Latest literature review of primaquine drug studies released

Over 40% of the world’s population is at risk of infection with Plasmodium vivax (P. vivax)¹, a species now recognised as causing significant sickness and death in poorly resourced malaria endemic communities. Primaquine is the only widely available antimalarial drug that can kill the P. vivaxhypnozoites, the latent stage of the parasite that can lie dormant in the patient’s liver for months or even years. Despite more than 60 years of widespread malaria treatment using primaquine; the clinical efficacy of the drug remains poorly understood. Indeed there is no clear consensus on the optimal dosing regimen or the appropriate study design required to define the efficacy of different treatment strategies.

To assess the current research evidence available, WWARN is releasing a literature review of all published antimalarial clinical studies that have used primaquine. The review presents systematically extracted data from 87 studies and assesses both the risk of recurrence and the effectiveness of different dosing levels of primaquine.

Key findings from the literature review include:

• Marked heterogeneity in the design of primaquine relapse prevention studies.
• The risk of recurrent malaria varies considerably according to dosing, partner drug, duration of follow-up and the geographic location of the study.
• Reports of serious adverse events were rare in G6PD normal patients and of a similar magnitude to that reported following other antimalarials such as mefloquine.

Key elements recommended for future antirelapse efficacy studies include:

• The combination of primaquine with a blood schizontocide drug known to be effective in the patient study population.
• Prolonged duration of patient follow up (12 months).
• Where possible the inclusion of a study control arm.
• An analysis of adverse effects of treatment and tolerability.
• It is also recommended that future studies are conducted in multiple locations and endemic settings so that the evidence gathered can reflect the geographically diverse epidemiology of P. vivax.

Read more about the background, methodology, detailed results and key findings from the Primaquine Literature Review. You can also download a number of supplementary plots and maps.

Review a summary of results from the analysis of our full publication library of references (consolidating 903 studies); and our key findings for artemisinin combination therapies (ACT) and Parasite Clearance.

This news update was written by Ric Price, Head of WWARN’s Clinical Group and Georgina Humphreys, WWARN Data Manager.

¹ Price R et al. Acute respiratory distress syndrome in Plasmodium vivax malaria: case report and review of the literature. Transactions of the Royal Society of Tropical Medicine 2007; 101(7):655-9.