Primaquine radical cure of Plasmodium vivax: a critical review of the literature

Malaria Journal

Research

George K John¹  J Kevin Baird²  Nicholas M Douglas³  Ric N Price⁴  Nicholas J White⁵  Francois Nosten⁶  Lorenz von Seidlein⁷ 

[1] Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK;Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK;Eijkman-Oxford Clinical Research Unit, Jalan Diponegoro No. 69, 10430, Jakarta, Indonesia;Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK;Global Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, 0811, Casuarina, Darwin, NT, Australia;Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK;Global Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, 0811, Casuarina, Darwin, NT, Australia;WorldWide Anti-malarial Resistance Network (WWARN), Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Old Road, Oxford, UK;Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK;Mahidol-Oxford Tropical Medicine Research Unit, 10400, Bangkok, Thailand;Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK;Shoklo Malaria Research Unit, 63110, Mae Sot, Tak, Thailand;Mahidol-Oxford Tropical Medicine Research Unit, 10400, Bangkok, Thailand;Global Health Division, Menzies School of Health Research, Charles Darwin University, PO Box 41096, 0811, Casuarina, Darwin, NT, Australia;Vivax Working Group, Asia-Pacific Malaria Elimination Network, Menzies School of Health Research, 0811, Darwin, NT, Australia;

关键词: Malaria;    Chloroquine;    Artesunate;    Vivax Malaria;    G6PD Deficiency;   

DOI  :  10.1186/1475-2875-11-280

 received in 2012-05-22, accepted in 2012-08-08,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundPrimaquine has been the only widely available hypnozoitocidal anti-malarial drug for half a century. Despite this its clinical efficacy is poorly characterized resulting in a lack of consensus over the optimal regimen for the radical cure of Plasmodium vivax.MethodsPublished studies since 1950 of the use of primaquine regimens for preventing P. vivax relapse were reviewed. Data were extracted systematically from available papers. Primaquine regimens were categorized according to the total dose administered: very low (≤2.5 mg/kg), low (>2.5 mg/kg- < 5.0 mg/kg) and high (≥ 5.0 mg/kg). The risk of recurrent infection were summarized across geographical regions and the odds ratios between treatment regimens calculated after stratifying by total treatment dose and duration of study follow up.ResultsData could be retrieved from 87 clinical trials presenting data in 59,735 patients enrolled into 156 treatment arms, conducted in 20 countries. There was marked heterogeneity in study design, particularly primaquine dosing and duration of follow up. The median rate of recurrence following very low dose of primaquine (n = 44) was 25% (range 0-90%) at 4–6 months, compared to 6.7 % (range 0-59%) following low dose primaquine (n = 82). High dose primaquine regimens were assessed in 28 treatment arms, and were associated with a median recurrence rate of 0% (Range: 0-15%) at one month. In 18 studies with control arms, the effectiveness of a very low dose primaquine regimen was no different from patients who did not receive primaquine (OR = 0.60, 95%CI 0.33-1.09, p = 0.09), whereas for the low dose regimens a significant difference was reported in 50% (6/12) of studies (overall OR = 0.14, 95%CI: 0.06-0.35, p < 0.001). Two studies enrolling 171 patients demonstrated high effectiveness of high dose primaquine compared to a control arm (OR = 0.03 (95%CI: 0.01-0.13); p < 0.0001).ConclusionsLow dose regimens retain adequate efficacy in some areas, but this is not uniform. The efficacy and safety of pragmatic high dose primaquine regimens needs to be assessed in a range of endemic and geographical locations. Such studies will require a prolonged period of follow up and comparison with control arms to account for confounding factors.

【 授权许可】

Unknown   
© John et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.