title: Differential effect of regional drug pressure on dihydrofolate reductase and dihydropteroate synthetase mutations in southern Mozambique.
abstract: The prevalence and frequency of the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) mutations associated with sulfadoxine-pyrimethamine (SP) resistance at 13 sentinel surveillance sites in southern Mozambique were examined regularly between 1999 and 2004. Frequency of the dhfr triple mutation increased from 0.26 in 1999 to 0.96 in 2003, remaining high in 2004. The dhps double mutation frequency peaked in 2001 (0.22) but declined to baseline levels (0.07) by 2004. Similarly, parasites with both dhfr triple and dhps double mutations had increased in 2001 (0.18) but decreased by 2004 (0.05). The peaking of SP resistance markers in 2001 coincided with a SP-resistant malaria epidemic in neighboring KwaZulu-Natal, South Africa. The decline in dhps (but not dhfr) mutations corresponded with replacement of SP with artemether-lumefantrine as malaria treatment policy in KwaZulu-Natal. Our results show that drug pressure can exert its influence at a regional level rather than merely at a national level.
authors.affiliation: Malaria Lead Programme, Medical Research Council, Durban, KwaZulu-Natal, South Africa. jaishree.raman@mrc.ac.za
authors.forename: Jaishree
authors.initials: J
authors.lastname: Raman
authors.forename: Brian
authors.initials: B
authors.lastname: Sharp
authors.forename: Immo
authors.initials: I
authors.lastname: Kleinschmidt
authors.forename: Cally
authors.initials: C
authors.lastname: Roper
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Streat
authors.forename: Val
authors.initials: V
authors.lastname: Kelly
authors.forename: Karen I
authors.initials: KI
authors.lastname: Barnes
mesh_terms: D000293:Adolescent; D000818:Animals; D002648:Child; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000032:analysis; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics*; D018432:Drug Resistance, Multiple / Q000235:genetics; D005260:Female; D051456:Gene Flow; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000453:epidemiology; D008297:Male; D009073:Mozambique; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D016054:DNA, Protozoan; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase