Heterogeneous distribution of Plasmodium falciparum drug resistance haplotypes in subsets of the host population.
BACKGROUND
The emergence of drug resistance is a major problem in malaria control. For mathematical modelling of the transmission and spread of drug resistance the determinant parameters need to be identified and measured. The underlying hypothesis is that mutations associated with drug resistance incur fitness costs to the parasite in absence of drug pressure. The distribution of drug resistance haplotypes in different subsets of the host population was investigated. In particular newly acquired haplotypes after radical cure were characterized and compared to haplotypes from persistent infections.


METHODS
Mutations associated with antimalarial drug resistance were analysed in parasites from children, adults, and new infections occurring after treatment. Twenty-five known single nucleotide polymorphisms from four Plasmodium falciparum genes associated with drug resistance were genotyped by DNA chip technology.


RESULTS
Haplotypes were found to differ between subsets of the host population. A seven-fold mutated haplotype was significantly reduced in adults compared to children and new infections, whereas parasites harbouring fewer mutations were more frequent in adults.


CONCLUSIONS
The reduced frequency of highly mutated parasites in chronic infections in adults is likely a result of fitness costs of drug resistance that increases with number of mutations and is responsible for reduced survival of mutant parasites.
Schoepflin
Sonja
S
Swiss Tropical Institute, Department of Medical Parasitology and Infection Biology, Socinstr.57, 4002 Basel, Switzerland. s_schoepflin@hotmail.com
Marfurt
Jutta
J
Goroti
Mary
M
Baisor
Moses
M
Mueller
Ivo
I
Felger
Ingrid
I
D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004351:Drug Resistance / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology*; D020411:Oligonucleotide Array Sequence Analysis; D010219:Papua New Guinea / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012424:Rural Population; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate