title: Complex dynamics and stability of resistance to antimalarial drugs.
abstract: A succession of antimalarial drugs has been deployed to treat human falciparum malaria but each has, in turn, been nullified by the spread of drug resistance. The consensus view has always been that, once present, resistance will inevitably rapidly increase to 100%. However, recent field evidence has shown this is not inevitable, and that drug resistance may initially spread and then stabilize at relatively low frequencies. It is proposed that intense competition between separate malaria clones co-infecting the same human can generate complex dynamics capable of explaining this observation. Standard population genetic analysis confirms this assertion. The dynamics underlying the evolution of antimalarial resistance may therefore be much more complex than previously realized, and can resolve the apparent paradox between field data and the underlying theory of the evolution of resistance. This explanation is novel and the results are equally applicable to other parasitic species where multiple infections of the same host are common.
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK. hastings@liverpool.ac.uk
authors.forename: I M
authors.initials: IM
authors.lastname: Hastings
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D003198:Computer Simulation; D004351:Drug Resistance / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D017125:Genes, Protozoan / Q000235:genetics; D005828:Genetics, Population; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D012641:Selection, Genetic
chemical_list: D000962:Antimalarials