"Investigating the rebound effects of seasonal malaria chemoprevention (SMC) in Mali"

总结 世卫组织建议在疟疾流行国家采用季节性疟疾化学预防措施， 自2012年以来，撒哈拉以南非洲季节性疟疾传播强劲。干预措施包括 对小于15岁的儿童给予全治疗剂量的磺胺嘧啶-乙胺嘧啶（SP）加阿莫地喹， 在疟疾传播季节，每4周对5岁的儿童进行一次，每年进行3至4轮。自2016年以来， 马里在全国范围内实施了该战略。虽然目标中的疟疾病例大幅减少， 2005年报告显示，5岁及以上儿童疟疾发病率呈上升趋势， 许多正在实施SMC的设置。拟议的研究考虑了以前的研究和试点数据 显示大约每八名儿童（12.5%）中有一名历史上没有接受过任何剂量或 治疗方案所需的四个剂量中的一个剂量。本研究旨在招募一个大型队列 允许对以前符合SMC的儿童与有效对照儿童进行大规模比较 小组（儿童以前不符合SMC），以阐明逐步淘汰SMC计划的影响， 年龄不合格。本R 01提案的主要目的是研究SMC的停药效应 通过以下三个具体目标：1）确定疟疾反弹 SMC入组后的发生率，包括其与重度疟疾和贫血的相关性; 2）评估 年龄特异性恶性疟原虫患病率、性寄生虫和无性寄生虫以及感染复数的变化 在SMC部署之后;和3）评估在SMC部署期间和之后对疟疾抗原的免疫应答的变化。 SMC合格性以及与疾病的关系。这项研究将提供有关 在5岁时停止SMC的影响，这可以大大有助于改善疟疾监测 其他低收入和中等收入国家的总体成果。

Summary Seasonal Malaria Chemoprevention (SMC) has been recommended by WHO for malaria endemic countries in sub-Saharan Africa with strong seasonal malaria transmission since 2012. The intervention consists of the administration of full treatment doses of Sulfadoxine-Pyrimethamine (SP) plus Amodiaquine to children less than 5 years of age every 4 weeks during the malaria transmission season for 3 to 4 rounds per year. Since 2016, Mali has implemented the strategy countrywide. While significant decreases in malaria cases among the target age group was observed, increasing trends in malaria among children 5 years and above is also reported in the many settings where SMC is being implemented. The proposed study considers previous studies and pilot data showing that approximately out of every eight children (12.5%) have historically received either no doses or a single dose out of a the required four doses for the treatment regimen. This study seeks to enroll a large cohort of children to permit a large-scale comparison between children previously compliant to SMC with a valid control group (children not previously compliant to SMC) to elucidate the effects of phasing out of the SMC program due to age ineligibility. The primary objective of this R01 proposal is to investigate the withdrawal effects of SMC due to age eligibility requirements through the following three specific aims: 1) Determine malaria rebound occurrence following SMC enrollment including its association with severe malaria and anemia; 2) Assess changes in the age-specific P. falciparum prevalence, sexual and asexual parasites, and multiplicity of infection following SMC deployment; and 3) Assess the change in immune response to malaria antigens during and following SMC eligibility and the relationship with disease. The study will provide valuable information on the impact of SMC stoppage at five years of age which can significant contribute improving monitoring malaria outcomes in other low- and middle-income countries overall.