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.
Highlights
Current World Health Organization (WHO) guidelines recommend the “addition of a single dose of primaquine (PQ) (0.75 mg/kg) to artemisinin-based combination therapy (ACT) for uncomplicated falciparum malaria as an anti-gametocyte medicine, as a component of a pre-elimination or an elimination programme” [1]
The previously high levels of malaria transmission may be one of the main reasons why primaquine has not been used widely in Africa, with only very frequent delivery of the drug being likely to have any impact on transmission [3]
Following 8 mg of primaquine, there were oocysts but no sporozoites in membrane-fed mosquitoes. He decided on the use of Artequick + 9 mg primaquine for mass drug administration (MDA) after performing safety studies using 8 mg and 10 mg doses in small numbers of individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency in South East Asia
Summary
Current World Health Organization (WHO) guidelines recommend the “addition of a single dose of primaquine (PQ) (0.75 mg/kg) to artemisinin-based combination therapy (ACT) for uncomplicated falciparum malaria as an anti-gametocyte medicine, as a component of a pre-elimination or an elimination programme” [1]. Following 8 mg of primaquine, there were oocysts but no sporozoites in membrane-fed mosquitoes He decided on the use of Artequick + 9 mg primaquine for MDA after performing safety studies using 8 mg and 10 mg doses in small numbers of individuals with G6PD deficiency in South East Asia. Further studies may be required to confirm the effect on infectiousness to wild mosquito populations as natural infections have been shown to be successful at very low gametocyte densities suggesting high vector susceptibility [30] Such feeding experiments may not be warranted or practical for larger field evaluations and a surrogate marker for transmission would be preferable. Pharmacovigilance could be supported to do a retrospective study following up women of reproductive age who have been treated with any dose of primaquine
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