Defence Services Medical Academy, Yangon, Myanmar.
Myanmar Oxford Clinical Research Unit, Yangon, Myanmar.
Malar J. 2018 Jul 11;17(1):258. doi: 10.1186/s12936-018-2404-4.
Artemisinin resistance in Plasmodium falciparum has emerged and spread in Southeast Asia. In areas where resistance is established longer courses of artemisinin-based combination therapy have improved cure rates.
The standard 3-day course of artemether-lumefantrine (AL) was compared with an extended 5-day regimen for the treatment of uncomplicated falciparum malaria in Kayin state in South-East Myanmar, an area of emerging artemisinin resistance. Late parasite clearance dynamics were described by microscopy and quantitative ultra-sensitive PCR. Patients were followed up for 42 days.
Of 154 patients recruited (105 adults and 49 children < 14 years) 78 were randomized to 3 days and 76 to 5 days AL. Mutations in the P. falciparum kelch13 propeller gene (k13) were found in 46% (70/152) of infections, with F446I the most prevalent propeller mutation (29%; 20/70). Both regimens were well-tolerated. Parasite clearance profiles were biphasic with a slower submicroscopic phase which was similar in k13 wild-type and mutant infections. The cure rates were 100% (70/70) and 97% (68/70) in the 3- and 5-day arms respectively. Genotyping of the two recurrences was unsuccessful.
Despite a high prevalence of k13 mutations, the current first-line treatment, AL, was still highly effective in this area of South-East Myanmar. The extended 5 day regimen was very well tolerated, and would be an option to prolong the useful therapeutic life of AL. Trial registration NCT02020330. Registered 24 December 2013, https://clinicaltrials.gov/NCT02020330.
疟原虫对青蒿素的耐药性已经出现并在东南亚传播。在耐药性确立的地区，更长疗程的青蒿素为基础的联合疗法提高了治愈率。
在缅甸东南部克伦邦，一个青蒿素耐药性新兴地区，比较了标准的 3 天青蒿琥酯-咯萘啶（AL）疗程与 5 天延长疗程治疗无并发症恶性疟的疗效。通过显微镜和定量超敏 PCR 描述晚期寄生虫清除动力学。对患者进行 42 天随访。
在招募的 154 例患者中（105 例成人和 49 例<14 岁的儿童），78 例随机分为 3 天组，76 例随机分为 5 天组。在 152 例感染中发现疟原虫kelch13 螺旋桨基因（k13）突变 46%（70/152），其中 F446I 是最常见的螺旋桨突变（29%；20/70）。两种方案均耐受良好。寄生虫清除模式呈双相，在 k13 野生型和突变感染中，亚微观阶段相似，速度较慢。3 天组和 5 天组的治愈率分别为 100%（70/70）和 97%（68/70）。对两个复发病例的基因分型不成功。
尽管 k13 突变率较高，但在缅甸东南部的这一地区，目前的一线治疗药物 AL 仍然非常有效。5 天的延长疗程耐受性非常好，是延长 AL 治疗有效期的一种选择。试验注册 NCT02020330。2013 年 12 月 24 日注册，网址：https://clinicaltrials.gov/NCT02020330。
