Multi-Country Trial Finds Shorter Malaria Treatment Regimens More Effective Than Standard Course
A multicenter EFFORT Trial published in The Lancet Infectious Diseases found that 7-day high-dose primaquine and single-dose tafenoquine significantly reduced P. vivax malaria recurrence compared to the standard 14-day low-dose primaquine regimen. The trial, conducted across Ethiopia, Pakistan, Indonesia, and Cambodia, supports WHO guidelines and potential geographic expansion of tafenoquine use.
The EFFORT Trial, a major multicenter randomized clinical trial, has confirmed the safety and effectiveness of two Plasmodium vivax malaria medications in G6PD-normal patients — high-dose primaquine administered over 7 days and single-dose tafenoquine — supporting more efficient treatment regimens to address the liver stage of the disease. The findings, published in The Lancet Infectious Diseases, are expected to influence the next phase of global malaria recommendations, including geographic expansion of tafenoquine use.
Led by researchers at Menzies School of Health Research, the trial enrolled patients across four P. vivax-endemic regions: Ethiopia, Pakistan, Indonesia, and Cambodia. In a collaboration of more than 60 researchers, the study compared three regimens: a 7-day high-dose primaquine course, the traditional 14-day low-dose primaquine course, and a single dose of tafenoquine.
Both high-dose primaquine and tafenoquine greatly reduced recurrence of P. vivax malaria compared with the standard 14-day low-dose regimen. Notably, tafenoquine performed well when co-administered with the blood-stage malaria drug artesunate–pyronaridine, supporting the need for future investigations into tafenoquine use with other artemisinin-based therapies.
The study is the first randomized clinical trial to provide real-world effectiveness evidence that directly supports the 2024 World Health Organization guideline for the use of high-dose primaquine in malaria treatment. Researchers also included qualitative and economic components to assess the feasibility, acceptability, and cost-effectiveness of implementing updated medication regimens in real-world settings.
The findings are now driving consultations across the trial countries to support policy change and planning toward P. vivax malaria treatment improvements. According to the principal investigator, the evidence directly supports both global and national treatment policy, providing countries with the data needed to support improved strategies for P. vivax malaria.