Shrinking the Malaria Map

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

New research to help guide use of primaquine in fighting falciparum malaria

26 February 2016

MEI and collaborators made a strong contribution this week to the peer-reviewed evidence base which informs policies and practices on malaria elimination.

Published in The Lancet Infectious Diseases, Primaquine to reduce transmission of Plasmodium falciparum malaria in Mali: a single-blind, dose-ranging, adaptive randomised phase 2 trial discusses results from the largest and most comprehensive contemporary trial on the efficacy of single low-dose primaquine (SLD-PQ) to prevent the transmission of P. falciparum. Approved by the FDA in 1952, primaquine has been used globally for the radical cure of P. vivax. Interest in primaquine has been reignited because of the drug’s ability to clear mature gametocytes of P. falciparum malaria which are responsible for ongoing transmission. In light of this, the WHO released a policy recommendation on primaquine as a gametocytocide in October 2012, but this recommendation did not have the statement “strong recommendation, high quality evidence” typical of other antimalarials. This study was undertaken to further strengthen the evidence needed to inform implementation of the recommendation, providing evidence that supports the use of low doses of primaquine in accelerating the elimination of falciparum malaria.

The paper (from MEI authors Joelle Brown, Ingrid Chen, Eugenie Poirot, Jimee Hwang and Roly Gosling) offers three key findings:

  • The 2012 WHO recommended SLD-PQ dose of 0.25mg/kg is efficacious and safe in trial participants without G6PD deficiency;
  • The lower limit of therapeutic dose range can be lowered to 0.125mg/kg; and
  • Current molecular methods that measure gametocyte prevalence and density are not good surrogates for measuring efficacy of reductions in P. falciparum transmission caused by artemisinin combination therapy or SLD-PQ.

Because rigorous evidence now exists that the SLD-PQ dose is efficacious, these findings may increase uptake of primaquine in national policy and implementation.