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  • Stepniewska, KasiaWorldWide Antimalarial Resistance Network, Oxford, England.;Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Clin Med, Oxford, England. (author)

Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide : a systematic review and meta-analysis of individual patient data

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-09-16
  • Springer Nature,2022
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-486053
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-486053URI
  • https://doi.org/10.1186/s12916-022-02504-zDOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:150676853URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

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  • Subject category:ref swepub-contenttype
  • Subject category:for swepub-publicationtype

Notes

  • BackgroundIn 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns.MethodsA systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models.ResultsData comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17-0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19-0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms.ConclusionsOur results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Allen, Elizabeth N.WorldWide Antimalarial Resistance Network, Oxford, England.;Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa. (author)
  • Humphreys, Georgina S.WorldWide Antimalarial Resistance Network, Oxford, England.;Univ Oxford, Green Templeton Coll, Oxford, England. (author)
  • Poirot, EugenieUniv Calif San Francisco, Global Hlth Grp, Malaria Eliminat Initiat, San Francisco, CA 94143 USA. (author)
  • Craig, ElaineWorldWide Antimalarial Resistance Network, Oxford, England.;Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Clin Med, Oxford, England. (author)
  • Kennon, KalynnWorldWide Antimalarial Resistance Network, Oxford, England.;Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Clin Med, Oxford, England. (author)
  • Yilma, DanielWorldWide Antimalarial Resistance Network, Oxford, England.;Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa.;Jimma Univ, Jimma Univ Clin Trial Unit, Dept Internal Med, Jimma, Ethiopia. (author)
  • Bousema, TeunLondon Sch Hyg & Trop Med, Dept Infect & Immun, London, England.;Radboud Univ Nijmegen Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands. (author)
  • Guerin, Philippe J.WorldWide Antimalarial Resistance Network, Oxford, England.;Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Clin Med, Oxford, England. (author)
  • White, Nicholas J.Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Clin Med, Oxford, England.;Mahidol Univ, Fac Trop Med, Bangkok, Thailand. (author)
  • Price, Ric N.WorldWide Antimalarial Resistance Network, Oxford, England.;Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Clin Med, Oxford, England.;Menzies Sch Hlth Res, Global & Trop Hlth Div, Darwin, NT, Australia.;Charles Darwin Univ, Darwin, NT, Australia. (author)
  • Raman, JaishreeNatl Inst Communicable Dis, Div Natl Hlth Lab Serv, Parasitol Reference Lab, Johannesburg, South Africa.;Univ Witwatersrand, Fac Hlth Sci, Wits Res Inst Malaria, Johannesburg, South Africa. (author)
  • Mårtensson, Andreas,1963-Uppsala universitet,Internationell barnhälsa och nutrition(Swepub:uu)andma331 (author)
  • Mwaiswelo, Richard O.Muhimbili Univ Hlth & Allied Sci, Dept Parasitol & Med Entomol, Dar Es Salaam, Tanzania.;Hubert Kairuki Mem Univ, Dept Microbiol Immunol & Parasitol, Dar Es Salaam, Tanzania. (author)
  • Bancone, GermanaUniv Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Clin Med, Oxford, England.;Mahidol Univ, Fac Trop Med, Shoklo Malaria Res Unit, Mahidol Oxford Trop Med Res Unit, Mae Sot, Thailand. (author)
  • Bastiaens, Guido J. H.Radboud Univ Nijmegen Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands.;Rijnstate Hosp, Lab Med Microbiol & Immunol, Arnhem, Netherlands. (author)
  • Bjorkman, AndersKarolinska Institutet (author)
  • Brown, Joelle M.Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA. (author)
  • D'Alessandro, UmbertoLondon Sch Hyg & Trop Med, Med Res Council Unit, Fajara, Gambia. (author)
  • Dicko, Alassane A.Univ Sci Tech & Technol Bamako, Fac Pharm, Malaria Res & Training Ctr, Bamako, Mali.;Univ Sci Tech & Technol Bamako, Fac Med & Dent, Bamako, Mali. (author)
  • El-Sayed, BadriaNatl Ctr Res, Trop Med Res Inst, Dept Epidemiol, Khartoum, Sudan. (author)
  • Elzaki, Salah-EldinNatl Ctr Res, Trop Med Res Inst, Dept Epidemiol, Khartoum, Sudan. (author)
  • Eziefula, Alice C.Univ Sussex, Brighton & Sussex Med Sch, Dept Global Hlth & Infect, Brighton, E Sussex, England. (author)
  • Goncalves, Bronner P.London Sch Hyg & Trop Med, Dept Infect & Immun, London, England. (author)
  • Hamid, Muzamil Mahdi AbdelUniv Khartoum, Inst Endem Dis, Khartoum, Sudan. (author)
  • Kaneko, AkiraKarolinska Institutet (author)
  • Kariuki, SimonKenya Med Res Inst KEMRI, Kisian, Kenya. (author)
  • Khan, WasifInt Ctr Diarrheal Dis Res, Infect Dis Div, Dhaka, Bangladesh. (author)
  • Kwambai, Titus K.Ctr Dis Control & Prevent, Dept Parasit Dis & Malaria, Kisumu, Kenya. (author)
  • Ley, BenediktMenzies Sch Hlth Res, Global & Trop Hlth Div, Darwin, NT, Australia.;Charles Darwin Univ, Darwin, NT, Australia. (author)
  • Ngasala, Billy E.Uppsala universitet,Internationell barnhälsa och nutrition,Muhimbili Univ Hlth & Allied Sci, Dept Parasitol & Med Entomol, Dar Es Salaam, Tanzania.(Swepub:uu)bilng827 (author)
  • Nosten, FrancoisUniv Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Clin Med, Oxford, England.;Mahidol Univ, Fac Trop Med, Shoklo Malaria Res Unit, Mahidol Oxford Trop Med Res Unit, Mae Sot, Thailand. (author)
  • Okebe, JosephMRC Unit, Dis Control & Eliminat Theme, Fajara, Gambia.;Univ Liverpool Liverpool Sch Trop Med, Liverpool, Merseyside, England. (author)
  • Samuels, Aaron M.Ctr Dis Control & Prevent, Dept Parasit Dis & Malaria, Kisumu, Kenya. (author)
  • Smit, Menno R.Univ Liverpool Liverpool Sch Trop Med, Liverpool, Merseyside, England. (author)
  • Stone, Will J. R.London Sch Hyg & Trop Med, Dept Infect & Immun, London, England.;Radboud Univ Nijmegen Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands. (author)
  • Sutanto, IngeUniv Indonesia, Fac Med, Dept Parasitol, Depok City, Indonesia. (author)
  • Ter Kuile, FeikoUniv Liverpool Liverpool Sch Trop Med, Liverpool, Merseyside, England. (author)
  • Tine, Roger C.Univ Cheikh Anta Diop, Fac Med, Dept Med Parasitol, Dakar, Senegal. (author)
  • Tiono, Alfred B.Ctr Natl Rech & Format Paludisme, Dept Biomed Sci, Ouagadougou, Burkina Faso. (author)
  • Drakeley, Chris J.London Sch Trop Med & Hyg, Dept Infect Biol, London, England. (author)
  • Gosling, RolyUniv Calif San Francisco, Global Hlth Grp, Malaria Eliminat Initiat, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA. (author)
  • Stergachis, AndyUniv Washington, Dept Pharm, Sch Pharm & Publ Hlth, Seattle, WA USA. (author)
  • Barnes, Karen, IWorldWide Antimalarial Resistance Network, Oxford, England.;Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa. (author)
  • Chen, IngridUniv Calif San Francisco, Global Hlth Grp, Malaria Eliminat Initiat, San Francisco, CA 94143 USA. (author)
  • WorldWide Antimalarial Resistance Network, Oxford, England.;Univ Oxford, Ctr Trop Med & Global Hlth, Nuffield Dept Clin Med, Oxford, England.WorldWide Antimalarial Resistance Network, Oxford, England.;Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa. (creator_code:org_t)

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  • In:BMC Medicine: Springer Nature20:11741-7015

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