Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases

Delhi, India

Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases

Delhi, India
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Sotgiu G.,University of Sassari | Centis R.,Care and Research Institute | D'Ambrosio L.,Care and Research Institute | Alffenaar J.-W.C.,University of Groningen | And 17 more authors.
European Respiratory Journal | Year: 2012

Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis. 12 studies (11 countries from three continents) reporting complete information on safety, tolerability, efficacy of linezolid-containing regimes in treating MDR-TB cases were identified based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Metaanalysis was performed using the individual data of 121 patients with a definite treatment outcome (cure, completion, death or failure). Most MDR-TB cases achieved sputum smear (86 (92.5%) out of 93) and culture (100 (93.5%) out of 107) conversion after treatment with individualised regimens containing linezolid (median (inter-quartile range) times for smear and culture conversions were 43.5 (21-90) and 61 (29-119) days, respectively) and 99 (81.8%) out of 121 patients were successfully treated. No significant differences were detected in the subgroup efficacy analysis (daily linezolid dosage ≤600 mg versus >600 mg). Adverse events were observed in 63 (58.9%) out of 107 patients, of which 54 (68.4%) out of 79 were major adverse events that included anaemia (38.1%), peripheral neuropathy (47.1%), gastro-intestinal disorders (16.7%), optic neuritis (13.2%) and thrombocytopenia (11.8%). The proportion of adverse events was significantly higher when the linezolid daily dosage exceeded 600 mg. The study results suggest an excellent efficacy but also the necessity of caution in the prescription of linezolid. Copyright©ERS 2012.

Banday K.M.,Immunology Group | Pasikanti K.K.,National University of Singapore | Chan E.C.Y.,National University of Singapore | Singla R.,Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases | And 3 more authors.
Analytical Chemistry | Year: 2011

Development of noninvasive methods for tuberculosis (TB) diagnosis, with the potential to be administered in field situations, remains as an unmet challenge. A wide array of molecules are present in urine and reflect the pathophysiological condition of a subject. With infection, an alteration in the molecular constituents is anticipated, characterization of which may form a basis for TB diagnosis. In the present study volatile organic compounds (VOCs) in human urine derived from TB patients and healthy controls were identified and quantified using headspace gas chromatography/mass spectrometry (GC/MS). We found significant (p < 0.05) increase in the abundance of o-xylene (6.37) and isopropyl acetate (2.07) and decreased level of 3-pentanol (0.59), dimethylstyrene (0.37), and cymol (0.42) in TB patients compared to controls. These markers could discriminate TB from healthy controls and related diseases like lung cancer and chronic obstructive pulmonary disorder. This study suggests a possibility of using urinary VOCs for the diagnosis of human TB. © 2011 American Chemical Society.

Maurya V.,University of Delhi | Aditya Gupta U.,University of Delhi | Dewan R.K.,Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases | Jain S.,OncQuest Laboratories New Delhi | Shah A.,University of Delhi
Archivos de Bronconeumologia | Year: 2013

Spontaneous, complete resolution of inflammatory pseudotumour (IPT) of lungs is exceptionally rare. A 44-year-old male was referred for evaluation for «non resolving pneumonitis». He had cough and minimal expectoration for 5 months, chest pain, haemoptysis and fever for a fortnight. Computed tomography of thorax (CT-thorax) confirmed the presence of a homogenous mass with irregular borders in right middle lobe with areas of breakdown and air bronchogram. Transbronchial lung biopsy was suggestive of «plasma cell granuloma». Thoracotomy disclosed a hard mass in right middle lobe adherent to lower lobe, chest wall and mediastinum which could not be removed. A wedge biopsy confirmed IPT. Chest radiograph after 4 weeks revealed significant resolution. CT-thorax a year later showed fibrotic scar. Till date, there are only five reports documenting 6 patients with spontaneous resolution of IPT of lungs and in 4 this occurred within 3 months of an invasive diagnostic intervention. © 2012 SEPAR.

Singh J.,All India Institute of Medical Sciences | Sankar M.M.,All India Institute of Medical Sciences | Kumar S.,All India Institute of Medical Sciences | Gopinath K.,All India Institute of Medical Sciences | And 4 more authors.
PLoS ONE | Year: 2013

Background:Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the leading causes of mortality and morbidity across all age groups throughout the world, especially in developing countries.Methodology/Principal Findings:In this study, we have included 432 open index cases with their 1608 household contacts in a prospective cohort study conducted from May 2007 to March 2009. The follow-up period was 2 years. All Index cases were diagnosed on the basis of suggestive signs and symptoms and sputum being AFB positive. Among the 432 index patients, 250 (57.9%) were males and 182 (42.1%) females; with mean age of 34±14.4 yr and 26±11.1 yr, respectively. Out of 1608 household contacts, 866 (53.9%) were males and 742 (46.1%) females; with mean age of 26.5±15.8 and 26.5±16.0 yr, respectively. Of the total 432 households, 304 (70.4%) had ≤4 members and 128 (29.6%) had ≥5 members. The median size of the family was four. Of the 1608 contacts, 1206 were able to provide sputum samples, of whom 83 (6.9%) were found MTB culture positive. Household contacts belonging to adult age group were predominantly (74, 89.2%) infected as compared to the children (9, 10.8%). On screening the contact relationship status with index patients, 52 (62.7%) were first-degree relatives, 18 (34.6%) second-degree relatives and 12 (14.5%) spouses who got infected from their respective index patients. Co-prevalent and incident tuberculosis was found in 52 (4.3%) and 31 (2.6%) contacts, respectively. In incident cases, the diagnosis could be made between 4 to 24 months of follow-up, after their baseline evaluation.Conclusion:Active household contact investigation is a powerful tool to detect and treat tuberculosis at early stages and the only method to control TB in high-TB-burden countries. © 2013 Singh et al.

Singh N.,Jawaharlal Institute of Postgraduate Medical Education & Research | Aggarwal A.N.,Jawaharlal Institute of Postgraduate Medical Education & Research | Behera D.,Jawaharlal Institute of Postgraduate Medical Education & Research | Behera D.,Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases
Expert Review of Anticancer Therapy | Year: 2012

Advanced lung cancer (LC) is an important cause of cancer-related morbidity and mortality in resource-constrained settings (RCSs). Cytological/pathological confirmation of diagnosis of LC is essential prior to treatment initiation for ruling out mimickers such as pulmonary tuberculosis. Accurate staging is necessary for optimal management, and investigations should be prioritized based on availability and cost-effectiveness. Platinum-based doublet chemotherapy remains the standard of care for advanced LC. Cost of therapy, lack of medical insurance and frequency of visits are important determinants of treatment regimen. EGF receptor mutation testing may not be readily available in RCSs and chemotherapy should be preferred for unselected patients with advanced non-small-cell lung cancer. Generic drugs may be more affordable than innovator brands. Treatment efficacy should be assessed with traditional end points (survival and objective response rates) as well as those relevant to RCSs (quality of life, toxicity profile and healthcare facility utilization). Issues related to LC treatment in first- and subsequent-line settings in RCSs are discussed in detail in this evidence-based review. © 2012 2012 Expert Reviews Ltd.

Singh S.,All India Institute of Medical Sciences | Singh J.,All India Institute of Medical Sciences | Kumar S.,All India Institute of Medical Sciences | Gopinath K.,All India Institute of Medical Sciences | And 3 more authors.
PLoS ONE | Year: 2012

Background: Delayed or missed diagnosis of TB continues to fuel the global TB epidemic, especially in resource limited settings. Use of serology for the diagnosis of tuberculosis, commonly used in India, is another factor. In the present study a commercially available serodiagnostic assay was assessed for its diagnostic value in combination with smear, culture and clinical manifestations. Methodology/Principal Findings: A total of 2300 subjects were recruited for the study, but 1041 subjects were excluded for various reasons. Thus 1259 subjects were included in the study of which 470 were pulmonary tuberculosis cases (440 of 470 were culture-positive) and 789 were their asymptomatic contacts. A house-to-house survey method was used. Blood samples were tested for IgM, IgA, and IgG antibodies using the Pathozyme Myco M (IgM), Myco A (IgA) and Myco G (IgG) enzyme immunoassay (EIA). Out of 470 PTB cases, BCG scar was positive in 82.34%. The Mantoux test and smear positivity rates in PTB cases were 94.3% (430/456), and 65.32% (307/470), respectively. Among the asymptomatic contacts, BCG scar was positive in 95.3% and Mantoux test was positive in 80.66% (442/548) contacts. No contact was found falsely smear positive. The sensitivity of IgM, IgA, and IgG EIA tests was 48.7%, 25.7% and 24.4%, respectively, while the specificity was 71.5%, 80.5%, 76.6%, respectively. Performance of EIAs was not affected by the previous BCG vaccination. However, prior BCG vaccination was statistically significantly (p = 0.005) associated with Mantoux test positivity in PTB cases but not in contacts (p = 0.127). The agreement between serology and Mantoux test was not significant. Conclusion: The commercial serological test evaluated showed poor sensitivity and specificity and suggests no utility for detection of pulmonary tuberculosis. © 2012 Singh et al.

Affandi J.S.,University of Western Australia | Kumar M.,All India Institute of Medical Sciences | Agarwal U.,Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases | Singh S.,All India Institute of Medical Sciences | Price P.,University of Western Australia
Disease Markers | Year: 2013

BACKGROUND: Up to 43% of HIV-infected patients co-infected with Mycobacterium tuberculosis experience exacerbations of tuberculosis (TB) after commencing antiretroviral therapy (ART). These are termed immune restoration disease (IRD). It is unclear why individual susceptibility varies. OBJECTIVE: We investigate if single nucleotide polymorphisms (SNP) in genes encoding cytokines, chemokines and their receptors associate with development of an IRD event in patients of two different ethnicities. METHODS: DNA samples were available from small well-characterised groups of HIV patients treated in Cambodia (TB-IRD, n=17; HIV^{+}TB^{+} controls, n=55) and India (TB-IRD, n=19; HIV^{+}TB^{+} controls, n= 43). HIV patients with a TB diagnosis but no evidence of IRD were included to control for susceptibility to TB per se. Sixteen SNP implicated in inflammation or mycobacterial disease were genotyped. RESULTS: Susceptibility to TB-IRD associated with carriage of TNFA-1031*T (rs1799964; P=0.05) and SLC11A1 D543N*G (rs17235409; P=0.04) in Cambodian patients and carriage of IL18-607*G (rs1946518; P=0.02) and VDR FokI (F/f)*T (rs10735810; P=0.05) in Indian patients. CONCLUSIONS: Associations between polymorphisms in immune-related genes and TB-IRD were found, but none were common across two ethnicities. © 2013 - IOS Press and the authors. All rights reserved.

Shen G.,New York University | Singh K.,New York University | Chandra D.,New York University | Chandra D.,Yeshiva University | And 8 more authors.
Infection and Immunity | Year: 2012

We have reported previously the identification of novel proteins of Mycobacterium tuberculosis by the immunoscreening of an expression library of M. tuberculosis genomic DNA with sera obtained from M. tuberculosis-infected rabbits at 5 weeks postinfection. In this study, we report the further characterization of one of these antigens, LipC (Rv0220). LipC is annotated as a member of the Lip family based on the presence of the consensus motif "GXSXG" characteristic of esterases. Although predicted to be a cytoplasmic enzyme, we provide evidence that LipC is a cell surface protein that is present in both the cell wall and the capsule of M. tuberculosis. Consistent with this localization, LipC elicits strong humoral immune responses in both HIV-negative (HIV -) and HIV-positive (HIV +) tuberculosis (TB) patients. The absence of anti-LipC antibodies in sera from purified protein derivative-positive (PPD +) healthy subjects confirms its expression only during active M. tuberculosis infection. Epitope mapping of LipC identified 6 immunodominant epitopes, 5 of which map to the exposed surface of the modeled LipC protein. The recombinant LipC (rLipC) protein also elicits proinflammatory cytokine and chemokine responses from macrophages and pulmonary epithelial cells. rLipC can hydrolyze short-chain esters with the carbon chain containing 2 to 10 carbon atoms. Together, these studies demonstrate that LipC is a novel cell surface-associated esterase of M. tuberculosis that is highly immunogenic and elicits both antibodies and cytokines/chemokines.©2012, American Society for Microbiology. All Rights Reserved. © 2012, American Society for Microbiology.

Singla R.,Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases | Caminero J.A.,University of Las Palmas de Gran Canaria | Caminero J.A.,Multi Drug Resistan Tuberculosis Unit | Jaiswal A.,Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases | And 4 more authors.
European Respiratory Journal | Year: 2012

Linezolid is identified as an effective drug with which to treat patients failing multidrug-resistant (MDR)-tuberculosis (TB) treatment. However, cost and safety are the concerns. In India, the average price of a 600-mg pill of linezolid is less than one US dollar, much cheaper than most of the third-line drugs. A prospective study of 29 MDR-TB treatment failure patients (16 with laboratory-proven extensively drug-resistant (XDR)-TB and the remaining 13 with MDR-TB with resistance to any quinolone but sensitive to injectables) was carried out in Delhi, India. All patients received daily unsupervised therapy with linezolid, one injectable agent, one fluoroquinolone and two or more other drugs. Patients received a median of six anti-mycobacterial agents. Besides linezolid, capreomycin, moxifloxacin, levofloxacin and amoxycillin-clavulanic acid were used in 41.4%, 58.6%, 41.4%, and 79.3% of patients. Out of a total of 29 patients, 89.7% patients achieved sputum smear and culture conversion; 72.4% showed interim favourable outcome; 10.3% died, 6.8% failed and 10.3% patients defaulted. Linezolid had to be stopped in three (10.3%) patients due to adverse reactions. The outcome of treatment of 16 XDR-TB patients was comparable to the other 13 MDR-TB patients. Linezolid is an effective, cheap and relatively safe drug for patients failing MDR-TB treatment, including those with confirmed XDR-TB. Copyright©ERS 2012.

Singla N.,Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases | Singla R.,Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases | Jain G.,Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases | Habib L.,Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases | Behera D.,Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases
International Journal of Tuberculosis and Lung Disease | Year: 2011

SETTING: Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases (LRS), a tertiary level tuberculosis (TB) institute in Delhi, India. OBJECTIVE: To study the profi le of TB among household contacts of multidrug-resistant TB (MDR-TB) patients. DESIGN: In a cross-sectional study, contacts of MDRTB patients were traced and clinical, radiological, bacteriological and pulmonary function tests were performed for evidence of TB infection and active disease. RESULTS: Between January 2005 and December 2008, 58 of 92 index MDR-TB patients could be traced. Of 302 contacts who could be studied, 16 (5.29%) developed TB: nine had pulmonary and seven had extrapulmonary disease; two (0.66%) had MDR-TB. Of the 302 contacts, 137 reported to the LRS Institute and were investigated. The most common symptoms observed were cough, chest pain and fever. The tuberculin skin test was positive in 109 of 135 (80.7%) contacts; among these, bacille Calmette-Guérin scar was present in 86. Pulmonary function tests revealed obstruction, restriction and mixed abnormalities. CONCLUSION: The majority of contacts of MDR-TB patients had drug-susceptible TB and the rate of MDRTB was very low. Evaluation of contacts of MDR-TB cases may lead to early diagnosis and prevention of TB. © 2011 The Union.

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