A Curative Immune Profile One Week after Treatment of Indian Kala-Azar Patients Predicts Success with a Short-Course Liposomal Amphotericin B Therapy
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Title |
A Curative Immune Profile One Week after Treatment of Indian Kala-Azar Patients Predicts Success with a Short-Course Liposomal Amphotericin B Therapy |
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Creator |
Mondal, Smriti
Bhattacharya, Pradyot Rahaman, Mehebubar Ali, Nahid Goswami, Rama Prosad |
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Subject |
Infectious Diseases and Immunology
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Description |
Background: The present pilot study investigating the minimum dose for short-course single and double-dose treatment of kala-azar with an apparently new liposomal formulation of amphotericin B, Fungisome, led to identification of immunological components for early detection of success and/or failure to cure. Methods: Patients were treated with 5, 7.5 (single-dose) and 10 mg/kg body weight (5 mg/kg double-dose) of Fungisome. Immunological investigations involving plasma cytokines and antigen-specific lymphoproliferation and cytokine responses from PBMCs were carried out before, 1 week after Fungisome treatment, at the time of relapse, and again after conventional amphotericin B treatment. Results: At 1-month follow-up all the patients showed 100% initial cure. However, total doses of 5, 7.5 and 10 mg/kg Fungisome showed 60%, 50% and 90% cure, respectively, at 6-months posttreatment. Patients successfully cured demonstrated downregulation of IL-12 and IL-10 in plasma, and two-fold or more elevation of IFN-c, IL-12 and TNF, and significant down-regulation of IL-10 and TGF-b in culture supernatants 1-week posttreatment irrespective of drug-dose. A differential immune profile, involving insignificant decline in IL-10 and IL-12 in plasma and negligible elevation of IFN-c, IL- 12 and TNF, and persistence of IL-10, despite decline in TGF-b in culture supernatants, in apparently cured individuals, corresponded with relapse within 6-months of treatment. Conclusion: Immunological investigations revealed significant curative and non-curative immunomodulation 1-week posttreatment, correlating with successful cure and relapse, respectively. Although immune-correlation was doseindependent, almost consistent curative response in patients treated with the highest dose 10 mg/kg reflected a definitive impact of the higher-dose on the immune response. Trial registration name and number: Clinical Trials Registry - India (CTRI) CTRI/2009/091/000764 |
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Date |
2010
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://www.eprints.iicb.res.in/87/1/PLOS_NEGLECTED_TROPICAL_DISEASES_4(7)__Article_Number_e764_;2010[61].pdf
Mondal, Smriti and Bhattacharya, Pradyot and Rahaman, Mehebubar and Ali, Nahid and Goswami, Rama Prosad (2010) A Curative Immune Profile One Week after Treatment of Indian Kala-Azar Patients Predicts Success with a Short-Course Liposomal Amphotericin B Therapy. PLoS Neglected Tropical Diseases, 4 (7). 01-08. |
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Relation |
http://dx.doi.org/:10.1186/1476-4598-9-58
http://www.eprints.iicb.res.in/87/ |
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