Malaria Transmission Intensity Likely Modifies RTS, S/AS01 Efficacy Due to a Rebound Effect in Ghana, Malawi, and Gabon
Malaria Transmission Intensity Likely Modifies RTS, S/AS01 Efficacy Due to a Rebound Effect in Ghana, Malawi, and Gabon
复制标题
DOI：
10.1093/infdis/jiac322
复制
发表时间：
2022-07-28
影响因子：
6.4
通讯作者：
Emch, Michael
中科院分区：
文献类型：
--
作者：
Bell, Griffin J.;Goel, Varun;Emch, Michael
RTS，S/AS 01已被世界卫生组织建议广泛实施。使用来自3个地点的数据，我们发现，由于被称为“反弹”或“延迟”malaria.Background RTS，S/AS 01的现象，在高传播地区的疫苗效力较低。RTS，S/AS 01是世界卫生组织（WHO）批准并推荐广泛使用的第一种疟疾疫苗。试验报告说，在发病率较高的地区，疫苗的效力较低，这可能是由于接种疫苗的儿童疟疾病例“反弹”。当对照组中自然获得的保护增加，同时接种疫苗的疫苗保护减弱时，接种疫苗的疟疾发病率可能高于对照组，导致疫苗效力下降。方法使用2009-2014年马拉维利隆圭、加纳金坦波和加蓬兰巴内III期试验（NCT 00866619）的数据，我们通过估计每个疫苗组随时间推移和不同传播环境下的疟疾发病率来评估这一假设。在使用生态变量估计传播强度后，我们拟合了疫苗接种、时间和传播强度之间的3向相互作用模型。结果随着时间的推移，对照组的发病率下降，疫苗组的发病率上升。最低传播强度组（0.25例/人年[CPPY]）的三次给药疗效在4.5年内从88.2%降至15.0%，而最高传播强度组（3 CPPY）的三次给药疗效从81.6%降至-27.7%。结论这些发现表明，干预措施，包括第四RTS，S剂量，保护接种个体在潜在的反弹期，应实施高传输设置。
RTS,S/AS01 has been recommended for widespread implementation by the World Health Organization. Using data from 3 sites, we found that vaccine efficacy was lower in higher-transmission areas due to a phenomenon known as "rebound" or "delayed" malaria.Background RTS,S/AS01 is the first malaria vaccine to be approved and recommended for widespread implementation by the World Health Organization (WHO). Trials reported lower vaccine efficacies in higher-incidence sites, potentially due to a "rebound" in malaria cases in vaccinated children. When naturally acquired protection in the control group rises and vaccine protection in the vaccinated wanes concurrently, malaria incidence can become greater in the vaccinated than in the control group, resulting in negative vaccine efficacies. Methods Using data from the 2009-2014 phase III trial (NCT00866619) in Lilongwe, Malawi; Kintampo, Ghana; and Lambarene, Gabon, we evaluate this hypothesis by estimating malaria incidence in each vaccine group over time and in varying transmission settings. After estimating transmission intensities using ecological variables, we fit models with 3-way interactions between vaccination, time, and transmission intensity. Results Over time, incidence decreased in the control group and increased in the vaccine group. Three-dose efficacy in the lowest-transmission-intensity group (0.25 cases per person-year [CPPY]) decreased from 88.2% to 15.0% over 4.5 years, compared with 81.6% to -27.7% in the highest-transmission-intensity group (3 CPPY). Conclusions These findings suggest that interventions, including the fourth RTS,S dose, that protect vaccinated individuals during the potential rebound period should be implemented for high-transmission settings.