Within-host ecology and drug resistance in malaria infections
Drug resistance is a major challenge for malaria control. Ideally, resistance could be detected when it is at a low level (drug ’tolerance’) and low frequency in a population, but current tools for detecting drug resistance struggle to do this, especially when infections are made up of multiple parasite genotypes. We’ve been developing new tools that capitalize on ultra deep, second generation sequencing to quantify changes in the structure of within-host parasite populations over the course of drug treatment and characterize any variation in drug tolerance within individual infections.
Looking at a cohort of patients from Tanzania — where resistance to current frontline antimalarials is not thought to be a major problem — we find substantial variation in the clearance rates of different parasite haplotypes, with some haplotypes clearing at rates as slow as those observed in Cambodian patients who are failing treatment by clinical measures. We show that if these slow-clearing parasites become more common, they could result in substantial increases in time to cure. Our results highlight the role of the within-host ecological context in the spread of drug resistant malaria parasites.