An optimised age-based dosing regimen for single low-dose primaquine for blocking malaria transmission in Cambodia

BMC Medicine

Research Article

Song Ngak¹  Philippe Buchy²  Arnaud Tarantola²  Didier Menard²  Rick M. Fairhurst³  Mark Debackere⁴  Rupam Tripura⁵  Naw Htee Khu⁵  Nicholas J. White⁶  Arjen M. Dondorp⁶  Mavuto Mukaka⁶  Walter Robert John Taylor⁷  Arantxa Roca-Felterer⁸  Sim Kheng⁹  Sinoun Muth⁹  Rithea Leang⁹  Neeraj Kak^1,10  Say Chy^1,11  Soy Ty Kheang^1,11 

[1] FHI 360 Cambodia Office, PO Box: 2586, #03, Street 330 Boeung Keng Kang III Khan Chamkamon, Phnom Penh, Cambodia;Institut Pasteur du Cambodge, PO Box 983, 5 Monivong Boulevard, 12201, Phnom Penh, Cambodia;Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 20852, Rockville, MD, USA;MSF Belgium Cambodia Malaria Program, PO Box 1933, #19, Street 388, Sangkat Tuol Svay Prey, Khan Chamkarmon, Phnom Penh, Cambodia;Mahidol Oxford Tropical Medicine Research Unit (MORU), 420/6 Rajvithi Road, Rajthevee, 10400, Bangkok, Thailand;Mahidol Oxford Tropical Medicine Research Unit (MORU), 420/6 Rajvithi Road, Rajthevee, 10400, Bangkok, Thailand;Oxford Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford, Old Road Campus, Roosevelt Drive, OX3 7FZ, Oxford, UK;Mahidol Oxford Tropical Medicine Research Unit (MORU), 420/6 Rajvithi Road, Rajthevee, 10400, Bangkok, Thailand;Oxford Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford, Old Road Campus, Roosevelt Drive, OX3 7FZ, Oxford, UK;Centre de Médecine Humanitaire, Hôpitaux Universitaires de Genève, Genève, Switzerland;Malaria Consortium, House #91 Street 95, Boeung Trabek, Chamkar Morn, Phnom Penh, Cambodia;National Center for Parasitology, Entomology and Malaria Control, Corner St. 92, Trapeng Svay Village, Sangkat Phnom Penh, Thmei, Khan Sen Sok, Phnom Penh, Cambodia;University Research Co., LLC Washington DC: 7200 Wisconsin Ave, 20814, Bethesda, MD, USA;University Research Co., LLC, MK Building, House #10 (2nd floor), St. 214, Chey Chumneas, Daun Penh, Phnom Penh, Cambodia;

关键词: Primaquine;    Malaria;    G6PD deficiency;    Dosing;    Cambodia;   

DOI  :  10.1186/s12916-016-0701-8

 received in 2016-04-18, accepted in 2016-09-20,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundIn 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested, leaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based SLDPQ regimen for Cambodia, the country most affected by ARPf.MethodsBy reviewing primaquine’s pharmacology, we defined a therapeutic dose range of 0.15–0.38 mg base/kg (9–22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1–20 mg) were tested using a modelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247 with other infections); age distributions were: 0.5–4 years (20.0 %, n = 5640), 5–12 years (9.1 %, n = 2559), 13–17 years (9.1 %, n = 2550), and ≥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to calculated mg base/kg doses and proportions of individuals receiving a therapeutic dose.ResultsFour age-dosing bands were defined: (1) 0.5–4 years, (2) 5–9 years, (3) 10–14 years, and (4) ≥15 years to receive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 % (1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median (1st–99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15–0.38), (2) 0.29 (0.18–0.45), (3) 0.27 (0.15–0.39), and (4) 0.29 (0.20–0.42).ConclusionsThis age-based SLDPQ regimen could contribute substantially to malaria elimination and requires urgent evaluation in Cambodia and other countries with similar anthropometric characteristics. It guides primaquine manufacturers on suitable tablet strengths and doses for paediatric-friendly formulations. Development of similar age-based dosing recommendations for Africa is needed.

【 授权许可】

CC BY   
© The Author(s). 2016