澳大利亚查尔斯达尔文大学Ric N Price小组近日探讨了短程伯氨喹用于根治间日疟原虫疟疾的疗效。该研究2019年9月14日发表于《柳叶刀》杂志上。

2014年7月20日至2017年11月25日，研究组在8个医疗机构（阿富汗、埃塞俄比亚、印度尼西亚和越南各两个）进行了一项随机、双盲、安慰剂对照的非劣效性试验。共招募了2336名患者，年龄大于6个月，葡萄糖-6-磷酸脱氢酶（G6PD）正常，间日疟首次发作。所有患者均接受标准血液裂殖体治疗，将其按2：2：1随机分为三组，935名接受7天的伯氨喹监护治疗（每天1.0 mg/kg），937名接受14天的伯氨喹监护治疗（每天0.5 mg/kg），464名接受安慰剂治疗。

治疗12个月后，7天伯氨喹组症状性复发性间日疟复发率为每人每年0.18，14天伯氨喹组为0.16，安慰剂组为0.96。7天组中有9名（1.0%）患者在开始治疗后42天内出现潜在性药物相关的严重不良反应，14天组中有1名（0.1%），安慰剂组中没有。严重不良反应中有4例严重溶血，其中7天组中3例，14天组中1例。

对于G6PD正常的患者，7天伯氨喹方案耐受性良好，不劣于14天伯氨喹方案。短程方案可能会提高患者的依从性，从而提高伯氨喹根治间日疟的疗效。

据悉，伯氨喹是唯一广泛使用预防间日疟原虫疟疾复发的药物，但标准的14天方案患者依从性很差。

附：英文原文

Title: Short-course primaquine for the radical cure of Plasmodium vivax malaria: a multicentre, randomised, placebo-controlled non-inferiority trial

Author: Walter R J Taylor, Kamala Thriemer, Lorenz von Seidlein, Prayoon Yuentrakul, Thanawat Assawariyathipat, Ashenafi Assefa, Sarah Auburn, Krisin Chand, Nguyen Hoang Chau, Phaik Yeong Cheah, Le Thanh Dong, Mehul Dhorda, Tamiru Shibru Degaga, Angela Devine, Lenny L Ekawati, Fahmi Fahmi, Asrat Hailu, Mohammad Anwar Hasanzai, Tran Tinh Hien, Htee Khu, Benedikt Ley, Yoel Lubell, Jutta Marfurt, Hussein Mohammad, Kerryn A Moore, Mohammad Nader Naddim, Ayodhia Pitaloka Pasaribu, Syahril Pasaribu, Cholrawee Promnarate, Awab Ghulam Rahim, Pasathron Sirithiranont, Hiwot Solomon, Herawati Sudoyo, Inge Sutanto, Ngo Viet Thanh, Nguyen Thi Tuyet-Trinh, Naomi Waithira, Adugna Woyessa, Fazal Yamin Yamin, Arjen Dondorp, Julie A Simpson, J Kevin Baird, Nicholas J White, Nicholas P Day, Ric N Price

Issue&Volume: 2019/09/14

Summary: 

Background

Primaquine is the only widely used drug that prevents Plasmodium vivax malaria relapses, but adherence to the standard 14-day regimen is poor. We aimed to assess the efficacy of a shorter course (7 days) of primaquine for radical cure of vivax malaria.

Methods

We did a randomised, double-blind, placebo-controlled, non-inferiority trial in eight health-care clinics (two each in Afghanistan, Ethiopia, Indonesia, and Vietnam). Patients (aged ≥6 months) with normal glucose-6-phosphate dehydrogenase (G6PD) and presenting with uncomplicated vivax malaria were enrolled. Patients were given standard blood schizontocidal treatment and randomly assigned (2:2:1) to receive 7 days of supervised primaquine (1·0 mg/kg per day), 14 days of supervised primaquine (0·5 mg/kg per day), or placebo. The primary endpoint was the incidence rate of symptomatic P vivax parasitaemia during the 12-month follow-up period, assessed in the intention-to-treat population. A margin of 0·07 recurrences per person-year was used to establish non-inferiority of the 7-day regimen compared with the 14-day regimen. This trial is registered at ClinicalTrials.gov (NCT01814683).

Findings

Between July 20, 2014, and Nov 25, 2017, 2336 patients were enrolled. The incidence rate of symptomatic recurrent P vivax malaria was 0·18 (95% CI 0·15 to 0·21) recurrences per person-year for 935 patients in the 7-day primaquine group and 0·16 (0·13 to 0·18) for 937 patients in the 14-day primaquine group, a difference of 0·02 (−0·02 to 0·05, p=0·3405). The incidence rate for 464 patients in the placebo group was 0·96 (95% CI 0·83 to 1·08) recurrences per person-year. Potentially drug-related serious adverse events within 42 days of starting treatment were reported in nine (1·0%) of 935 patients in the 7-day group, one (0·1%) of 937 in the 14-day group and none of 464 in the control arm. Four of the serious adverse events were significant haemolysis (three in the 7-day group and one in the 14-day group).

Interpretation

In patients with normal G6PD, 7-day primaquine was well tolerated and non-inferior to 14-day primaquine. The short-course regimen might improve adherence and therefore the effectiveness of primaquine for radical cure of P vivax malaria.

DOI: 10.1016/S0140-6736(19)31285-1

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31285-1/fulltext