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Refractoriness to the treatment of sodium stibogluconate in Indian kala-azar field isolates persist in in vitro and in vivo experimental models.
Parasitol Res. 2005 Jun; 96(4):216-23.PR

Abstract

Ever since their discovery about 60 years ago as therapeutic agent for visceral leishmaniasis (VL) or kala-azar, pentavalent antimonials (Sb(v)) have remained the first line treatment of choice all over the world including India. But recently, the number of kala-azar patients unresponsive to sodium stibogluconate (SSG) therapy, is steadily increasing in India. In this study, three clinical isolates, of which two were from SSG unresponsive and one from SSG responsive patients were evaluated for their infectivity and for their chemotherapeutic responses in vitro (macrophage-amastigote system) and in vivo (in hamsters). Persistence of SSG resistance was also checked by repeated passages in vitro as well as in vivo. The drug resistant strains (2039 and 2041) did not respond to SSG therapy both in vitro as well as in vivo but strains 2001 and Dd8 showed full sensitivity to SSG treatment. All the four strains responded well to amphotericin B and miltefosine treatment both in macrophages and in hamsters. The specific chemotherapeutic responses of all the strains to SSG were consistently persistent after repeated passages in cultures and in vivo, which indicates that these isolates are truly refractory to SSG treatment in field conditions. Two isolates were also transfected with green fluorescent protein (GFP) for the development of in vitro assay for studying antileishmanial activities of new and reference drugs in macrophages by flow cytometry.

Authors+Show Affiliations

Division of Parasitology, Central Drug Research Institute, Post Box No. 173, Lucknow 226 001, India. anuradha_dube@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15868188

Citation

Dube, Anuradha, et al. "Refractoriness to the Treatment of Sodium Stibogluconate in Indian Kala-azar Field Isolates Persist in in Vitro and in Vivo Experimental Models." Parasitology Research, vol. 96, no. 4, 2005, pp. 216-23.
Dube A, Singh N, Sundar S, et al. Refractoriness to the treatment of sodium stibogluconate in Indian kala-azar field isolates persist in in vitro and in vivo experimental models. Parasitol Res. 2005;96(4):216-23.
Dube, A., Singh, N., Sundar, S., & Singh, N. (2005). Refractoriness to the treatment of sodium stibogluconate in Indian kala-azar field isolates persist in in vitro and in vivo experimental models. Parasitology Research, 96(4), 216-23.
Dube A, et al. Refractoriness to the Treatment of Sodium Stibogluconate in Indian Kala-azar Field Isolates Persist in in Vitro and in Vivo Experimental Models. Parasitol Res. 2005;96(4):216-23. PubMed PMID: 15868188.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Refractoriness to the treatment of sodium stibogluconate in Indian kala-azar field isolates persist in in vitro and in vivo experimental models. AU - Dube,Anuradha, AU - Singh,Nasib, AU - Sundar,Shyam, AU - Singh,Neeloo, Y1 - 2005/05/03/ PY - 2004/11/16/received PY - 2005/02/03/accepted PY - 2005/5/4/pubmed PY - 2005/10/7/medline PY - 2005/5/4/entrez SP - 216 EP - 23 JF - Parasitology research JO - Parasitol Res VL - 96 IS - 4 N2 - Ever since their discovery about 60 years ago as therapeutic agent for visceral leishmaniasis (VL) or kala-azar, pentavalent antimonials (Sb(v)) have remained the first line treatment of choice all over the world including India. But recently, the number of kala-azar patients unresponsive to sodium stibogluconate (SSG) therapy, is steadily increasing in India. In this study, three clinical isolates, of which two were from SSG unresponsive and one from SSG responsive patients were evaluated for their infectivity and for their chemotherapeutic responses in vitro (macrophage-amastigote system) and in vivo (in hamsters). Persistence of SSG resistance was also checked by repeated passages in vitro as well as in vivo. The drug resistant strains (2039 and 2041) did not respond to SSG therapy both in vitro as well as in vivo but strains 2001 and Dd8 showed full sensitivity to SSG treatment. All the four strains responded well to amphotericin B and miltefosine treatment both in macrophages and in hamsters. The specific chemotherapeutic responses of all the strains to SSG were consistently persistent after repeated passages in cultures and in vivo, which indicates that these isolates are truly refractory to SSG treatment in field conditions. Two isolates were also transfected with green fluorescent protein (GFP) for the development of in vitro assay for studying antileishmanial activities of new and reference drugs in macrophages by flow cytometry. SN - 0932-0113 UR - https://www.unboundmedicine.com/medline/citation/15868188/Refractoriness_to_the_treatment_of_sodium_stibogluconate_in_Indian_kala_azar_field_isolates_persist_in_in_vitro_and_in_vivo_experimental_models_ L2 - https://dx.doi.org/10.1007/s00436-005-1339-1 DB - PRIME DP - Unbound Medicine ER -