Diversity and Drug Resistance in Plasmodium falciparum Malaria Infections

Plasmodium falciparum malaria infections often consist of multiple co-infecting strains with different phenotypic traits and responses to drug treatment. Traditional techniques used to study malaria infections do not account for co-infections and are unable to reveal the presence of rare drug resistant phenotypes within diverse infections. However, high-throughput sequencing can uncover parasite genotypes (or haplotypes) at low relative abundances within individual hosts. We detect 29 infections with signatures of drug resistance by quantifying haplotype-specific clearance curves, and five infections using a novel approach inspired by Fisher’s fundamental theorem. A second set of analyses reveal that parasite density and initial haplotype richness have a positive and negative relationship with the probability of an infection persisting after 72 hours of treatment, respectively. Overall, this study shows the utility of high-throughput sequencing for detecting variation in drug sensitivity and provides insight on the within-host dynamics of diverse infections.M.Sc