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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. Source

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. Source

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. Source

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 18 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. Source

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. Source

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