Genetic typing reveals monomorphism between antimony sensitive and resistant Leishmania donovani isolates from visceral leishmaniasis or post kala-azar dermal leishmaniasis cases in India

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). Re...

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Published inParasitology research (1987) Vol. 111; no. 4; pp. 1559 - 1568
Main Authors Subba Raju, B. V., Gurumurthy, Srividya, Kuhls, Katrin, Bhandari, Vasundhra, Schnonian, Gabriele, Salotra, Poonam
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LanguageEnglish
Published Berlin/Heidelberg Springer-Verlag 01.10.2012
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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.
AbstractList 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.
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.
Audience Academic
Author Gurumurthy, Srividya
Subba Raju, B. V.
Kuhls, Katrin
Bhandari, Vasundhra
Salotra, Poonam
Schnonian, Gabriele
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Issue 4
Keywords Visceral Leishmaniasis Case
Indian Isolate
Intraspecies Variation
Visceral Leishmaniasis
Indian Strain
Infection
Kinetoplastida
Protozoa
Protozoal disease
Typing
Leishmania donovani
Parasite
Antimony
Genetics
Kala azar
Leishmaniasis
Parasitosis
Language English
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SSID ssj0017644
Score 2.0916815
Snippet 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),...
SourceID proquest
gale
crossref
pubmed
pascalfrancis
springer
SourceType Aggregation Database
Index Database
Publisher
StartPage 1559
SubjectTerms Adolescent
Adult
Analysis
Antimony - pharmacology
Antiprotozoal Agents - pharmacology
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Child
Child, Preschool
Drug Resistance
Female
Fundamental and applied biological sciences. Psychology
General aspects
General aspects and techniques. Study of several systematic groups. Models
Genetic polymorphisms
Genotype
Humans
Immunology
India
Invertebrates
Kala-azar
Leishmania donovani
Leishmania donovani - classification
Leishmania donovani - drug effects
Leishmania donovani - genetics
Leishmania donovani - isolation & purification
Leishmania infantum
Leishmaniasis, Visceral - parasitology
Male
Medical Microbiology
Microbiology
Microsatellite Repeats
Middle Aged
Original Paper
Polymorphism, Genetic
Young Adult
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
URI https://link.springer.com/article/10.1007/s00436-012-2996-5
https://www.ncbi.nlm.nih.gov/pubmed/22752721
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Volume 111
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