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青蒿琥酯和伯氨喹对恶性疟原虫无性和有性阶段寄生虫的活性。

Activities of artesunate and primaquine against asexual- and sexual-stage parasites in falciparum malaria.

作者信息

Pukrittayakamee Sasithon, Chotivanich Kesinee, Chantra Arun, Clemens Ralf, Looareesuwan Sornchai, White Nicholas J

机构信息

Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

出版信息

Antimicrob Agents Chemother. 2004 Apr;48(4):1329-34. doi: 10.1128/AAC.48.4.1329-1334.2004.

Abstract

The activities of primaquine in combination with quinine or artesunate against asexual- and sexual-stage parasites were assessed in 176 adult Thai patients with uncomplicated Plasmodium falciparum malaria. Patients were randomized to one of the six following 7-day oral treatment regimens: (i) quinine alone, (ii) quinine with tetracycline, (iii) quinine with primaquine at 15 mg/day, (iv) quinine with primaquine at 30 mg/day, (v) artesunate alone, or (vi) artesunate with primaquine. Clinical recovery occurred in all patients. There were no significant differences in fever clearance times, rates of P. falciparum reappearance, or recurrent vivax malaria between the six treatment groups. Patients treated with artesunate alone or in combination with primaquine had significantly shorter parasite clearance times (mean +/- standard deviation = 65 +/- 18 versus 79 +/- 21 h) and lower gametocyte carriage rates (40 versus 62.7%) than those treated with quinine (P < or = 0.007). Primaquine did not affect the therapeutic response (P > 0.2). Gametocytemia was detected in 98 patients (56% [22% before treatment and 34% after treatment]). Artesunate reduced the appearance of gametocytemia (relative risk [95% confidence interval] = 0.34 [0.17 to 0.70]), whereas combinations containing primaquine resulted in shorter gametocyte clearance times (medians of 66 versus 271 h for quinine groups and 73 versus 137 h for artesunate groups; P < or = 0.038). These results suggest that artesunate predominantly inhibits gametocyte development whereas primaquine accelerates gametocyte clearance in P. falciparum malaria.

摘要

在176例成年泰国单纯性恶性疟患者中评估了伯氨喹与奎宁或青蒿琥酯联合使用对无性和有性期疟原虫的作用。患者被随机分为以下六种7日口服治疗方案之一:(i)单独使用奎宁,(ii)奎宁与四环素联用,(iii)奎宁与15毫克/日的伯氨喹联用,(iv)奎宁与30毫克/日的伯氨喹联用,(v)单独使用青蒿琥酯,或(vi)青蒿琥酯与伯氨喹联用。所有患者均实现临床康复。六个治疗组在退热时间、恶性疟再现率或间日疟复发方面无显著差异。单独使用青蒿琥酯或与伯氨喹联用治疗的患者,其寄生虫清除时间显著短于使用奎宁治疗的患者(平均±标准差=65±18小时对79±21小时),配子体携带率也更低(40%对62.7%)(P≤0.007)。伯氨喹不影响治疗反应(P>0.2)。98例患者(56%[治疗前22%,治疗后34%])检测到配子体血症。青蒿琥酯降低了配子体血症的出现率(相对危险度[95%置信区间]=0.34[0.17至0.70]),而含伯氨喹的联合用药使配子体清除时间缩短(奎宁组中位数为66对271小时,青蒿琥酯组为73对137小时;P≤0.038)。这些结果表明,在恶性疟中,青蒿琥酯主要抑制配子体发育,而伯氨喹加速配子体清除。

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