Efficacy and safety of pyronaridine-artesunate plus single-dose primaquine for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Cambodia [Clinical Therapeutics]

In Cambodia, multi-drug resistant Plasmodium falciparum undermines the treatment of uncomplicated malaria and new therapeutic options are needed. Pyronaridine-artesunate has not previously been evaluated in eastern Cambodia. This single-arm, open-label, prospective study was conducted July–December 2017 at Koh Gnek (Mondulkiri) and Veun Sai (Rattanakiri) health centers in eastern Cambodia. Eligible patients were aged ≥7 years (females 12–18 years excluded), weighing ≥20 kg, with microscopically confirmed P. falciparum mono-infection and fever. Oral pyronaridine-artesunate was administered once daily for three days, dosed according to body weight, plus a single dose of primaquine on day 0. Sixty patients were recruited to Koh Gnek, 61 to Veun Sai. The primary outcome, day 42 PCR-adjusted adequate clinical and parasitological response (ACPR) was 98.3% (95% CI 88.4–99.8) in Koh Gnek and 96.7% (95% CI 87.3–99.2) in Veun Sai (Kaplan–Meier). In a per-protocol analysis, the proportion of patients with day 42 PCR-adjusted ACPR was 98.3% ([57/58] 95% CI 90.8–100.0) at Koh Gnek and 96.7% ([58/60] 95% CI 88.5–99.6) at Veun Sai. The Kelch13 (C580Y) mutation was present in 70.0% (77/110) of isolates. Copy number was increased in 61.3% (73/119) of isolates for Pfpm2 and 1.7% (2/119) for Pfmdr1. There was no relationship between outcome and pyronaridine IC₅₀. Adverse events were consistent with malaria and there were no serious adverse events. Pyronaridine-artesunate has high efficacy in eastern Cambodia and could be used to increase the diversity of anti-malarial therapy in the region.

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