Therapeutic efficacy of pyronaridine-artesunate (Pyramax) in treating malaria in the central highlands of Vietnam.

UNLABELLED

The emergence and spread of chloroquine-resistant have necessitated the assessment of alternative blood schizonticidal drugs. In Vietnam, chloroquine-resistant malaria has been reported. In an open-label, single-arm trial, the safety, tolerability, and efficacy of pyronaridine-artesunate (Pyramax, PA) was evaluated in Dak Nong province, Vietnam. A 3-day course of PA was administered to adults and children (≥20 kg) infected with . Patients also received primaquine (0.25 mg/kg daily for 14 days). PA was well tolerated with transient asymptomatic increases in liver transaminases. The per-protocol proportion of patients with day 42 PCR-unadjusted adequate clinical and parasitological response was 96.0% (95% CI, 84.9%-99.0%, = 48/50). The median parasite clearance time was 12 h (range, 12-36 h), with a median fever clearance time of 24 h (range, 12-60 h). Single nucleotide polymorphisms (SNPs) as potential genetic markers of reduced drug susceptibility were analyzed in three putative drug resistance markers, , , and . Insertion at position K10 of the gene was found in 74.6% (44/59) of isolates. SNPs at Y976F and F1076L were present in 61% (36/59) and 78% (46/59), respectively. Amplification of gene (two copies) was found in 5.1% (3/59) of parasite samples. Only 5.1% (3/59) of isolates had mutation 552I of the gene. Overall, PA rapidly cleared blood asexual stages and was highly efficacious in treating vivax malaria, with no evidence of artemisinin resistance found. PA provides an alternative to chloroquine treatment for vivax malaria in Vietnam.

CLINICAL TRIALS

This study is registered with the Australian New Zealand Clinical Trials Registry as ACTRN12618001429246.