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首页> 外文期刊>PLoS Medicine >The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network
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The risk of Plasmodium vivax parasitaemia after P. falciparum malaria: An individual patient data meta-analysis from the WorldWide Antimalarial Resistance Network

机译：P. falciparum疟疾后疟原虫寄生虫血浆的风险：来自全球抗疟线网络的个体患者数据荟萃分析

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Background There is a high risk of Plasmodium vivax parasitaemia following treatment of falciparum malaria. Our study aimed to quantify this risk and the associated determinants using an individual patient data meta-analysis in order to identify populations in which a policy of universal radical cure, combining artemisinin-based combination therapy (ACT) with a hypnozoitocidal antimalarial drug, would be beneficial. Methods and findings A systematic review of Medline, Embase, Web of Science, and the Cochrane Database of Systematic Reviews identified efficacy studies of uncomplicated falciparum malaria treated with ACT that were undertaken in regions coendemic for P. vivax between 1 January 1960 and 5 January 2018. Data from eligible studies were pooled using standardised methodology. The risk of P. vivax parasitaemia at days 42 and 63 and associated risk factors were investigated by multivariable Cox regression analyses. Study quality was assessed using a tool developed by the Joanna Briggs Institute. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42018097400). In total, 42 studies enrolling 15,341 patients were included in the analysis, including 30 randomised controlled trials and 12 cohort studies. Overall, 14,146 (92.2%) patients had P. falciparum monoinfection and 1,195 (7.8%) mixed infection with P. falciparum and P. vivax. The median age was 17.0 years (interquartile range [IQR] = 9.0–29.0 years; range = 0–80 years), with 1,584 (10.3%) patients younger than 5 years. 2,711 (17.7%) patients were treated with artemether-lumefantrine (AL, 13 studies), 651 (4.2%) with artesunate-amodiaquine (AA, 6 studies), 7,340 (47.8%) with artesunate-mefloquine (AM, 25 studies), and 4,639 (30.2%) with dihydroartemisinin-piperaquine (DP, 16 studies). 14,537 patients (94.8%) were enrolled from the Asia-Pacific region, 684 (4.5%) from the Americas, and 120 (0.8%) from Africa. At day 42, the cumulative risk of vivax parasitaemia following treatment of P. falciparum was 31.1% (95% CI 28.9–33.4) after AL, 14.1% (95% CI 10.8–18.3) after AA, 7.4% (95% CI 6.7–8.1) after AM, and 4.5% (95% CI 3.9–5.3) after DP. By day 63, the risks had risen to 39.9% (95% CI 36.6–43.3), 42.4% (95% CI 34.7–51.2), 22.8% (95% CI 21.2–24.4), and 12.8% (95% CI 11.4–14.5), respectively. In multivariable analyses, the highest rate of P. vivax parasitaemia over 42 days of follow-up was in patients residing in areas of short relapse periodicity (adjusted hazard ratio [AHR] = 6.2, 95% CI 2.0–19.5; p = 0.002); patients treated with AL (AHR = 6.2, 95% CI 4.6–8.5; p 0.001), AA (AHR = 2.3, 95% CI 1.4–3.7; p = 0.001), or AM (AHR = 1.4, 95% CI 1.0–1.9; p = 0.028) compared with DP; and patients who did not clear their initial parasitaemia within 2 days (AHR = 1.8, 95% CI 1.4–2.3; p 0.001). The analysis was limited by heterogeneity between study populations and lack of data from very low transmission settings. Study quality was high. Conclusions In this meta-analysis, we found a high risk of P. vivax parasitaemia after treatment of P. falciparum malaria that varied significantly between studies. These P. vivax infections are likely attributable to relapses that could be prevented with radical cure including a hypnozoitocidal agent; however, the benefits of such a novel strategy will vary considerably between geographical areas.
机译：背景技术在治疗恶性疟疾疟疾后，疟原虫寄生虫的风险很高。我们的研究旨在使用个体患者数据META分析量化这种风险和相关的决定因素，以识别普遍激进治疗的政策，将蒿属植物的联合治疗（ACT）与催眠灭绝抗疟药的政策相结合的人群将是有利。方法和调查结果和调查系统审查Medline，Embase，Science Web，系统评论的Cochrane数据库确定了在1960年1月1日至2018年1月1日至2018年1月5日之间进行了在地区委员会委员会委员会委员会委员会委员会委员会委员会的简单恶毒疟原虫。使用标准化方法汇集了合格研究的数据。通过多变量的COX回归分析研究了第42和63天和63天和第63天和相关危险因素的风险。使用Joanna Briggs Institute开发的工具评估研究质量。该研究在国际上的系统评价前瞻性登记册中注册（Prospero：CRD42018097400）。共有42项注册15,341名患者的研究均包括在分析中，包括30项随机对照试验和12项队列研究。总体而言，14,146名（92.2％）患者具有P.Malciparum单蛋白，1,195（7.8％）混合感染P. Falciparum和P.Vivax。中位年龄为17.0岁（局势范围[IQR] = 9.0-29.0岁;范围= 0-80岁），1,584名（10.3％）患者年轻超过5年。 2,711名（17.7％）患者用蒿甲醚 - Lumefantrine（Al，13项研究）治疗，651（4.2％），用艺术 - 积极（AA，6项研究），7,340（47.8％），与艺术 - Mefloquine（AM，25项研究）进行7,340（47.8％）和4,639（30.2％），二氢氨基氨苄蛋白 - 滴点（DP，16项研究）。 14,537名患者（94.8％）从亚太地区，684（4.5％）的亚太地区注册，来自非洲的120（0.8％）。在第42天，在AA后，在A1，14.1％（95％CI 10.8-18.3）之后，vivax副血症血症的累积风险为AA后，14.1％（95％CI 10.8-18.3），7.4％（95％CI 6.7 -8.1）在DP后4.5％（95％CI 3.9-5.3）。在63天，风险上升至39.9％（95％CI 36.6-43.3），42.4％（95％CI 34.7-51.2），22.8％（95％CI 21.24.4），12.8％（95％CI 11.4分别为-14.5）。在多变量分析中，在居住在短复发周期（调整后危险比[AHR] = 6.2,95％CI 2.0-19.5; P = 0.002）的患者中，P.Vivax副血症的最高速率是42天的后续随访患者.P = 0.002） ;用Al处理的患者（AHR = 6.2,95％CI 4.6-8.5; P <0.001），AA（AHR = 2.3,95％CI 1.4-3.7; P = 0.001），或AM（AHR = 1.4,95％CI 1.0 -1.9; p = 0.028）与DP相比;在2天内没有清除其初始寄生虫的患者（AHR = 1.8,95％CI 1.4-2.3; P <0.001）。该分析受到研究群体之间的异质性和来自非常低的传输设置之间的数据的限制。学习质量很高。结论在这种荟萃分析中，我们发现在治疗研究之间进行了显着变化的恶性疟原虫疟疾后P.Vivax Parasititititititaemia的风险很高。这些P.Vivax感染可能是可归因的，以便重复，可防止包括催眠剂的自由基固化;但是，在地理区域之间这种新策略的好处会有所不同。

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