WorldWide Antimalarial Resistance Network (WWARN), Oxford, UK.
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford, OX3 7FZ, UK.
Malar J. 2017 Dec 13;16(1):488. doi: 10.1186/s12936-017-2135-y.
There is no agreed standard method to assess the efficacy of anti-malarials for uncomplicated falciparum in pregnancy despite an increased risk of adverse outcomes for the mother and the fetus. The aim of this review is to present the currently available evidence from both observational and interventional cohort studies on anti-malarial efficacy in pregnancy and summarize the variability of assessment and reporting found in the review process.
Efficacy methodology and assessment of artemisinin-based treatments (ABT) and quinine-based treatments (QBT) were reviewed systematically using seven databases and two clinical trial registries (protocol registration-PROSPERO: CRD42017054808). Pregnant women in all trimesters with parasitologically confirmed uncomplicated falciparum malaria were included irrespective of symptoms. This review attempted to re-calculate proportions of treatment success applying the same definition as the standard WHO methodology for non-pregnant populations. Aggregated data meta-analyses using data from randomized control trials (RCTs) comparing different treatments were performed by random effects model.
A total of 48 eligible efficacy studies were identified including 7279 treated Plasmodium falciparum episodes. While polymerase chain reaction (PCR) was used in 24 studies for differentiating recurrence, the assessment and reporting of treatment efficacy was heterogeneous. When the same definition could be applied, PCR-corrected treatment failure of ≥ 10% at any time points was observed in 3/30 ABT and 3/7 QBT arms. Ten RCTs compared different combinations of ABT but there was a maximum of two published RCTs with PCR-corrected outcomes for each comparison. Five RCTs compared ABT and QBT. Overall, the risk of treatment failure was significantly lower in ABT than in QBT (risk ratio 0.22, 95% confidence interval 0.07-0.63), although the actual drug combinations and outcome endpoints were different. First trimester women were included in 12 studies none of which were RCTs of ABT.
Efficacy studies in pregnancy are not only limited in number but use varied methodological assessments. In five RCTs with comparable methodology, ABT resulted in higher efficacy than QBT in the second and third trimester of pregnancy. Individual patient data meta-analysis can include data from observational cohort studies and could overcome some of the limitations of the current assessment given the paucity of data in this vulnerable group.
尽管孕妇及其胎儿的不良结局风险增加，但对于治疗妊娠合并无并发症恶性疟原虫感染的抗疟药物，目前仍缺乏公认的标准方法来评估其疗效。本综述的目的是介绍目前来自观察性和干预性队列研究的关于妊娠期间抗疟药物疗效的现有证据，并总结在综述过程中发现的评估和报告的变异性。
使用七个数据库和两个临床试验注册处（方案注册-PROSPERO：CRD42017054808）系统地回顾了疗效方法学以及基于青蒿素的治疗（ABT）和奎宁的治疗（QBT）的评估。纳入了所有妊娠三期中经寄生虫学确认的患有无并发症恶性疟原虫感染的孕妇，无论其症状如何。本综述尝试应用与非妊娠人群相同的世卫组织标准方法，重新计算治疗成功率的比例。通过随机效应模型对比较不同治疗方法的随机对照试验（RCT）的汇总数据进行了荟萃分析。
共确定了 48 项符合条件的疗效研究，其中包括 7279 例治疗的恶性疟原虫感染病例。虽然 24 项研究使用聚合酶链反应（PCR）来区分复发，但治疗疗效的评估和报告存在很大的异质性。当可以应用相同的定义时，在 3/30 项 ABT 和 3/7 项 QBT 治疗组中，任何时间点 PCR 校正的治疗失败率均≥10%。10 项 RCT 比较了不同的 ABT 组合，但对于每个比较，只有最多两项发表的 RCT 具有 PCR 校正的结果。5 项 RCT 比较了 ABT 和 QBT。总体而言，ABT 的治疗失败风险明显低于 QBT（风险比 0.22，95%置信区间 0.07-0.63），尽管实际的药物组合和结局终点不同。12 项研究纳入了孕早期妇女，但没有一项是 ABT 的 RCT。
妊娠期间的疗效研究不仅数量有限，而且使用了不同的方法学评估。在 5 项具有可比性方法学的 RCT 中，ABT 在妊娠第二和第三孕期的疗效优于 QBT。个体患者数据荟萃分析可以纳入来自观察性队列研究的数据，并且可以克服当前评估方法的一些局限性，因为在这个脆弱群体中数据很少。
