Single low-dose primaquine for malaria control in Africa: a systematic review of safety, efficacy and implementation barriers

Since 2012, the WHO has recommended a single low dose of primaquine (SLDPQ, 0.25 mg/kg) alongside artemisinin-based combination therapies (ACTs) to block Plasmodium falciparum transmission and combat artemisinin resistance. Despite its proven benefits, SLDPQ adoption in African malaria policies rema...

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Main Authors: Alphonse Ouedraogo, Sodiomon Bienvenu Sirima, Joseph Nyandwi, Didier Ménard, Tianle Ye, Emmanuelle Caspar, Denis Niyomwungere, Lucas Thiebaut, Pierre-Emeric Strubel, Omega Raobela, Rianasoambolanoro Rakotosaona, Arsène Ratsimbasoa
Format: Article
Language:English
Published: BMJ Publishing Group 2025-08-01
Series:BMJ Global Health
Online Access:https://gh.bmj.com/content/10/8/e020264.full
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author Alphonse Ouedraogo
Sodiomon Bienvenu Sirima
Joseph Nyandwi
Didier Ménard
Tianle Ye
Emmanuelle Caspar
Denis Niyomwungere
Lucas Thiebaut
Pierre-Emeric Strubel
Omega Raobela
Rianasoambolanoro Rakotosaona
Arsène Ratsimbasoa
author_facet Alphonse Ouedraogo
Sodiomon Bienvenu Sirima
Joseph Nyandwi
Didier Ménard
Tianle Ye
Emmanuelle Caspar
Denis Niyomwungere
Lucas Thiebaut
Pierre-Emeric Strubel
Omega Raobela
Rianasoambolanoro Rakotosaona
Arsène Ratsimbasoa
author_sort Alphonse Ouedraogo
collection DOAJ
description Since 2012, the WHO has recommended a single low dose of primaquine (SLDPQ, 0.25 mg/kg) alongside artemisinin-based combination therapies (ACTs) to block Plasmodium falciparum transmission and combat artemisinin resistance. Despite its proven benefits, SLDPQ adoption in African malaria policies remains limited. We conducted a systematic review of studies published between 2012 and 2023 on the safety, efficacy and implementation of SLDPQ in Africa. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched 7 databases and screened 819 records. Eligible studies focused on SLDPQ co-administered with ACTs for treating uncomplicated P. falciparum malaria in African contexts. Data were extracted and analysed from 41 studies, including 15 randomised controlled trials (RCTs) and 26 non-trial studies. SLDPQ was found to be safe and well-tolerated, including in glucose-6-phosphate dehydrogenase deficiency individuals and children under 5. Eight RCTs confirmed significant reductions in gametocyte carriage, validating SLDPQ’s individual-level efficacy. However, evidence on community-level impact remains limited. Key implementation barriers include persistent misconceptions about primaquine toxicity, absence of paediatric formulations and operational challenges in health systems. Most studies used the WHO-recommended dose (0.25 mg/kg), but higher doses and age-based regimens were also investigated. This review supports SLDPQ as a safe and effective tool for malaria transmission reduction in Africa. Addressing barriers to implementation, through health worker training, community sensitisation and operational research, is essential to accelerate its adoption. The ongoing Implementing Primaquine Single Low Dose in Africa project aims to generate real-world evidence across three countries, with a focus on paediatric use and health system integration. SLDPQ scale-up should be prioritised within malaria elimination strategies across sub-Saharan Africa.
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spelling doaj-art-4f2ff1a04a2140c3bfe9d7c5aa2af49f2025-08-20T03:44:05ZengBMJ Publishing GroupBMJ Global Health2059-79082025-08-0110810.1136/bmjgh-2025-020264Single low-dose primaquine for malaria control in Africa: a systematic review of safety, efficacy and implementation barriersAlphonse Ouedraogo0Sodiomon Bienvenu Sirima1Joseph Nyandwi2Didier Ménard3Tianle Ye4Emmanuelle Caspar5Denis Niyomwungere6Lucas Thiebaut7Pierre-Emeric Strubel8Omega Raobela9Rianasoambolanoro Rakotosaona10Arsène Ratsimbasoa11Groupe de Recherche Action en Santé, Ouagadougou, Burkina FasoGroupe de Recherche Action en Santé, Ouagadougou, Burkina FasoInstitut National de Santé Publique, Bujumbura, BurundiUR3073, University of Strasbourg, Strasbourg, FranceUniversity of Strasbourg, Strasbourg, FranceUR3073, University of Strasbourg, Strasbourg, FranceInstitut National de Santé Publique, Bujumbura, BurundiUR3073, University of Strasbourg, Strasbourg, FranceUR3073, University of Strasbourg, Strasbourg, FranceMinsitère de la Santé, Government of Madagascar, Antananarivo, Antananarivo Province, MadagascarEcole Supérieure Polytechnique d’Antananarivo, Université d’Antananarivo, Antananarivo, MadagascarCNARP, Antananarivo, Antananarivo Province, MadagascarSince 2012, the WHO has recommended a single low dose of primaquine (SLDPQ, 0.25 mg/kg) alongside artemisinin-based combination therapies (ACTs) to block Plasmodium falciparum transmission and combat artemisinin resistance. Despite its proven benefits, SLDPQ adoption in African malaria policies remains limited. We conducted a systematic review of studies published between 2012 and 2023 on the safety, efficacy and implementation of SLDPQ in Africa. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched 7 databases and screened 819 records. Eligible studies focused on SLDPQ co-administered with ACTs for treating uncomplicated P. falciparum malaria in African contexts. Data were extracted and analysed from 41 studies, including 15 randomised controlled trials (RCTs) and 26 non-trial studies. SLDPQ was found to be safe and well-tolerated, including in glucose-6-phosphate dehydrogenase deficiency individuals and children under 5. Eight RCTs confirmed significant reductions in gametocyte carriage, validating SLDPQ’s individual-level efficacy. However, evidence on community-level impact remains limited. Key implementation barriers include persistent misconceptions about primaquine toxicity, absence of paediatric formulations and operational challenges in health systems. Most studies used the WHO-recommended dose (0.25 mg/kg), but higher doses and age-based regimens were also investigated. This review supports SLDPQ as a safe and effective tool for malaria transmission reduction in Africa. Addressing barriers to implementation, through health worker training, community sensitisation and operational research, is essential to accelerate its adoption. The ongoing Implementing Primaquine Single Low Dose in Africa project aims to generate real-world evidence across three countries, with a focus on paediatric use and health system integration. SLDPQ scale-up should be prioritised within malaria elimination strategies across sub-Saharan Africa.https://gh.bmj.com/content/10/8/e020264.full
spellingShingle Alphonse Ouedraogo
Sodiomon Bienvenu Sirima
Joseph Nyandwi
Didier Ménard
Tianle Ye
Emmanuelle Caspar
Denis Niyomwungere
Lucas Thiebaut
Pierre-Emeric Strubel
Omega Raobela
Rianasoambolanoro Rakotosaona
Arsène Ratsimbasoa
Single low-dose primaquine for malaria control in Africa: a systematic review of safety, efficacy and implementation barriers
BMJ Global Health
title Single low-dose primaquine for malaria control in Africa: a systematic review of safety, efficacy and implementation barriers
title_full Single low-dose primaquine for malaria control in Africa: a systematic review of safety, efficacy and implementation barriers
title_fullStr Single low-dose primaquine for malaria control in Africa: a systematic review of safety, efficacy and implementation barriers
title_full_unstemmed Single low-dose primaquine for malaria control in Africa: a systematic review of safety, efficacy and implementation barriers
title_short Single low-dose primaquine for malaria control in Africa: a systematic review of safety, efficacy and implementation barriers
title_sort single low dose primaquine for malaria control in africa a systematic review of safety efficacy and implementation barriers
url https://gh.bmj.com/content/10/8/e020264.full
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