Different patterns of pfcrt and pfmdr1 polymorphisms in P. falciparum isolates from Nigeria and Brazil: the potential role of antimalarial drug selection pressure

Am J Trop Med Hyg. 2012 Feb;86(2):211-3. doi: 10.4269/ajtmh.2012.11-0368.

Abstract

The effect of antimalarial drug selection on pfcrt and pfmdr1 polymorphisms in Plasmodium falciparum isolates from two distinct geographical locations was determined in 70 and 18 P. falciparum isolates from Nigeria and Brazil, respectively, using nested polymerase chain reaction and direct DNA sequencing approaches. All isolates from Brazil and 72% from Nigeria harbored the mutant SVMNT and CVIET pfcrt haplotype, respectively. The pfcrt CVMNT haplotype was also observed in (7%) of the Nigerian samples. One hundred percent (100%) and 54% of the parasites from Brazil and Nigeria, respectively, harbored wild-type pfmdr1Asn86. We provide first evidence of emergence of the CVMNT haplotype in West Africa. The high prevalence of pfcrt CVIET and SVMNT haplotypes in Nigeria and Brazil, respectively, is indicative of different selective pressure by chloroquine and amodiaquine. Continuous monitoring of pfcrt SVMNT haplotype is required in endemic areas of Africa, where artesunate-amodiaquine combination is used for treatment of acute uncomplicated malaria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amodiaquine / therapeutic use
  • Antimalarials / therapeutic use*
  • Artemisinins / therapeutic use
  • Brazil / epidemiology
  • DNA Copy Number Variations
  • Drug Combinations
  • Genotype
  • Haplotypes
  • Humans
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / epidemiology
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism
  • Multidrug Resistance-Associated Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / metabolism
  • Multigene Family
  • Mutation
  • Nigeria / epidemiology
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / isolation & purification
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / metabolism
  • Sequence Analysis, DNA

Substances

  • Antimalarials
  • Artemisinins
  • Drug Combinations
  • Mdr1 protein, Plasmodium falciparum
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • PfCRT protein, Plasmodium falciparum
  • Protozoan Proteins
  • amodiaquine, artesunate drug combination
  • Amodiaquine