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Open Access Highly Accessed Meeting report

Rationale for short course primaquine in Africa to interrupt malaria transmission

Alice C Eziefula1, Roly Gosling2, Jimee Hwang23, Michelle S Hsiang24, Teun Bousema1, Lorenz von Seidlein5, Chris Drakeley1* and on behalf of the Primaquine in Africa Discussion Group

Author Affiliations

1 Malaria Centre, London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK

2 Global Health Group, University of California, San Francisco, 50 Beale Street, San Francisco, CA, 94105, USA

3 Malaria Branch, Centers for Disease Control and Prevention, 1600 Clifton Rd, Atlanta, GA, 30333, USA

4 Department of Pediatrics, University of California, San Francisco, San Francisco, CA, 94143, USA

5 Menzies School of Health Research, Casuarina, NT, 0811, Australia

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Malaria Journal 2012, 11:360  doi:10.1186/1475-2875-11-360

Published: 30 October 2012

Abstract

Following the recent successes of malaria control in sub-Saharan Africa, the gametocytocidal drug primaquine needs evaluation as a tool to further reduce the transmission of Plasmodium falciparum malaria. The drug has scarcely been used in Africa because of concerns about its safety in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The evidence base for the use of primaquine as a transmission blocker is limited by a lack of comparable clinical and parasitological endpoints between trials. In March 2012, a group of experts met in London to discuss the existing evidence on the ability of primaquine to block malaria transmission, to define the roadblocks to the use of primaquine in Africa and to develop a roadmap to enable its rapid, safe and effective deployment. The output of this meeting is a strategic plan to optimize trial design to reach desired goals efficiently. The roadmap includes suggestions for a series of phase 1, 2, 3 and 4 studies to address specific hurdles to primaquine’s deployment. These include ex-vivo studies on efficacy, primaquine pharmacokinetics and pharmacodynamics and dose escalation studies for safety in high-risk groups. Phase 3 community trials are proposed, along with Phase 4 studies to evaluate safety, particularly in pregnancy, through pharmacovigilance in areas where primaquine is already deployed. In parallel, efforts need to be made to address issues in drug supply and regulation, to map G6PD deficiency and to support the evaluation of alternative gametocytocidal compounds.

Keywords:
Plasmodium falciparum; Malaria; Primaquine; 8-aminoquinoline; Transmission; Gametocyte; Glucose-6-phosphate dehydrogenase deficiency; G6PD; Africa