Background: In 2012, the World Health Organization recommended the addition of single low-dose primaquine\n(SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of\nPlasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group\nwas non-pregnant patients aged ââ?°Â¥ 1 year (later changed to ââ?°Â¥ 6 months) with acute uncomplicated falciparum\nmalaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested,\nleaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based\nSLDPQ regimen for Cambodia, the country most affected by ARPf.\nMethods: By reviewing primaquineââ?¬â?¢s pharmacology, we defined a therapeutic dose range of 0.15ââ?¬â??0.38 mg base/\nkg (9ââ?¬â??22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1ââ?¬â??20 mg) were tested using a\nmodelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247\nwith other infections); age distributions were: 0.5ââ?¬â??4 years (20.0 %, n = 5640), 5ââ?¬â??12 years (9.1 %, n = 2559), 13ââ?¬â??17\nyears (9.1 %, n = 2550), and ââ?°Â¥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to\ncalculated mg base/kg doses and proportions of individuals receiving a therapeutic dose.\nResults: Four age-dosing bands were defined: (1) 0.5ââ?¬â??4 years, (2) 5ââ?¬â??9 years, (3) 10ââ?¬â??14 years, and (4) ââ?°Â¥15 years to\nreceive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 %\n(1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median\n(1stââ?¬â??99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15ââ?¬â??0.38), (2) 0.29 (0.18ââ?¬â??0.45), (3) 0.27 (0.15ââ?¬â??0.\n39), and (4) 0.29 (0.20ââ?¬â??0.42).\nConclusions: This age-based SLDPQ regimen could contribute substantially to malaria elimination and requires\nurgent evaluation in Cambodia and other countries with similar anthropometric characteristics. It guides\nprimaquine manufacturers on suitable tablet strengths and doses for paediatric-friendly formulations.\nDevelopment of similar age-based dosing recommendations for Africa is needed.
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