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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dc.contributor.authorTaylor, W Robert
dc.contributor.authorNaw, Htee Khu
dc.contributor.authorMaitland, Kathryn
dc.contributor.authorWilliams, Thomas N
dc.contributor.authorKapulu, Melissa
dc.contributor.authorD’Alessandro, Umberto
dc.contributor.authorBerkley, James A
dc.contributor.authorBejon, Philip
dc.contributor.authorOkebe, Joseph
dc.contributor.authorAchan, Jane
dc.contributor.authorAmambua, Alfred Ngwa
dc.contributor.authorAffara, Muna
dc.contributor.authorNwakanma, Davis
dc.contributor.authorvan Geertruyden, Jean-Pierre
dc.contributor.authorMavoko, Muhindo
dc.contributor.authorLutumba, Pascal
dc.contributor.authorMatangila, Junior
dc.contributor.authorBrasseur, Philipe
dc.contributor.authorPiola, Patrice
dc.contributor.authorRandremanana, Rindra
dc.contributor.authorLasry, Estrella
dc.contributor.authorFanello, Caterina
dc.contributor.authorOnyamboko, Marie
dc.contributor.authorSchramm, Birgit
dc.contributor.authorYah, Zolia
dc.contributor.authorJones, Joel
dc.contributor.authorFairhurst, Rick M
dc.contributor.authorDiakite, Mahamadou
dc.contributor.authorMalenga, Grace
dc.contributor.authorMolyneux, Malcolm
dc.contributor.authorRwagacondo, Claude
dc.contributor.authorObonyo, Charles
dc.date.accessioned2021-10-08T06:54:44Z
dc.date.available2021-10-08T06:54:44Z
dc.date.issued2018
dc.description.abstractBACKGROUND: 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.
dc.identifier.apacitationTaylor, W. R., Naw, H. K., Maitland, K., Williams, T. N., Kapulu, M., , ... Obonyo, C. (2018). Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria – a proposed model-derived age-based regimen for sub-Saharan Africa. <i>BMC Medicine</i>, 16(1), 174 - 177. http://hdl.handle.net/11427/34323en_ZA
dc.identifier.chicagocitationTaylor, W Robert, Htee Khu Naw, Kathryn Maitland, Thomas N Williams, Melissa Kapulu, , James A Berkley, et al "Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria – a proposed model-derived age-based regimen for sub-Saharan Africa." <i>BMC Medicine</i> 16, 1. (2018): 174 - 177. http://hdl.handle.net/11427/34323en_ZA
dc.identifier.citationTaylor, W.R., Naw, H.K., Maitland, K., Williams, T.N., Kapulu, M., , Berkley, J.A. & Bejon, P. et al. 2018. Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria – a proposed model-derived age-based regimen for sub-Saharan Africa. <i>BMC Medicine.</i> 16(1):174 - 177. http://hdl.handle.net/11427/34323en_ZA
dc.identifier.issn1741-7015
dc.identifier.ris TY - Journal Article AU - Taylor, W Robert AU - Naw, Htee Khu AU - Maitland, Kathryn AU - Williams, Thomas N AU - Kapulu, Melissa AU - D’Alessandro, Umberto AU - Berkley, James A AU - Bejon, Philip AU - Okebe, Joseph AU - Achan, Jane AU - Amambua, Alfred Ngwa AU - Affara, Muna AU - Nwakanma, Davis AU - van Geertruyden, Jean-Pierre AU - Mavoko, Muhindo AU - Lutumba, Pascal AU - Matangila, Junior AU - Brasseur, Philipe AU - Piola, Patrice AU - Randremanana, Rindra AU - Lasry, Estrella AU - Fanello, Caterina AU - Onyamboko, Marie AU - Schramm, Birgit AU - Yah, Zolia AU - Jones, Joel AU - Fairhurst, Rick M AU - Diakite, Mahamadou AU - Malenga, Grace AU - Molyneux, Malcolm AU - Rwagacondo, Claude AU - Obonyo, Charles AB - 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. DA - 2018 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - BMC Medicine LK - https://open.uct.ac.za PY - 2018 SM - 1741-7015 T1 - Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria – a proposed model-derived age-based regimen for sub-Saharan Africa TI - Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria – a proposed model-derived age-based regimen for sub-Saharan Africa UR - http://hdl.handle.net/11427/34323 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34323
dc.identifier.vancouvercitationTaylor WR, Naw HK, Maitland K, Williams TN, Kapulu M, , 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. 2018;16(1):174 - 177. http://hdl.handle.net/11427/34323.en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Medicine
dc.publisher.facultyFaculty of Health Sciences
dc.sourceBMC Medicine
dc.source.journalissue1
dc.source.journalvolume16
dc.source.pagination174 - 177
dc.source.urihttps://dx.doi.org/10.1186/s12916-017-0990-6
dc.subject.otherAge-based dosing
dc.subject.otherMalaria
dc.subject.otherPlasmodium falciparum
dc.subject.otherPrimaquine
dc.subject.otherTransmission blocking
dc.subject.otherAdolescent
dc.subject.otherAdult
dc.subject.otherAfrica South of the Sahara
dc.subject.otherAge Factors
dc.subject.otherAged
dc.subject.otherAged, 80 and over
dc.subject.otherAntimalarials
dc.subject.otherChild
dc.subject.otherChild, Preschool
dc.subject.otherClinical Protocols
dc.subject.otherDose-Response Relationship, Drug
dc.subject.otherFemale
dc.subject.otherGlucosephosphate Dehydrogenase Deficiency
dc.subject.otherHumans
dc.subject.otherInfant
dc.subject.otherMalaria, Falciparum
dc.titleSingle low-dose primaquine for blocking transmission of Plasmodium falciparum malaria – a proposed model-derived age-based regimen for sub-Saharan Africa
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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