title: Genetic diversity of Plasmodium falciparum parasites from Kenya is not affected by antifolate drug selection.
abstract: The genotypes of merozoite surface protein-1, merozoite surface protein-2 and glutamine rich protein are frequently used to distinguish recrudescence from reinfection when parasitaemia reappears after antimalarial drug treatment. However, none of the previous reports has clearly assessed the change of genetic diversity following drug treatment. In the present study, we have assessed the impact of pyrimethamine/sulfadoxine and chlorproguanil/dapsone on the genetic diversity of isolates and the multiplicity of infection in patient isolates from Kilifi, Kenya. We have analysed the length polymorphism of merozoite surface protein-1, merozoite surface protein-2 and glutamine rich protein and the data clearly show that treatment with pyrimethamine/sulfadoxine and chlorproguanil/dapsone did not change the multiplicity of infection found in patients, in contrast to the selection that these drugs exert on the genes encoded by the target enzymes. In addition, we report that children of less than 2 years tend to have fewer numbers of clones per isolate when compared with older children. Overall, this study shows that the selection for genes that confer drug resistance is not a factor in reducing the genetic diversity of parasite clones in a patient.
authors.affiliation: Kenya Medical Research Institute (KEMRI)/Wellcome Trust collaborative Research Program, Wellcome Trust Research Laboratories, P O Box 43640, Nairobi, Kenya. anzila@wtnairobi.mimcom.net
authors.forename: A M
authors.initials: AM
authors.lastname: Nzila
authors.forename: E K
authors.initials: EK
authors.lastname: Mberu
authors.forename: E
authors.initials: E
authors.lastname: Nduati
authors.forename: A
authors.initials: A
authors.lastname: Ross
authors.forename: W M
authors.initials: WM
authors.lastname: Watkins
authors.forename: C H
authors.initials: CH
authors.lastname: Sibley
mesh_terms: D017677:Age Distribution; D000483:Alleles; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D001831:Body Temperature; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics*; D005334:Fever / Q000150:complications / Q000469:parasitology; D005493:Folic Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D017125:Genes, Protozoan / Q000235:genetics; D014644:Genetic Variation / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007223:Infant; D007630:Kenya; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology*; D020066:Merozoite Surface Protein 1 / Q000235:genetics; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development / Q000302:isolation & purification; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics
chemical_list: D000953:Antigens, Protozoan; D000962:Antimalarials; D005493:Folic Acid Antagonists; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; C072492:glutamate-rich protein, Plasmodium