Data from: Chemotherapy, within-host ecology and the fitness of drug-resistant malaria parasites

A major determinant of the rate at which drug-resistant malaria parasites spread through a population is the ecology of resistant and sensitive parasites sharing the same host. Drug treatment can significantly alter this ecology by removing the drug-sensitive parasites, leading to competitive release of resistant parasites. Here, we test the hypothesis that the spread of resistance can be slowed by reducing drug treatment and hence restricting competitive release. Using the rodent malaria model Plasmodium chabaudi, we found that low-dose chemotherapy did reduce competitive release. A higher drug dose regimen exerted stronger positive selection on resistant parasites for no detectable clinical gain. We estimated instantaneous selection coefficients throughout the course of replicate infections to analyze the temporal pattern of the strength and direction of within-host selection. The strength of selection on resistance varied through the course of infections, even in untreated infections, but increased immediately following drug treatment, particularly in the high-dose groups. Resistance remained under positive selection for much longer than expected from the half life of the drug. Although there are many differences between mice and people, our data do raise the question whether the aggressive treatment regimens aimed at complete parasite clearance are the best resistance-management strategies for humans.

complete data file
Experimental data from Huijben et al 2010, Evolution 64: 2952-2968. Given are measurements of mouse body weight, red blood cell density, asexual parasite densities of resistant clone, asexual parasite densities of susceptible clone, gametocyte densities of resistant clone, gametocyte densities of susceptible clone from day 3-21 post-infection, plus days 24,26 and 28. Measurement units are provided in excel file. Mice that died during the acute infection were excluded from the infection and are not included in the data file.
SH1 dryad data file.xls

Huijben, Silvie; Nelson, William A.; Wargo, Andrew R. et al. (2013). Data from: Chemotherapy, within-host ecology and the fitness of drug-resistant malaria parasites [Dataset]. Dryad. https://doi.org/10.5061/dryad.4h0g0