Therapeutic efficacy of the recently WHO-recommended antimalarial artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria: systematic review and meta-analysis

Emergence of resistance to antimalarial drugs is a major challenge to malaria control and elimination strategies, and has crucial implications for global public health. Artesunate-pyronaridine (AS-PY) is among the most recently recommended artemisinin-based combination therapies (ACTs) endorsed by the world health organization (WHO) in 2022, and represents an additional promising tool in the global malaria control arsenal for the treatment of uncomplicated Plasmodium falciparum . Regular monitoring of the efficacy of antimalarial drugs are recommended to assess the development of antimicrobial resistance. This study aims to determine the pooled therapeutic efficacy of AS-PY for the treatment of uncomplicated Plasmodium falciparum malaria comprehensively. This systematic review and meta-analysis was conducted to evaluate the therapeutic efficacy of AS-PY for the treatments of uncomplicated Plasmodium falciparum malaria. The study was conducted adhering to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline. Relevant published articles retrieved from different databases, PubMed, Google Scholar, African Journals Library (AJOL), and Clinical Trials.gov until April 2026. Two independent reviewers performed screening of studies, data extractions, and assessed methodological quality. For studies conducted in multi center sites, result from all study site were aggregated to generate a single study-level effect estimate before conducting meta-analysis we pooled the effect estimate using a random-effects model. Heterogeneity quantified with I2. Key results reported with 95% CIs. Fifteen studies involving 4689 participants were included to assess the therapeutic efficacy of AS-PY. The overall Day 28, PCR-corrected adequate clinical and parasitological response (ACPR) for treating uncomplicated Plasmodium falciparum malaria was 99.0% (95% CI: 98.0–99.0% p < 0.001) which is highly efficacious. A random-effect model was employed due to the presence of moderate heterogeneity I 2 = 47.44, p< 0.001). Most studies included in this systematic review and meta-analysis reported greater than 97% of Day 28 therapeutic efficacy of AS-PY. The sub-group analysis showed that Day 28 therapeutic efficacy of AS-PY in Africa was 98.4%, Asian continent 97.1%, and 99.1% in multicenter involving both African and Asian countries. This systematic review and meta-analysis suggest that AS-PY therapy is efficacious and can serve as a first-line artemisinin-based combination therapy option for the treatment of uncomplicated Plasmodium falciparum malaria. Due to its High therapeutic efficacy, malaria endemic country that reported partial artemether lumefantrine resistance better to consider AS-PY as a treatment option after performing a thorough therapeutic efficacy monitoring and pharmacovigilance studies.