Intermittent preventive therapy for malaria with monthly artemether-lumefantrine for the post-discharge management of severe anaemia in children aged 4-59 months in southern Malawi: a multicentre, randomised, placebo-controlled trial
Intermittent preventive therapy for malaria with monthly artemether-lumefantrine for the post-discharge management of severe anaemia in children aged 4-59 months in southern Malawi: a multicentre, randomised, placebo-controlled trial
复制标题
DOI：
10.1016/s1473-3099(11)70320-6
复制
发表时间：
2012-03-01
影响因子：
56.3
通讯作者：
ter Kuile, Feiko O.
中科院分区：
文献类型：
--
作者：
Phiri, Kamija;Esan, Michael;ter Kuile, Feiko O.
背景 非洲患有严重疟疾贫血的幼儿再次入院或出院 6 个月内死亡的风险很高。我们的目的是评估使用蒿甲醚-本芴醇进行 3 个月的化学预防是否可以降低这种风险。 方法 我们在马拉维的四家医院进行了一项随机、安慰剂对照、多中心试验，测试出院后间歇性预防治疗 (IPTpd) 对因严重疟疾贫血入院的 4-59 个月儿童的有效性和安全性。所有完成输血的恢复期儿童在出院时均接受了蒿甲醚苯芴醇治疗，并根据计算机生成的序列随机分配在出院后 1 个月和 2 个月接受安慰剂或蒿甲醚苯芴醇治疗，分别提供约 1 个月和 3 个月的保护。患者和研究人员在整个研究过程中都被蒙蔽。主要终点是入组后 1 至 6 个月内因全因严重贫血或严重疟疾而重新入院的综合终点。该试验已注册，编号 ISRCTN89727873。结果 在 1414 名入组儿童中，708 名被分配接受安慰剂，706 名被分配接受干预。 6 个月后，192 名儿童 (14%) 死亡或因严重疟疾或严重贫血而再次入院。随机分组后 1-6 个月，安慰剂组的 85 名儿童发生了 109 起主要事件，干预组的 74 名儿童发生了 86 起主要事件（调整后的保护效力 [PE] 31%，95% Cl 5-50；绝对率每 100 名儿童年减少 11.7，95% Cl 1.8-18.9；p=0.024）。保护作用在 IPTpd 期间（1-3 个月）最大，安慰剂组 49 名儿童发生 58 起主要事件，干预组 34 名儿童发生 37 起主要事件（PE 41%，10-62；p=0.01），但在第三个月后不再持续（4-6 个月，PE 17%，-27 至 45；p=0-395）。当包括第一个月的发作时，即在首次服用 IPTpd 之前，当两组均受益于出院时提供的蒿甲醚-本芴醇的治疗后预防效果时，6 个月的总累积 PE 为 26%（-2 至 46；1）=0.06）。 解释 在疟疾传播严重的地区，对患有严重疟疾贫血的儿童使用 IPTpd 进行化学预防可能会降低因严重贫血或疟疾再次入院。需要进行研究来证实这些发现并调查不同的实施机制和成本效益。资助荷兰非洲能力发展和针对贫困相关疾病的临床干预伙伴关系、瑞银擎天基金会和盖茨疟疾伙伴关系。
Background Young children with severe malarial anaemia in Africa are at high risk of readmittance to hospital or death within 6 months of discharge. We aimed to assess whether 3 months of chemoprevention with artemether-lumefantrine reduced this risk.Methods We did a randomised, placebo-controlled, multicentre trial in four hospitals in Malawi testing the efficacy and safety of intermittent preventive therapy post-discharge (IPTpd) in children aged 4-59 months admitted for severe malarial anaemia. All convalescent children who had completed a blood transfusion received artemether lumefantrine at discharge and were randomly assigned by a computer-generated sequence to receive placebo or artemether-lumefantrine at 1 month and 2 months after discharge, providing about 1 month and 3 months of protection, respectively. Patients and study staff were masked throughout the study. The primary endpoint was a composite of all-cause mortality or hospital readmittance because of all-cause severe anaemia or severe malaria between 1 and 6 months after enrolment. This trial is registered, number ISRCTN89727873.Results Of 1414 children enrolled, 708 were assigned to receive placebo and 706 the intervention. By 6 months, 192 children (14%) had died or were readmitted with severe malaria or severe anaemia. 1-6 months after randomisation, 109 primary events occurred in 85 children in the placebo group and 86 in 74 children in the intervention group (adjusted protective efficacy [PE] 31%, 95% Cl 5-50; absolute rate reduction 11.7 per 100 children years, 95% Cl 1.8-18.9; p=0.024). The protective effect was greatest during the IPTpd period (1-3 months), when 58 primary events occurred in 49 children in the placebo group and 37 in 34 children in the intervention group (PE 41%, 10-62; p=0.01), but was not sustained after the third month (4-6 months, PE 17%, -27 to 45; p=0-395). When episodes in the first month were included-ie, before the first dose of IPTpd, when both groups benefited from the post-treatment prophylactic effect of artemether-lumefantrine provided at discharge-the overall cumulative PE by 6 months was 26% (-2 to 46; 1)=0.06).Interpretation In areas with intense malaria transmission, chemoprevention with IPTpd given to children with severe malarial anaemia might reduce rates of readmittance to hospital for severe anaemia or malaria. Studies to confirm these findings and to investigate different delivery mechanisms and cost-effectiveness are needed.Funding The Netherlands African Partnership for Capacity Development and Clinical Interventions Against Poverty Related Diseases, the UBS-Optimus Foundation, and the Gates Malaria Partnership.