BACKGROUND Artemisinin-based combination therapy (ACT) is recommended to improve malaria treatment efficacy and limit drug-resistant parasites selection in malaria endemic areas. 5 years after they were adopted, the efficacy and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ), the first-line treatments for uncomplicated malaria were assessed in Burkina Faso. METHODS In total, 440 children with uncomplicated Plasmodium falciparum malaria were randomized to receive either AL or ASAQ for 3 days and were followed up weekly for 42 days. Blood samples were collected to investigate the ex vivo susceptibility of P. falciparum isolates to lumefantrine, dihydroartemisinin (the active metabolite of artemisinin derivatives) and monodesethylamodiaquine (the active metabolite of amodiaquine). The modified isotopic micro test technique was used to determine the 50% inhibitory concentration (IC50) values. Primary endpoints were the risks of treatment failure at days 42. RESULTS Out of the 440 patients enrolled, 420 (95.5%) completed the 42 days follow up. The results showed a significantly higher PCR unadjusted cure rate in ASAQ arm (71.0%) than that in the AL arm (49.8%) on day 42, and this trend was similar after correction by PCR, with ASAQ performing better (98.1%) than AL (91.1%). Overall adverse events incidence was low and not significantly different between the two treatment arms. Ex vivo results showed that 6.4% P. falciparum isolates were resistant to monodesthylamodiaquine. The coupled in vivo/ex vivo analysis showed increased IC50 values for lumefantrine and monodesethylamodiaquine at day of recurrent parasitaemia compared to baseline values while for artesunate, IC50 values remained stable at baseline and after treatment failure (p > 0.05). CONCLUSION These findings provide substantial evidence that AL and ASAQ are highly efficacious for the treatment of uncomplicated malaria in children in Burkina Faso. However, the result of P. falciparum susceptibility to the partner drugs advocates the need to regularly replicate such surveillance studies. This would be particularly indicated when amodiaquine is associated in seasonal malaria chemoprophylaxis (SMC) mass drug administration in children under 5 years in Burkina Faso. Trial registration clinicaltrials, NCT00808951. Registered 05 December 2008,https://clinicaltrials.gov/ct2/show/NCT00808951?cond=NCT00808951&rank=1.

中文翻译：

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蒿甲醚-氟美特林和青蒿琥酯-氨二喹作为儿童单纯性恶性疟疾的一线治疗的体内/体外疗效：在布基纳法索的一项开放标签随机对照试验。

背景技术推荐使用基于青蒿素的联合疗法（ACT）来提高疟疾治疗的效率并限制疟疾流行地区的耐药性寄生虫选择。在布基纳法索评估了一线治疗蒿甲醚-萤石碱（AL）和青蒿琥酯-氨二喹（ASAQ）的有效性和安全性后，对一线治疗疟疾进行了评估。方法总共440例无并发症的恶性疟原虫疟疾患儿被随机分配接受AL或ASAQ治疗3天，每周接受随访42天。收集血液样本以研究恶性疟原虫分离株对lumantantrine，双氢青蒿素（青蒿素衍生物的活性代谢产物）和单去乙基叠二醌（阿莫地喹的活性代谢产物）的体外敏感性。改良的同位素微测试技术用于确定50％抑制浓度（IC50）值。主要终点指标是在第42天治疗失败的风险。结果在440名患者中，有420名（95.5％）完成了42天的随访。结果显示，在第42天，ASAQ组的PCR未调整治愈率（71.0％）明显高于AL组（49.8％），经过PCR校正后，这种趋势相似，ASAQ的治愈率更高（98.1％） AL（91.1％）。总体不良事件发生率低，两个治疗组之间无显着差异。离体结果显示，6.4％的恶性疟原虫分离株对单去甲氨二喹具有抗性。体内/离体耦合分析显示，与寄生虫血症相比，复发性寄生虫血症当日卢美他汀和单去甲氨二喹的IC50值增加，而青蒿琥酯的IC50值在基线和治疗失败后保持稳定（p> 0.05）。结论这些发现提供了重要的证据，表明AL和ASAQ对布基纳法索儿童单纯性疟疾的治疗非常有效。但是，恶性疟原虫对伴侣药物的敏感性结果提示需要定期重复此类监测研究。当阿莫地喹与布基纳法索5岁以下儿童的季节性疟疾化学预防（SMC）大规模药物管理相关时，将特别指出这一点。试用注册临床试验，NCT00808951。2008年12月5日注册，https：