Genetic polymorphisms associated with sulphadoxine-pyrimethamine drug resistance among Plasmodium falciparum field isolates in malaria endemic areas of Assam

J Postgrad Med. 2015 Jan-Mar;61(1):9-14. doi: 10.4103/0022-3859.147019.

Abstract

Background: The emergence of antimalarial drug resistance malaria parasite is widespread in North eastern region of India. During January 2012-December 2013, we conducted active surveillance for detection of antifolate resistance-associated genetic polymorphisms in Plasmodium falciparum malaria parasite from different malaria endemic areas of Assam.

Materials and methods: A total of 281 field samples were collected from suspected malaria patients of which 106 malaria P. falciparum positive cases were detected in microscopic slide examination. A nested PCR was done for amplification of a 648 bp portion of the dhfr gene and 710 bp portion of the dhps gene.

Results: Mutation analysis revealed existence of three different haplotypes of the P. falciparum dhfr gene of which ANRNI was highly prevalent (90%). Triple mutant haplotypes AIRNI (N51I+C59R+S108N) of the dhfr gene associated with pyrimethamine resistance were prevalent in Chirang district of Assam. Whereas, dhps mutation study revealed that triple mutant haplotype AGEAA (S436A+A437G+K540E) associated with Sulphadoxine resistance was found among 26% of P. falciparum field isolates. However, P. falciparum dhfr-dhps two locus mutation analysis showed that there were a total of nine dhfr-dhps genotypes.

Conclusion: It was noticed that 93.62% (88/94) isolates had mutations in the sequences of both enzymes, which is an indication of prevalence of high grade of Sulphadoxine - pyrimethamine resistance in P. falciparum malaria parasites in Assam.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antimalarials / pharmacology*
  • Child
  • Child, Preschool
  • DNA, Protozoan / genetics
  • Drug Combinations
  • Drug Resistance / genetics*
  • Female
  • Gene Amplification / genetics
  • Haplotypes
  • Humans
  • India / epidemiology
  • Infant
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / genetics
  • Male
  • Middle Aged
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / isolation & purification
  • Polymerase Chain Reaction / methods
  • Polymorphism, Single Nucleotide
  • Population Surveillance
  • Protozoan Proteins / genetics
  • Pyrimethamine / pharmacology*
  • Sulfadoxine / pharmacology*
  • Young Adult

Substances

  • Antimalarials
  • DNA, Protozoan
  • Drug Combinations
  • Protozoan Proteins
  • Sulfadoxine
  • Pyrimethamine