Centre National de Recherche Et de Formation Sur Le Paludisme, Ouagadougou, Burkina Faso.
Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, US President's Malaria Initiative, Atlanta, GA, USA.
Malar J. 2021 Jan 19;20(1):48. doi: 10.1186/s12936-021-03585-6.
The World Health Organization recommends regularly assessing the efficacy of artemisinin-based combination therapy (ACT), which is a critical tool in the fight against malaria. This study evaluated the efficacy of two artemisinin-based combinations recommended to treat uncomplicated Plasmodium falciparum malaria in Burkina Faso in three sites: Niangoloko, Nanoro, and Gourcy.
This was a two-arm randomized control trial of the efficacy of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Children aged 6-59 months old were monitored for 42 days. The primary outcomes of the study were uncorrected and PCR-corrected efficacies to day 28 for AL and 42 for DP. Molecular markers of resistance to artemisinin derivatives and partner drugs were also analysed.
Of 720 children enrolled, 672 reached study endpoints at day 28, 333 in the AL arm and 339 in the DP arm. PCR-corrected 28-day per protocol efficacy in the AL arm was 74% (64-83%) in Nanoro, 76% (66-83%) in Gourcy, and 92% (84-96%) in Niangoloko. The PCR-corrected 42-day per protocol efficacy in the DP arm was 84% (75-89%) in Gourcy, 89% (81-94%) in Nanoro, and 97% (92-99%) in Niangoloko. No Pfk13 mutation previously associated with artemisinin-resistance was observed. No statistically significant association was found between treatment outcome and presence of the 86Y mutation in the Pfmdr1 gene. There was also no association observed between treatment outcome and Pfpm2 or Pfmdr1 copy number variation.
The results of this study indicate evidence of inadequate efficacy of AL at day 28 and DP at day 42 in the same two sites. A change of first-line ACT may be warranted in Burkina Faso. Trial Registry Pan African Clinical Trial Registry Identifier: PACTR201708002499311. Date of registration: 8/3/2017 https://pactr.samrc.ac.za/Search.aspx.
世界卫生组织建议定期评估青蒿素类复方疗法（ACT）的疗效，这是抗击疟疾的重要工具。本研究在布基纳法索的三个地点（尼安戈洛科、纳诺罗和古尔西）评估了两种推荐用于治疗无并发症恶性疟原虫疟疾的青蒿素类复方的疗效：青蒿琥酯-阿莫地喹（AL）和双氢青蒿素-哌喹（DP）。对 6-59 个月大的儿童进行了 42 天的监测。该研究的主要结局是未校正和 PCR 校正的 AL 在第 28 天和 DP 在第 42 天的疗效。还分析了对青蒿素衍生物和联合用药的耐药性的分子标志物。
在纳入的 720 名儿童中，有 672 名在第 28 天达到了研究终点，其中 333 名在 AL 组，339 名在 DP 组。在 AL 组中，PCR 校正的 28 天方案疗效在纳诺罗为 74%（64-83%），在古尔西为 76%（66-83%），在尼安戈洛科为 92%（84-96%）。在 DP 组中，PCR 校正的 42 天方案疗效在古尔西为 84%（75-89%），在纳诺罗为 89%（81-94%），在尼安戈洛科为 97%（92-99%）。未观察到先前与青蒿素耐药性相关的 Pfk13 突变。在 Pfmdr1 基因中 86Y 突变的存在与治疗结果之间未发现统计学上的显著关联。在 Pfpm2 或 Pfmdr1 拷贝数变异与治疗结果之间也未观察到关联。
本研究结果表明，在同一两个地点，AL 在第 28 天和 DP 在第 42 天的疗效不足。布基纳法索可能需要更换一线 ACT。试验注册 泛非临床试验注册中心标识符：PACTR201708002499311。注册日期：2017 年 8 月 8 日。https://pactr.samrc.ac.za/Search.aspx。
