odense Patient Data Explorative Network, Institute of Clinical Research, Odense University Hospital/University of Southern Denmark, Odense, Denmark.
Int J Infect Dis. 2024 Nov;148:107224. doi: 10.1016/j.ijid.2024.107224. Epub 2024 Aug 30.
Between 2003 and 2019, three trials (randomised controlled trials [RCTs]) in Guinea-Bissau randomised infants to an early 2-dose measles vaccine (MV) schedule at 4 and 9 months vs standard MV at 9 months. The RCTs produced contradictory mortality results; the effect being beneficial in the 2-dose group in the first but tending to have higher mortality in the last two RCTs. We hypothesised that increased frequency of campaigns with oral polio vaccine (C-OPV) explained the pattern.
We performed per-protocol analysis of individual-level survival data from the three RCTs in Cox proportional hazards models yielding hazard ratios (HR) for the 2-dose vs the 1-dose MV group. We examined whether timing of C-OPVs and early administration of OPV0 (birth to day 14) affected the HRs for 2-dose/1-dose MV.
The combined HR(2-dose/1-dose) was 0.79 (95% confidence interval: 0.62-1.00) for children receiving no C-OPV-before-enrolment, but 1.39 (0.97-1.99) for those receiving C-OPV-before-enrolment (homogeneity, P = 0.01). C-OPV-before-enrolment had a beneficial effect in the 1-dose group but tended to have a negative effect in the 2-dose group, especially in females. These effects were amplified further by early administration of OPV0.
In the absence of C-OPVs, an early 2-dose MV strategy had beneficial effects on mortality, but frequent C-OPVs may have benefitted the 1-dose group more than the 2-dose MV group, leading to varying results depending on the intensity of C-OPVs.
2003 年至 2019 年期间，在几内亚比绍进行的三项试验（随机对照试验[RCT]）将婴儿随机分配至 4 个月和 9 个月时接受两剂麻疹疫苗（MV）方案，与 9 个月时接受标准 MV 方案进行比较。这些 RCT 产生了相互矛盾的死亡率结果；在第一组中，两剂量组的效果是有益的，但在最后两项 RCT 中，两剂量组的死亡率趋于更高。我们假设，口服脊髓灰质炎疫苗（C-OPV）的接种频率增加解释了这一模式。
我们在 Cox 比例风险模型中对来自这三项 RCT 的个体生存数据进行了按方案分析，得出了两剂量组与单剂量 MV 组的危险比（HR）。我们研究了 C-OPV 的时间安排以及出生至第 14 天给予 OPV0 的早期接种是否会影响两剂量/单剂量 MV 的 HR。
未在登记前接受 C-OPV 的儿童的合并 HR（两剂量/单剂量）为 0.79（95%置信区间：0.62-1.00），而在登记前接受 C-OPV 的儿童为 1.39（0.97-1.99）（同质性，P=0.01）。在单剂量组中，C-OPV 在前登记时具有有益的效果，但在两剂量组中，特别是在女性中，C-OPV 在前登记时可能具有负面影响。OPV0 的早期给药进一步放大了这些影响。
在没有 C-OPV 的情况下，早期两剂量 MV 策略对死亡率有有益的影响，但频繁的 C-OPV 可能使单剂量组受益多于两剂量 MV 组，导致根据 C-OPV 的强度而产生不同的结果。
