Effectiveness of tafenoquine and primaquine for radical cure of Plasmodium vivax: a meeting report from dissemination of results of the EFFORT trial to stakeholders in Pakistan

Abstract

Plasmodium vivax remains the predominant cause of malaria in Pakistan, accounting for approximately 85% of confirmed cases. The recurrent nature of P. vivax, driven by dormant liver-stage hypnozoites, poses a major obstacle to malaria control. Pakistan currently uses a 14-day low-dose primaquine regimen (3.5 mg/kg total dose) without routine G6PD testing, a strategy limited by poor adherence and suboptimal efficacy. In 2024, the World Health Organization (WHO) recommended high-dose primaquine (7 mg/kg) or single-dose tafenoquine (300 mg) as more effective alternatives, but evidence on their programmatic implementation remains limited. The EFFORT clinical trial evaluated the safety and effectiveness of 7-day-high-dose primaquine and single-dose tafenoquine compared to the standard 14-day-low-dose regimen. Conducted across four endemic countries, including Pakistan, the trial found both regimens to be well tolerated and effective in preventing relapse. In Pakistan, the added benefit of high-dose primaquine over the standard regimen was modest but consistent with findings from other South Asian countries. The findings of EFFORT highlight significant benefits of tafenoquine in P. vivax endemic settings beyond those currently endorsed in the 2024 WHO guidelines. A national dissemination meeting was held at the Aga Khan University hospital Karachi on 10th April 2025 organized by Aga Khan University and Menzies School of Health Research. The meeting brought together national and provincial stakeholders to review study results and explore implications for radical cure policy and implementation in Pakistan. Key themes included policy alignment, phased implementation of tafenoquine and G6PD testing, planning and funding constraints, private sector engagement, and the importance of sustained dialogue between researchers and malaria program leaders.