Drug resistance-virulence relationship in Plasmodium falciparum causing severe malaria in an area of seasonal and unstable transmission

Acta Trop. 2006 Feb;97(2):181-7. doi: 10.1016/j.actatropica.2005.10.004. Epub 2005 Dec 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Adolescent
  • Adult
  • Alleles
  • Animals
  • Child
  • Child, Preschool
  • DNA, Protozoan / chemistry
  • DNA, Protozoan / genetics
  • Drug Resistance / genetics
  • Female
  • Humans
  • Infant
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / parasitology*
  • Male
  • Membrane Proteins / genetics*
  • Membrane Transport Proteins
  • Middle Aged
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / pathogenicity*
  • Polymerase Chain Reaction
  • Protozoan Proteins / genetics*
  • Seasons
  • Virulence / genetics

Substances

  • ATP-Binding Cassette Transporters
  • DNA, Protozoan
  • Membrane Proteins
  • Membrane Transport Proteins
  • PfCRT protein, Plasmodium falciparum
  • Protozoan Proteins
  • mdr gene protein, Plasmodium