HMN 2026: How Multi-country malaria trial shows a more efficient way to treat the disease

Landmark findings from a major malaria clinical trial led by Menzies School of Health Research (Menzies) and international collaborators have confirmed the safety and effectiveness of two Plasmodium vivax (P. vivax) malaria medications in G6PD-normal patients—high-dose primaquine and single-dose tafenoquine—supporting more efficient treatment regimens to address the liver stage of the disease.

Published today in The Lancet Infectious Diseases, these findings from the multi-country EFFORT Trial are expected to influence the next phase of global malaria recommendations, supporting a geographic expansion of the use of tafenoquine.

Led by Menzies’ Professor Kamala Thriemer, the study is also the first randomized clinical trial to provide real-world (effectiveness) evidence that directly supports the 2024 World Health Organization (WHO) guideline for the use of high-dose primaquine in malaria treatment.

In a collaboration of more than 60 researchers, working across four P. vivax-endemic regions (Ethiopia, Pakistan, Indonesia and Cambodia), the trial compared a 7-day high-dose primaquine regimen, the traditional low dose 14-day course, and a single dose of tafenoquine.

Both high-dose primaquine and tafenoquine greatly reduced recurrence of P. vivax malaria compared with the standard regimen. Importantly, tafenoquine performed well when co-administered with the blood stage malaria drug artesunate–pyronaridine, supporting the need for future investigations into the use of tafenoquine with other artemisinin-based therapies.

Real-world impact and next steps

To further strengthen the real-world relevance of these findings, researchers also included qualitative and economic components to assess the feasibility, acceptability, and cost-effectiveness of implementing updated medication regimens in real-world settings.

These findings are now driving consultations across the trial countries to help drive policy change and planning towards P. vivax malaria treatment.

Principal Investigator and Menzies Principal Research Fellow Kamala Thriemer says, “The evidence generated through this partnership directly supports both global and national treatment policy and provides countries with the evidence needed to support improved strategies for P. vivax malaria. Tafenoquine is a single dose treatment to prevent relapsing malaria which can currently only be given with chloroquine. Our data provide the evidence to further explore the use of tafenoquine with the widely used artemisinin-based treatments.”

Menzies director, Prof Alan Cass, says, “The EFFORT trial contributes high-quality, real-world evidence regarding the safety and effectiveness of key medications and regimens in the treatment of vivax malaria. The research collaboration, through combining robust trial conduct with work focused on translation of the resulting evidence into policy and practice, is superbly placed to support national and global efforts to eliminate malaria.”

Co-investigator and researcher Prof Najia Ghanchi says, “This study has been a major milestone for Pakistan, one of the countries with the highest disease burden for vivax malaria. The results clearly support the introduction of single-dose tafenoquine alongside appropriate G6PD testing to prevent relapse and reduce the burden of disease.”

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