在加蓬兰巴雷内，使用蒿甲醚-本芴醇和青蒿琥酯-阿莫地喹治疗无并发症恶性疟原虫疟疾的疗效、耐受性和安全性监测：一项开放标签临床试验。
Monitoring of efficacy, tolerability and safety of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Lambaréné, Gabon: an open-label clinical trial.
机构信息
Centre de Recherches Médicales de Lambaréné, BP: 242, Lambaréné, Gabon.
Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.
出版信息
Malar J. 2019 Dec 16;18(1):424. doi: 10.1186/s12936-019-3015-4.
BACKGROUND
Malaria remains a major public health problem, affecting mainly low-and middle-income countries. The management of this parasitic disease is challenged by ever increasing drug resistance. This study, investigated the therapeutic efficacy, tolerability and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ), used as first-line drugs to treat uncomplicated malaria in Lambaréné, Gabon.
METHODS
A non-randomized clinical trial was conducted between October 2017 and March 2018 to assess safety, clinical and parasitological efficacy of fixed-doses of AL and AS-AQ administered to treat uncomplicated Plasmodium falciparum malaria in children aged from 6 months to 12 years. After 50 children were treated with AL, another 50 children received ASAQ. The 2009 World Health Organization protocol for monitoring of the efficacy of anti‑malarial drugs was followed. Molecular markers msp1 and msp2 were used to differentiate recrudescence and reinfection. For the investigation of artemisinin resistant markers, gene mutations in Pfk13 were screened.
RESULTS
Per-protocol analysis on day 28 showed a PCR corrected cure rate of 97% (95% CI 86-100) and 95% (95% CI 84-99) for AL and AS-AQ, respectively. The most frequent adverse event in both groups was asthenia. No mutations in the kelch-13 gene associated with artemisinin resistance were identified. All participants had completed microscopic parasite clearance by day 3 post-treatment.
CONCLUSION
This study showed that AL and AS-AQ remain efficacious, well-tolerated, and are safe to treat uncomplicated malaria in children from Lambaréné. However, a regular monitoring of efficacy and a study of molecular markers of drug resistance to artemisinin in field isolates is essential. Trial registration ANZCTR, ACTRN12616001600437. Registered 18 November, http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12616001600437p&isBasic=True.
背景
疟疾仍然是一个主要的公共卫生问题，主要影响中低收入国家。这种寄生虫病的治疗受到日益增加的药物耐药性的挑战。本研究调查了青蒿琥酯-咯萘啶（AL）和青蒿琥酯-阿莫地喹（AS-AQ）在加蓬兰巴雷内作为治疗无并发症疟疾的一线药物的治疗效果、耐受性和安全性。
方法
2017 年 10 月至 2018 年 3 月期间，进行了一项非随机临床试验，以评估 AL 和 AS-AQ 固定剂量治疗 6 个月至 12 岁儿童无并发症恶性疟原虫疟疾的安全性、临床和寄生虫学疗效。在 50 名儿童接受 AL 治疗后，另外 50 名儿童接受了 ASAQ。采用 2009 年世界卫生组织监测抗疟药物疗效的方案。使用 msp1 和 msp2 分子标记物来区分复发和再感染。为了调查青蒿素耐药标记物，筛选 Pfk13 基因中的基因突变。
结果
28 天的意向治疗分析显示，AL 和 AS-AQ 的 PCR 校正治愈率分别为 97%（95%CI 86-100）和 95%（95%CI 84-99）。两组中最常见的不良事件是乏力。未发现与青蒿素耐药相关的 kelch-13 基因突变。所有参与者在治疗后第 3 天显微镜下寄生虫清除率均已完成。
结论
本研究表明，AL 和 AS-AQ 仍然有效、耐受性良好，可安全治疗兰巴雷内儿童的无并发症疟疾。然而，定期监测疗效和研究现场分离株中抗青蒿素药物耐药的分子标记物至关重要。试验注册 ANZCTR，ACTRN12616001600437。于 2018 年 11 月 18 日注册，http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12616001600437&isBasic=True。
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