BACKGROUND Seasonal malaria chemoprevention (SMC) has shown high protective efficacy against clinical malaria and severe malaria in a series of clinical trials. We evaluated the effectiveness of SMC treatments against clinical malaria when delivered at scale through national malaria control programmes in 2015 and 2016. METHODS AND FINDINGS Case-control studies were carried out in Mali and The Gambia in 2015, and in Burkina Faso, Chad, Mali, Nigeria, and The Gambia in 2016. Children aged 3-59 months presenting at selected health facilities with microscopically confirmed clinical malaria were recruited as cases. Two controls per case were recruited concurrently (on or shortly after the day the case was detected) from the neighbourhood in which the case lived. The primary exposure was the time since the most recent course of SMC treatment, determined from SMC recipient cards, caregiver recall, and administrative records. Conditional logistic regression was used to estimate the odds ratio (OR) associated with receipt of SMC within the previous 28 days, and SMC 29 to 42 days ago, compared with no SMC in the past 42 days. These ORs, which are equivalent to incidence rate ratios, were used to calculate the percentage reduction in clinical malaria incidence in the corresponding time periods. Results from individual countries were pooled in a random-effects meta-analysis. In total, 2,126 cases and 4,252 controls were included in the analysis. Across the 7 studies, the mean age ranged from 1.7 to 2.4 years and from 2.1 to 2.8 years among controls and cases, respectively; 42.2%-50.9% and 38.9%-46.9% of controls and cases, respectively, were male. In all 7 individual case-control studies, a high degree of personal protection from SMC against clinical malaria was observed, ranging from 73% in Mali in 2016 to 98% in Mali in 2015. The overall OR for SMC within 28 days was 0.12 (95% CI: 0.06, 0.21; p < 0.001), indicating a protective effectiveness of 88% (95% CI: 79%, 94%). Effectiveness against clinical malaria for SMC 29-42 days ago was 61% (95% CI: 47%, 72%). Similar results were obtained when the analysis was restricted to cases with parasite density in excess of 5,000 parasites per microlitre: Protective effectiveness 90% (95% CI: 79%, 96%; P<0.001), and 59% (95% CI: 34%, 74%; P<0.001) for SMC 0-28 days and 29-42 days ago, respectively. Potential limitations include the possibility of residual confounding due to an association between exposure to malaria and access to SMC, or differences in access to SMC between patients attending a clinic and community controls; however, neighbourhood matching of cases and controls, and covariate adjustment, attempted to control for these aspects, and the observed decline in protection over time, consistent with expected trends, argues against a major bias from these sources. CONCLUSIONS SMC administered as part of routine national malaria control activities provided a very high level of personal protection against clinical malaria over 28 days post-treatment, similar to the efficacy observed in clinical trials. The case-control design used in this study can be used at intervals to ensure SMC treatments remain effective.

中文翻译：

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大规模实施 SMC 时季节性疟疾化学预防 (SMC) 治疗的有效性：5 个国家的病例对照研究。

背景技术季节性疟疾化学预防（SMC）在一系列临床试验中显示出对临床疟疾和重症疟疾的高保护功效。我们评估了 2015 年和 2016 年通过国家疟疾控制计划大规模提供 SMC 治疗对临床疟疾的有效性。方法和结果 病例对照研究于 2015 年在马里和冈比亚以及布基纳法索、乍得、马里进行、尼日利亚和冈比亚，2016 年。在选定的医疗机构就诊的 3-59 个月的儿童被招募为病例。从病例居住的社区同时（在发现病例之日或之后不久）招募每个病例的两名对照。主要暴露是自最近一次 SMC 治疗以来的时间，根据 SMC 收件人卡、护理人员召回和行政记录确定。条件逻辑回归用于估计与过去 28 天内和 29 至 42 天前接受 SMC 相关的优势比 (OR)，与过去 42 天内未接受 SMC 相比。这些与发病率比率相当的 OR 用于计算相应时间段内临床疟疾发病率的降低百分比。来自各个国家的结果汇总在随机效应荟萃分析中。分析中总共包括 2,126 例病例和 4,252 例对照。在 7 项研究中，对照组和病例的平均年龄分别为 1.7 至 2.4 岁和 2.1 至 2.8 岁；对照组和病例中分别有 42.2%-50.9% 和 38.9%-46.9% 是男性。在所有 7 项个体病例对照研究中，观察到 SMC 对临床疟疾的高度个人保护，从 2016 年马里的 73% 到 2015 年马里的 98%。 SMC 在 28 天内的总体 OR 为 0.12 (95% CI: 0.06, 0.21; p < 0.001)，表明保护效果为 88% (95% CI: 79%, 94%)。SMC 29-42 天前对临床疟疾的有效率为 61% (95% CI: 47%, 72%)。当分析仅限于寄生虫密度超过每微升 5,000 只寄生虫的病例时，获得了类似的结果：保护效果 90%（95% CI：79%、96%；P<0.001）和 59%（95% CI： SMC 0-28 天和 29-42 天前分别为 34%、74%；P<0.001)。潜在的限制包括由于接触疟疾和接触 SMC 之间的关联而可能产生残余混淆，或在就诊患者和社区对照之间获得 SMC 的差异；然而，病例和对照的邻域匹配以及协变量调整试图控制这些方面，并且观察到的保护随时间下降，与预期趋势一致，反对这些来源的主要偏差。结论 SMC 作为国家常规疟疾控制活动的一部分，在治疗后 28 天内提供了非常高水平的个人针对临床疟疾的保护，与临床试验中观察到的功效相似。本研究中使用的病例对照设计可以间隔使用，以确保 SMC 治疗保持有效。并且随着时间的推移观察到的保护下降，与预期趋势一致，反对这些来源的主要偏见。结论 SMC 作为国家常规疟疾控制活动的一部分，在治疗后 28 天内提供了非常高水平的个人针对临床疟疾的保护，与临床试验中观察到的功效相似。本研究中使用的病例对照设计可以间隔使用，以确保 SMC 治疗保持有效。并且随着时间的推移观察到的保护下降，与预期趋势一致，反对这些来源的主要偏见。结论 SMC 作为国家常规疟疾控制活动的一部分，在治疗后 28 天内提供了非常高水平的个人针对临床疟疾的保护，与临床试验中观察到的功效相似。本研究中使用的病例对照设计可以间隔使用，以确保 SMC 治疗保持有效。