title: An optimised age-based dosing regimen for single low-dose primaquine for blocking malaria transmission in Cambodia.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors: National Center for Parasitology, Entomology and Malaria Control, Corner St. 92, Trapeng Svay Village, Sangkat Phnom Penh, Thmei, Khan Sen Sok, Phnom Penh, Cambodia.
authors: Rithea
authors: R
authors: Leang
authors: Mahidol Oxford Tropical Medicine Research Unit (MORU), 420/6 Rajvithi Road, Rajthevee, Bangkok, 10400, Thailand.
authors: Naw Htee
authors: NH
authors: Khu
authors: Mahidol Oxford Tropical Medicine Research Unit (MORU), 420/6 Rajvithi Road, Rajthevee, Bangkok, 10400, Thailand.|Oxford Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford, OX3 7FZ, UK.
authors: Mavuto
authors: M
authors: Mukaka
authors: MSF Belgium Cambodia Malaria Program, #19, Street 388, Sangkat Tuol Svay Prey, Khan Chamkarmon, PO Box 1933, Phnom Penh, Cambodia.
authors: Mark
authors: M
authors: Debackere
authors: Mahidol Oxford Tropical Medicine Research Unit (MORU), 420/6 Rajvithi Road, Rajthevee, Bangkok, 10400, Thailand.
authors: Rupam
authors: R
authors: Tripura
authors: University Research Co., LLC, MK Building, House #10 (2nd floor), St. 214, Chey Chumneas, Daun Penh, Phnom Penh, Cambodia.
authors: Soy Ty
authors: ST
authors: Kheang
authors: University Research Co., LLC, MK Building, House #10 (2nd floor), St. 214, Chey Chumneas, Daun Penh, Phnom Penh, Cambodia.
authors: Say
authors: S
authors: Chy
authors: University Research Co., LLC Washington DC: 7200 Wisconsin Ave, Bethesda, MD, 20814, USA.
authors: Neeraj
authors: N
authors: Kak
authors: Institut Pasteur du Cambodge, 5 Monivong Boulevard, PO Box 983, Phnom Penh, 12201, Cambodia.
authors: Philippe
authors: P
authors: Buchy
authors: Institut Pasteur du Cambodge, 5 Monivong Boulevard, PO Box 983, Phnom Penh, 12201, Cambodia.
authors: Arnaud
authors: A
authors: Tarantola
authors: Institut Pasteur du Cambodge, 5 Monivong Boulevard, PO Box 983, Phnom Penh, 12201, Cambodia.
authors: Didier
authors: D
authors: Menard
authors: Malaria Consortium, House #91 Street 95, Boeung Trabek, Chamkar Morn, Phnom Penh, Cambodia.
authors: Arantxa
authors: A
authors: Roca-Felterer
authors: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.
authors: Rick M
authors: RM
authors: Fairhurst
authors: National Center for Parasitology, Entomology and Malaria Control, Corner St. 92, Trapeng Svay Village, Sangkat Phnom Penh, Thmei, Khan Sen Sok, Phnom Penh, Cambodia.
authors: Sim
authors: S
authors: Kheng
authors: National Center for Parasitology, Entomology and Malaria Control, Corner St. 92, Trapeng Svay Village, Sangkat Phnom Penh, Thmei, Khan Sen Sok, Phnom Penh, Cambodia.
authors: Sinoun
authors: S
authors: Muth
authors: FHI 360 Cambodia Office, #03, Street 330 Boeung Keng Kang III Khan Chamkamon, PO Box: 2586, Phnom Penh, Cambodia.
authors: Song
authors: S
authors: Ngak
authors: Mahidol Oxford Tropical Medicine Research Unit (MORU), 420/6 Rajvithi Road, Rajthevee, Bangkok, 10400, Thailand.|Oxford Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford, OX3 7FZ, UK.
authors: Arjen M
authors: AM
authors: Dondorp
authors: Mahidol Oxford Tropical Medicine Research Unit (MORU), 420/6 Rajvithi Road, Rajthevee, Bangkok, 10400, Thailand.|Oxford Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford, OX3 7FZ, UK.
authors: Nicholas J
authors: NJ
authors: White
authors: Mahidol Oxford Tropical Medicine Research Unit (MORU), 420/6 Rajvithi Road, Rajthevee, Bangkok, 10400, Thailand. bob@tropmedres.ac.|Oxford Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford, OX3 7FZ, UK. bob@tropmedres.ac.|Centre de Médecine Humanitaire, Hôpitaux Universitaires de Genève, Genève, Switzerland. bob@tropmedres.ac.
authors: Walter Robert John
authors: WR
authors: Taylor
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000962:Antimalarials / Q000008:administration & dosage*; D002160:Cambodia; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D004359:Drug Therapy, Combination; D005260:Female; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000378:metabolism / Q000469:parasitology; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000201:enzymology / Q000517:prevention & control / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011319:Primaquine / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000962:Antimalarials; D011319:Primaquine
keywords: Cambodia; Dosing; G6PD deficiency; Malaria; Primaquine