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 in | Parasitology research (1987) Vol. 111; no. 4; pp. 1559 - 1568 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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Springer-Verlag
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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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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 |
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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 |
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