Allelic polymorphism in the Plasmodium vivax dihydrofolate reductase gene among Indian field isolates

S K Prajapati1, H Joshi, N Valecha

  • 1National Institute of Malaria Research (ICMR), Delhi, India.

Insights

Pyrimethamine resistance in Plasmodium vivax is increasing, with mutant genotypes becoming more common from north to south India. This geographical pattern in dihydrofolate reductase gene mutations may be linked to malaria transmission dynamics.

Area of Science:

  • Malariology
  • Molecular Epidemiology
  • Parasitic Diseases

Background:

  • Plasmodium vivax is a significant cause of malaria globally.
  • Pyrimethamine is an essential antimalarial drug.
  • Drug resistance, particularly to pyrimethamine, poses a threat to malaria control.

Purpose of the Study:

  • To investigate the geographical distribution of point mutations in the P. vivax dihydrofolate reductase (Pvdhfr) gene.
  • To assess the prevalence of pyrimethamine resistance-associated mutations in P. vivax isolates across India.

Main Methods:

  • Analysis of 129 P. vivax isolates from diverse Indian geographical regions.
  • Genotyping of the P. vivax dihydrofolate reductase gene to identify specific point mutations.
  • Statistical analysis to determine geographical patterns and significance.

Main Results:

  • A significant north-to-south gradient in the frequency of mutant Pvdhfr genotypes was observed (p <0.0001).
  • Wild-type genotypes were most common in northern India, while mutant genotypes predominated in southern coastal regions.
  • Isolates from the Car-Nicobar islands exclusively harbored mutant genotypes.

Conclusions:

  • The study reveals a distinct geographical stratification of pyrimethamine resistance-associated mutations in P. vivax across India.
  • The observed mutation patterns suggest a potential association with varying malaria transmission intensities.
  • Understanding these geographical trends is crucial for effective malaria treatment strategies and drug resistance monitoring.