Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
National Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam.
Antimicrob Agents Chemother. 2021 Jul 16;65(8):e0009521. doi: 10.1128/AAC.00095-21.
Chloroquine (CQ) is the first-line treatment for Plasmodium vivax malaria in most countries where malaria is endemic. Monitoring P. vivax CQ resistance (CQR) is critical but remains challenged by the difficulty to distinguish real treatment failure from reinfection or liver relapse. The therapeutic efficacy of CQ against uncomplicated P. vivax malaria was evaluated in Gia Lai Province, Vietnam. Sixty-seven patients were enrolled and followed for 42 days using microscopy and quantitative PCR. Adequate clinical and parasitological response (ACPR) was 100% (66/66) on day 28 but 75.4% (49/65) on day 42. Eighteen recurrences (27.7%) were detected, with a median time to recurrence of 42 days (interquartile range [IQR], 35 to 42) and blood CQ concentration of <100 ng/ml. Primary infections leading to recurrence occurred in younger individuals (median age for ACPR = 25 years [IQR, 20 to 28]; recurrences = 18 [16 to 21]; = 0.002) had a longer parasite clearance time (PCT for ACPR 47.5 h [IQR, 36.2 to 59.8 h]; recurrences = 54.2 [48.4 to 62.0]; = 0.035) and higher gene expression (median relative expression ratio for ACPR 0.09 [IQR, 0.05 to 0.22]; recurrences = 0.20 [0.15 to 0.56]; = 0.002), but showed no differences in CQ sensitivity. Parasite genotyping by microsatellites, single nucleotide polymorphism (SNP) barcoding, and whole-genome sequencing (WGS) identified a majority of homologous recurrences, with 80% (8/10) showing >98% identity by descent to paired day 0 samples. This study shows that CQ remained largely efficacious to treat P. vivax in Gia Lai; i.e., recurrences occurred late (>day 28) and in the presence of low blood CQ concentrations. However, the combination of both WGS and gene expression analysis () data with clinical data (PCT) allowed us to identify potential emergence of low-grade CQR, which should be closely monitored. (This study has been registered at ClinicalTrials.gov under identifier NCT02610686.).
氯喹（CQ）是大多数疟疾流行国家治疗间日疟原虫的一线药物。监测间日疟原虫对 CQ 的耐药性（CQR）至关重要，但由于难以区分真正的治疗失败与再感染或肝复发，因此仍然具有挑战性。在越南嘉莱省评估了 CQ 治疗无并发症间日疟的疗效。招募了 67 名患者，并通过显微镜检查和定量 PCR 随访 42 天。第 28 天的完全临床和寄生虫学应答（ACPR）为 100%（66/66），但第 42 天为 75.4%（49/65）。检测到 18 例复发（27.7%），复发的中位时间为 42 天（四分位距 [IQR]，35 至 42），血 CQ 浓度＜100ng/ml。导致复发的原发性感染发生在年龄较小的个体中（ACPR 的中位年龄为 25 岁[IQR，20 至 28]；复发者为 18 岁[16 至 21]；=0.002），其寄生虫清除时间较长（ACPR 的 PCT 为 47.5 小时[IQR，36.2 至 59.8 小时]；复发者为 54.2 小时[48.4 至 62.0]；=0.035），基因表达更高（ACPR 的中位相对表达比为 0.09[IQR，0.05 至 0.22]；复发者为 0.20[0.15 至 0.56]；=0.002），但 CQ 敏感性无差异。微卫星、单核苷酸多态性（SNP）条码和全基因组测序（WGS）对寄生虫进行基因分型，确定了大多数同源复发，其中 80%（8/10）与配对第 0 天样本的同源性>98%。本研究表明，CQ 治疗嘉莱省间日疟原虫仍然非常有效；即复发发生在较晚（＞第 28 天）且血 CQ 浓度较低时。然而，将 WGS 和基因表达分析（）数据与临床数据（PCT）相结合，使我们能够识别潜在的低级别 CQR 的出现，应密切监测。（本研究已在 ClinicalTrials.gov 注册，标识符为 NCT02610686。）
