Efficacy and Safety of Pyronaridine-Artesunate for the Treatment of Uncomplicated Plasmodium falciparum and Plasmodium vivax Malaria in Myanmar.

Four single-arm, prospective, clinical studies of pyronaridine-artesunate efficacy in uncomplicated or malaria were conducted in Myanmar between 2017 and 2019. Eligible subjects were aged at least 6 years, with microscopically confirmed ( = 196) or mono-infection ( = 206). Patients received pyronaridine-artesunate once daily for 3 days with follow-up until day 42 for or day 28 for . For the primary efficacy analysis, adequate clinical and parasitological response (ACPR) in the per-protocol population at day 42 for malaria was 100% (88/88; 95% CI: 95.9, 100) in northern Myanmar (Kachin State and northern Shan State), and 100% (101/101; 95% CI: 96.4, 100) in southern Myanmar (Tanintharyi Region and Kayin State). day-3 parasite clearance was observed for 96.9% (190/196) of patients. Mutations in the Kelch propeller domain () were detected in 39.0% (69/177) of isolates: F446I (14.7% [26/177]), R561H (13.0% [23/177]), C580Y (10.2% [18/177]), and P574L (1.1% [2/177]). For , the day-28 ACPR was 100% (104/104; 95% CI: 96.5, 100) in northern Myanmar and 100% (97/97; 95% CI: 96.3, 100) in southern Myanmar. Across both studies, 100% (206/206) of patients had day-3 parasite clearance. There were no adverse events. Pyronaridine-artesunate had excellent efficacy in Myanmar against and and was well tolerated. This study supports the inclusion of pyronaridine-artesunate in national malaria treatment guidelines for Myanmar.