Efficacy and Safety of Pyronaridine-Artesunate plus Single-Dose Primaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Eastern Cambodia

• Published in: Antimicrobial agents and chemotherapy Vol. 63; no. 3
• Main Authors: Leang, Rithea, Mairet-Khedim, Melissa, Chea, Huch, Huy, Rekol, Khim, Nimol, Mey Bouth, Denis, Dorina Bustos, Maria, Ringwald, Pascal, Witkowski, Benoit
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.03.2019
• Subjects: Adolescent; Antimalarials; Antimalarials - therapeutic use; Artesunate; Artesunate - therapeutic use; Cambodia; Carrier Proteins - genetics; Child; Clinical Therapeutics; Drug Resistance, Multiple - genetics; Female; Humans; Malaria, Falciparum; Malaria, Falciparum - drug therapy; Malaria, Falciparum - parasitology; Male; Naphthyridines; Naphthyridines - therapeutic use; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Plasmodium falciparum - isolation & purification; Primaquine; Primaquine - therapeutic use; Prospective Studies; Cambodia; artemisinin; Plasmodium falciparum; drug resistance; Cambodia; pyronaridine-artesunate
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.02242-18

In Cambodia, multidrug-resistant undermines the treatment of uncomplicated malaria, and new therapeutic options are needed. Pyronaridine-artesunate has not previously been evaluated in eastern Cambodia. We conducted a single-arm, open-label, prospective study between July and December 2017 at the Koh Gnek (Mondulkiri) and Veun Sai (Rattanakiri) health centers in eastern Cambodia. Eligible patients were aged ≥7 years (females, ages 12 to 18 years, were excluded), weighing ≥20 kg, with microscopically confirmed monoinfection and fever. Oral pyronaridine-artesunate was administered once daily for 3 days, dosed according to body weight, plus a single dose of primaquine on day 0. Sixty patients were recruited to Koh Gnek, and 61 patients were recruited to Veun Sai. The primary outcomes, i.e., the day 42 PCR-adjusted adequate clinical and parasitological responses (ACPRs), were 98.3% (95% confidence interval [CI], 88.4 to 99.8) in Koh Gnek and 96.7% (95% CI, 87.3 to 99.2) in Veun Sai (Kaplan-Meier). In a per-protocol analysis, the proportions of patients with day 42 PCR-adjusted ACPRs were 98.3% (57/58; 95% CI, 90.8 to 100.0) at Koh Gnek and 96.7% (58/60; 95% CI, 88.5 to 99.6) at Veun Sai. The (C580Y) mutation was present in 70.0% (77/110) of isolates. The copy numbers were increased in 61.3% (73/119) of isolates for and in 1.7% (2/119) for There was no relationship between outcome and the 50% inhibitory concentration of pyronaridine. 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 antimalarial therapy in the region. (This study is registered in the Australian New Zealand Clinical Trials Registry [ANZCTR] under no. ACTRN12618001300268.).