International Statistics and Epidemiology Group, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
Malaria Research and Training Centre, Bamako, Mali.
BMC Med. 2022 Oct 7;20(1):352. doi: 10.1186/s12916-022-02536-5.
A recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01 malaria vaccine (primary series and two seasonal boosters) and seasonal malaria chemoprevention (four monthly cycles per year) was markedly more effective than either intervention given alone in preventing clinical malaria, severe malaria, and deaths from malaria.
In order to help optimise the timing of these two interventions, trial data were reanalysed to estimate the duration of protection against clinical malaria provided by RTS,S/AS01 when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01 with the group who received SMC alone. The duration of protection from SMC was also estimated comparing the combined intervention group with the group who received RTS,S/AS01 alone. Three methods were used: Piecewise Cox regression, Flexible parametric survival models and Smoothed Schoenfeld residuals from Cox models, stratifying on the study area and using robust standard errors to control for within-child clustering of multiple episodes.
The overall protective efficacy from RTS,S/AS01 over 6 months was at least 60% following the primary series and the two seasonal booster doses and remained at a high level over the full malaria transmission season. Beyond 6 months, protective efficacy appeared to wane more rapidly, but the uncertainty around the estimates increases due to the lower number of cases during this period (coinciding with the onset of the dry season). Protection from SMC exceeded 90% in the first 2-3 weeks post-administration after several cycles, but was not 100%, even immediately post-administration. Efficacy begins to decline from approximately day 21 and then declines more sharply after day 28, indicating the importance of preserving the delivery interval for SMC cycles at a maximum of four weeks.
The efficacy of both interventions was highest immediately post-administration. Understanding differences between these interventions in their peak efficacy and how rapidly efficacy declines over time will help to optimise the scheduling of SMC, malaria vaccination and the combination in areas of seasonal transmission with differing epidemiology, and using different vaccine delivery systems.
The RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218.
最近在布基纳法索和马里开展的一项 5920 名儿童试验表明，季节性疫苗接种与 RTS,S/AS01 疟疾疫苗（基础系列和两次季节性加强针）和季节性疟疾化学预防（每年四个月周期）联合应用，显著优于单独应用任何一种干预措施，能够更有效地预防临床疟疾、重症疟疾和疟疾死亡。
为了帮助优化这两种干预措施的时机，我们重新分析了试验数据，以评估 RTS,S/AS01 在季节性使用时预防临床疟疾的持续时间，方法是比较接受 SMC 和 RTS,S/AS01 联合治疗的组与单独接受 SMC 治疗的组。还通过比较联合干预组与单独接受 RTS,S/AS01 治疗的组来估计 SMC 的保护持续时间。使用了三种方法：分段 Cox 回归、灵活参数生存模型和 Cox 模型的平滑 Schoenfeld 残差，按研究区域分层，并使用稳健标准误差来控制多次发作的儿童内聚类。
基础系列和两次季节性加强针后 6 个月内，RTS,S/AS01 的总体保护效力至少为 60%，在整个疟疾传播季节仍保持较高水平。6 个月后，由于在此期间病例数较少（恰逢旱季开始），估计值的不确定性增加，保护效力似乎下降得更快。SMC 的保护作用在几个周期后给药后 2-3 周内超过 90%，但并非 100%，甚至在给药后立即也并非 100%。效力从大约第 21 天开始下降，然后在第 28 天后急剧下降，这表明必须将 SMC 周期的给药间隔最长保持在 4 周。
两种干预措施的效力在给药后立即最高。了解这些干预措施在峰值效力和效力随时间下降的速度方面的差异，将有助于优化 SMC、疟疾疫苗接种以及在具有不同流行病学特征的季节性传播地区的组合应用，并使用不同的疫苗接种系统。
本研究中收集数据的 RTS,S-SMC 试验在 clinicaltrials.gov 上注册：NCT03143218。
