Leprosy

projects 2008-2012

Underlining mechanism/s and precipitating factor/s involved in the reversal reaction (RR) and nerve damage in leprosy

Principal Investigator Dr. Vanaja P Shetty

Collaborators National JALMA Institute for Leprosy and Other Mycobacterial Diseases. (Dr. Kiran V Katoch (Director) and Dr. Mohan Natrajan)

Project team Dr. Mrudula Save, Dr. Sunil Ghate, Ms. Anju Dighe  (FMR)

Funder Indian Council of Medical Research (ICMR) task force study

Duration August 2006 – August 2010

Budget Rs.29.94 Lakhs

Background

Immunological imbalances termed as reaction and the ensuing deformities which affect a significant proportion of leprosy patients is and will constitute a major problem in coming years in the leprosy control programmes.

Several scientific studies have attempted to understand the cause of reaction and it is generally believed that the presence of bacterial component (antigen) (hitherto undefined) trigger these reactions. The present study deviates from this general belief on the basis of several clinical studies that implicate the presence of live M. leprae against a background of antigens. The first goal of this study therefore was to demonstrate the presence of live/actively growing focus of M. leprae in borderline leprosy patients presenting with clinical reaction in skin or peripheral nerve lesions.

Demonstration of live active bacteria in skin and where ever possible nerve biopsies through molecular biology technique is substantiated with assessment of inflammatory/suppressive molecules expressed by immune and nervous system cells. Molecular screening assays on lesion material are also expected to determine which bacterial genes light up during immunological reactions so that their product can be tested on skin/nerve biopsies. Viability of bacteria in patient’s lesion will be compared to the gold standard mouse foot pad growth assay.

This study using three viability markers viz. growth in the foot pad, detection of M. leprae secretory protein i.e. Ag 85 and detection of ML specific 16srRNA using in situ PCR; demonstrates the presence of viable M. leprae in a significantly higher proportion of T1R+ lesions and during its recurrence  implicating its role in the reaction precipitation in patients .

Preliminary findings also showed over expression of M. leprae genes associated with growth and metabolic activity such as pykA, fas and rpoT as well as quantitative expression of tlyA gene in real time PCR were in support of the above findings.

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