Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.

Autor:	Taylor, W. Robert, Naw, Htee Khu, Maitland, Kathryn, Williams, Thomas N., Kapulu, Melissa, D'Alessandro, Umberto, Berkley, James A., Bejon, Philip, Okebe, Joseph, Achan, Jane, Amambua, Alfred Ngwa, Affara, Muna, Nwakanma, Davis, van Geertruyden, Jean-Pierre, Mavoko, Muhindo, Lutumba, Pascal, Matangila, Junior, Brasseur, Philipe, Piola, Patrice, Randremanana, Rindra
Předmět:	MALARIA prevention PRIMAQUINE PLASMODIUM falciparum GLUCOSE-6-phosphate dehydrogenase deficiency PHARMACOKINETICS PUBLIC health INFECTIOUS disease transmission THERAPEUTICS DRUG therapy for malaria MALARIA transmission AGE distribution ANTIMALARIALS COMPARATIVE studies DOSE-effect relationship in pharmacology RESEARCH methodology MEDICAL cooperation MEDICAL protocols INBORN errors of metabolism PROTOZOA RESEARCH RESEARCH funding EVALUATION research
Zdroj:	BMC Medicine; 1/18/2018, Vol. 16 Issue 1, p1-N.PAG, 14p, 5 Charts, 5 Graphs
Abstrakt:	Background: In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa.Methods: Using data on the anti-infectivity efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals aged ≥6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg PQ base for infants aged 6-11 months because they have the highest rate of baseline anaemia and the highest risks of AHA and CSA. We modelled an anthropometric database of 661,979 African individuals aged ≥6 months (549,127 healthy individuals, 28,466 malaria patients and 84,386 individuals with other infections/illnesses) by the Box-Cox transformation power exponential and tested PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ doses.Results: From the Box-Cox transformation power exponential model, five age categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n = 12,155, 1.84%) and (v) ≥15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5, 7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38), (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886), 93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8% (327,620/328,132), respectively.Conclusions: We plan to test the safety of this age-based dosing regimen in a large randomised placebo-controlled trial (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate pharmacokinetics, it should be used to support malaria elimination. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
Externí odkaz:	Zobrazit plný text záznamu Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.