Higher-Dose Primaquine to Prevent Relapse of Plasmodium vivax Malaria.
Higher-Dose Primaquine to Prevent Relapse of Plasmodium vivax Malaria.
复制标题
DOI：
10.1056/nejmoa2104226
复制
发表时间：
2022-03-31
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
在美洲大部分地区，预防间日疟原虫疟疾复发的推荐治疗方法是伯氨喹，总剂量为每公斤体重3.5毫克，尽管有证据表明疗效中等。在巴西进行的这项试验中，我们评估了三种伯氨喹方案，以预防至少5岁儿童和显微镜证实的间日疟原虫单一感染的成人间日疟原虫疟疾复发。所有患者均接受氯喹直接观察3天（总剂量为25 mg/kg）。第1组在7天内接受总伯氨喹剂量为3.5 mg/kg（0.5 mg/kg/天），未观察给药;第2组接受与第1组相同的方案，但观察给药;第3组在14天内接受总伯氨喹剂量为7.0 mg/kg（也为0.5 mg/kg/天），观察给药。我们对患者进行了168天的监测。我们在第1组招募了63名患者，在第2组招募了96名患者，在第3组招募了95名患者。患者的中位年龄为22.4岁（范围：5.4 - 79.8岁）。到第28天，观察到3例间日疟原虫复发：第1组2例，第2组1例。到第168天，共发生70例复发：第1组24例，第2组34例，第3组12例。未发现严重不良事件。第168天，第1组、第2组和第3组中无复发的患者百分比分别为58%（95%置信区间[CI]，44 - 70）、59%（95% CI，47 - 69）和86%（95% CI，76 - 92）。生存分析显示，第1组和第3组之间第168天无复发百分比的差异为27个百分点（97.5%CI，10至44; P<0.001），第2组和第3组之间的差异为27个百分点（97.5%CI，12至42; P<0.001）。到第168天，伯氨喹以每公斤7.0毫克的总剂量给药在预防间日疟复发方面比以每公斤3.5毫克的总剂量给药具有更高的效力。（由美国国际开发署支持; ClinicalTrials.gov编号，NCT 03610399。
In most of the Americas, the recommended treatment to prevent relapse of Plasmodium vivax malaria is primaquine at a total dose of 3.5 mg per kilogram of body weight, despite evidence of only moderate efficacy. In this trial conducted in Brazil, we evaluated three primaquine regimens to prevent relapse of P. vivax malaria in children at least 5 years of age and in adults with microscopy-confirmed P. vivax monoinfection. All the patients received directly observed chloroquine for 3 days (total dose, 25 mg per kilogram). Group 1 received a total primaquine dose of 3.5 mg per kilogram (0.5 mg per kilogram per day) over 7 days with unobserved administration; group 2 received the same regimen as group 1 but with observed administration; and group 3 received a total primaquine dose of 7.0 mg per kilogram over 14 days (also 0.5 mg per kilogram per day) with observed administration. We monitored the patients for 168 days. We enrolled 63 patients in group 1, 96 in group 2, and 95 in group 3. The median age of the patients was 22.4 years (range, 5.4 to 79.8). By day 28, three P. vivax recurrences were observed: 2 in group 1 and 1 in group 2. By day 168, a total of 70 recurrences had occurred: 24 in group 1, 34 in group 2, and 12 in group 3. No serious adverse events were noted. On day 168, the percentage of patients without recurrence was 58% (95% confidence interval [CI], 44 to 70) in group 1, 59% (95% CI, 47 to 69) in group 2, and 86% (95% CI, 76 to 92) in group 3. Survival analysis showed a difference in the day 168 recurrence-free percentage of 27 percentage points (97.5% CI, 10 to 44; P<0.001) between group 1 and group 3 and a difference of 27 percentage points (97.5% CI, 12 to 42; P<0.001) between group 2 and group 3. The administration of primaquine at a total dose of 7.0 mg per kilogram had higher efficacy in preventing relapse of P. vivax malaria than a total dose of 3.5 mg per kilogram through day 168. (Supported by the U.S. Agency for International Development; ClinicalTrials.gov number, NCT03610399.)