Vantaux Amélie, Kim Saorin, Piv Eakpor, Chy Sophy, Berne Laura, Khim Nimol, Lek Dysoley, Siv Sovannaroth, Mukaka Mavuto, Taylor Walter R, Ménard Didier
Malaria Molecular Epidemiology Unit, Institut Pasteur of Cambodia, Phnom Penh, Cambodia
Malaria Molecular Epidemiology Unit, Institut Pasteur of Cambodia, Phnom Penh, Cambodia.
Antimicrob Agents Chemother. 2020 May 21;64(6). doi: 10.1128/AAC.02108-19.
Since 2012, a single low dose of primaquine (SLDPQ; 0.25 mg/kg of body weight) with artemisinin-based combination therapies has been recommended as the first-line treatment of acute uncomplicated malaria to interrupt its transmission, especially in low-transmission settings of multidrug resistance, including artemisinin resistance. Policy makers in Cambodia have been reluctant to implement this recommendation due to primaquine safety concerns and a lack of data on its efficacy. In this randomized controlled trial, 109 Cambodians with acute uncomplicated malaria received dihydroartemisinin-piperaquine (DP) alone or combined with SLDPQ on the first treatment day. The transmission-blocking efficacy of SLDPQ was evaluated on days 0, 1, 2, 3, 7, 14, 21, and 28, and recrudescence by reverse transcriptase PCR (RT-PCR) (gametocyte prevalence) and membrane feeding assays with mosquitoes (gametocyte infectivity). Without the influence of recrudescent infections, DP-SLDPQ reduced gametocyte carriage 3-fold compared to that achieved with DP. Of 48 patients tested on day 0, only 3 patients were infectious to mosquitoes (∼6%). Posttreatment, three patients were infectious on day 14 (3.5%, 1/29) and on the 1st and 7th days of recrudescence (8.3%, 1/12 for each); this overall low infectivity precluded our ability to assess its transmission-blocking efficacy. Our study confirms the effective gametocyte clearance of SLDPQ when combined with DP in multidrug-resistant infections and the negative impact of recrudescent infections due to poor DP efficacy. Artesunate-mefloquine (ASMQ) has replaced DP, and ASMQ-SLDPQ has been deployed to treat all patients with symptomatic infections to further support the elimination of multidrug-resistant in Cambodia. (This study has been registered at ClinicalTrials.gov under identifier NCT02434952.).
自2012年以来，推荐使用单剂量低剂量伯氨喹（SLDPQ；0.25毫克/千克体重）联合青蒿素类复方疗法作为急性非复杂性疟疾的一线治疗方法，以阻断其传播，尤其是在包括青蒿素耐药性在内的多药耐药低传播环境中。由于对伯氨喹安全性的担忧以及缺乏其疗效数据，柬埔寨的政策制定者一直不愿实施这一建议。在这项随机对照试验中，109名患有急性非复杂性疟疾的柬埔寨人在首次治疗日单独接受双氢青蒿素哌喹（DP）或联合SLDPQ治疗。在第0、1、2、3、7、14、21和28天评估SLDPQ的传播阻断效果，并通过逆转录酶聚合酶链反应（RT-PCR）（配子体流行率）和蚊虫膜饲试验（配子体感染性）评估复发情况。在无复发感染影响的情况下，与DP相比，DP-SLDPQ使配子体携带率降低了3倍。在第0天检测的48名患者中，只有3名患者对蚊虫具有传染性（约6%）。治疗后，3名患者在第14天具有传染性（3.5%，1/29），在复发的第1天和第7天具有传染性（均为8.3%，1/12）；这种总体较低的感染性使我们无法评估其传播阻断效果。我们的研究证实，在多药耐药感染中，SLDPQ与DP联合使用时可有效清除配子体，以及由于DP疗效不佳导致的复发感染的负面影响。青蒿琥酯甲氟喹（ASMQ）已取代DP，并且已采用ASMQ-SLDPQ治疗所有有症状感染的患者，以进一步支持在柬埔寨消除多药耐药性。（本研究已在ClinicalTrials.gov上注册，标识符为NCT02434952。）
