Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa
© 2018 The Author(s). 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 tre...
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Medicine W. Robert Taylor Htee Khu Naw Kathryn Maitland Thomas N. Williams Melissa Kapulu Umberto D'Alessandro James A. Berkley Philip Bejon Joseph Okebe Jane Achan Alfred Ngwa Amambua Muna Affara Davis Nwakanma Jean Pierre van Geertruyden Muhindo Mavoko Pascal Lutumba Junior Matangila Philipe Brasseur Patrice Piola Rindra Randremanana Estrella Lasry Caterina Fanello Marie Onyamboko Birgit Schramm Zolia Yah Joel Jones Rick M. Fairhurst Mahamadou Diakite Grace Malenga Malcolm Molyneux Claude Rwagacondo Charles Obonyo Endalamaw Gadisa Abraham Aseffa Mores Loolpapit Marie Claire Henry Grant Dorsey Chandy John Sodiomon B. Sirima Karen I. Barnes Peter Kremsner Nicholas P. Day Nicholas J. White Mavuto Mukaka Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa |
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© 2018 The Author(s). 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. |
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Unité de Recherche sur les Maladies Infectieuses et Tropicales émergentes |
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Unité de Recherche sur les Maladies Infectieuses et Tropicales émergentes W. Robert Taylor Htee Khu Naw Kathryn Maitland Thomas N. Williams Melissa Kapulu Umberto D'Alessandro James A. Berkley Philip Bejon Joseph Okebe Jane Achan Alfred Ngwa Amambua Muna Affara Davis Nwakanma Jean Pierre van Geertruyden Muhindo Mavoko Pascal Lutumba Junior Matangila Philipe Brasseur Patrice Piola Rindra Randremanana Estrella Lasry Caterina Fanello Marie Onyamboko Birgit Schramm Zolia Yah Joel Jones Rick M. Fairhurst Mahamadou Diakite Grace Malenga Malcolm Molyneux Claude Rwagacondo Charles Obonyo Endalamaw Gadisa Abraham Aseffa Mores Loolpapit Marie Claire Henry Grant Dorsey Chandy John Sodiomon B. Sirima Karen I. Barnes Peter Kremsner Nicholas P. Day Nicholas J. White Mavuto Mukaka |
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Article |
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W. Robert Taylor Htee Khu Naw Kathryn Maitland Thomas N. Williams Melissa Kapulu Umberto D'Alessandro James A. Berkley Philip Bejon Joseph Okebe Jane Achan Alfred Ngwa Amambua Muna Affara Davis Nwakanma Jean Pierre van Geertruyden Muhindo Mavoko Pascal Lutumba Junior Matangila Philipe Brasseur Patrice Piola Rindra Randremanana Estrella Lasry Caterina Fanello Marie Onyamboko Birgit Schramm Zolia Yah Joel Jones Rick M. Fairhurst Mahamadou Diakite Grace Malenga Malcolm Molyneux Claude Rwagacondo Charles Obonyo Endalamaw Gadisa Abraham Aseffa Mores Loolpapit Marie Claire Henry Grant Dorsey Chandy John Sodiomon B. Sirima Karen I. Barnes Peter Kremsner Nicholas P. Day Nicholas J. White Mavuto Mukaka |
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W. Robert Taylor |
title |
Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa |
title_short |
Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa |
title_full |
Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa |
title_fullStr |
Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa |
title_full_unstemmed |
Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa |
title_sort |
single low-dose primaquine for blocking transmission of plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-saharan africa |
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2019 |
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https://repository.li.mahidol.ac.th/handle/123456789/46997 |
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th-mahidol.469972019-08-28T13:27:05Z 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 Htee Khu Naw Kathryn Maitland Thomas N. Williams Melissa Kapulu Umberto D'Alessandro James A. Berkley Philip Bejon Joseph Okebe Jane Achan Alfred Ngwa Amambua Muna Affara Davis Nwakanma Jean Pierre van Geertruyden Muhindo Mavoko Pascal Lutumba Junior Matangila Philipe Brasseur Patrice Piola Rindra Randremanana Estrella Lasry Caterina Fanello Marie Onyamboko Birgit Schramm Zolia Yah Joel Jones Rick M. Fairhurst Mahamadou Diakite Grace Malenga Malcolm Molyneux Claude Rwagacondo Charles Obonyo Endalamaw Gadisa Abraham Aseffa Mores Loolpapit Marie Claire Henry Grant Dorsey Chandy John Sodiomon B. Sirima Karen I. Barnes Peter Kremsner Nicholas P. Day Nicholas J. White Mavuto Mukaka Unité de Recherche sur les Maladies Infectieuses et Tropicales émergentes Universite de Kinshasa Queen Elizabeth Central Hospital Malawi Malawi-Liverpool-Wellcome Trust Clinical Research Programme Institut Pasteur de Madagascar Centre de Recherche Entomologique de Cotonou Medical Research Council Laboratories Gambia Armauer Hansen Research Institute Kenya Medical Research Institute Wellcome Trust Research Laboratories Nairobi African Medical Research Foundation Nairobi London School of Hygiene & Tropical Medicine Indiana University-Purdue University Indianapolis University of California, San Francisco Wellcome Trust National Institute of Allergy and Infectious Diseases Universität Tübingen Universiteit Antwerpen Epicentre Mahidol University Hôpitaux universitaires de Genève Nuffield Department of Clinical Medicine Medecins Sans Frontieres University of Cape Town Kinshasa Mahidol Oxford Research Unit USTTB National Malaria Control Programme Groupe de Recherche Action en Santé (GRAS) National Malaria Control Program Kinshasa School of Public Health Centre National de Recherche et de Formation sur le Paludisme Medicine © 2018 The Author(s). 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. 2019-08-28T06:27:05Z 2019-08-28T06:27:05Z 2018-01-18 Article BMC Medicine. Vol.16, No.1 (2018) 10.1186/s12916-017-0990-6 17417015 2-s2.0-85040766967 https://repository.li.mahidol.ac.th/handle/123456789/46997 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85040766967&origin=inward |