Efficacy and safety of intermittent preventive treatment and intermittent screening and treatment versus single screening and treatment with dihydroartemisinin-piperaquine for the control of malaria in pregnancy in Indonesia: a cluster-randomised, open-label, superiority trial
Efficacy and safety of intermittent preventive treatment and intermittent screening and treatment versus single screening and treatment with dihydroartemisinin-piperaquine for the control of malaria in pregnancy in Indonesia: a cluster-randomised, open-label, superiority trial
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DOI：
10.1016/s1473-3099(19)30156-2
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发表时间：
2019-09-01
影响因子：
56.3
通讯作者：
ter Kuile, Feiko O.
中科院分区：
文献类型：
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作者：
Ahmed, Rukhsana;Poespoprodjo, Jeanne R.;ter Kuile, Feiko O.
背景恶性疟原虫和间日疟原虫感染是亚太地区不良妊娠结局的重要原因。我们假设双氢青蒿素-哌喹每月间歇预防治疗(IPT)或间歇筛查和治疗(IST)在减少妊娠期疟疾方面比现有的单一筛查和治疗(SST)策略更有效。SST策略用于在首次产前就诊时筛查妇女疟疾感染，然后被动发现病例，并对发热病例进行管理。方法我们在印度尼西亚Sumba(疟疾低传播点)和巴布亚(中度疟疾传播点)进行了一项开放标签、三臂、整群随机、优势试验。符合条件的参与者是怀孕16-30周的人。通过计算机生成的列表，将产前诊所(每年至少有10个新怀孕病例与地点、大小和疟疾风险相匹配)随机分配到IPT、IST或SST集群。在IPT组，参与者接受固定剂量的双氢青蒿素-哌喹组合(每天4毫克和18毫克/公斤)。在IST组，参与者每月接受一次疟疾快速诊断测试，而在SST组，他们只在登记时进行筛查。在所有小组中，发烧的参与者都接受了疟疾测试。任何检测呈阳性的参与者都接受双氢青蒿素-哌喹治疗，而不考虑症状。主要结果是母亲在分娩时感染疟疾。实验室工作人员并不知道小组分配的情况。分析包括所有随机分配的参与者提供的结果数据，并针对临床水平的分组进行了调整。该试验已完成，并在ISRCTN注册，编号为34010937。在2013年5月16日至2016年4月21日期间，78个集群(Sumba有57个，巴布亚有21个)被随机分配到SST、IPT或IST集群(每个集群26个集群)。在3553名接受资格筛选的妇女中，有2279人参加(744人在SST组，681人在IPT组，854人在IST组)。在登记时，IST的疟疾流行率(5.7%)低于SST(12.6%)和IPT(10.6%)群组。分娩时，SST组的疟疾患病率为20.2%(128/633)，而IPT组为11.6%(61/528，相对危险度为0.59，95%可信区间为0.42-0.83，p=0.0022)，IST组为11.8%(84/713，P=0.0005)。与妊娠、产褥期和围产期有关的情况是母亲最常见的严重不良事件，婴儿感染和感染是最常见的不良事件。在母亲或婴儿的严重不良事件方面，两组之间没有差异。解释IST与分娩时疟疾患病率低于SST有关，但这一组在登记时疟疾患病率也较低，这使得解释IST的效果具有挑战性。应考虑对高敏感性疟疾快速诊断试验进行进一步研究。在疟疾中度或高度传播的亚太地区，每月使用双氢青蒿素-哌喹的IPT是SST的一种很有前途的替代方案。版权所有(C)2019作者(S)。爱思唯尔有限公司出版。
Background Plasmodium falciparum and Plasmodium vivax infections are important causes of adverse pregnancy outcomes in the Asia-Pacific region. We hypothesised that monthly intermittent preventive treatment (IPT) or intermittent screening and treatment (IST) with dihydroartemisinin-piperaquine is more effective in reducing malaria in pregnancy than the existing single screening and treatment (SST) strategy, which is used to screen women for malaria infections at the first antenatal visit followed by passive case detection, with management of febrile cases.Methods We did an open-label, three-arm, cluster-randomised, superiority trial in Sumba (low malaria transmission site) and Papua (moderate malaria transmission site), Indonesia. Eligible participants were 16-30 weeks pregnant. Clusters (antenatal clinics with at least ten new pregnancies per year matched by location, size, and malaria risk) were randomly assigned (1:1:1) via computer-generated lists to IPT, IST, or SST clusters. In IPT clusters, participants received the fixed-dose combination of dihydroartemisinin-piperaquine (4 and 18 mg/kg per day). In IST clusters, participants were screened with malaria rapid diagnostic tests once a month, whereas, in SST clusters, they were screened at enrolment only. In all groups, participants with fever were tested for malaria. Any participant who tested positive received dihydroartemisinin-piperaquine regardless of symptoms. The primary outcome was malaria infection in the mother at delivery. Laboratory staff were unaware of group allocation. Analyses included all randomly assigned participants contributing outcome data and were adjusted for clustering at the clinic level. This trial is complete and is registered with ISRCTN, number 34010937.Findings Between May 16, 2013, and April 21, 2016, 78 clusters (57 in Sumba and 21 in Papua) were randomly assigned to SST, IPT, or IST clusters (26 clusters each). Of 3553 women screened for eligibility, 2279 were enrolled (744 in SST clusters, 681 in IPT clusters, and 854 in IST clusters). At enrolment, malaria prevalence was lower in IST (5.7%) than in SST (12.6%) and IPT (10.6%) clusters. At delivery, malaria prevalence was 20.2% (128 of 633) in SST clusters, compared with 11.6% (61 of 528) in IPT clusters (relative risk [RR] 0.59, 95% CI 0.42-0.83, p=0.0022) and 11.8% (84 of 713) in IST clusters (0.56, 0.40-0.77, p=0.0005). Conditions related to the pregnancy, the puerperium, and the perinatal period were the most common serious adverse events for the mothers, and infections and infestations for the infants. There were no differences between groups in serious adverse events in the mothers or in their infants.Interpretation IST was associated with a lower prevalence of malaria than SST at delivery, but the prevalence of malaria in this group was also lower at enrolment, making interpretation of the effect of IST challenging. Further studies with highly sensitive malaria rapid diagnostic tests should be considered. Monthly IPT with dihydroartemisinin-piperaquine is a promising alternative to SST in areas in the Asia-Pacific region with moderate or high transmission of malaria. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.