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biomarkers for tuberculosis

Surendra K Sharma, Anunay Gupta, Ashutosh Biswas, Abhishek Sharma, Atul Malhotra, K T Prasad, Sreenivas Vishnubhatla, Sajal Ajmani, Hridesh Mishra, Manish Soneja, Shobha Broor
BACKGROUND & OBJECTIVES: Acute respiratory distress syndrome (ARDS) is a common disorder in critically ill patients and is associated with high mortality. There is a paucity of literature on this condition from developing countries. This prospective observational study was designed to find out the aetiology, outcomes and predictors of mortality in ARDS. METHODS: Sixty four consecutive patients who satisfied American-European Consensus Conference (AECC) definition of ARDS from medical Intensive Care Unit (ICU) of a tertiary care centre in New Delhi, India, were enrolled in the study...
June 2016: Indian Journal of Medical Research
Jin Lin, Yan Wang, Ye-Qing Zou, Xin Chen, Bo Huang, Jing Liu, Yan-Mei Xu, Jing Li, Jing Zhang, Wei-Ming Yang, Qing-Hua Min, Fan Sun, Shu-Qi Li, Qiu-Fang Gao, Xiao-Zhong Wang
MicroRNAs (miRNAs) have been found to play important regulatory roles in various physiological and pathological processes. MiRNAs also exhibit high stability and are present at high concentrations in human bodily fluids. Consequently, miRNAs may represent attractive and novel diagnostic biomarkers for certain clinical conditions. Recently, the capacity for extracellular vesicles, including microvesicles and exosomes, to carry miRNAs that participate in cell-to-cell communication has been described. In the present study, the miRNA expression patterns for three kinds of pleural effusions that were obtained from patients with pneumonia (group A), pulmonary tuberculosis (group B), and lung cancer (group C) were detected with high-throughput sequencing...
October 14, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Soumya Swaminathan, Jotam G Pasipanodya, Geetha Ramachandran, A K Hemanth Kumar, Shashikant Srivastava, Devyani Deshpande, Eric Nuermberger, Tawanda Gumbo
BACKGROUND:  The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown. METHODS:  Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Jennifer K Roe, Niclas Thomas, Eliza Gil, Katharine Best, Evdokia Tsaliki, Stephen Morris-Jones, Sian Stafford, Nandi Simpson, Karolina D Witt, Benjamin Chain, Robert F Miller, Adrian Martineau, Mahdad Noursadeghi
BACKGROUND. Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB...
October 6, 2016: JCI Insight
Bryce M Buddle, H Martin Vordermeier, R Glyn Hewinson
In this article we present experimental Mycobacterium bovis infection models in domestic livestock species and how these models were applied to vaccine development, biomarker discovery, and the definition of specific antigens for the differential diagnosis of infected and vaccinated animals. In particular, we highlight synergies between human and bovine tuberculosis (TB) research approaches and data and propose that the application of bovine TB models could make a valuable contribution to human TB vaccine research and that close alignment of both research programs in a one health philosophy will lead to mutual and substantial benefits...
August 2016: Microbiology Spectrum
Xu Qian, Duc T M Nguyen, Yaojun Li, Jianxin Lyu, Edward A Graviss, Tony Y Hu
BACKGROUND: There is an urgent need for methods that can rapidly and accurately assess therapeutic responses in patients with active tuberculosis (TB) in order to predict treatment outcomes. Exposure to bacterial pathogens can rapidly activate the plasma contact system, triggering the release of bradykinin (BK) and its metabolite desArg(9)-bradykinin (DABK) to induce inflammation and innate immune responses. We hypothesized that serum BK and DABK levels might act as sensitive immune response signatures for changes in Mycobacterium tuberculosis (Mtb) burden, and therefore examined how serum levels of these markers corresponded with anti-TB therapy in a small cohort of active TB cases...
September 28, 2016: Tuberculosis
Yamilé López-Hernández, Omar Patiño-Rodríguez, Sandra Teresa Orta-García, Juan Manuel Pinos-Rodríguez
An adequate and effective tuberculosis diagnosis system has been identified by World Health Organization (WHO) as a priority in the fighting against this disease. Over the years, several methods have been developed to identify the bacillus, but bacterial culture remains one of the most affordable for most countries. For rapid, accurate identification, however, it is more feasible to implement molecular techniques, taking advantage of the availability of public databases containing protein sequences. Mass spectrometry has become an interesting technique for identification of tuberculosis...
October 8, 2016: Journal of Applied Microbiology
Simon Blankley, Christine M Graham, Jacob Turner, Matthew P R Berry, Chloe I Bloom, Zhaohui Xu, Virginia Pascual, Jacques Banchereau, Damien Chaussabel, Ronan Breen, George Santis, Derek M Blankenship, Marc Lipman, Anne O'Garra
BACKGROUND: Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB) patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis...
2016: PloS One
Katie R Tallman, Samantha R Levine, Kimberly Elizabeth Beatty
Mycobacterium tuberculosis (Mtb) is the deadliest bacterial pathogen in the world. An estimated one-third of humans harbor Mtb in a dormant state. These asymptomatic, latent infections impede tuberculosis eradication due to the long-term potential for reactivation. Dormant Mtb has reduced enzymatic activity, but hydrolases that remain active facilitate pathogen survival. We targeted Mtb esterases, a diverse set of enzymes in the serine hydrolase family, and studied their activities using both activity-based probes (ABPs) and fluorogenic esterase substrates...
October 3, 2016: ACS Infectious Diseases
Ida Wergeland, Jörg Assmus, Anne Ma Dyrhol-Riise
BACKGROUND: Interferon gamma release assays (IGRAs) do not discriminate between active tuberculosis (TB) and latent TB infection (LTBI), which limit their use in TB endemic areas. Subjects with QuantiFERON-TB (QFT) results around the diagnostic cut-off more likely show inconsistent results on serial testing which makes the interpretation of the assay difficult. We have studied potential biomarkers in patients with various stages of TB infection and with borderline QFT tests compared to those with higher values...
2016: PloS One
Yuzo Suzuki, Masahiro Shirai, Kazuhiro Asada, Seiichi Miwa, Masato Karayama, Yutaro Nakamura, Naoki Inui, Toshihiro Shirai, Hiroshi Hayakawa, Satoshi Baba, Takafumi Suda
RATIONALE: Tuberculosis (TB) is a leading cause of death among infectious diseases worldwide. Accumulated knowledge has revealed that macrophages are deeply involved in the progression and pathogenesis of TB. We hypothesized that the evaluation of a macrophage activation marker may be useful in the diagnosis and assessment of pulmonary TB. OBJECTIVES: To examine the utility of the macrophage-activation marker sCD163 as a diagnostic tool and measure of disease severity for pulmonary TB and tuberculous pleurisy...
September 29, 2016: Annals of the American Thoracic Society
Diana Gassó, Joaquín Vicente, Gregorio Mentaberre, Ramón Soriguer, Rocío Jiménez Rodríguez, Nora Navarro-González, Asta Tvarijonaviciute, Santiago Lavín, Pedro Fernández-Llario, Joaquim Segalés, Emmanuel Serrano
Reactive oxygen and nitrogen species (ROS-RNS) are important defence substances involved in the immune response against pathogens. An excessive increase in ROS-RNS, however, can damage the organism causing oxidative stress (OS). The organism is able to neutralise OS by the production of antioxidant enzymes (AE); hence, tissue damage is the result of an imbalance between oxidant and antioxidant status. Though some work has been carried out in humans, there is a lack of information about the oxidant/antioxidant status in the presence of tuberculosis (TB) in wild reservoirs...
2016: PloS One
Alexandre Drouin, Sébastien Giguère, Maxime Déraspe, Mario Marchand, Michael Tyers, Vivian G Loo, Anne-Marie Bourgault, François Laviolette, Jacques Corbeil
BACKGROUND: The identification of genomic biomarkers is a key step towards improving diagnostic tests and therapies. We present a reference-free method for this task that relies on a k-mer representation of genomes and a machine learning algorithm that produces intelligible models. The method is computationally scalable and well-suited for whole genome sequencing studies. RESULTS: The method was validated by generating models that predict the antibiotic resistance of C...
September 26, 2016: BMC Genomics
Lenette L Lu, Amy W Chung, Tracy R Rosebrock, Musie Ghebremichael, Wen Han Yu, Patricia S Grace, Matthew K Schoen, Fikadu Tafesse, Constance Martin, Vivian Leung, Alison E Mahan, Magdalena Sips, Manu P Kumar, Jacquelynne Tedesco, Hannah Robinson, Elizabeth Tkachenko, Monia Draghi, Katherine J Freedberg, Hendrik Streeck, Todd J Suscovich, Douglas A Lauffenburger, Blanca I Restrepo, Cheryl Day, Sarah M Fortune, Galit Alter
While a third of the world carries the burden of tuberculosis, disease control has been hindered by a lack of tools, including a rapid, point-of-care diagnostic and a protective vaccine. In many infectious diseases, antibodies (Abs) are powerful biomarkers and important immune mediators. However, in Mycobacterium tuberculosis (Mtb) infection, a discriminatory or protective role for humoral immunity remains unclear. Using an unbiased antibody profiling approach, we show that individuals with latent tuberculosis infection (Ltb) and active tuberculosis disease (Atb) have distinct Mtb-specific humoral responses, such that Ltb infection is associated with unique Ab Fc functional profiles, selective binding to FcγRIII, and distinct Ab glycosylation patterns...
October 6, 2016: Cell
Chikere A Anusiem, Paul O Okonkwo
Tuberculosis (TB) is a major public health problem in the world. Further elucidation of the pathogenesis and identification of suitable biomarkers of the disease have remained research priorities. Interleukin-1 beta (IL-1 β) signaling is known to be high in active tuberculosis. In this study, we followed up a cohort of adult sputum-positive tuberculosis patients and investigated the impact of anti-tuberculosis treatment on the serum concentrations of IL-1 β. The protocol was approved by the Ethics Committee of University of Nigeria Teaching Hospital Enugu...
September 16, 2016: American Journal of Therapeutics
Miguel Santin, Francisco Morandeira-Rego, Fernando Alcaide, Ramón Rabuñal, Luís Anibarro, Ramón Agüero-Balbín, Xavier Casas-Garcia, Elvira Pérez-Escolano, Maria D Navarro, Francisca Sánchez, Amparo Coira-Nieto, Matilde Trigo-Daporta, Amaya Martinez-Meñaca, Araceli Gonzalez-Cuevas, Maria D López-Prieto, Ángel Domínguez-Castellano, Neus Jové
OBJECTIVE: Previous reports have identified interleukin-2 (IL-2), quantified in the supernatants of QuantiFERON(®)-TB Gold In-tube (QFT) after 72 hours of incubation, as a potential biomarker for distinguishing between latent and active tuberculosis (TB). However, its validity has not been tested in an appropriate clinical cohort. METHODS: A multicentre study of 161 consecutive adult patients undergoing evaluation for active TB at eight TB Units in Spain. IFN-γ and IL-2 were assessed in the supernatant of QFT after 16-24 h and 72 h incubation...
September 16, 2016: Clinical Microbiology and Infection
Giovanni Delogu, Valentina Vanini, Gilda Cuzzi, Teresa Chiacchio, Flavio De Maio, Basem Battah, Carmela Pinnetti, Alessandro Sampaolesi, Andrea Antinori, Delia Goletti
RATIONALE: Heparin-binding haemagglutinin (HBHA) has been proposed as an immunological biomarker for discriminating active tuberculosis (TB) from latent TB infection (LTBI) and to identify those at higher risk of progressing to active disease. Few data are available in immune compromised patients, which are those with increased risk of TB reactivation. OBJECTIVE: To evaluate the immune response to HBHA in HIV-infected subjects with LTBI (HIV-LTBI) or active TB (HIV-TB) in comparison with the immune response to additional Mycobacterium tuberculosis (Mtb) or HIV and CMV antigens...
September 16, 2016: Scandinavian Journal of Immunology
Cristal Reyna, Felix Mba Medie, Matthew M Champion, Patricia A Champion
Mass spectrometry (MS) for the detection of proteins is an indispensable tool for evaluating the biological processes of the proteome. Proteomics frequently requires proteolysis of proteins into peptide fragments. Proteins can be refractory to ideal proteolysis at the sequence level rendering them difficult to analyze by routine proteomics methods. EsxA (ESAT-6, Early Secreted Antigen, 6kDa) is a major virulence determinant of Mycobacterium tuberculosis, the cause of human tuberculosis. EsxA is routinely used to evaluate mycobacterial virulence in the laboratory and as a biomarker for tuberculosis in humans...
2016: Scientific Reports
Payam Nahid, Susan E Dorman, Narges Alipanah, Pennan M Barry, Jan L Brozek, Adithya Cattamanchi, Lelia H Chaisson, Richard E Chaisson, Charles L Daley, Malgosia Grzemska, Julie M Higashi, Christine S Ho, Philip C Hopewell, Salmaan A Keshavjee, Christian Lienhardt, Richard Menzies, Cynthia Merrifield, Masahiro Narita, Rick O'Brien, Charles A Peloquin, Ann Raftery, Jussi Saukkonen, H Simon Schaaf, Giovanni Sotgiu, Jeffrey R Starke, Giovanni Battista Migliori, Andrew Vernon
The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline...
October 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Meng-Li Zheng, Nai-Kang Zhou, Cheng-Hua Luo
In our study, we aimed to profile a panel microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary tuberculosis (PTB) and to illuminate the molecular mechanisms in the development of PTB. Firstly, gene expression profile of E-GEOD-49951 was downloaded from ArrayExpress database, and quantile-adjusted conditional maximum likelihood method was utilized to identify statistical difference between miRNAs of Mycobacterium tuberculosis (MTB)-infected individuals and healthy subjects. Furthermore, in order to assess the performance of our methodology, random forest (RF) classification model was utilized to identify the top 10 miRNAs with better Area Under The Curve (AUC) using 10-fold cross-validation method...
September 8, 2016: Microbial Pathogenesis
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