Health-care provider compliance with a revised Plasmodium vivax radical cure algorithm incorporating tafenoquine and quantitative G6PD testing in the Peruvian Amazon: a prospective observational study

Background: Plasmodium vivax relapse remains a key barrier to malaria elimination in Latin America. Historically, radical cure relied on multi-day primaquine regimens, often without prior glucose-6-phosphate dehydrogenase (G6PD) testing. In November 2024, WHO issued a recommendation specific to South America for radical cure with primaquine or single-dose tafenoquine after testing G6PD activity. We assessed the operational feasibility of implementing this revised radical cure algorithm, integrating point-of-care quantitative G6PD testing to guide primaquine or tafenoquine selection, under routine care, measured by health-care provider (HCP) compliance. Methods: This prospective, observational study in Loreto, Peru (Aug 2022–Dec 2024) evaluated implementation of a revised radical cure algorithm among patients by trained routine HCPs across 14 health facilities. HCP compliance was assessed from the provider (correct algorithm application in ≥80% of patients per HCP role) and patient perspectives (proportion correctly treated per algorithm). Safety endpoints included acute haemolytic anaemia (AHA) and other serious adverse events. Findings: Among 187 HCPs and 987 patients, HCP compliance was 96.6% (172/178) from the provider perspective and 98.7% (974/987) from the patient perspective, with similar results across urban/periurban and remote/rural facilities. Incorrect treatments (1.3%; 13/987) were mostly due to operational lapses in treatment sequencing and eligibility among G6PD-normal individuals. Ten patients (1.1%; 10/916) developed symptoms suggestive of AHA; one met suspected AHA criteria, unconfirmed. Eight patients (0.8%; 8/986) experienced serious adverse events attributable to severe malaria; all recovered. Interpretation: HCPs across participating facilities achieved high compliance with the revised radical cure algorithm from both perspectives and consistently across urban/periurban and remote/rural settings. Incorrect treatments were infrequent and no AHA was confirmed. These findings demonstrate that HCP at the participating facilities can successfully implement the revised radical cure algorithm, contributing to the operational evidence base informing its scale-up in Peru and the Americas. Funding: Unitaid (Grant number 2021-43-VIV).