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Felix S Dube, Mamadou Kaba, F J Lourens Robberts, Lemese Ah Tow, Sugnet Lubbe, Heather J Zar, Mark P Nicol
BACKGROUND: Lower respiratory tract infection in children is increasingly thought to be polymicrobial in origin. Children with symptoms suggestive of pulmonary tuberculosis (PTB) may have tuberculosis, other respiratory tract infections or co-infection with Mycobacterium tuberculosis and other pathogens. We aimed to identify the presence of potential respiratory pathogens in nasopharyngeal (NP) samples from children with suspected PTB. METHOD: NP samples collected from consecutive children presenting with suspected PTB at Red Cross Children's Hospital (Cape Town, South Africa) were tested by multiplex real-time RT-PCR...
October 24, 2016: BMC Infectious Diseases
Kristian Tonby, Ida Wergeland, Nora V Lieske, Dag Kvale, Kjetil Tasken, Anne M Dyrhol-Riise
BACKGROUND: Tuberculosis (TB) causes a major burden on global health with long and cumbersome TB treatment regimens. Host-directed immune modulating therapies have been suggested as adjunctive treatment to TB antibiotics. Upregulated cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) signaling pathway may cause a dysfunctional immune response that favors survival and replication of Mycobacterium tuberculosis (Mtb). METHODS: Blood samples were obtained from patients with latent TB (n = 9) and active TB (n = 33) before initiation of anti-TB chemotherapy...
October 24, 2016: BMC Infectious Diseases
Bharathkumar Inturi, Gurubasavaraj V Pujar, Madhusudhan N Purohit
Mycobacterium tuberculosis enoyl-ACP reductase (InhA) has been validated as a promising target for antitubercular agents. Isoniazid (INH), the most prescribed drug to treat tuberculosis (TB), inhibits a NADH-dependent InhA that provides precursors of mycolic acids, which are components of the mycobacterial cell wall. It is a pro-drug that needs activation to form the inhibitory INH-NAD adduct by KatG coding for catalase-peroxidase. The INH resistance of M. tuberculosis is caused by mutations in KatG, which may lead to multidrug-resistant TB (MDR-TB)...
October 24, 2016: Archiv der Pharmazie
Jie Tang, Ce Chen, Cheng Zha, Zhaohua Wang, Chen Zhang, Linli Zeng, Baiqing Li
Objective To investigate the differences of proportions of tumor necrosis factor α (TNF-α)-producing cells in peripheral blood γδ T cells stimulated with Mycobacterium tuberculosis heat resistant antigen (MTB-HAg) among patients with pulmonary tuberculosis (PTB), latent tuberculosis infection (LTBI) and healthy subjects (HC). Methods The peripheral blood specimens were collected from 15 normal adults, which were divided into HC group (n=9) and LTBI group (n=6), by enzyme-linked immunospot (ELISPOT) kit for diagnosis of Mycobacterium tuberculosis infection, and 12 patients with active PTB...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Paul Elkington, Marc Tebruegge, Salah Mansour
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and provided original proof that an infectious agent can cause human disease. However, key steps in TB pathogenesis remain poorly understood. We propose that autoimmunity is a critical and overlooked process driving pathology in TB, and present clinical and experimental observations supporting this hypothesis.
October 19, 2016: Trends in Immunology
Juan Sebastián Saavedra, Sebastián Urrego, María Eugenia Toro, Carlos Santiago Uribe, Jenny García, Olga Hernández, Juan Carlos Arango, Ángela Beatriz Pérez, Andrés Franco, Isabel Cristina Vélez, Helena Del Corral
OBJECTIVE: To determine the diagnostic accuracy of Thwaites Index (TI) in a Colombian population to distinguish meningeal tuberculosis (MTB) from bacterial meningitis (BM) and from non-tuberculous meningitis. Exploratory analyses were conducted to assess the TI's validity for patients with human immunodeficiency virus (HIV) and children above six-years-old. METHODS: The study included 527 patients, the TI was calculated and results compared with those of a reference standard established by expert neurologists...
November 15, 2016: Journal of the Neurological Sciences
Giulia Cattaneo, Daniela Ubiali, Enrica Calleri, Marco Rabuffetti, Georg C Höfner, Klaus T Wanner, Marcela C De Moraes, Leonardo K B Martinelli, Diógenes Santiago Santos, Giovanna Speranza, Gabriella Massolini
Mycobacterium tuberculosis (Mtb) purine nucleoside phosphorylase (PNP, EC has been identified as a target for the development of specific inhibitors with potential antimycobacterial activity. We hereby described the development and validation of a new 96-well LC-ESI-MS/MS method to assess the inhibition activity of nucleoside analogues towards MtbPNP and the human PNP (HsPNP). Enzyme activity was determined by monitoring the phosphorolysis of inosine (Ino) to hypoxanthine (Hpx). The enzymatic assay (v = 0...
November 2, 2016: Analytica Chimica Acta
Larry D Teeter, Padmaja Vempaty, Duc T M Nguyen, Jane Tapia, Sharon Sharnprapai, Smita Ghosh, J Steven Kammerer, Roque Miramontes, Wendy A Cronin, Edward A Graviss
BACKGROUND: Tracking the dissemination of specific Mycobacterium tuberculosis (Mtb) strains using genotyped Mtb isolates from tuberculosis patients is a routine public health practice in the United States. The present study proposes a standardized cluster investigation method to identify epidemiologic-linked patients in Mtb genotype clusters. The study also attempts to determine the proportion of epidemiologic-linked patients the proposed method would identify beyond the outcome of the conventional contact investigation...
October 21, 2016: BMC Infectious Diseases
Bini Mathew, Judith Varady Hobrath, Larry Ross, Michele C Connelly, Hava Lofton, Malini Rajagopalan, R Kiplin Guy, Robert C Reynolds
A variety of commercial analogs and a newer series of Sulindac derivatives were screened for inhibition of M. tuberculosis (Mtb) in vitro and specifically as inhibitors of the essential mycobacterial tubulin homolog, FtsZ. Due to the ease of preparing diverse analogs and a favorable in vivo pharmacokinetic and toxicity profile of a representative analog, the Sulindac scaffold may be useful for further development against Mtb with respect to in vitro bacterial growth inhibition and selective activity for Mtb FtsZ versus mammalian tubulin...
2016: PloS One
Viboon Boonsarngsuk, Siriwan Saengsri, Pitak Santanirand
BACKGROUND: Intrathoracic tuberculous (TB) lymphadenitis is a diagnostic challenge to the clinician. Although endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) can obtain a sample from the affected lymph node, the diagnosis of TB lymphadenitis by cytopathology remains inaccurate. OBJECTIVE: To evaluate the efficacy of EBUS-TBNA rinse fluid TB polymerase chain reaction (PCR) assay for the diagnosis of intrathoracic TB lymphadenitis. METHODS: A retrospective study was conducted on 102 patients who underwent EBUS-TBNA for diagnostic evaluation of intrathoracic lymphadenopathy...
October 21, 2016: Infectious Diseases
Jin Kyung Kim, Hye-Mi Lee, Ki-Sun Park, Dong-Min Shin, Tae Sung Kim, Yi Sak Kim, Hyun-Woo Suh, Soo Yeon Kim, In Soo Kim, Jin-Man Kim, Ji-Woong Son, Kyung Mok Sohn, Sung Soo Jung, Chaeuk Chung, Sang-Bae Han, Chul-Su Yang, Eun-Kyeong Jo
Autophagy is an important antimicrobial effector process that defends against Mycobacterium tuberculosis (Mtb), the human pathogen causing tuberculosis (TB). MicroRNAs (miRNAs), endogenous noncoding RNAs, are involved in various biological functions and act as post-transcriptional regulators to target mRNAs. The process by which miRNAs affect antibacterial autophagy and host defense mechanisms against Mtb infections in human monocytes and macrophages is largely uncharacterized. In this study, we show that Mtb significantly induces the expression of MIR144*/hsa-miR-144-5p, which targets the 3'-untranslated region of DRAM2 (DNA damage regulated autophagy modulator 2) in human monocytes and macrophages...
October 20, 2016: Autophagy
Madhukar Pai, Mark P Nicol, Catharina C Boehme
Rapid and accurate diagnosis is critical for timely initiation of anti-tuberculosis (TB) treatment, but many people with TB (or TB symptoms) do not have access to adequate initial diagnosis. In many countries, TB diagnosis is still reliant on sputum microscopy, a test with known limitations. However, new diagnostics are starting to change the landscape. Stimulated, in part, by the success and rollout of Xpert MTB/RIF, an automated, molecular test, there is now considerable interest in new technologies. The landscape looks promising with a pipeline of new tools, particularly molecular diagnostics, and well over 50 companies actively engaged in product development, and many tests have been reviewed by WHO for policy endorsement...
October 2016: Microbiology Spectrum
Yong Suk Jo, Ju-Hee Park, Jung Kyu Lee, Eun Young Heo, Hee Soon Chung, Deog Kyeom Kim
The prevalence and clinical implications of discordance between Xpert MTB/RIF assays and the AdvanSure TB/NTM real-time polymerase chain reaction (PCR) for bronchial washing specimens have not been studied in pulmonary TB (PTB) patients. The discordant proportion and its clinical impact were evaluated in 320 patients from the bronchoscopy registry whose bronchial washing specimens were tested simultaneously with Xpert MTB/RIF and the TB/NTM PCR assay for three years, and the accuracy of the assays, including the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were studied...
2016: PloS One
Sahajal Dhooria, Nalini Gupta, Amanjit Bal, Inderpaul Singh Sehgal, Ashutosh Nath Aggarwal, Sunil Sethi, Digambar Behera, Ritesh Agarwal
BACKGROUND: In patients with intrathoracic lymphadenopathy, differentiating tuberculosis from sarcoidosis is often difficult. We hypothesized that Xpert MTB/RIF assay, a semi-automated hemi-nested PCR would help in this regard. OBJECTIVE: To evaluate the performance of Xpert MTB/RIF in the differential diagnosis of tuberculosis and sarcoidosis. METHODS: This was a retrospective analysis of patients with intrathoracic lymphadenopathy who underwent endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA), and were diagnosed as either tuberculosis or sarcoidosis...
October 7, 2016: Sarcoidosis, Vasculitis, and Diffuse Lung Diseases: Official Journal of WASOG
Teklay Gebrecherkos, Baye Gelaw, Belay Tessema
BACKGROUND: In correctional settings tuberculosis is a public health concern. The incarcerated population is at greater risk for tuberculosis (TB) than the general population. The aim of this study was to determine the prevalence of smear positive pulmonary tuberculosis (PTB) and associated risk factors in prison settings. METHODS: A cross-sectional study was conducted among prisoners of North Gondar zone where all inmates with a history of cough for ≥ 2 weeks were included...
October 18, 2016: BMC Public Health
Glennah Kerubo, Evans Amukoye, Stefan Niemann, Samuel Kariuki
BACKGROUND: Anti-tuberculosis drug resistance is an emerging health problem in Kenya and especially in slums. Slum environments create a conducive environment for the spread of tuberculosis (TB) due to high population density and lack of basic amenities such as decent housing, access to clean water, lack of drainage and basic sanitation. Furthermore, ineffective health services in crowded and poorer populations, poor patient compliance, a large pool of untreated cases, delayed diagnosis and inappropriate treatment regimens are likely to favour selection and spread of drug resistant Mycobacterium tuberculosis (Mtb) strains in such settings, however, precise data on this problem are only sparsely available...
October 19, 2016: BMC Infectious Diseases
Rahul Pal, Saif Hameed, Sharda Sharma, Zeeshan Fatima
Novel strategies to combat the ever increasing burden of drug resistance in Mycobacterium tuberculosis (MTB) causing tuberculosis (TB) remains a global concern. The ability of MTB to sense and adapt to restricted iron conditions in the hostile environment is essential for their survival and confers the basis of their success as dreadful pathogen. The striking and clinically relevant virulence trait of MTB is its ability to form biofilms and adhere to the host cells. The present study elucidated the effect of iron deprivation on biofilm formation and cell adherence of Mycobacterium smegmatis, a non-pathogenic surrogate of MTB...
October 15, 2016: Brazilian Journal of Infectious Diseases
Gilberto Ayala, Julio Garay, Miguel Aragon, Tom Decroo, Rony Zachariah
Objective To describe trends in tuberculosis (TB) notification and treatment outcomes in 25 prisons in El Salvador from 2009-2014 and to determine if a set of interventions introduced in 2011 affected TB case finding and management. Methods This was operational research that utilized a retrospective cohort study of program data from 2009-2014. The package of interventions introduced in 2011 provides staff training, engages inmates in TB case finding, and offers diagnosis through mobile X-ray and Xpert® MTB/RIF...
January 2016: Revista Panamericana de Salud Pública, Pan American Journal of Public Health
Fatemeh Nooshabadi, Hee-Jeong Yang, Yunfeng Cheng, Madeleine S Durkee, Hexin Xie, Jianghong Rao, Jeffrey D Cirillo, Kristen C Maitland
Tuberculosis is a pulmonary disease with an especially high mortality rate in immuno-compromised populations, specifically children and HIV positive individuals. The causative agent, Mycobacterium tuberculosis (Mtb), is a very slow growing and difficult organism to work with, making both diagnosis and development of effective treatments cumbersome. We utilize a fiber-optic fluorescence microendoscope integrated with a whole-body imaging system for in vivo Mtb detection. The system exploits an endogenous enzyme of Mtb (β-lactamase, or BlaC) using a BlaC-specific NIR fluorogenic substrate...
October 18, 2016: Journal of Biophotonics
Diego G Ghiano, Agustina de la Iglesia, Nina Liu, Peter J Tonge, Héctor R Morbidoni, Guillermo R Labadie
A collection of 1,2,3-triazoles unsaturated fatty acid mimics were efficiently synthesized by click chemistry. The 1,4-disubstituted analogs prepared covered different alkyl chain lengths and triazole positions. The compounds were subsequently tested against Mycobacterium tuberculosis, being most of them active with some of the analogs displaying activity at micromolar concentration. The most potent member of the series has the triazole moiety on the C-2 position with a carbon chain of eight or ten carbon atoms...
September 28, 2016: European Journal of Medicinal Chemistry
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