Therapeutic efficacy monitoring of pyronaridine-artesunate (Pyramax®) in treating uncomplicated Plasmodium falciparum malaria in Gia Lai province, Vietnam from 2022 to 2023.

Abstract

Objectives: We assessed the therapeutic efficacy of pyronaridine-artesunate (Pyramax®) for the treatment of uncomplicated Plasmodium falciparum malaria in Gia Lai province, Central Vietnam where parasites are partially resistant to artemisinins.

Methods: In an open-label, single-arm trial, Pyramax® was administered to 120 patients (adults and children) infected with P. falciparum residing in Gia Lai province from March 2022 to December 2023. Patients received Pyramax® once daily for 3 days and single-dose primaquine under direct observation therapy. Patients' Day 7 blood pyronaridine concentrations were measured by liquid chromatography-mass spectrometry to determine drug exposure.

Results: After Pyramax® treatment, the proportion of patients with PCR-adjusted adequate clinical and parasitological response at Day 42 was 92.5% (95% CI: 85.5-96.2; 98/106). The median parasite and fever clearance times were 84 h (range: 24-132) and 36 h (range: 12-108), respectively. The median (IQR) parasite clearance half-life was 7.4 h (6.3-8.4), with 50.4% (60/119) of patients had parasites detected by microscopy at 72 h after commencing treatment, suggestive of partial artemisinin resistance. The eight patients who experienced malaria recrudescence had lower (P = 0.065) blood pyronaridine concentrations (mean 39.6 ng/mL, median 33.3 ng/mL, range: 12.4-90.5) compared to the 95 patients who were malaria-free by Day 42 (median 47.6 ng/mL, range: 10.6-123.0).

Conclusions: Although Pyramax® remains efficacious in treating P. falciparum, the lower pyronaridine concentrations in patients who had recrudescent malaria are worrisome and suggest that reduced pyronaridine exposure may be responsible for the Pyramax® treatment failures.