Preventive malaria treatment among school-aged children in sub-Saharan Africa: a systematic review and meta-analyses.
Preventive malaria treatment among school-aged children in sub-Saharan Africa: a systematic review and meta-analyses.
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DOI：
10.1016/s2214-109x(20)30325-9
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
Chico RM
中科院分区：
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作者：
Cohee LM;Opondo C;Clarke SE;Halliday KE;Cano J;Shipper AG;Barger-Kamate B;Djimde A;Diarra S;Dokras A;Kamya MR;Lutumba P;Ly AB;Nankabirwa JI;Njagi JK;Maiga H;Maiteki-Sebuguzi C;Matangila J;Okello G;Rohner F;Roschnik N;Rouhani S;Sissoko MS;Staedke SG;Thera MA;Turner EL;Van Geertruyden JP;Zimmerman MB;Jukes MCH;Brooker SJ;Allen E;Laufer MK;Chico RM
在撒哈拉以南非洲，5至15岁学龄儿童感染疟疾的负担没有得到充分重视，这是恶性疟原虫人-蚊传播的一个重要来源。需要采取更多的干预措施来控制和消除疟疾。我们的目的是评估疟疾的预防性治疗是否可能是减少学龄儿童恶性疟原虫感染和贫血以及降低寄生虫传播的有效手段。在这项系统性综述和两项荟萃分析中，我们检索了在线数据库PubMed、Embase、科克伦CENTRAL和Clinicaltrials.gov，以查找1990年1月1日至2018年12月14日期间发表的干预研究。我们纳入了随机研究，这些研究评估了撒哈拉以南非洲5-15岁无症状学龄儿童抗疟治疗对恶性疟原虫感染和贫血患病率、临床疟疾和认知功能的影响。我们首先提取研究级荟萃分析的数据，然后联系研究小组，请求为单个参与者数据荟萃分析提供数据。关注的结果包括显微镜检查发现的恶性疟原虫感染的患病率、贫血（研究定义的值或血红蛋白低于年龄校正和性别校正值）、随访期间的临床疟疾（基于研究特定定义的感染和症状）和代码传输测试评分。我们通过治疗类型和保护时间来评估效果，并通过传输设置来探索效果修改。对于研究水平的荟萃分析，我们使用固定效应和随机效应模型计算了二元结局的风险比和连续结局和汇总结局的标准化平均差异。我们使用分层广义线性模型对个体参与者数据进行荟萃分析。本研究在PROSPERO注册，CRD 42016030197。在确定的628项研究中，13项符合研究水平荟萃分析的条件（n=16 309）。来自11项研究的研究人员为个体参与者数据荟萃分析提供了至少一种结局的数据（n= 15658）。干预和研究设计高度异质性;总体偏倚风险较低。在研究水平的荟萃分析中，治疗与恶性疟原虫患病率（风险比[RR] 0.27，95%CI 0.17 - 0.44）、贫血（0.77，0.65 - 0.91）和临床疟疾（0.40，0.28 - 0.56）的降低相关;未列出认知结局的结果，因为只有3项试验的数据可用。在我们的个体参与者数据荟萃分析中，我们发现治疗显著降低了恶性疟原虫的患病率（校正RR [ARR] 0.46，95% CI 0.40 - 0.53; p<0.0001; 15 648例个体; 11项研究），贫血（ARR 0.85，0.77 - 0.92; p<0.0001; 15026例患者; 11项研究）和随后的临床疟疾（ARR 0.50，0.39 - 0.60; p<0.0001; 1815例患者; 4项研究）。我们检测到对10岁以上儿童认知功能的边际影响（标准化测试得分的校正平均差异为0.36，0.01 - 0.71; p= 0.044; 3962人; 5项研究），尽管我们发现在所有年龄段合并时没有显著影响。学龄儿童的疟疾预防性治疗显著降低了恶性疟原虫的流行率、贫血和随后在传播环境中发生临床疟疾的风险。决策者和方案管理人员应考虑对疟疾进行预防性治疗，以保护这一年龄组，并推进消灭疟疾的目标，同时权衡这些益处与化学预防的潜在风险。
The burden of malaria infection in sub-Saharan Africa among school-aged children aged 5–15 years is underappreciated and represents an important source of human-to-mosquito transmission of Plasmodium falciparum. Additional interventions are needed to control and eliminate malaria. We aimed to assess whether preventive treatment of malaria might be an effective means of reducing P falciparum infection and anaemia in school-aged children and lowering parasite transmission. In this systematic review and two meta-analyses, we searched the online databases PubMed, Embase, Cochrane CENTRAL, and Clinicaltrials.gov for intervention studies published between Jan 1, 1990, and Dec 14, 2018. We included randomised studies that assessed the effect of antimalarial treatment among asymptomatic school-aged children aged 5–15 years in sub-Saharan Africa on prevalence of P falciparum infection and anaemia, clinical malaria, and cognitive function. We first extracted data for a study-level meta-analysis, then contacted research groups to request data for an individual participant data meta-analysis. Outcomes of interest included prevalence of P falciparum infection detected by microscopy, anaemia (study defined values or haemoglobin less than age-adjusted and sex-adjusted values), clinical malaria (infection and symptoms on the basis of study-specific definitions) during follow-up, and code transmission test scores. We assessed effects by treatment type and duration of time protected, and explored effect modification by transmission setting. For study-level meta-analysis, we calculated risk ratios for binary outcomes and standardised mean differences for continuous outcomes and pooled outcomes using fixed-effect and random-effects models. We used a hierarchical generalised linear model for meta-analysis of individual participant data. This study is registered with PROSPERO, CRD42016030197. Of 628 studies identified, 13 were eligible for the study-level meta-analysis (n=16 309). Researchers from 11 studies contributed data on at least one outcome (n=15 658) for an individual participant data meta-analysis. Interventions and study designs were highly heterogeneous; overall risk of bias was low. In the study-level meta-analysis, treatment was associated with reductions in P falciparum prevalence (risk ratio [RR] 0·27, 95% CI 0·17–0·44), anaemia (0·77, 0·65–0·91), and clinical malaria (0·40, 0·28–0·56); results for cognitive outcomes are not presented because data were only available for three trials. In our individual participant data meta-analysis, we found treatment significantly decreased P falciparum prevalence (adjusted RR [ARR] 0·46, 95% CI 0·40–0·53; p<0·0001; 15 648 individuals; 11 studies), anaemia (ARR 0·85, 0·77–0·92; p<0·0001; 15 026 individuals; 11 studies), and subsequent clinical malaria (ARR 0·50, 0·39–0·60; p<0·0001; 1815 individuals; four studies) across transmission settings. We detected a marginal effect on cognitive function in children older than 10 years (adjusted mean difference in standardised test scores 0·36, 0·01–0·71; p=0·044; 3962 individuals; five studies) although we found no significant effect when combined across all ages. Preventive treatment of malaria among school-aged children significantly decreases P falciparum prevalence, anaemia, and risk of subsequent clinical malaria across transmission settings. Policy makers and programme managers should consider preventive treatment of malaria to protect this age group and advance the goal of malaria elimination, while weighing these benefits against potential risks of chemoprevention.