Novel quadruple mutations in dihydropteroate synthase genes of Plasmodium falciparum in West Bengal, India

Trop Med Int Health. 2012 Nov;17(11):1329-34. doi: 10.1111/j.1365-3156.2012.03071.x. Epub 2012 Aug 22.

Abstract

Objective: To evaluate the anti-folate (sulphadoxine)-resistant pattern in Kolkata, one of the malaria endemic zones of Eastern India.

Methods: At first, 107 P. falciparum suspected cases were enrolled in this study. Ninety isolates (84.11%) of 107 suspected cases were analysed, as they had mono-infection with P. falciparum. In vitro susceptibility assays were performed in all 90 isolates. Parasitic DNA was isolated by phenol-chloroform extraction method and polymerase chain reaction was followed by restriction fragment length polymorphism analysis of different codons of the pfdhps gene (436, 437, 540, 581 and 613).

Results: Among 90 isolates from Kolkata, dhps mutant isolates at codons 436, 437, 540, 581 and 613 were found in 53.33%, 67.78%, 46.66%, 15.56% and 45.55%, respectively. In vitro sulphadoxine resistance was found in 49 isolates (54.44%). Interestingly we found 33 isolates (36.67%) with quadruple AGEAT mutant allele, of which 32 isolates (96.97%) were highly sulphadoxine resistant (P < 0.01) in vitro.

Conclusion: Our present findings implicate that because of enormous drug (sulphfadoxine) pressure, novel AGEAT mutation was highly correlated (P < 0.01) with sulphadoxine resistance.

Keywords: Plasmodium falciparum; drug‐resistant malaria; malaria resistente a medicamentos; mutación cuádruple; mutation quadruple; paludisme résistant aux médicaments; pfdhps; quadruple mutation; sulfadoxina; sulfadoxine; sulphadoxine.

MeSH terms

  • Antimalarials / therapeutic use
  • DNA, Protozoan / genetics
  • Dihydropteroate Synthase / genetics*
  • Drug Resistance
  • Genotype
  • Humans
  • India
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / genetics*
  • Molecular Sequence Data
  • Mutation*
  • Plasmodium falciparum / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Protozoan Proteins / genetics*
  • Sulfadoxine / therapeutic use

Substances

  • Antimalarials
  • DNA, Protozoan
  • Protozoan Proteins
  • Sulfadoxine
  • Dihydropteroate Synthase

Associated data

  • GENBANK/Z30659