title: The fitness of drug-resistant malaria parasites in a rodent model: multiplicity of infection.
abstract: Malaria infections normally consist of more than one clonally replicating lineage. Within-host interactions between sensitive and resistant parasites can have profound effects on the evolution of drug resistance. Here, using the Plasmodium chabaudi mouse malaria model, we ask whether the costs and benefits of resistance are affected by the number of co-infecting strains competing with a resistant clone. We found strong competitive suppression of resistant parasites in untreated infections and marked competitive release following treatment. The magnitude of competitive suppression depended on competitor identity. However, there was no overall effect of the diversity of susceptible parasites on the extent of competitive suppression or release. If these findings generalize, then transmission intensity will impact on resistance evolution because of its effect on the frequency of mixed infections, not because of its effect on the distribution of clones per host. This would greatly simplify the computational problems of adequately capturing within-host ecology in models of drug resistance evolution in malaria.
authors: Department of Biology, Center for Infectious Disease Dynamics, Pennsylvania State University, University Park, PA 16802, USA. silviehuijben@gmail.com
authors: S
authors: S
authors: Huijben
authors: D G
authors: DG
authors: Sim
authors: W A
authors: WA
authors: Nelson
authors: A F
authors: AF
authors: Read
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D005075:Biological Evolution; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology*; D056084:Genetic Fitness / Q000502:physiology*; D006790:Host-Parasite Interactions; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016788:Plasmodium chabaudi / Q000187:drug effects* / Q000502:physiology; D011739:Pyrimethamine / Q000494:pharmacology; D012641:Selection, Genetic; D013045:Species Specificity
chemical_list: D000962:Antimalarials; D011739:Pyrimethamine