National JALMA Institute for Leprosy & Other Mycobacterial Diseases

Institute Profile

The Institute during its nearly two decades of existence has grown into one of the major national and international institutions devoted to leprosy research.  The institute has (a) Clinical division :  Medical and Surgical units, Medical Sociology unit and other supportive units/sections like Physiotherapy, X-rays, Clinical pathology etc. (b) Laboratory division : Immunology and Human Genetics, Electron microscopy, Biochemistry, Microbiology and Molecular Biology, Pathology, Experimental leprosy laboratories etc. (c) Supporting units : Biostatistics, Photography, Library, Administration Section and (d) Field unit for Epidemiology of Leprosy at Agra and at Ghatampur (Kanpur),U.P.

The Institute has a total of 209 staffs out of which 22 staffs are scientists of different cadres.  Rest of the staffs are comprised of Administrative and Supporting Staffs. The Institute has a 60 bedded hospital for the treatment and care of in-patients.  In the outpatient, on an average daily 300 patients are given treatment and care.

Aims and Objectives :

The main objectives of the Institute are to develop and standardise techniques of investigation for diagnosis, treatment and assessment for better management of leprosy with ultimate goal of eradication of this disease by helping the National Leprosy Eradication Programme (NLEP). It is pursuing its main goals by the following activities :

(i)                  Developing newer modified methods of early diagnosis, assessment of treatment and also investigating the disease at patient and community level;

(ii)                Improving the methods of treatment;

(iii)               Conducting epidemiological studies such as intervention studies, investigations related to transmission and risk factors and methodological investigations;

(iv)              Job oriented training to medical professionals who are engaged in National Leprosy Eradication Programme (NLEP);

(v)                Transferring the technology developed/established at this Institute to other scientists and medical professionals working in different institutions in the country.

(vi)              Education and training to students and professionals for human resource development.

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Staff & Departmental  Structure

Director

DeputyDirector

Clinical Division

1.      Medical Unit-I 

2.      MedicalUnit-II

Reconstructive Surgery and Physiotherapy 

Nursing and Other Supportive Staff

Laboratory Division

1. Department of Biochemistry 

2.  Experimental Leprosy

3. Electron Microscopy

4. Department of Immunology

5. Department of Microbiology

6. Department of Pathology

7. Instrumentation

Supportive Units

1. Statistical Unit
2. Medical Sociology Unit
3. Administration
4. Photography
5. Library
6. Electrical Division
7. Hindi Office
8. Other Units

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Thrust Areas :

The Institute is fulfilling its research objectives by carrying out research on the following thrust areas : (i) Early diagnosis, (ii) Improving and monitoring treatment, (iii) Prevention and correction of deformities, (iv) Transmission of disease, (v) Field studies, (vi) Operational research and (vii) Studies on other mycobacteria.  Most of the research programmes are multidisciplinary and goal oriented.

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Research Contributions :

During the last 24 years under ICMR administration, the institute has made rapid progress in almost all aspects of leprosy research.  Major research contributions are summarised below :

I.                    Clinical and therapeutic Studies :

(i)                 Clinical Studies :

Clinical studies have provided original information about various aspects of disease and its diagnosis :

(a)    M.leprae has been observed to be excreted through breast milk in addition to major portals of exit such as nose, mouth and skin.

(b)  Higher frequency of cardiovascular system involvement in leprosy patients as compared to controls has been observed.

(c) Clinical evidence for upper motor neuron type of involvement coroborated by biochemical and serological findings have been observed in a certain proportion of lepromatous cases.

(d)   Histology of Mitsuda Lepromin reaction was observed to have a fair correlation with clinical and histological classification of patients.  In cases like facial lesions and nerve involvement, histology of lepromin response may be utilized for the classification of cases instead of biopsies from vital areas of face and motor/mixed nerves.

(e)    Leprosy in nerves has been observed to have a spectrum like that of skin lesions. Further, nerve abscess has been commonly observed in ulnar nerves.  Also classification of nerves and bony changes in reactions have been observed in clinical studies.

(f)  Hematogenous spread of the disease was established even in tuberculoid cases and almost a continous bacterimia in advanced disease has been found.

(g)  Histological confirmation of non-specific picture in indeterminate disease has shown to be enhanced using immunological (antigen detection) markers and molecular (in-situ hybridisation) markers.

(ii)               Treatment of Leprosy :

For treatment purposes cases have been broadly classified into multibacillary (MB) and paucibacillary (PB) leprosy.  Taking advantage of heavy patient load of the patients, several studies aimed at testing the efficacy of drugs, regimens as well as newer alternate regimens have been undertaken :

Treatment of MB leprosy :

 Several important leads for evolution of multidrug regimens for better treatment of MB leprosy has emerged from this Institute :

(a)    Primary dapsone resistance was for the first time reported from this
       part of the world at this Institute.

(b)  The concept of short course regimens for leprosy was developed and tested at this Institute.  While the short course of rifampicin followed by dapsone monotherapy was found to have limitations, pulsed rifampicin administration was therapeutically observed to be as good as daily or intermittent administration.

(c)    DDS and clofazimine administration was observed to be effective in killing M.leprae in 9-12 months including rifampicin resistant mutants, indicating that with present regimen treatment cannot be reduced to less than this period.

(d)   While the MDT was found to be generally effective in MB cases, a proportion of highly bacilliferous cases were found to harbour viable persisters both by mouse foot pad and ATP bioluminescence methods.  These cases have been now reported to have a high risk of relapses thus necessatating modification of the treatment.

(e)    Based on the results of studies of clofazimine absorption, a modified WHO regimen (minus loading dose of clofazimine) has been designed, tried and found to be effective.

(f)     A MDT regimen supplemented with one year of pyrazinamide administration has been found to have effect on persisters and subsequent faster bacteriological clearance.

(g)    Clofazimine colouration in long term treated patients of North India has been observed to be very common, however, there is no problem with its social acceptance.

(h)    Combined chemotherapeutic and immuno-therapeutic regimens have been designed and found to enhance killing and clearance of bacilli.  Further, these have been found effective to reduce the duration of treatment specially in cases with high bacterial load.

(i) A NLEP approved new regimen comprising of conventional recommended MDT together with newer drugs like ofloxacin and minocycline is being tried.  Regimen has been found safe, well tolerated and follow-up is continuing.

Treatment of PB leprosy :

(a)    The studies at this Institute demonstrated that for TT/BT cases a short course chemotherapy of 12-15 months was possible and gave the concept of short/fixed course of treatment for leprosy.

(b) The beneficial effects as well as limitations of the WHO recommended MDT for PB leprosy were observed in the studies at the Institute.  Supplementation of another six months of dapsone to WHO regimen has been found to take care of the problems of persisting residual activity, late reactions and relapses.

(c)    A prothionamide containing six month regimen for PB leprosy was developed, found safe and effective.

(d)    To make the treatment uniform for general services, a 3 drug combination comprising of dapsone, clofazimine and rifampicin (same as for MB cases but for a limited duration of 6 months) is being tried for PB cases.  Intake has been completed and follow-up is continuing.

(iii)               Surgical Studies :

(a)    Nerve decompression has been found to provide quick relief from pain in leprosy with severe neuritis. Decompression has also been observed to hasten sensory motor recovery in some cases.

(b)  Many surgical procedures involving muscle/tendon transfer have been standardised and improved to correct claw hand deformities and have been found to be useful in restoring the shape and function to a great extent.

(c)    A tendon transfer procedure for the prevention of `Z' deformity of thumb has been established.

(d)   An one stage nasal reconstruction using bone grafts to correct the collapse of nasal bridge has been successfully established.

(e)    A technique with flap mobilisation for the repair of nasal fistula has been developed and found useful.

(f)     A foot pressure model study to understand the mechanisms of plantar ulceration in leprosy patients revealed that foot pressures are abnormal even in slow walking in leprosy patients with plantar anaesthesia. Surgical procedures like drop foot correction, resection of metatarsal head appear to be helpful in correcting this imbalance significantly.

II.                 Laboratory Research :

(i) Immunological Studies :

(a)    Dharmendra antigen used for testing the status of resistance to infection has been restandardised at this Institute and is being supplied throughout India and abroad.

(b)   Fluorrescent leprosy antibody absorption (FLA-ABS) test of Abe was standardised, tried in the patients and contacts.  It was observed that contact population with FLA-ABS test positivity and lepromin negativity was at higher risk of developing disease.

(c)    A monoclonal antibody based specific serological test (SACT) was developed at the institute and has been found reproducible in several laboratories in the world. While the test was found to have limitation in populations with low transmission, this assay showed clear promise for monitoring chemotherapeutic response in patients.

(d)   Immunological mechanisms of granuloma in leprosy have been extensively studied and have led to better understanding of underlying pathophysiological mechanisms.

(e)    The studies at this Institute showed the presence of antigens/antibodies in the urine and CSF of leprosy patients.  These original observations indicated a better scope for developing diagnostics as well as for studying the systemic aspects of leprosy in a better way.

(f)     Extensive studies on circulating immune complexes (CICs) showed the role of CICs in immune modulation as well as reactions. The cases undergoing repeated lepra reactions were observed to have reduced solubilisation of immune complexes by complement.

(g)    Using liposome as vehicle, soluble antigen of M.leprae for the first time has been shown to induce a late delayed type hypersensitivity (DTH) reactions.

(h)    An ELISA technique has been developed using phenolpthelin as a substrate.

(i)      A significantly lower levels of IgG3 antibody to M.leprae, PGL-1 and lipoarabinomanan have been found to correlate with the precipitation of ENL (type II) reactions.

(ii) Studies on metabolism, viability and identification/typing of mycobacteria:

(a)    Studies to understand the metabolic cycle(s) of M.leprae have shown that leprosy bacillus is a micro-aerophilic aerobic organisms, and has the enzymes of TCA cycle as well as glyoxylate bypass.  Various nutrients and phsio-chemical factors important for in-vitro ATP synthesis have been identified.  Based on these observations, an in-vitro drug screening system for leprosy bacilli from clinical specimens has been developed.

(b)   Measurement of bacillary ATP as a parameter of viability assessment of M.leprae has been established. A sensitive ATP extraction- bioluminscence assay for mycobacteria including M.leprae has been developed at this Institute and found to be useful for monitoring treatment in MB cases.

(c)    A new scheme based on protein electrophoregrams and isoenzyme patterns of mycobacterial species has been developed for identification of pathogenic mycobacteria.

(d)   A new class of mycolates has been identified in M.leprae derived from leprosy specimens.  The usefulness and limitations of analysis of mycolic acids, glycolipids and phospholipids in mycobacterial identification and typing has been established.

(e)    New techniques based on mycobacterial superoxide dismutases (SOD) have been developed for identification and classification of mycobacteria including M.leprae and tubercle bacilli.

(iii)              Molecular biology of Mycobacteria :

(a)    A novel stepwise procedure for purification of nucleic acids from mycobacteria has been developed at this Institute.  The technique has been further developed for application to the clinical specimens from leprosy lesions.

(b)   New techniques for studying the genetic relatedness/diversity among mycobacteria have been developed and their role in the molecular epidemiology is being evaluated.  These include ribosomal DNA-fingerprinting techniques for pure growths as well as rDNA-PCR applicable to clinical specimens directly. 

(c)    Several variable regions of RNA genes have been identified for the development of probes.  Some probes targetting rRNA and a quantitative hybridization (microdensitometry) have been developed and are being studied for their usefulness in the diagnosis of leprosy.  These ribosomal RNA probes and rRNA-PCR techniques have been demonstrated to correlate with viability and diagnosis of active disease.  This strategy has been shown for the first time at CJIL, is an accepted concept now.

 

(iv)              Pharmacokinetic Studies :

(a)    In long-term pursued studies, the pharmacokinetic patterns of various anti-leprotic drugs have been studied.  While the currently used drugs were found to be free from any therapeutically relevant adverse interactions, a major proportion of monthly loading doses of clofazimine has been found to be excreted unabsorbed.

(b)   Permeability of various drugs across cell membranes of mycobacteria and macrophages are being evaluated for improving the understanding of response or lack of response to therapy.

 

(v)               Experimental Leprosy :

(a)    With a view to better understand the dynamics of transmission of infection, the viability of M.leprae outside human body has been investigated.  M.leprae has been found to remain viable for 7 to 46 days under different environmental conditions.

(b)   Since long mouse foot pad model has been established at this institute and is in use for determination of drug resistance, viability monitoring of chemotherapeutic trials as well as other experimental purposes.  Using this model, the protective efficacy of several candidate antileprosy vaccines was established at this Institute.

(c)    Scientists of the institute were successfully able to establish an armadillo colony - these armadillos, imported from USA, were adapted on Indian diet and were successfully infected to serve as a source of M.leprae.  The harvested organisms were used for research by several groups.

(vii)  Human Genetics :Genetic association of HLA with susceptibility or resistance has been investigated for several years.  While the results obtained so far do not show any clear association with any of the HLA antigens the studies are continuing using newer molecular approaches using non-HLA genes.

(viii)         Biostatistics :

(a)   Statistical techniques with better discriminatory value for assessing the diagnostic value of any new method have been evaluated and selected.

(b) Selection and adaption of appropriate software programmes for numerical taxonomy of mycobacteria is being carried out.  Centroid linkage analysis of electrophoregrams has been observed to be suitable for taxonomy.

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Publications/presentations/awards :

During the last 24 years, scientists of the Institute have published over 500 research papers in scientific and foreign journals.  Most of these publications have been highly cited all over the world.  Also more than 700 papers have been presented in various national and international conferences.

The scientists of the Institute have been invited to many national and international meetings/conferences and as experts to various bodies.  Further, the scientists of the Institute have been the recipients of 23 awards/honors during this period.

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Referral Centre for Mycobacterial Diseases and Mycobacterial Repository Centre :

The Institute has been identified as a Referral Centre for Mycobacterial Diseases for the purpose of testing of immunodiagnostics and Biotechnological products.  Further, a Mycobacterial Repository Centre (DBT) has been established at this Institute to serve as a source of reference, indigenous strains as well as for epidemiological characterization of mycobacteria.The Repository has more than 2000 well characterised isolates with their DNA fingerprinting.

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