First case of artemisinin treatment failure of Plasmodium falciparum malaria from Tanzania

Emergence of Artemisinin-resistant (ART-R) parasites in different pockets of Africa would pose a major health crisis. While the presence of Artemisinin resistant Plasmodium falciparum has been well documented in many Southeast Asian countries, only two cases of de novo emergence of artemisinin resistance have been reported from Africa to date: one from Equatorial Guinea(Lu et al., 2017) and the other one from Rwanda(Uwimana et al., 2020). Both studies have implicated M579I and R561H mutations in the Kelch13 protein in the underlying resistance phenotype. Here we report an ART-R P. falciparum clinical case in Oman that was contracted in Dar es Salaam, Tanzania (East Africa) and resulted in treatment failure. We provide a comprehensive mutational footprint of the genome of this imported clinical isolate in Oman and provide detailed phylogenomic evidence of the East African origin of the parasite. By employing a CRISPR-Cas9-mediated gene editing protocol, we provide functional evidence implicating a I723V mutation in the PfATPase6 gene in low level of Artemisinin tolerance in a lab-adapted line (NF54) of the parasite by Ring-stage Survival Assays (RSA).