Therapeutic Responses to Different Antimalarial Drugs in Vivax Malaria

The therapeutic responses to the eight most widely used antimalarial drugs were assessed in 207 adult patients with Plasmodium vivax malaria. This parasite does not cause marked sequestration, so parasite clearance can be used as a direct measure of antimalarial activity. The activities of these drugs in descending order were artesunate, artemether, chloroquine, mefloquine, quinine, halofantrine, primaquine, and pyrimethamine-sulfadoxine (PS). Therapeutic responses to PS were poor; parasitemias did not clear in 5 of the 12 PS-treated patients, whereas all the other patients made an initial recovery. Of 166 patients monitored for ≥28 days, 35% had reappearance of vivax malaria 11 to 65 days later and 7% developed falciparum malaria 5 to 21 days after the start of treatment. There were no significant differences in the times taken for vivax malaria reappearance among the different groups except for those given mefloquine and chloroquine, in which all vivax malaria reappearances developed >28 days after treatment, suggesting suppression of the first relapse by these slowly eliminated drugs. There was no evidence of chloroquine resistance. The antimalarial drugs vary considerably in their intrinsic activities and stage specificities of action.

本研究对207名感染间日疟原虫（Plasmodium vivax）的成年患者接受8种临床最常用抗疟药物后的治疗应答情况进行了评估。该类疟原虫不会引发显著的红细胞扣押（sequestration）现象，因此可将寄生虫清除率直接作为抗疟药物活性的量化评估指标。按药物活性从高到低排序，依次为青蒿琥酯（artesunate）、蒿甲醚（artemether）、氯喹（chloroquine）、甲氟喹（mefloquine）、奎宁（quinine）、卤泛群（halofantrine）、伯氨喹（primaquine）以及乙胺嘧啶-磺胺多辛（pyrimethamine-sulfadoxine，PS）。乙胺嘧啶-磺胺多辛（PS）的治疗应答效果不佳：12名接受该药物治疗的患者中有5名未实现寄生虫血症清除，而其余所有患者均获得了初始临床康复。在166名接受≥28天随访监测的患者中，35%的患者在治疗开始后11至65天出现间日疟复发，另有7%的患者在治疗开始后5至21天并发恶性疟。除甲氟喹与氯喹给药组外，其余各组患者的间日疟复发时间无显著统计学差异；甲氟喹与氯喹给药组的所有间日疟复发均发生在治疗后28天以上，提示这两种代谢清除速率较慢的药物可抑制间日疟的首次复发。本研究未观察到氯喹耐药的相关证据。各类抗疟药物的固有抗疟活性以及作用阶段特异性均存在显著差异。