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Ahuja S.D.,Bureau of Tuberculosis | Ashkin D.,A.G. Holley Hospital | Avendano M.,University of Toronto | Banerjee R.,Mayo Medical School | And 66 more authors.
PLoS Medicine | Year: 2012

Background: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. Methods and Findings: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]).Conclusions:In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment.Please see later in the article for the Editors' Summary. © 2012 Ahuja et al.

Awan I.N.,Pmas Arid Agriculture University | Ali Rizvi S.K.,Pmas Arid Agriculture University | Nadeem Saqib M.A.,Quaid-i-Azam University | Shahzad M.I.,Pmas Arid Agriculture University | And 6 more authors.
Pakistan Journal of Zoology | Year: 2012

Tuberculosis (TB) is a fatal and contagious disease. The annual death toll occurring from TB is approximately 2 million according to World Health Organization (WHO). The removal of disease from global face needs immediate treatment for which early diagnosis is pre-requisite. Existing tests for the diagnosis of TB are not efficient and robust. In the present study Mycobacterium tuberculosis specific six antigens namely cfp-10, esat-6 and hspx, along with three antigens which are components of immunodominant mycolyl transferases ag85a, ag85b, ag85c were expressed and purified to evaluate their potential use in immunoassays like Western blotting and multiplex microbead immunoassay. Protein expression of all six antigenic genes was optimized for time and different concentrations of inducer isopropyl β-D-1-thiogalactopyranoside. Protein products were confirmed by Western blotting and purified through immobilized metal affinity chromatography (IMAC) technique using columns having affinity for His-tag. Each fluorescently labeled set of microbeads were coated with one of the M. tuberculosis specific antigenic proteins and later on human plasma samples of reactivated TB patients along with healthy BCG as well as tuberculin skin test negative controls were tested for presence of antibodies against these antigenic proteins individually in a multiplex format. The results were generated in median fluorescence intensity form which detected antibodies against M. tuberculosis specific antigenic proteins only in reactivated TB patients. This system detected antibodies against four antigenic proteins in 100% of reactivated TB patients. Thus, M. tuberculosis antigens described in this study seem to have purified at the level to be used in the development of immunoassays for the detection of M. tuberculosis infection in TB patients of different categories like active and latent TB. © 2012 Zoological Society of Pakistan.

Banu S.,International Center for Diarrhoeal Disease Research | Rahman M.T.,International Center for Diarrhoeal Disease Research | Uddin M.K.M.,International Center for Diarrhoeal Disease Research | Khatun R.,International Center for Diarrhoeal Disease Research | And 6 more authors.
PLoS ONE | Year: 2015

Background: Understanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. Methods: The study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU). Results: A total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as 'modern' and 100 (30%) strains as 'ancestral'. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%. Conclusions: Implementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh. © 2015, Public Library of Science. All rights reserved.

Soomro M.H.,Isra University of Pakistan | Shahzad F.,University of Bergen | Khan M.A.,Association for Social Development | Qadeer E.,National TB Control Program | Morkve O.,University of Bergen
Journal of Medicine (Bangladesh) | Year: 2015

Background: Tuberculosis is a serious global public health, social and economical problem that affects millions of people particularly in low income countries. The aim of this study was to see the loss to follow up pattern in Tuberculosis patients in district Rawalpindi, Pakistan. Materials and method: A cross-sectional study was conducted in district Rawalpindi between August and October 2010. All sputum smear positive Tuberculosis patients diagnosed and treated in public sector, urban and rural diagnostic centers of the district Rawalpindi during the year 2008 were included in the study.All cases other (smear negative pulmonary and extra-pulmonary) than sputum smear positive and all private hospitals were excluded. Results: A total of 451 patients were enrolled in the study. Majority of the patients (89.6%) were provided with the treatment support. Geographically dropout rate was observed higher in urban patients than in rural 18.7% vs. 10.5%. On the other hand by patient gender, drop out was seen more in male patients than in females 16.5% vs. 13.1%. By patients age groups, interestingly patients under the childhood age group all the patients completed the treatment while drop out was observed more in older age group. Conclusions: Loss to follow up pattern was seen more in urban patients, by gender more in male patients and by age groups observed more in older patients. © 2015, J MEDICINE. All rights received.

Khan I.H.,University of California at Davis | Ravindran R.,University of California at Davis | Krishnan V.V.,University of California at Davis | Krishnan V.V.,California State University, Fresno | And 11 more authors.
Clinical and Vaccine Immunology | Year: 2011

Two billion people are infected with Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), worldwide. Ten million to 20 million of the infected individuals develop disease per year. TB is a treatable disease, provided that it is diagnosed in a timely manner. The current TB diagnostic methods are subjective, inefficient, or not cost-effective. Antibody-based blood tests can be used efficiently and cost-effectively for TB diagnosis. A major challenge is that different TB patients generate antibodies against different antigens. Therefore, a multiplex immunoassay approach is needed. We have developed a multiplex panel of 28 M. tuberculosis antigen-coated microbeads. Plasma samples were obtained from over 300 pulmonary TB patients and healthy controls in a country where TB is endemic, Pakistan. Multiplex data were analyzed using computational tools by multivariate statistics, classification algorithms, and cluster analysis. The results of antibody profile-based detection, using 16 selected antigens, closely correlated with those of the sputum-based diagnostic methods (smear microscopy and culture) practiced in countries where TB is endemic. Multiplex microbead immunoassay had a sensitivity and specificity of approximately 90% and 80%, respectively. These antibody profiles could potentially be useful for the diagnosis of nonpulmonary TB, which accounts for approximately 20% of cases of disease. Since an automated, high-throughput version of this multiplex microbead immunoassay could analyze thousands of samples per day, it may be useful for the diagnosis of TB in millions of patients worldwide. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

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