Weekly primaquine for radical cure of patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase deficiency.
Weekly primaquine for radical cure of patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase deficiency.
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DOI：
10.1371/journal.pntd.0011522
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发表时间：
2023-09
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
--
作者：
世界卫生组织建议患有间日疟原虫疟疾和葡萄糖-6-磷酸脱氢酶（G6PD）缺乏的患者应每周服用一次伯氨喹，持续 8 周，但有关其抗复发功效和安全性的数据有限。在对两种伯氨喹疗法治疗间日疟疾的多中心、随机临床试验中，G6PD 缺乏症患者被排除，并参加了一项单独的为期 12 个月的观察性研究。他们接受每周剂量为 0.75 mg/kg 的伯氨喹治疗，持续 8 周 (PQ8W) 加二氢青蒿素哌喹（印度尼西亚）或氯喹（阿富汗、埃塞俄比亚、越南）。 G6PD 状态通过荧光斑点测试进行诊断，并通过当地流行的 G6PD 变体的基因分型进行确认。在所有患者和基因型确诊的 G6PD 变异患者中，对 PQ8W 后的间日疟原虫复发风险和随后的血液学恢复进行了表征，并与参加主要随机对照试验的患者进行了比较。 2014年7月至2017年11月期间，阿富汗（6例）、埃塞俄比亚（5例）、印度尼西亚（19例）和越南（20例）招募了42名男性患者和8名女性患者。通过基因分型证实 31 名患者患有 G6PD 缺陷：Viangchan (14)、地中海 (4)、357A-G (3)、广州 (2)、开平 (2)，以及 A-、查塔姆、高河、卢迪亚纳、奥里萨邦和瓦努阿熔岩各 1 例。两名患者患有复发性间日疟原虫寄生虫血症（第 68 天和第 207 天）。间日疟原虫疟疾复发的总体 12 个月累积风险为 5.1%（95% CI：1.3-18.9），复发发病率为每 1000 人年 46.8 例（95% CI：11.7-187.1）。在随机对照试验的所有治疗组中，与 G6PD 正常患者相比，接受 PQ8W 治疗的 G6PD 缺陷患者的间日疟原虫复发风险较低。 26 名已确诊的半合子男性中，有两名在第一次给药后血红蛋白显着下降 (>5g/dl)，但能够完成 8 周的治疗方案。 PQ8W 在预防间日疟原虫复发方面非常有效。虽然 PQ8W 在一系列不同 G6PD 变体的大多数患者中具有良好的耐受性，但首次给药后可能会出现血红蛋白显着下降，需要临床监测。该试验已在 ClinicalTrials.gov 上注册 (NCT01814683)。 50 名患有间日疟原虫和葡萄糖-6-磷酸脱氢酶 (G6PD) 缺乏症的患者接受了世界卫生组织推荐的伯氨喹治疗方案，每周一次，每次 0.75 毫克/公斤体重，持续 8 周。大多数患者的治疗非常有效且耐受性良好。两名患者的血红蛋白显着下降（>5g/dl），其中一名患者因静脉输液而住院；两人都能够完成伯氨喹治疗方案。
The World Health Organization recommends that primaquine should be given once weekly for 8-weeks to patients with Plasmodium vivax malaria and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but data on its antirelapse efficacy and safety are limited. Within the context of a multicentre, randomised clinical trial of two primaquine regimens in P. vivax malaria, patients with G6PD deficiency were excluded and enrolled into a separate 12-month observational study. They were treated with a weekly dose of 0.75 mg/kg primaquine for 8 weeks (PQ8W) plus dihydroartemisinin piperaquine (Indonesia) or chloroquine (Afghanistan, Ethiopia, Vietnam). G6PD status was diagnosed using the fluorescent spot test and confirmed by genotyping for locally prevalent G6PD variants. The risk of P. vivax recurrence following PQ8W and the consequent haematological recovery were characterized in all patients and in patients with genotypically confirmed G6PD variants, and compared with the patients enrolled in the main randomised control trial. Between July 2014 and November 2017, 42 male and 8 female patients were enrolled in Afghanistan (6), Ethiopia (5), Indonesia (19), and Vietnam (20). G6PD deficiency was confirmed by genotyping in 31 patients: Viangchan (14), Mediterranean (4), 357A-G (3), Canton (2), Kaiping (2), and one each for A-, Chatham, Gaohe, Ludhiana, Orissa, and Vanua Lava. Two patients had recurrent P. vivax parasitaemia (days 68 and 207). The overall 12-month cumulative risk of recurrent P. vivax malaria was 5.1% (95% CI: 1.3–18.9) and the incidence rate of recurrence was 46.8 per 1000 person-years (95% CI: 11.7–187.1). The risk of P. vivax recurrence was lower in G6PD deficient patients treated with PQ8W compared to G6PD normal patients in all treatment arms of the randomised controlled trial. Two of the 26 confirmed hemizygous males had a significant fall in haemoglobin (>5g/dl) after the first dose but were able to complete their 8 week regimen. PQ8W was highly effective in preventing P. vivax recurrences. Whilst PQ8W was well tolerated in most patients across a range of different G6PD variants, significant falls in haemoglobin may occur after the first dose and require clinical monitoring. This trial is registered at ClinicalTrials.gov (NCT01814683). Fifty patients with P. vivax malaria and glucose-6-phosphate dehydrogenase (G6PD) deficiency were given the WHO-recommended, primaquine regimen of 0.75 mg/kg body weight once per week for 8 weeks. Treatment was highly effective and well tolerated in most patients. Two patients had a significant (>5g/dl) fall in haemoglobin and one was hospitalised for intravenous fluids; both were able to complete the primaquine regimen.
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影响因子：
9.3
作者：
Kheng S;Muth S;Taylor WR;Tops N;Kosal K;Sothea K;Souy P;Kim S;Char CM;Vanna C;Ly P;Ringwald P;Khieu V;Kerleguer A;Tor P;Baird JK;Bjorge S;Menard D;Christophel E
通讯作者：
Christophel E
地中海型葡萄糖-6-磷酸脱氢酶缺乏症对间日疟原虫疟疾的保护作用。
影响因子：
7.7
作者：
Awab GR;Aaram F;Jamornthanyawat N;Suwannasin K;Pagornrat W;Watson JA;Woodrow CJ;Dondorp AM;Day NP;Imwong M;White NJ
通讯作者：
White NJ
影响因子：
6.4
作者：
Betuela, Inoni;Rosanas-Urgell, Anna;Mueller, Ivo
通讯作者：
Mueller, Ivo
影响因子：
2.7
作者：
Cheah PY;Steinkamp N;von Seidlein L;Price RN
通讯作者：
Price RN
影响因子：
3.1
作者：
Chu, Cindy S.;Hwang, Jimee
通讯作者：
Hwang, Jimee