Epicentre, 8 rue Saint-Sabin, 75011, Paris, France.
Epicentre Research Centre, Maradi, Niger.
Malar J. 2018 Jan 25;17(1):52. doi: 10.1186/s12936-018-2200-1.
Malaria endemic countries need to assess efficacy of anti-malarial treatments on a regular basis. Moreover, resistance to artemisinin that is established across mainland South-East Asia represents today a major threat to global health. Monitoring the efficacy of artemisinin-based combination therapies is of paramount importance to detect as early as possible the emergence of resistance in African countries that toll the highest burden of malaria morbidity and mortality.
A WHO standard protocol was used to assess efficacy of the combinations artesunate-amodiaquine (AS-AQ Winthrop), dihydroartemisinin-piperaquine (DHA-PPQ, Eurartesim) and artemether-lumefantrine (AM-LM, Coartem) taken under supervision and respecting pharmaceutical recommendations. The study enrolled for each treatment arm 212 children aged 6-59 months living in Maradi (Niger) and suffering with uncomplicated falciparum malaria. The Kaplan-Meier 42-day PCR-adjusted cure rate was the primary outcome. A standardized parasite clearance estimator was used to assess delayed parasite clearance as surrogate maker of suspected artemisinin resistance.
No early treatment failures were found in any of the study treatment arms. The day-42 PCR-adjusted cure rate estimates were 99.5, 98.4 and 99.0% in the AS-AQ, DHA-PPQ and AM-LM arms, respectively. The reinfection rate (expressed also as Kaplan-Meier estimates) was higher in the AM-LM arm (32.4%) than in the AS-AQ (13.8%) and the DHA-PPQ arm (24.9%). The parasite clearance rate constant was 0.27, 0.26 and 0.25 per hour for AS-AQ, DHA-PPQ and AM-LM, respectively.
All the three treatments evaluated largely meet WHO criteria (at least 95% efficacy). AS-AQ and AL-LM may continue to be used and DHA-PPQ may be also recommended as first-line treatment for uncomplicated falciparum malaria in Maradi. The parasite clearance rate were consistent with reference values indicating no suspected artemisinin resistance. Nevertheless, the monitoring of anti-malarial drug efficacy should continue. Trial registration details Registry number at ClinicalTrial.gov: NCT01755559.
疟疾流行国家需要定期评估抗疟治疗的疗效。此外，在整个东南亚大陆确立的抗青蒿素耐药性目前对全球健康构成了重大威胁。监测青蒿素为基础的联合疗法的疗效对于尽早发现非洲国家青蒿素耐药性的出现至关重要，因为这些国家疟疾发病率和死亡率最高。
采用世界卫生组织标准方案评估青蒿琥酯-阿莫地喹（AS-AQ Winthrop）、双氢青蒿素-哌喹（DHA-PPQ，Eurartesim）和青蒿素-甲氟喹（ART-LM，Coartem）在监督下和遵守药品建议的情况下的疗效。每个治疗组招募了 212 名年龄在 6-59 个月的马里（尼日尔）儿童，患有无并发症的恶性疟原虫疟疾。主要结局是 42 天 PCR 调整后的治愈率的 Kaplan-Meier 曲线。标准化寄生虫清除估计值用于评估疑似青蒿素耐药性的寄生虫清除延迟作为替代标志物。
在任何研究治疗组中均未发现早期治疗失败。第 42 天 PCR 调整后的治愈率估计值分别为 AS-AQ、DHA-PPQ 和 AM-LM 组的 99.5%、98.4%和 99.0%。在 AM-LM 组（32.4%）的再感染率（也以 Kaplan-Meier 估计值表示）高于 AS-AQ 组（13.8%）和 DHA-PPQ 组（24.9%）。寄生虫清除率常数分别为 0.27、0.26 和 0.25 小时/小时，用于 AS-AQ、DHA-PPQ 和 AM-LM。
评估的所有三种治疗方法均符合世界卫生组织的标准（至少 95%的疗效）。AS-AQ 和 AM-LM 可继续使用，DHA-PPQ 也可作为马里无并发症恶性疟的一线治疗药物。寄生虫清除率与参考值一致，表明无疑似青蒿素耐药性。然而，应继续监测抗疟药物的疗效。试验注册详情 ClinicalTrial.gov 登记号：NCT01755559。
