Genetic markers for antimony resistant clinical isolates differentiation from Indian Kala-azar

Acta Trop. 2016 Dec:164:177-184. doi: 10.1016/j.actatropica.2016.09.012. Epub 2016 Sep 11.

Abstract

Visceral Leishmaniasis or Kala-azar is caused by the protozoan parasites belonging to the Genus Leishmania. Once thought eradicated from the Indian subcontinent, the disease came back with drug resistance to almost all prevalent drugs. Molecular epidemiological studies revealed the polymorphic nature of the population of the main player of the disease, Leishmania donovani and involvement of other species (L. tropica) and other genus (Leptomonas) with the disease. This makes control measures almost futile. It also strongly demands the characterization of each and every isolate mandatory which is not done. In this background, the present study has been carried out to assess the genetic attributes of each clinical isolates (n=26) of KA and PKDL patients from India and Bangladesh. All the isolates were characterized through Restriction Fragment Length Polymorphism (RFLP) analysis to ascertain their species identity. 46.2% of the isolates were found to be Sodium Stibogluconate (SSG) resistant by amastigote-macrophage model. When the clinical isolates were subjected to Single Stranded Conformation Polymorphism (SSCP) of Internal Transcribed Spacer 1 (ITS1), Internal Transcribed Spacer 2 (ITS2) and some anonymous markers, the drug resistant Leishmania isolates of SSG can be distinguished from the sensitive isolates distinctly. This study showed for the first time, the genetic markers for SSG drug resistance of Indian Kala-azar clinical isolates.

Keywords: Drug resistance; Genetic markers; Indian kala-azar; L. tropica; Leishmania donovani; Single stranded conformation polymorphism.

Publication types

  • Observational Study

MeSH terms

  • Antimony / pharmacology*
  • Antiprotozoal Agents / pharmacology*
  • Bangladesh / epidemiology
  • Bone Marrow / parasitology
  • Cluster Analysis
  • DNA, Protozoan / drug effects
  • DNA, Protozoan / genetics*
  • Drug Resistance / drug effects
  • Drug Resistance / genetics*
  • Gene Expression Regulation
  • Genes, Protozoan
  • Genetic Markers / genetics
  • Humans
  • India / epidemiology
  • Leishmania donovani / classification
  • Leishmania donovani / drug effects
  • Leishmania donovani / genetics*
  • Leishmania donovani / isolation & purification*
  • Leishmaniasis, Visceral / epidemiology
  • Leishmaniasis, Visceral / parasitology*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Phylogeny
  • Polymorphism, Restriction Fragment Length
  • Sequence Analysis, DNA

Substances

  • Antiprotozoal Agents
  • DNA, Protozoan
  • Genetic Markers
  • Antimony