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Title: An optimised age-based dosing regimen for single low-dose primaquine for blocking malaria transmission in Cambodia
Authors: Rithea Leang
Naw Htee Khu
Mavuto Mukaka
Mark Debackere
Rupam Tripura
Soy Ty Kheang
Say Chy
Neeraj Kak
Philippe Buchy
Arnaud Tarantola
Didier Menard
Arantxa Roca-Felterer
Rick M. Fairhurst
Sim Kheng
Sinoun Muth
Song Ngak
Arjen M. Dondorp
Nicholas J. White
Walter Robert John Taylor
National Center for Parasitology, Entomology and Malaria Control
Mahidol University
Nuffield Department of Clinical Medicine
University Research Co., LLC
University Research Co., LLC
Institut Pasteur du Cambodge
Malaria Consortium
National Institute of Allergy and Infectious Diseases
FHI 360 Cambodia Office
Hôpitaux universitaires de Genève
Keywords: Medicine
Issue Date: 27-Oct-2016
Citation: BMC Medicine. Vol.14, No.1 (2016)
Abstract: © 2016 The Author(s). Background: In 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. Methods: By 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. Results: Four 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). Conclusions: This 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.
ISSN: 17417015
Appears in Collections:Scopus 2016-2017

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