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

W Robert Taylor 1, 2, * Htee Khu Naw 2 Kathryn Maitland 3, 4 Thomas Williams 3, 4 Melissa Kapulu 3, 5 Umberto d'Alessandro 6 James Berkley 3, 5 Philip Bejon 3, 5 Joseph Okebe 6 Jane Achan 6 Alfred Ngwa Amambua 6 Muna Affara 6 Davis Nwakanma 6 Jean-Pierre van Geertruyden 7 Muhindo Mavoko 8 Pascal Lutumba 8 Junior Matangila 8 Philipe Brasseur 9 Patrice Piola 10 Rindra Randremanana 11 Estrella Lasry 12 Caterina Fanello 5, 13 Marie Onyamboko 13, 12 Birgit Schramm 11 Zolia Yah 14 Joel Jones 14 Rick Fairhurst 15 Mahamadou Diakite 16 Grace Malenga 17 Malcolm Molyneux 18 Claude Rwagacondo 14 Charles Obonyo 19 Endalamaw Gadisa 20 Abraham Aseffa 20 Mores Loolpapit 21 Marie-Claire Henry 22 Grant Dorsey 23 Chandy John 24 Sodiomon Sirima 25, 26 Karen Barnes 27 Peter Kremsner 28 Nicholas Day 2, 5 Nicholas White 2, 5 Mavuto Mukaka 2, 5
Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [84 references]  Display  Hide  Download

https://hal-riip.archives-ouvertes.fr/pasteur-01920763
Contributor : Volatiana Manohisoa Randriamanantsoa <>
Submitted on : Tuesday, November 13, 2018 - 2:39:06 PM
Last modification on : Wednesday, August 7, 2019 - 12:16:02 PM
Long-term archiving on : Thursday, February 14, 2019 - 3:10:55 PM

File

Single low dose primaquine for...
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

W Robert Taylor, Htee Khu Naw, Kathryn Maitland, Thomas Williams, Melissa Kapulu, et al.. Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria – a proposed model-derived age-based regimen for sub-Saharan Africa. BMC Medicine, BioMed Central, 2018, 16 (1), pp.11. ⟨10.1186/s12916-017-0990-6⟩. ⟨pasteur-01920763⟩

Share

Metrics

Record views

63

Files downloads

90