Update in Tuberculosis and Nontuberculous Mycobacterial Disease 2010

Yew, Wing Wai; Sotgiu, Giovanni; Migliori, Giovanni Battista

doi:10.1164/rccm.201102-0325up

Cited by 13 publications

(12 citation statements)

References 57 publications

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“…1,2 Emergence of multiple-drug resistant M. Tuberculosis strains and notable increase in the rate of non-tuberculous mycobacteria are features mandates paying more attention to identify the potential conditions, which can predispose individuals to acquire such infections. 3–5 Bacillus Calmette-Guérin (BCG) vaccination aims to prevent early-life infections with M. Tuberculosis . 3,4 The BCG vaccine was developed by Albert Calmette and Camille Guerin in France between 1908 and 1921.…”

Section: Introductionmentioning

confidence: 99%

Bacillus Calmette-Guérin (BCG) complications associated with primary immunodeficiency diseases

Norouzi

Aghamohammadi

Mamishi

et al. 2012

Journal of Infection

150

115

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Section: Introductionmentioning

confidence: 99%

Bacillus Calmette-Guérin (BCG) complications associated with primary immunodeficiency diseases

Norouzi

Aghamohammadi

Mamishi

et al. 2012

Journal of Infection

150

115

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“…The ability of nontuberculous mycobacteria (NTM) to cause disease is clearly described in the literature, and its importance is increasing progressively, with an increasing amount of various species being cultured and isolated in laboratories [1][2][3] .…”

Section: Introductionmentioning

confidence: 99%

Rapid detection and differentiation of mycobacterial species using a multiplex PCR system

Lima

Duarte

Montenegro

et al. 2013

Rev. Soc. Bras. Med. Trop.

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Introduction:The early diagnosis of mycobacterial infections is a critical step for initiating treatment and curing the patient. Molecular analytical methods have led to considerable improvements in the speed and accuracy of mycobacteria detection. Methods: The purpose of this study was to evaluate a multiplex polymerase chain reaction system using mycobacterial strains as an auxiliary tool in the differential diagnosis of tuberculosis and diseases caused by nontuberculous mycobacteria (NTM) Results: Forty mycobacterial strains isolated from pulmonary and extrapulmonary origin specimens from 37 patients diagnosed with tuberculosis were processed. Using phenotypic and biochemical characteristics of the 40 mycobacteria isolated in LJ medium, 57.5% (n=23) were characterized as the Mycobacterium tuberculosis complex (MTBC) and 20% (n=8) as nontuberculous mycobacteria (NTM), with 22.5% (n=9) of the results being inconclusive. When the results of the phenotypic and biochemical tests in 30 strains of mycobacteria were compared with the results of the multiplex PCR, there was 100% concordance in the identifi cation of the MTBC and NTM species, respectively. A total of 32.5% (n=13) of the samples in multiplex PCR exhibited a molecular pattern consistent with NTM, thus disagreeing with the fi nal diagnosis from the attending physician. Conclusions: Multiplex PCR can be used as a differential method for determining TB infections caused by NTM a valuable tool in reducing the time necessary to make clinical diagnoses and begin treatment. It is also useful for identifying species that were previously not identifi able using conventional biochemical and phenotypic techniques.

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“…Standard treatment for TB has remained unchanged for more than 30 years (2), and multidrug-and extensively drugresistant strains are progressively emerging (3,4). Mortality rates remain high among patients even after they have commenced TB treatment (5,6). A characteristic hallmark of TB is tissue destruction, causing morbidity, mortality, and transmission of infection.…”

mentioning

confidence: 99%

Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases

Walker

Clark²,

Oni

et al. 2012

Am J Respir Crit Care Med

125

136

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Rationale: Tuberculosis kills more than 1.5 million people per year, and standard treatment has remained unchanged for more than 30 years. Tuberculosis (TB) drives matrix metalloproteinase (MMP) activity to cause immunopathology. In advanced HIV infection, tissue destruction is reduced, but underlying mechanisms are poorly defined and no current antituberculous therapy reduces host tissue damage. Objectives: To investigate MMP activity in patients with TB with and without HIV coinfection and to determine the potential of doxycycline to inhibit MMPs and decrease pathology. Methods: Concentrations of MMPs and cytokines were analyzed by Luminex array in a prospectively recruited cohort of patients. Modulation of MMP secretion and Mycobacterium tuberculosis growth by doxycycline was studied in primary human cells and TB-infected guinea pigs. Measurements and Main Results: HIV coinfection decreased MMP concentrations in induced sputum of patients with TB. MMPs correlated with clinical markers of tissue damage, further implicating dysregulated protease activity in TB-driven pathology. In contrast, cytokine concentrations were no different. Doxycycline, a licensed MMP inhibitor, suppressed TB-dependent MMP-1 and -9 secretion from primary human macrophages and epithelial cells by inhibiting promoter activation. In the guinea pig model, doxycycline reduced lung TB colony forming units after 8 weeks in a dose-dependent manner compared with untreated animals, and in vitro doxycycline inhibited mycobacterial proliferation. Conclusions: HIV coinfection in patients with TB reduces concentrations of immunopathogenic MMPs. Doxycycline decreases MMP activity in a cellular model and suppresses mycobacterial growth in vitro and in guinea pigs. Adjunctive doxycycline therapy may reduce morbidity and mortality in TB.Keywords: lung; mycobacteria; immunopathology; protease inhibitors Tuberculosis (TB) continues to kill more than 1.5 million people a year (1). Standard treatment for TB has remained unchanged for more than 30 years (2), and multidrug-and extensively drugresistant strains are progressively emerging (3, 4). Mortality rates remain high among patients even after they have commenced TB treatment (5, 6). A characteristic hallmark of TB is tissue destruction, causing morbidity, mortality, and transmission of infection. However, the mediators of this immunopathology are incompletely understood (7,8), preventing the design of rational therapies to reduce immunemediated host damage and improve outcomes in TB.TB is primarily a disease of the lung (9, 10). In advanced HIV infection, with severely reduced CD4 cell counts, TB infection is common, but there is reduced tissue destruction and cavitation rarely occurs (11). The underlying cause of divergent pathology in HIV-TB coinfection is poorly defined, and greater understanding of this tissue destruction may identify novel therapeutic approaches to limit morbidity and mortality. The biochemistry of the lung extracellular matrix predicts that matrix metalloproteinases (MMPs) will be ...

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Update in Tuberculosis and Nontuberculous Mycobacterial Disease 2010

Cited by 13 publications

References 57 publications

Bacillus Calmette-Guérin (BCG) complications associated with primary immunodeficiency diseases

Bacillus Calmette-Guérin (BCG) complications associated with primary immunodeficiency diseases

Rapid detection and differentiation of mycobacterial species using a multiplex PCR system

Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases

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