PLoS Med：开发出针对儿童的新型疟疾联合药物疗法

  近日，发表于国际杂志PLoS Medicine上的一篇研究论文中，来自西澳大学的研究人员表示，一种青蒿素-萘醌药物组合或许可以用于治疗患无并发症疟疾的儿童。

  疟疾是一种以蚊为媒介进行传播的寄生虫病，其每年可导致将近60万人死亡，许多不同种类的寄生虫均可以引发疟疾，而在某些地区，比如在巴布亚新几内亚，两种名为恶性疟原虫和间日疟原虫的寄生虫是引发疟疾感染的主要原因，这两种疟原虫对当前的抗疟疾药物反应并不一样。

  文章中，研究人员将当前推荐的疗法，即蒿甲醚-本芴醇药物疗法同新型疗法青蒿素-萘醌疗法治疗无并发症疟疾患病儿童的效果进行了对比，研究人员随机选取了186名恶性疟原虫感染的儿童及17名间日疟原虫感染的儿童进行研究，结果显示，新型疗法青蒿素-萘醌在治疗恶性疟原虫感染上并不逊色于蒿甲醚-本芴醇药物疗法，而且相比标准疗法而言，新型疗法还可以更有效地治疗间日疟原虫的感染。

  最终，研究者Moses Laman总结道，文章中我们证实了青蒿素-萘醌组合药物的效力、耐受性及安全性，而且每日三个剂量进行该联合药物的服用可以有效治疗在多种疟原虫流行地区患无并发症疟疾的儿童。（转化医学网360zhyx.com）

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转化医学网推荐的原文阅读：

Artemisinin-Naphthoquine versus Artemether-Lumefantrine for Uncomplicated Malaria in Papua New Guinean Children: An Open-Label Randomized Trial.
PLoS Medicine DOI: 10.1371/journal.pmed.1001773
Moses Laman, Brioni R. Moore, John M. Benjamin, Gumul Yadi, Cathy Bona, Jonathan Warrel, Johanna H. Kattenberg, Tamarah Koleala, Laurens Manning, Bernadine Kasian, Leanne J. Robinson, Naomi Sambale, Lina Lorry, Stephan Karl, Wendy A. Davis, Anna Rosanas-Urgell, Ivo Mueller, Peter M. Siba, Inoni Betuela, Timothy M. E. Davis.
Background
Artemisinin combination therapies (ACTs) with broad efficacy are needed where multiple Plasmodium species are transmitted, especially in children, who bear the brunt of infection in endemic areas. In Papua New Guinea (PNG), artemether-lumefantrine is the first-line treatment for uncomplicated malaria, but it has limited efficacy against P. vivax. Artemisinin-naphthoquine should have greater activity in vivax malaria because the elimination of naphthoquine is slower than that of lumefantrine. In this study, the efficacy, tolerability, and safety of these ACTs were assessed in PNG children aged 0.5–5 y.
Methods and Findings
An open-label, randomized, parallel-group trial of artemether-lumefantrine (six doses over 3 d) and artemisinin-naphthoquine (three daily doses) was conducted between 28 March 2011 and 22 April 2013. Parasitologic outcomes were assessed without knowledge of treatment allocation. Primary endpoints were the 42-d P. falciparum PCR-corrected adequate clinical and parasitologic response (ACPR) and the P. vivax PCR-uncorrected 42-d ACPR. Non-inferiority and superiority designs were used for falciparum and vivax malaria, respectively. Because the artemisinin-naphthoquine regimen involved three doses rather than the manufacturer-specified single dose, the first 188 children underwent detailed safety monitoring. Of 2,542 febrile children screened, 267 were randomized, and 186 with falciparum and 47 with vivax malaria completed the 42-d follow-up. Both ACTs were safe and well tolerated. P. falciparum ACPRs were 97.8% and 100.0% in artemether-lumefantrine and artemisinin-naphthoquine-treated patients, respectively (difference 2.2% [95% CI −3.0% to 8.4%] versus −5.0% non-inferiority margin, p = 0.24), and P. vivax ACPRs were 30.0% and 100.0%, respectively (difference 70.0% [95% CI 40.9%–87.2%], p<0.001). Limitations included the exclusion of 11% of randomized patients with sub-threshold parasitemias on confirmatory microscopy and direct observation of only morning artemether-lumefantrine dosing.
Conclusions
Artemisinin-naphthoquine is non-inferior to artemether-lumefantrine in PNG children with falciparum malaria but has greater efficacy against vivax malaria, findings with implications in similar geo-epidemiologic settings within and beyond Oceania.