title: Virulence, drug sensitivity and transmission success in the rodent malaria, Plasmodium chabaudi.
abstract: Here, we test the hypothesis that virulent malaria parasites are less susceptible to drug treatment than less virulent parasites. If true, drug treatment might promote the evolution of more virulent parasites (defined here as those doing more harm to hosts). Drug-resistance mechanisms that protect parasites through interactions with drug molecules at the sub-cellular level are well known. However, parasite phenotypes associated with virulence might also help parasites survive in the presence of drugs. For example, rapidly replicating parasites might be better able to recover in the host if drug treatment fails to eliminate parasites. We quantified the effects of drug treatment on the in-host survival and between-host transmission of rodent malaria (Plasmodium chabaudi) parasites which differed in virulence and had never been previously exposed to drugs. In all our treatment regimens and in single- and mixed-genotype infections, virulent parasites were less sensitive to pyrimethamine and artemisinin, the two antimalarial drugs we tested. Virulent parasites also achieved disproportionately greater transmission when exposed to pyrimethamine. Overall, our data suggest that drug treatment can select for more virulent parasites. Drugs targeting transmission stages (such as artemisinin) may minimize the evolutionary advantage of virulence in drug-treated infections.
authors.affiliation: Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, UK. petra.schneider@ed.ac.uk
authors.forename: Petra
authors.initials: P
authors.lastname: Schneider
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Bell
authors.forename: Derek G
authors.initials: DG
authors.lastname: Sim
authors.forename: Aidan J
authors.initials: AJ
authors.lastname: O'Donnell
authors.forename: Simon
authors.initials: S
authors.lastname: Blanford
authors.forename: Krijn P
authors.initials: KP
authors.lastname: Paaijmans
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Read
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Reece
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005838:Genotype; D008288:Malaria / Q000469:parasitology / Q000635:transmission*; D051379:Mice; D008810:Mice, Inbred C57BL; D021261:Parasitic Sensitivity Tests; D016788:Plasmodium chabaudi / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D011739:Pyrimethamine / Q000494:pharmacology*; D014774:Virulence
chemical_list: D000962:Antimalarials; D011739:Pyrimethamine