Seven-Year Efficacy of RTS,S/AS01 Malaria Vaccine among Young African Children.
Seven-Year Efficacy of RTS,S/AS01 Malaria Vaccine among Young African Children.
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DOI：
10.1056/nejmoa1515257
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发表时间：
2016-06-30
期刊：
影响因子：
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通讯作者：
Bejon P
中科院分区：
文献类型：
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作者：
Olotu A;Fegan G;Wambua J;Nyangweso G;Leach A;Lievens M;Kaslow DC;Njuguna P;Marsh K;Bejon P
正在对候选疟疾疫苗RTS S/AS01进行评估，以便为将其纳入常规疫苗接种计划的决定提供信息。我们对5至17个月大的儿童进行了7年的随访，随机分配接受三剂RTS、S/AS01疫苗或狂犬病（对照）疫苗。终点为临床疟疾（体温≥37.5°C，感染恶性疟原虫每立方毫米约2500只）。在一项没有预先规定的分析中，利用儿童家周围1公里范围内居民的疟疾流行情况，估计了每个儿童的疟疾暴露情况。RTS，S/AS01组与对照组的疫苗效力定义为1减去风险比或发病率比乘以100。在7年的随访中，我们在223名随机分配到RTS，S/AS01组的儿童中发现1002例临床疟疾发作，在224名随机分配到对照组的儿童中发现992例发作。通过负二项回归评估，意向治疗组的疫苗效力为4.4%(95%可信区间[CI]， - 17.0至21.9;P = 0.66)，按方案分析的疫苗效力为7.0% （95% CI, - 14.5至24.6;P = 0.52）。疫苗效力随着时间的推移而减弱（接种疫苗和时间之间的相互作用P = 0.006），包括在疟疾寄生虫暴露率高于平均水平的儿童中，第5年出现负效力（意向治疗分析：- 43.5%;95% CI, - 100.3至- 2.8 [P = 0.03]；按方案分析：- 56.8%;95% CI, - 118.7至- 12.3 [P = 0.008]）。接种RTS，S/AS01的三剂疫苗最初对临床疟疾具有保护作用，但这一结果在疟疾寄生虫暴露率高于平均水平的地区的后期被反弹所抵消。（由适宜卫生技术方案疟疾疫苗倡议和其他机构资助；ClinicalTrials.gov编号，NCT00872963。）
The candidate malaria vaccine RTS,S/AS01 is being evaluated in order to inform a decision regarding its inclusion in routine vaccination schedules. We conducted 7 years of follow-up in children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of either the RTS,S/AS01 vaccine or a rabies (control) vaccine. The end point was clinical malaria (temperature of ≥37.5°C and infection with Plasmodium falciparum of >2500 parasites per cubic millimeter). In an analysis that was not prespecified, the malaria exposure of each child was estimated with the use of information on the prevalence of malaria among residents within a 1-km radius of the child’s home. Vaccine efficacy was defined as 1 minus the hazard ratio or the incidence-rate ratio, multiplied by 100, in the RTS,S/AS01 group versus the control group. Over 7 years of follow-up, we identified 1002 episodes of clinical malaria among 223 children randomly assigned to the RTS,S/AS01 group and 992 episodes among 224 children randomly assigned to the control group. The vaccine efficacy, as assessed by negative binomial regression, was 4.4% (95% confidence interval [CI], −17.0 to 21.9; P = 0.66) in the intention-to-treat analysis and 7.0% (95% CI, −14.5 to 24.6; P = 0.52) in the per-protocol analysis. Vaccine efficacy waned over time (P = 0.006 for the interaction between vaccination and time), including negative efficacy during the fifth year among children with higher-than-average exposure to malaria parasites (intention-to-treat analysis: −43.5%; 95% CI, −100.3 to −2.8 [P = 0.03]; per-protocol analysis: −56.8%; 95% CI, −118.7 to −12.3 [P = 0.008]). A three-dose vaccination with RTS,S/AS01 was initially protective against clinical malaria, but this result was offset by rebound in later years in areas with higher-than-average exposure to malaria parasites. (Funded by the PATH Malaria Vaccine Initiative and others; ClinicalTrials.gov number, NCT00872963.)