Tun Kyaw Myo, Jeeyapant Atthanee, Imwong Mallika, Thein Min, Aung Sai Soe Moe, Hlaing Tin Maung, Yuentrakul Prayoon, Promnarate Cholrawee, Dhorda Mehul, Woodrow Charles J, Dondorp Arjen M, Ashley Elizabeth A, Smithuis Frank M, White Nicholas J, Day Nicholas P J
Defence Services Medical Research Centre, Naypyitaw, Myanmar.
Myanmar Oxford Clinical Research Unit, Yangon, Myanmar.
Malar J. 2016 Mar 31;15:185. doi: 10.1186/s12936-016-1240-7.
Artemisinin resistance in Plasmodium falciparum extends across Southeast Asia where it is associated with worsening partner drug resistance and a decline in the efficacy of frontline artemisinin-based combination therapy. Dihydroartemisinin-piperaquine (DP) is an essential component of preventive and curative treatment in the region, but its therapeutic efficacy has fallen in Cambodia.
A prospective clinical and parasitological evaluation of DP was conducted at two sites in Upper Myanmar between August 2013 and December 2014, enrolling 116 patients with acute uncomplicated falciparum malaria. Patients received DP orally for 3 days together with primaquine 0.25 mg/kg on admission. Parasite clearance half-lives based on 6 hourly blood smears, and day 42 therapeutic responses were assessed as well as parasite K13 genotypes.
Median parasite clearance half-life was prolonged, and clearance half-life was greater than 5 h in 21% of patients. Delayed parasite clearance was significantly associated with mutations in the propeller region of the parasite k13 gene. The k13 F446I mutation was found in 25.4% of infections and was associated with a median clearance half-life of 4.7 h compared with 2.7 h for infections without k13 mutations (p < 0.001). There were no failures after 42 days of follow-up, although 18% of patients had persistent parasitaemia on day 3.
The dominant k13 mutation observed in Upper Myanmar, F446I, appears to be associated with an intermediate rate of parasite clearance compared to other common mutations described elsewhere in the Greater Mekong Subregion. Discerning this phenotype requires relatively detailed clearance measurements, highlighting the importance of methodology in assessing artemisinin resistance.
恶性疟原虫对青蒿素的耐药性在东南亚地区广泛存在，这与伴侣药物耐药性加剧以及一线青蒿素联合疗法疗效下降有关。双氢青蒿素哌喹（DP）是该地区预防和治疗的重要组成部分，但在柬埔寨其治疗效果有所下降。
2013年8月至2014年12月期间，在缅甸上缅甸的两个地点对DP进行了前瞻性临床和寄生虫学评估，纳入了116例急性非复杂性恶性疟患者。患者入院时口服DP 3天，并同时服用伯氨喹0.25mg/kg。根据每6小时一次的血涂片评估寄生虫清除半衰期、第42天的治疗反应以及寄生虫K13基因型。
寄生虫清除半衰期中位数延长，21%的患者清除半衰期超过5小时。寄生虫清除延迟与寄生虫k13基因螺旋桨区域的突变显著相关。在25.4%的感染中发现了k13 F446I突变，与无k13突变的感染相比，其清除半衰期中位数为4.7小时，而无k13突变的感染为2.7小时（p<0.001）。随访42天后无治疗失败病例，尽管18%的患者在第3天仍有持续性寄生虫血症。
在缅甸上缅甸观察到的主要k13突变F446I，与大湄公河次区域其他地方描述的其他常见突变相比，似乎与寄生虫清除的中间速率有关。识别这种表型需要相对详细的清除测量，突出了方法学在评估青蒿素耐药性中的重要性。
