Whole genome sequencing to evaluate the resistance landscape following antimalarial treatment failure with fosmidomycin-clindamycin

Abstract

Novel antimalarial therapies are needed in the face of emerging resistance to artemisinin combination therapies. A previous study found a high cure rate in Mozambican children with uncomplicated Plasmodium falciparum malaria 7 days post treatment with a fosmidomycin-clindamycin combination. However, 28-day cure rates were low (45.9%), due to parasite recrudescence. We sought to identify any genetic changes underlying parasite recrudescence. To this end, we utilized a selective whole genome amplification method to amplify parasite genomes from blood spot DNA samples. Parasite genomes from pre-treatment and post-recrudescence samples were subjected to whole genome sequencing to identify nucleotide variants. We find that our data do not support the existence of a genetic change responsible for recrudescence following fosmidomycin-clindamycin treatment. Additionally, we find that previously described resistance alleles for these drugs do not represent biomarkers of recrudescence. Future studies should continue to optimize fosmidomycin combinations for use as antimalarial therapies