Université Sorbonne Paris Cité, Université Paris Descartes, Inserm, INTS, Unité Biologie Intégrée du Globule Rouge, Laboratoire d'Excellence GR-Ex, Paris, France.
Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Service des Maladies Infectieuses et Tropicales, Paris, France.
J Travel Med. 2017 Mar 1;24(2). doi: 10.1093/jtm/taw093.
Artesunate (AS) is the WHO first-line treatment of severe malaria in endemic countries, in adults and children. However, despite solid evidence that AS is safe and more effective than quinine in endemic areas, its deployment in non-endemic areas has been slow, due in part to the absence of a full good manufacturing practice (GMP) qualification (although prequalification has been granted in 2010). Prospective comparative trials were not conducted in travellers, but several retrospective studies and case reports are providing insights into the efficacy and safety of AS in imported severe malaria.
We performed a systematic review on AS use in non-endemic areas for the treatment of imported severe malaria, using the Prisma method for bibliographic reports. Post-AS delayed haemolysis (PADH) was defined by delayed haemolytic episodes occurring 7-30 days after treatment initiation. We summarized prescription guidelines and generated answers to frequently asked questions regarding the use of AS in travellers with severe malaria.
We analysed 12 retrospectives and 1 prospective study as well as 7 case reports of AS treatment in 624 travellers. Of 574 patients with reported outcome, 23 died (4%). No death was attributed to AS toxicity. Non-haematological side effects were uncommon and mainly included mild hepatitis, neurological, renal, cutaneous and cardiac manifestations. PADH occurred in 15% of the treated patients. No death or sequelae were reported. Overall blood transfusion was administered in 50% of travellers with PADH.
AS is highly efficacious in travellers with severe malaria. The frequency of PADH supports the need of weekly follow-up of haematological parameters during 1 month. Full GMP qualification for the drug and rapid approval by drug agencies is warranted, backed by clear recommendations for optimal use.
青蒿琥酯（AS）是世界卫生组织在流行地区治疗重症疟疾的一线药物，适用于成人和儿童。然而，尽管有确凿的证据表明青蒿琥酯在流行地区比奎宁更安全、更有效，但由于缺乏完整的良好生产规范（GMP）认证（尽管在 2010 年已获得预认证），其在非流行地区的应用进展缓慢。旅行者中没有进行前瞻性对照试验，但一些回顾性研究和病例报告为青蒿琥酯治疗输入性重症疟疾的疗效和安全性提供了一些见解。
我们采用 Prisma 方法对非流行地区青蒿琥酯治疗输入性重症疟疾的文献报告进行了系统评价。青蒿琥酯治疗后迟发性溶血（PADH）定义为治疗开始后 7-30 天发生的迟发性溶血发作。我们总结了处方指南，并针对旅行者重症疟疾使用青蒿琥酯的常见问题提供了答案。
我们分析了 12 项回顾性研究和 1 项前瞻性研究以及 7 例青蒿琥酯治疗的病例报告，共涉及 624 例旅行者。在报告结局的 574 例患者中，有 23 例死亡（4%）。没有死亡归因于青蒿琥酯毒性。非血液学不良反应少见，主要包括轻度肝炎、神经、肾脏、皮肤和心脏表现。接受治疗的患者中有 15%发生 PADH。没有死亡或后遗症报告。PADH 患者总体上有 50%接受了输血。
青蒿琥酯对旅行者重症疟疾具有高度疗效。PADH 的发生频率支持在 1 个月内每周监测血液学参数的必要性。该药应获得完整的 GMP 认证并迅速获得药物管理机构的批准，同时应提供最佳使用的明确建议。
