The development and spread of artemisinin-resistant Plasmodium falciparum malaria in Greater Mekong Subregion has created impetus for continuing global monitoring of efficacy of artemisinin-based combination therapies (ACTs). This post analyses is aimed to evaluate changes in early treatment response markers 10 years after the adoption of ACTs as first-line treatments of uncomplicated falciparum malaria in Nigeria. At 14 sentinel sites in six geographical areas of Nigeria, we evaluated treatment responses in 1341 children under 5 years and in additional 360 children under 16 years with uncomplicated malaria enrolled in randomized trials of artemether-lumefantrine versus artesunate-amodiaquine at 5-year interval in 2009–2010 and 2014–2015 and at 2-year interval in 2009–2010 and 2012–2015, respectively after deployment in 2005. Asexual parasite positivity 1 day after treatment initiation (APPD1) rose from 54 to 62% and 2 days after treatment initiation from 5 to 26% in 2009–2010 to 2014–2015 (P = 0.002 and P <  0.0001, respectively). Parasite clearance time increased significantly from 1.6 days (95% confidence interval [CI]: 1.55–1.64) to 1.9 days (95% CI, 1.9–2.0) and geometric mean parasite reduction ratio 2 days after treatment initiation decreased significantly from 11 000 to 4700 within the same time period (P <  0.0001 for each). Enrolment parasitaemia > 75 000 μl− 1, haematocrit > 27% 1 day post-treatment initiation, treatment with artemether-lumefantrine and enrolment in 2014–2015 independently predicted APPD1. In parallel, Kaplan-Meier estimated risk of recurrent infections by day 28 rose from 8 to 14% (P = 0.005) and from 9 to 15% (P = 0.02) with artemether-lumefantrine and artesunate-amodiaquine, respectively. Mean asexual parasitaemia half-life increased significantly from 1.1 h to 1.3 h within 2 years (P <  0.0001). These data indicate declining parasitological responses through time to the two ACTs may be due to emergence of parasites with reduced susceptibility or decrease in immunity to the infections in these children. Pan African Clinical Trial Registration PACTR201508001188143 , 3 July 2015; PACTR201508001191898 , 7 July 2015 and PACTR201508001193368 , 8 July 2015 PACTR201510001189370 , 3 July 2015; PACTR201709002064150 , 1 March 2017; https://www.pactr.samrca.ac.za

中文翻译：

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在尼日利亚作为一线抗疟药部署十年后，儿童恶性疟原虫感染对青蒿素联合治疗的反应性下降

大湄公河次区域抗青蒿素恶性疟原虫疟疾的发展和传播为持续监测青蒿素联合疗法 (ACTs) 的疗效提供了动力。这篇文章分析旨在评估在尼日利亚采用 ACT 作为非复杂性恶性疟疾的一线治疗 10 年后早期治疗反应标志物的变化。在尼日利亚六个地理区域的 14 个哨点，我们评估了 1341 名 5 岁以下儿童和另外 360 名 16 岁以下无并发症疟疾儿童的治疗反应，这些儿童参加了 5 年间隔的蒿甲醚-苯芴醇与青蒿琥酯-阿莫地喹的随机试验2009-2010 年和 2014-2015 年以及 2009-2010 年和 2012-2015 年的 2 年间隔，分别在 2005 年部署后。2009-2010 年至 2014-2015 年，治疗开始后 1 天（APPD1）的无性寄生虫阳性率从 54% 上升到 62%，治疗开始后 2 天从 5% 上升到 26%（分别为 P = 0.002 和 P < 0.0001）。寄生虫清除时间从 1.6 天（95% 置信区间 [CI]：1.55-1.64）显着增加至 1.9 天（95% CI，1.9-2.0），治疗开始后 2 天的几何平均寄生虫减少率从 11 000 显着下降至4700 在同一时间段内（每个 P < 0.0001）。入组寄生虫血症 > 75 000 μl-1，治疗开始后 1 天血细胞比容 > 27%，使用蒿甲醚-苯芴醇治疗和 2014-2015 年入组独立预测 APPD1。与此同时，Kaplan-Meier 估计到第 28 天反复感染的风险从 8% 上升到 14%（P = 0.005）和从 9% 上升到 15%（P = 0. 02）分别与蒿甲醚-苯芴醇和青蒿琥酯-阿莫地喹。平均无性寄生虫血症半衰期在 2 年内从 1.1 小时显着增加至 1.3 小时（P < 0.0001）。这些数据表明，随着时间的推移，对这两种 ACT 的寄生虫学反应下降可能是由于这些儿童的易感性降低或对感染的免疫力降低的寄生虫的出现。泛非临床试验注册 PACTR201508001188143，2015 年 7 月 3 日；PACTR201508001191898，2015 年 7 月 7 日和 PACTR201508001193368，2015 年 7 月 8 日 PACTR201510001189370，2015 年 7 月 3 日；PACTR201709002064150，2017 年 3 月 1 日；https://www.pactr.samrca.ac.za