Molecular mimicry between Mycobacterium leprae proteins (50S ribosomal protein L2 and Lysyl-tRNA synthetase) and myelin basic protein: a possible mechanism of nerve damage in leprosy.

Autoantibodies against various components of host are known to occur in leprosy. Nerve damage is the primary cause of disability associated with leprosy. The aim of this study was to detect the level of autoantibodies and lympho-proliferative response against myelin basic protein (MBP) in leprosy patients (LPs) and their correlation with clinical phenotypes of LPs.

Evaluation of gidB alterations responsible for streptomycin resistance in Mycobacterium tuberculosis.

Objectives: To evaluate gidB alterations for possible impact on the cumulative mechanism underlying the acquisition of high-level streptomycin resistance in Mycobacterium tuberculosis.

Methods: Fifty-two isolates with high streptomycin resistance and 23 isolates with low streptomycin resistance were sequenced for mutational analysis in the rpsL, rrs and gidB region. As the gidB protein has a complex substrate and no activity assay has yet been formulated, mutants of interest were subjected to in silico modelling and were structurally mapped together with active-site amino acid residues for assessment of the relevance to activity of the mutations found.

Grade-III Paraplegia in Spinal Tuberculosis: Follow up of A Case Report and Review of Literature.

This is a case report of spinal tuberculosis which could not be diagnosed in the early stages. Individuals who work in hospital settings and suffer from psychological stress need to be aware of the various hospital acquired infections and consequences of late diagnoses. A CT scan is indicated to rule out the spinal involvement, at the beginning of a severe backache, which does not respond to painkillers, rest, and if X-ray is normal.

Histological diagnosis of early and suspicious leprosy by in situ PCR.

Leprosy is a chronic mycobacterial disease whose diagnosis is primarily based on clinico-pathological examination and supported by slit skin smears for the presence of acid fast bacilli (AFB). However, definitive diagnosis of early leprosy and those suspected to have the disease but not histologically confirmed pose major public health problems. The present study reports the utility of the in situ Polymerase Chain Reaction amplification (PCR) directed at a 530bp fragment of DNA encoding the 36kd antigen of the causative Mycobacterium leprae for the diagnosis of such patients using skin biopsies of lesions.

Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28-triggered proximal biochemical events, leading to T-cell unresponsiveness in mycobacterial diseases.

Background: Advanced stages of leprosy show T cell unresponsiveness and lipids of mycobacterial origin are speculated to modulate immune responses in these patients. Present study elucidates the role of phenolicglycolipid (PGL-1) and Mannose-capped lipoarabinomannan (Man-LAM) on TCR- and TCR/CD28- mediated signalling.

Results: We observed that lipid antigens significantly inhibit proximal early signalling events like Zap-70 phosphorylation and calcium mobilization.

Risk of developing disability in pre and post-multidrug therapy treatment among multibacillary leprosy: Agra MB Cohort study.

Objectives: If leprosy is a public health problem, it is due to the disabilities it causes. Surprisingly little is known about the risk of disabilities. Even now, mainly cross-sectional studies report disability prevalence.

Absence of nucleotide-binding oligomerization domain-containing protein 2 variants in patients with leprosy and tuberculosis.

Crohn's disease-associated NOD 2 variants (Arg702Trp and 3020insC) were found to be monomorphic (wild), and 7 subjects were heterozygous for Gly908Arg SNP in 263 patients with tuberculosis, 260 patients with leprosy and 270 healthy controls residing in northern Indian states. This is the first report to suggest the minimal role of these variants in susceptibility/resistance to TB and leprosy in this population.

An attempt towards prevention and management of disabilities and deformities in leprosy.

History of prevention of deformities is practically as old as the appearance of the deformities themselves, unfortunately without much understanding to start with. In medieval era and even earlier, leprosy and deformities were treated synonymously and the disease's infectivity too was closely associated with appearance of deformities. Hence, to reduce chances of deformities caused by leprosy in healthy population, the patients having deformities were driven away from the society presuming that only deformed patients spread the disease.

Potential of a metabolic gene (accA3) of M. leprae as a marker for leprosy reactions.

Understanding the mechanism(s) of reactions in leprosy remains a challenging task for both clinicians and basic scientists. While there is some understanding of host processes associated with different type of lepra reactions, there is very little information about bacterial factors triggering these inflammatory processes. This study is continuation of our earlier research programme on leprosy genomics in which significant transcription of 11 genes was observed during active disease and these included accA3 gene.

Study of rifampicin resistance and comparison of dapsone resistance of M. leprae in pre- and post-MDT era.

The aim of this study to study the drug resistance patterns of dapsone (pre- and post-MDT) and rifampicin (post-MDT era). All the 84 patients from pre-MDT period (1985-1990) and 77 patients for post-MDT period (1990-2002) reporting to a tertiary care hospital-NJIL & OMD, Agra and referred for drug susceptibility testing were included in the study. Drug resistance was studied by mouse foot pad method.

A simple and rapid method of sample preparation from culture filtrate of M. tuberculosis for two-dimensional gel electrophoresis.

Sample preparation for Two-dimensional gel electrophoresis (2DE) is tedious and not sufficient to provide a comparative profile of secreted proteins for various strains of M. tuberculosis. High lipid content in mycobacteria limits the use of common methods as it can hinder the 2DE run.

Mycobacterial antigen(s) induce anergy by altering TCR- and TCR/CD28-induced signalling events: insights into T-cell unresponsiveness in leprosy.

Present study investigates the role of Mycobacterium leprae (M. leprae) antigens on TCR- and TCR/CD28-induced signalling leading to T-cell activation and further correlates these early biochemical events with T-cell anergy, as prevailed in advanced stages of leprosy. We observed that both whole cell lystae (WCL) and soluble fraction of M.

Changing profile of disease in leprosy patients diagnosed in a tertiary care centre during years 1995-2000.

A hospital based retrospective study was carried out to determine change in the profile of disease in leprosy patients taking 1995 as baseline and compared with the profile seen in year 2000. A total of 2149 and 1703 cases were studied respectively of year 1995 and 2000. Male to female ratio slightly increased from 2.

Dissection of relationship between small heat shock proteins and mycobacterial diseases.

Mycobacteria belong to a genus which has membership ranging from saprophytes to deadly pathogens that cause several infectious diseases affecting a large population of the world. Among them, tuberculosis and leprosy are the major granulomatous mycobacterial diseases. While there are successes and failures in the fight against these infections, mechanisms of pathogenesis continue to be a challenge to clinicians and biologists alike.

Serological diagnosis of tuberculosis.

Objective: To evaluate the efficacy of ELISA for the detection of IgG antibodies against antigen 85 complex (Ag 85 complex) of Mycobacterium tuberculosis.

Methods: Children of either sex, 0-18 years of age, attending the outpatient department and admitted in the casualty and wards of the Department of Pediatrics, S.N.

Long term follow-up results of 1 year MDT in MB leprosy patients treated with standard MDT + once a month Minocycline and Ofloxacin.

Background: This study was initiated in consultation with the National Leprosy Eradication Programme (NLEP) in mid nineties to try new treatment regimens for leprosy which were more robust in terms of control of reactions, long term relapses, operationally easier to undertake and feasible in field conditions. It was also envisaged to see if the addition of newer bactericidal drugs would be beneficial.

Objectives: (i) To test the feasibility, safety and response of the patients to the new regimen.

Diagnostic potential of Ag85C in comparison to various secretory antigens for childhood tuberculosis.

Childhood tuberculosis is difficult to diagnose. A rapid, simple and relatively inexpensive diagnostic test will be crucial to future control efforts. Therefore, efficacy and diagnostic potential of different secretory antigens of Mycobacterium tuberculosis (CFP-10, Ag85complex, Ag85 A, B, C) and their combinations along with ESAT-6 in the detection of antibody profiles of childhood tuberculosis cases were evaluated using ELISA technique and reactivity was compared with the gold standards (smear, culture and IS6110 targeted PCR).

Molecular typing of Mycobacterium tuberculosis isolates from a rural area of Kanpur by spoligotyping and mycobacterial interspersed repetitive units (MIRUs) typing.

Molecular typing of Mycobacterium tuberculosis isolates has greatly facilitated the understanding of epidemiology of tuberculosis (TB). This study was done to characterize prevalent genotypes of M. tuberculosis on a collection of 97 isolates based on spoligotyping and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing in rural area of Kanpur, North India.

Does clofazimine (B663) reach Mycobacterium leprae persisting in Schwann cells and endothelial cells of endoneurial blood vessels in peripheral nerves?

Peripheral nerve biopsies from 10 Lepromatous leprosy (LL) patients who were on multidrug treatment (MDT) were investigated by light and electron microscopy. Clofazimine (CLF) has been included as an essential component of MDT, which is the standard WHO regimen for treatment of leprosy. The patients receiving continuous MDT for a long period had viable bacilli in Schwann cells (SCs) of peripheral nerves whereas they had disappeared from the skin.

Potential of Mw as a prophylactic vaccine against pulmonary tuberculosis.

Mycobacterium w (Mw), is a cultivable, non-pathogenic mycobacterium and has been tried extensively as an immunomodulator in leprosy. This has been found to be safe and has shown beneficial immunoprophylactic effect in population based, double blind placebo controlled trials in North India. These effects were also observed in the vaccine trials in South India.

Recent advances in molecular biology of leprosy.

The last three decades have witnessed rapid progress in understanding the molecular biology of Mycobacterium leprae. Following the availability of complete genome sequence of leprosy bacillus in 2001, things have drastically changed. With the information about genetic structure, several techniques have been developed for diagnosis, molecular epidemiology and also detection of drug resistance.

Tissue distribution and deposition of clofazimine in mice following oral administration with or without isoniazid.

Tissue distribution and deposition of clofazimine (CAS 2030-63-9) in mice were investigated following administration of clofazimine with or without isoniazid (CAS 54-85-3). Balb/c mice were administered clofazimine suspension in mustard oil orally at a daily dose of 20 mg/kg body weight either alone or along with isoniazid (10 mg/kg body weight) for 15 or 30 days. Various tissues (liver, lung, spleen, small intestine, heart, kidneys, mesentric fat, foot pad and nerve) and pooled plasma were analysed for clofazimine in all the treated groups.

Predominance of three copies of tandem repeats in rpoT gene of Mycobacterium leprae from Northern India.

This study has been carried out to get understanding of the origin among the strains of Mycobacterium leprae in patients from Northern India by using number of tandem repeats in rpoT gene as marker. Biopsies were collected from hundred leprosy cases (paucibacillary (PB) as well as multibacillary (MB)) across the spectrum from patients attending clinic at JALMA or diagnosed in Field Unit at Ghatampur (Kanpur). These biopsies were homogenized and DNA was extracted by a physiochemical procedure.

The paradox of pyrazinamide: an update on the molecular mechanisms of pyrazinamide resistance in Mycobacteria.

Pyrazinamide (PZA) is an important front line anti-tuberculosis drug because of its sterilizing activity against semi-dormant tubercle bacilli. In spite of its remarkable role in shortening the treatment duration from 9 months to 6 months when used in combination with Rifampicin and Isoniazid, PZA remains a difficult paradox because of its incompletely understood mode of action and mechanism of resistance. PZA is a nicotinamide analog prodrug which is converted into the active bactericidal form pyrazinoic acid by the bacterial enzyme pyrazinamidase (PZase).