Department of Tropical Medicine and Parasitology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Department of International Affairs and Tropical Medicine, School of Medicine, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Malar J. 2020 Feb 18;19(1):76. doi: 10.1186/s12936-020-03157-0.
Usage of chloroquine was discontinued from the treatment of Plasmodium falciparum infection in almost all endemic regions because of global spread of resistant parasites. Since the first report in Malawi, numerous epidemiological studies have demonstrated that the discontinuance led to re-emergence of chloroquine-susceptible P. falciparum, suggesting a possible role in future malaria control. However, most studies were cross-sectional, with few studies looking at the persistence of chloroquine recovery in long term. This study fills the gap by providing, for a period of at least 6 years, proof of persistent re-emergence/stable recovery of susceptible parasite populations using both molecular and phenotypic methods.
Ex vivo drug-susceptibility assays to chloroquine (n = 319) and lumefantrine (n = 335) were performed from 2013 to 2018 in Gulu, Northern Uganda, where chloroquine had been removed from the official malaria treatment regimen since 2006. Genotyping of pfcrt and pfmdr1 was also performed.
Chloroquine resistance (≥ 100 nM) was observed in only 3 (1.3%) samples. Average IC values for chloroquine were persistently low throughout the study period (17.4-24.9 nM). Parasites harbouring pfcrt K76 alleles showed significantly lower ICs to chloroquine than the parasites harbouring K76T alleles (21.4 nM vs. 43.1 nM, p-value = 3.9 × 10). Prevalence of K76 alleles gradually increased from 71% in 2013 to 100% in 2018.
This study found evidence of stable persistence of chloroquine susceptibility with the fixation of pfcrt K76 in Northern Uganda after discontinuation of chloroquine in the region. Accumulation of similar evidence in other endemic areas in Uganda could open channels for possible future re-use of chloroquine as an option for malaria treatment or prevention.
由于全球耐药寄生虫的传播，几乎所有流行地区都停止将氯喹用于治疗恶性疟原虫感染。自马拉维首次报告以来，许多流行病学研究表明，停止使用氯喹导致对氯喹敏感的恶性疟原虫再次出现，这表明氯喹可能在未来的疟疾控制中发挥作用。然而，大多数研究都是横断面研究，很少有研究关注氯喹恢复的长期持久性。本研究通过使用分子和表型方法，至少在 6 年内提供了敏感寄生虫种群持续重新出现/稳定恢复的证据，填补了这一空白。
在北乌干达的古卢，从 2013 年到 2018 年，对 319 例氯喹（n=319）和 335 例青蒿琥酯（n=335）的体外药物敏感性进行了检测。在 2006 年停止使用氯喹作为官方疟疾治疗方案后，还对 pfcrt 和 pfmdr1 进行了基因分型。
仅在 3 个样本（1.3%）中观察到氯喹耐药（≥100nM）。整个研究期间，氯喹的平均 IC 值一直很低（17.4-24.9nM）。携带 pfcrt K76 等位基因的寄生虫对氯喹的 IC 值明显低于携带 K76T 等位基因的寄生虫（21.4nM 与 43.1nM，p 值=3.9×10）。K76 等位基因的流行率逐渐从 2013 年的 71%增加到 2018 年的 100%。
本研究发现，在北乌干达停止使用氯喹后，恶性疟原虫对氯喹的敏感性稳定持续存在，pfcrt K76 固定。在乌干达其他流行地区积累类似证据，可以为氯喹未来作为疟疾治疗或预防的选择重新使用开辟渠道。
