Gametocyte production and transmission fitness of African and Asian <i>Plasmodium falciparum</i> isolates with differential susceptibility to artemisinins

The emergence of <i>Plasmodium falciparum</i> parasites partially resistant to artemisinins (ART-R) poses a significant threat to recent gains in malaria control. ART-R has been associated with PfKelch13 (K13) mutations, which differ in fitness costs. This study investigates the gametocyte production and transmission fitness of African and Asian <i>P. falciparum</i> isolates with different K13 genotypes across multiple mosquito species. We tested three ART-sensitive (ART-S) isolates (NF54, NF135, and NF180) and three ART-R isolates (ARN1G, 3815, and PAT-023) for sexual conversion and transmission to <i>Anopheles stephensi, An. gambiae,</i> and <i>An. coluzzii</i>. ART-R levels were quantified <i>in vitro</i> using the Ring-stage Survival Assay (RSA), and the transmission-reducing effects of dihydroartemisinin (DHA) on mature gametocytes were assessed. Results showed that ART-S parasite lines consistently produced gametocytes and transmitted effectively in all three mosquito species. ART-R isolates showed variability: ARN1G maintained high transmission levels, whereas 3815 showed limited transmission potential despite higher sporozoite loads in <i>An. coluzzii</i>. The African ART-R isolate PAT-023 demonstrated low gametocyte commitment but was transmitted efficiently in both <i>An. gambiae</i> and <i>An. coluzzii</i>. DHA exposure reduced mosquito infectivity for all isolates, regardless of K13 genotype. These findings, based on a limited number of field isolates, suggest that ART-R parasites remain transmissible across different <i>Anopheles</i> species. However, ART-R does not appear to confer a direct transmission advantage. This study highlights the complexity of ART-R dynamics and underscores the need for further research to inform malaria control strategies in regions where ART-R parasites are circulating.