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缅甸东北部间日疟原虫疟疾对氯喹和伯氨喹治疗的反应

Therapeutic responses of Plasmodium vivax malaria to chloroquine and primaquine treatment in northeastern Myanmar.

作者信息

Yuan Lili, Wang Ying, Parker Daniel M, Gupta Bhavna, Yang Zhaoqing, Liu Huaie, Fan Qi, Cao Yaming, Xiao Yuping, Lee Ming-chieh, Zhou Guofa, Yan Guiyun, Baird J Kevin, Cui Liwang

机构信息

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China Department of Entomology, Pennsylvania State University, University Park, Pennsylvania, USA.

Institute of Tropical Medicine, Third Military Medical University, Chongqing, China.

出版信息

Antimicrob Agents Chemother. 2015 Feb;59(2):1230-5. doi: 10.1128/AAC.04270-14. Epub 2014 Dec 15.

Abstract

Chloroquine-primaquine (CQ-PQ) continues to be the frontline therapy for radical cure of Plasmodium vivax malaria. Emergence of CQ-resistant (CQR) P. vivax parasites requires a shift to artemisinin combination therapies (ACTs), which imposes a significant financial, logistical, and safety burden. Monitoring the therapeutic efficacy of CQ is thus important. Here, we evaluated the therapeutic efficacy of CQ-PQ for P. vivax malaria in northeast Myanmar. We recruited 587 patients with P. vivax monoinfection attending local malaria clinics during 2012 to 2013. These patients received three daily doses of CQ at a total dose of 24 mg of base/kg of body weight and an 8-day PQ treatment (0.375 mg/kg/day) commencing at the same time as the first CQ dose. Of the 401 patients who finished the 28-day follow-up, the cumulative incidence of recurrent parasitemia was 5.20% (95% confidence interval [CI], 3.04% to 7.36%). Among 361 (61%) patients finishing a 42-day follow-up, the cumulative incidence of recurrent blood-stage infection reached 7.98% (95% CI, 5.20% to 10.76%). The cumulative risk of gametocyte carriage at days 28 and 42 was 2.21% (95% CI, 0.78% to 3.64%) and 3.93% (95% CI, 1.94% to 5.92%), respectively. Interestingly, for all 15 patients with recurrent gametocytemia, this was associated with concurrent asexual stages. Genotyping of recurrent parasites at the merozoite surface protein 3α gene locus from 12 patients with recurrent parasitemia within 28 days revealed that 10 of these were the same genotype as at day 0, suggesting recrudescence or relapse. Similar studies in 70 patients in the same area in 2007 showed no recurrent parasitemias within 28 days. The sensitivity to chloroquine of P. vivax in northeastern Myanmar may be deteriorating.

摘要

氯喹-伯氨喹(CQ-PQ)仍然是间日疟原虫疟疾根治的一线治疗方法。耐氯喹(CQR)间日疟原虫的出现需要转向青蒿素联合疗法(ACTs),这带来了巨大的经济、后勤和安全负担。因此,监测氯喹的治疗效果很重要。在此,我们评估了CQ-PQ在缅甸东北部治疗间日疟原虫疟疾的疗效。我们招募了2012年至2013年期间在当地疟疾诊所就诊的587例单纯感染间日疟原虫的患者。这些患者每日服用3剂CQ,总剂量为24毫克碱基/千克体重,并从第一剂CQ开始同时进行为期8天的伯氨喹治疗(0.375毫克/千克/天)。在完成28天随访的401例患者中,复发性寄生虫血症的累积发生率为5.20%(95%置信区间[CI],3.04%至7.36%)。在完成42天随访的361例(61%)患者中,复发性血液阶段感染的累积发生率达到7.98%(95%CI,5.20%至10.76%)。在第28天和第42天配子体携带的累积风险分别为2.21%(95%CI,0.78%至3.64%)和3.93%(95%CI,1.94%至5.92%)。有趣的是,对于所有15例复发性配子体血症患者,这与同时存在的无性阶段有关。对28天内复发性寄生虫血症的12例患者的裂殖子表面蛋白3α基因位点的复发性寄生虫进行基因分型,发现其中10例与第0天的基因型相同,提示复发或再燃。2007年在同一地区对70例患者进行的类似研究显示,28天内无复发性寄生虫血症。缅甸东北部间日疟原虫对氯喹的敏感性可能正在下降。

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