Shrinking the Malaria Map

UCSF Global Health Group’s Malaria Elimination Initiative (MEI)

Primaquine dose escalation study

MRTC researchers in the field in Mali

Research paper: Primaquine to reduce transmission of Plasmodium falciparum malaria in Mali: a single-blind, dose-ranging, adaptive randomised phase 2 trial

Study protocol: Phase 2a dose escalation study of the efficacy, safety and pharmacokinetics of low single-dose primaquine for gametocytocidal activity against P. falciparum in sub-Saharan Africa

Research Summary: In partnership with the Malaria Research and Training Centre (MRTC) in Mali and other research collaborators,* the UCSF Global Health Group’s Malaria Elimination Initiative (MEI) conducted a phase 2 randomized control trial on the use of single low dose primaquine (SLD-PQ) when used in conjunction with artemisinin combination therapy (ACT) to block Plasmodium falciparum transmission. This study is the largest and most comprehensive trial to take place on the efficacy of SLD-PQ to prevent the transmission of P. falciparum, bringing the first contemporary evidence to support the WHO recommendation of the efficacy of a 0.25 mg/kg dose of SLD-PQ in conjunction with the modern ACT, dihydroartemisinin piperaquine (DP). The study used the membrane feeding assay (the gold standard for infectivity measurements), doubled the evidence available on the subject, and was the first study to confirm that infectivity measurements assessing gametocyte density and prevalence alone are limited, as they cannot differentiate between infectious and non-infectious gametocytes that persist after primaquine.

The trial took place from January 2013 through November 2014 in Oulessebougou, Mali where malaria is seasonal from about July through January. The study team was very busy the entire year, keeping the colony of Anopheles gambiae mosquitoes alive and happy to ensure that they were healthy enough to survive for a week after receiving the first malaria-infected blood meal through the membrane feeding assay, upon enrollment of participants. The Malian study team was comprised of a collection of energetic doctors, pharmacists, epidemiologists, and laboratory researchers. MEI team members had a brilliant time collaborating with the Malian team, with frequent phone calls, emails, and visits to the site situated in the beautiful countryside south of Mali’s capital city, Bamako. Ongoing research with this study team will provide the highest safe dose of SLD-PQ, to be reported in due course. Together this collection of studies will provide the therapeutic dose range of SLD-PQ, facilitating dosing practices for the WHO recommendation in all field settings.

*List of research partners – further designated in the publication: Malaria Research and Training Centre (Bamako, Mali); Centers for Disease Control and Prevention (Atlanta, GA, USA); London School of Hygiene & Tropical Medicine (London, United Kingdom); President’s Malaria Initiative (Washington, DC, USA); Radboud University Medical Center (Nijmegen, Netherlands); University of Helsinki and Helsinki University Hospital (Helsinki, Finland); University of Oxford (Oxford, United Kingdom)