title: Genetic typing reveals monomorphism between antimony sensitive and resistant Leishmania donovani isolates from visceral leishmaniasis or post kala-azar dermal leishmaniasis cases in India.
abstract: Resistance to pentavalent antimonials has emerged as a major hurdle to the treatment and control of visceral leishmaniasis (VL), also known as kala-azar (KA), caused by Leishmania donovani. In India, over 60% of KA patients are unresponsive to the first-line drug sodium antimony gluconate (SAG). Resistance determinants in laboratory strains are partly known; however, the mechanism operating in field isolates is not well understood. In this study, we attempted to analyze the genetic polymorphism between SAG sensitive and resistant parasites using a total of 52 L. donovani isolates obtained either from bone marrow of VL patients or from skin lesions of post kala-azar dermal leishmaniasis (PKDL) patients that constitute an important reservoir of parasite. The clinical isolates were analyzed in comparison with L. donovani parasites from reference strains belonging to distinct geographical locations, at internal transcribed spacer 1 region; coding region of gp63 and nine microsatellite repeat regions. Our results demonstrated that both SAG resistant (n = 26) and sensitive (n = 19) Indian isolates, whether causing VL or PKDL, were monomorphic at all the genetic loci tested, unlike the L. donovani in East African or Leishmania infantum in Mediterranean countries where intraspecies variations exist at these loci. Further, the Indian isolates were found closest to the Kenyan isolates of L. donovani on the basis of fragment analysis of microsatellite markers.
authors: National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi 110029, India.
authors: B V
authors: BV
authors: Subba Raju
authors: Srividya
authors: S
authors: Gurumurthy
authors: Katrin
authors: K
authors: Kuhls
authors: Vasundhra
authors: V
authors: Bhandari
authors: Gabriele
authors: G
authors: Schnonian
authors: Poonam
authors: P
authors: Salotra
mesh_terms: D000293:Adolescent; D000328:Adult; D000965:Antimony / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India; D007893:Leishmania donovani / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D007898:Leishmaniasis, Visceral / Q000469:parasitology*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D000981:Antiprotozoal Agents; D000965:Antimony