Competitive release of drug resistance following drug treatment of mixed Plasmodium chabaudi infections.
BACKGROUND
Malaria infections are often genetically diverse, potentially leading to competition between co-infecting strains. Such competition is of key importance in the spread of drug resistance.


METHODS
The effects of drug treatment on within-host competition were studied using the rodent malaria Plasmodium chabaudi. Mice were infected simultaneously with a drug-resistant and a drug-sensitive clone and were then either drug-treated or left untreated. Transmission was assessed by feeding mice to Anopheles stephensi mosquitoes.


RESULTS
In the absence of drugs, the sensitive clone competitively suppressed the resistant clone; this resulted in lower asexual parasite densities and also reduced transmission to the mosquito vector. Drug treatment, however, allowed the resistant clone to fill the ecological space emptied by the removal of the sensitive clone, allowing it to transmit as well as it would have done in the absence of competition.


CONCLUSIONS
These results show that under drug pressure, resistant strains can have two advantages: (1) they survive better than sensitive strains and (2) they can exploit the opportunities presented by the removal of their competitors. When mixed infections are common, such effects could increase the spread of drug resistance.
de Roode
Jacobus C
JC
Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, King's Buildings, West Mains Road, Edinburgh EH9 3 JT, Scotland, United Kingdom. j.de.roode@ed.ac.uk
Culleton
Richard
R
Bell
Andrew S
AS
Read
Andrew F
AF
D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology*; D005260:Female; D005838:Genotype; D007303:Insect Vectors / Q000469:parasitology; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology* / Q000635:transmission; D051379:Mice; D008808:Mice, Inbred CBA; D016788:Plasmodium chabaudi / Q000187:drug effects* / Q000235:genetics; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use
D000962:Antimalarials; D011739:Pyrimethamine