Department of Medicine, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Madhava Nagar, Manipal, Karnataka, 576104, India.
Manipal McGill Centre for Infectious Diseases, Prasanna School of Public Health, Manipal Academy of Higher Education, Madhava Nagar, Manipal, Karnataka, 576104, India.
Malar J. 2018 Sep 3;17(1):321. doi: 10.1186/s12936-018-2472-5.
Radical cure of Plasmodium vivax malaria requires treatment with a blood schizonticide and a hypnozoitocide (primaquine) to eradicate the dormant liver stages. There has been uncertainty about the operational effectiveness and optimum dosing of the currently recommended 14-day primaquine (PQ) course.
A two centre, randomized, open-label, two arm study was conducted in South India. Patients were randomized to receive either high dose (0.5 mg base/kg body weight) or conventional dose (0.25 mg/kg) PQ for 14 days. Plasma concentrations of PQ and carboxyprimaquine (CPQ) on the 7th day of treatment were measured by reverse phase high performance liquid chromatography. Study subjects were followed up for 6 months. Recurrent infections were genotyped using capillary fragment length polymorphism of two PCR-amplified microsatellite markers (MS07 and MS 10).
Fifty patients were enrolled. Baseline characteristics and laboratory features did not differ significantly between the groups. Mean age of the study population was 42 ± 16.0 years. Recurrences 80-105 days later occurred in 4 (8%) patients, two in each the groups. All recurrences had the same microsatellite genotype as that causing the index infection suggesting all were relapses. One relapse was associated with low CPQ concentrations suggesting poor adherence.
This small pilot trial supports the effectiveness of the currently recommended lower dose (0.25 mg/kg/day) 14 day PQ regimen for the radical cure of vivax malaria in South India. Trial registration Clinical Trials Registry-India, CTRI/2017/03/007999. Registered 3 March 2017, http://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&compid=19&EncHid=82755.86366 .
根治间日疟需要使用血裂殖体杀灭剂和休眠体杀灭剂（伯氨喹）来消除潜伏在肝脏中的疟原虫。目前推荐的 14 天伯氨喹（PQ）疗程的实际效果和最佳剂量一直存在不确定性。
在印度南部进行了一项为期 2 中心、随机、开放标签、双臂研究。患者被随机分为高剂量（0.5mg 碱基/kg 体重）或常规剂量（0.25mg/kg）PQ 组，疗程为 14 天。在治疗第 7 天，通过反相高效液相色谱法测量 PQ 和羧基伯氨喹（CPQ）的血浆浓度。研究对象随访 6 个月。使用两个 PCR 扩增微卫星标记（MS07 和 MS10）的毛细管片段长度多态性对复发性感染进行基因分型。
共纳入 50 例患者。两组间基线特征和实验室特征无显著差异。研究人群的平均年龄为 42±16.0 岁。80-105 天后发生 4 例（8%）复发病例，两组各 2 例。所有复发病例的微卫星基因型与引起指数感染的基因型相同，提示均为复发。1 例复发与 CPQ 浓度低有关，提示药物依从性差。
这项小型试点试验支持目前推荐的低剂量（0.25mg/kg/天）14 天 PQ 方案用于根治印度南部的间日疟。试验注册临床试验注册印度，CTRI/2017/03/007999。2017 年 3 月 3 日注册，http://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&compid=19&EncHid=82755.86366。
