title: Drug resistance-virulence relationship in Plasmodium falciparum causing severe malaria in an area of seasonal and unstable transmission.
abstract: The pathogenesis of severe Plasmodium falciparum malaria is still obscure, but is believed to be multi-factorial, and among the important factors are intrinsic parasite-properties. Here we investigated the association between clinical manifestation of P. falciparum malaria (an indicator of virulence) and two parasite properties--drug resistance and gametocyte production. Among 996 P. falciparum infections detected in the out-patient clinic of Gedarif Hospital in eastern Sudan, there was no significant association between the incidence of severe versus mild disease and the presence of resistant alleles at the chloroquine-resistance transporter locus (pfcrt-T76) and the multi-drug-resistance locus (pfmdr1-Y86). However, among severe cases, there was a significantly lower prevalence of parasites carrying resistant alleles among patients that died versus survived. There was a trend towards a higher gametocyte rate among severe malaria patients compared with uncomplicated malaria cases. These results are discussed in relation to the fitness of drug resistant parasites.
authors.affiliation: Malaria Research Centre (MalRC), Department of Biochemistry, Faculty of Medicine, University of Khartoum, P.O. Box 102, Khartoum, Sudan. gehaha2002@yahoo.com
authors.forename: Hayder A
authors.initials: HA
authors.lastname: Giha
authors.forename: Mustafa I
authors.initials: MI
authors.lastname: Elbashir
authors.forename: Ishraga E
authors.initials: IE
authors.lastname: A-Elbasit
authors.forename: Thoraya M E
authors.initials: TM
authors.lastname: A-Elgadir
authors.forename: Gehad E
authors.initials: GE
authors.lastname: ElGhazali
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Mackinnon
authors.forename: Hamza A
authors.initials: HA
authors.lastname: Babiker
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D000818:Animals; D002648:Child; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000235:genetics / Q000472:pathogenicity*; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000235:genetics*; D012621:Seasons; D014774:Virulence / Q000235:genetics
chemical_list: D018528:ATP-Binding Cassette Transporters; D016054:DNA, Protozoan; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium