2012 - 2013年在多哥开展的青蒿素联合疗法治疗非复杂性疟疾的疗效试验及k13螺旋桨结构域突变研究 - Suppr

Therapeutic efficacy trial of artemisinin-based combination therapy for the treatment of uncomplicated malaria and investigation of mutations in k13 propeller domain in Togo, 2012-2013.

作者信息

Dorkenoo Améyo M, Yehadji Degninou, Agbo Yao M, Layibo Yao, Agbeko Foli, Adjeloh Poukpessi, Yakpa Kossi, Sossou Efoe, Awokou Fantchè, Ringwald Pascal

机构信息

Faculté des Sciences de la Sante, Université de Lomé, BP 1515, Lomé, Togo.

Ministere de la Sante et de la Protection Sociale, Angle avenue Sarakawa et avenue du 2 Fevrier, BP 336, Lomé, Togo.

出版信息

Malar J. 2016 Jun 22;15:331. doi: 10.1186/s12936-016-1381-8.

BACKGROUND

Since 2005, the Togo National Malaria Control Programme has recommended two different formulations of artemisinin-based combination therapy (ACT), artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL), for the treatment of uncomplicated malaria. Regular efficacy monitoring of these two combinations is conducted every 2 or 3 years. This paper reports the latest efficacy assessment results and the investigation of mutations in the k13 propeller domain.

METHODS

The study was conducted in 2012-2013 on three sentinel sites of Togo (Lomé, Sokodé and Niamtougou). Children aged 6-59 months, who were symptomatically infected with Plasmodium falciparum, were treated with either AL (Coartem(®), Novartis Pharma, Switzerland) or ASAQ (Co-Arsucam(®), Sanofi Aventis, France). The WHO standard protocol for anti-malarial treatment evaluation was used. The primary end-point was 28-day adequate clinical and parasitological response (ACPR), corrected to exclude reinfection using polymerase-chain reaction (PCR) genotyping.

RESULTS

A total of 523 children were included in the study. PCR-corrected ACPR was 96.3-100 % for ASAQ and 97-100 % for AL across the three study sites. Adverse events were negligible: 0-4.8 % across all sites, for both artemisinin-based combinations. Upon investigation of mutations in the k13 propeller domain, only 9 (1.8 %) mutations were reported, three in each site. All mutant parasites were cleared before day 3. All day 3 positive patients were infected with k13 wild type parasites.

CONCLUSIONS

The efficacy of AL and ASAQ remains high in Togo, and both drugs are well tolerated. ASAQ and AL would be recommended for the treatment of uncomplicated malaria in Togo.

背景

自2005年以来，多哥国家疟疾控制规划推荐使用两种不同配方的青蒿素联合疗法（ACT），即青蒿琥酯-阿莫地喹（ASAQ）和蒿甲醚-本芴醇（AL），用于治疗非复杂性疟疾。每2或3年对这两种联合疗法进行一次常规疗效监测。本文报告了最新的疗效评估结果以及对k13螺旋桨结构域突变的调查。

方法

该研究于2012 - 2013年在多哥的三个哨点（洛美、索科德和尼亚姆图古）进行。对年龄在6至59个月、有恶性疟原虫症状性感染的儿童，使用AL（科泰复（®），瑞士诺华制药）或ASAQ（科-阿苏卡姆（®），法国赛诺菲安万特）进行治疗。采用了世界卫生组织抗疟治疗评估的标准方案。主要终点是28天充分临床和寄生虫学反应（ACPR），经聚合酶链反应（PCR）基因分型校正以排除再感染。

结果

该研究共纳入523名儿童。在三个研究地点，ASAQ经PCR校正后的ACPR为96.3% - 100%，AL为97% - 100%。不良事件可忽略不计：在所有地点，两种基于青蒿素的联合疗法的不良事件发生率均为0% - 4.8%。在对k13螺旋桨结构域的突变进行调查时，仅报告了9例（1.8%）突变，每个地点各3例。所有突变寄生虫在第3天前均被清除。所有第3天呈阳性的患者均感染了k13野生型寄生虫。