eLife assessment
This important work addressed the identifcation of antimalarial drug resistance mutations that do not readily transmit to new human hosts, focusing on azithromycin resistance. The technically challenging analyses of azithromycin-resistant parasites as they traverse the mosquito host and human liver are conducted using state-of-the-art tools, including humanized mice. While the claim regarding the lack of transmission by atovaquone-resistant P. berghei is convincing, the evidence for the lack of transmission by atovaquone-resistant P. falciparum is insufficient. This work will appeal to biologists and biomedical scientists in parasitology and drug discovery, offering insights into combating antimalarial drug resistance and understanding the fitness costs associated with drug-resistant parasites.