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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
 
Creator Mondal, Smriti
Bhattacharya, Pradyot
Rahaman, Mehebubar
Ali, Nahid
Goswami, Rama Prosad
 
Subject Infectious Diseases and Immunology
 
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
 
Date 2010
 
Type Article
PeerReviewed
 
Format application/pdf
 
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.
 
Relation http://dx.doi.org/:10.1186/1476-4598-9-58
http://www.eprints.iicb.res.in/87/