1Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
2Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Am J Trop Med Hyg. 2020 Dec;103(6):2224-2232. doi: 10.4269/ajtmh.20-0852. Epub 2020 Oct 15.
Artemether-lumefantrine (AL) is a first-line agent for uncomplicated malaria caused by . The WHO recommends periodic therapeutic efficacy studies of antimalarial drugs for the detection of malaria parasite drug resistance and to inform national malaria treatment policies. We conducted a therapeutic efficacy study of AL in a high malaria transmission region of northern Zambia from December 2014 to July 2015. One hundred children of ages 6 to 59 months presenting to a rural health clinic with uncomplicated falciparum malaria were admitted for treatment with AL (standard 6-dose regimen) and followed weekly for 5 weeks. Parasite counts were taken every 6 hours during treatment to assess parasite clearance. Recurrent episodes during follow-up ( = 14) were genotyped to distinguish recrudescence from reinfection and to identify drug resistance single nucleotide polymorphisms (SNPs) and multidrug resistance protein 1 () copy number variation. Day 7 lumefantrine concentrations were measured for correspondence with posttreatment reinfection. All children who completed the parasite clearance portion of the study ( = 94) were microscopy-negative by 72 hours. The median parasite elimination half-life was 2.7 hours (interquartile range: 2.1-3.3). Genotype-corrected therapeutic efficacy was 98.8% (95% CI: 97.6-100). Purported artemisinin and lumefantrine drug resistance SNPs in , , and were detected but did not correlate with parasite recurrence, nor did day 7 lumefantrine concentrations. In summary, AL was highly effective for the treatment of uncomplicated falciparum malaria in northern Zambia during the study period. The high incidence of recurrent parasitemia was consistent with reinfection due to high, perennial malaria transmission.
蒿甲醚-本芴醇（AL）是治疗无并发症疟疾的一线药物，这种疟疾由 引起。世界卫生组织（WHO）建议定期进行抗疟药物疗效研究，以发现疟原虫的药物耐药性并为国家疟疾治疗政策提供依据。我们在赞比亚北部一个疟疾高传播地区进行了一项关于 AL 的疗效研究，研究时间为 2014 年 12 月至 2015 年 7 月。100 名年龄在 6 至 59 个月的儿童因患有无并发症的恶性疟疾病例而在农村诊所就诊，接受 AL（标准 6 剂疗程）治疗，并在接下来的 5 周内每周进行一次随访。在治疗期间每 6 小时进行一次寄生虫计数，以评估寄生虫清除情况。在随访期间（=14）出现了复发性发作，通过基因分型来区分复发和再感染，并确定药物耐药性单核苷酸多态性（SNP）和多药耐药蛋白 1（）拷贝数变异。测量第 7 天的青蒿素浓度以对应治疗后再感染的情况。完成寄生虫清除部分研究的所有儿童（=94）在 72 小时后均为显微镜阴性。寄生虫消除半衰期中位数为 2.7 小时（四分位距：2.1-3.3）。校正后的治疗效果为 98.8%（95%CI：97.6-100）。在 ， ，和 中检测到的所谓青蒿素和本芴醇耐药 SNP 与寄生虫复发无关，第 7 天的青蒿素浓度也无关。总之，在研究期间，AL 对赞比亚北部无并发症恶性疟疾的治疗非常有效。高复发寄生虫血症的发生率与因高、常年疟疾传播而导致的再感染一致。
