PROJECT SUMMARY

PROJECT DESCRIPTION

Background: The most recent estimates showed that the global burden of vivax malaria is between 13.7 and 15.0 million cases per year. There is now compelling evidence that vivax malaria is associated with significant morbidity and mortality, and policymakers recognize the importance of its control and ultimate elimination. P. vivax is harder to eliminate than P. falciparum due to important biological differences. Unlike P. falciparum, P. vivax can form dormant liver stages (hypnozoites) that can reactivate weeks to months after an acute infection (relapse). The combination of treatment for the acute blood stages (schizontocidal) plus the liver stages (hypnozoiticidal) of the P. vivax parasite is referred to as “radical cure”. Primaquine (PQ) and tafenoquine (TQ) are 8-aminoquinoline drugs used to eliminate the hypnozoite stages of the parasite and thereby prevent relapses. While PQ is widely available, TQ, a drug with a longer half-life, was only recently registered with the US Food and Drug Administration (US FDA), Australian Therapeutic Goods Administration (TGA) and regulatory authorities in three vivax-endemic countries (Thailand, Brazil and Peru). Although TQ is an important alternative to PQ, it has not yet been included in the World Health Organization (WHO) treatment guidelines. TQ, as a single dose regimen, has significant advantages over the longer courses of PQ needed to achieve a radical cure of P. vivax. The current data shows that the recommended fixed dose of 300mg TQ in adults is too low and compromised by a lack of weight-based dosing. To ensure maximal impact on health outcomes, the recommended dose for TQ must be optimised for clinical practice. Study objectives:

•        To compare the efficacy of a revised weight-based TQ regimen (TQRevised: target dose 7.5mg/kg) with high dose primaquine (PQ7: 7mg/kg over 7 days)

•        To compare the antirelapse efficacy of TQRevised with the fixed-dose TQ regimen (TQStandard: 300mg fixed dose)

•        To compare the tolerability and safety of TQRevised, TQStandard and PQ7

•        To understand the feasibility and acceptability of a weight-based dosing scheme

Methodology: A multicenter, health care facility-based, randomized, controlled, parallel-group open-label, non-inferiority trial in patients presenting with uncomplicated P. vivax malaria. The study will be conducted in Arba Minch General Hospital, Gamo zone, Southern Ethiopia regional state, Ethiopia, from June 2024 to June 2027 for about three years with a total cost of 359,228 (three hundred fifty-nine thousand two hundred twenty-eight) USD, sponsored by Menzies School of Health Research. Expected outcomes: The incidence risk (time to first event) of any P. vivax parasitemia during the 4-month follow-up period as determined by microscopy compared between TQRevised and the PQ7 (non-inferiority) and between TQRevised and TQStandard (superiority). Result dissemination plan: All Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any other scientific publications arising from the study. The result will be disseminated to zonal and regional health offices, MoH, MoE, EFDA, and Menzies School of Health Research (Menzies).