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Tuberculosis biomarker

Fred R Sattler, Daniel Chelliah, Xingye Wu, Alejandro Sanchez, Michelle A Kendall, Evelyn Hogg, David Lagat, Umesh Lalloo, Valdilea Veloso, Diane V Havlir, Alan Landay
Background: The risk of short-term death for treatment naive patients dually infected with Mycobacterium tuberculosis and HIV may be reduced by early anti-retroviral therapy. Of those dying, mechanisms responsible for fatal outcomes are unclear. We hypothesized that greater malnutrition and/or inflammation when initiating treatment are associated with an increased risk for death. Methods: We utilized a retrospective case-cohort design among participants of the ACTG A5221 study who had baseline CD4 < 50 cells/mm3 ...
2018: Pathogens & Immunity
Sheetal Verma, Peicheng Du, Damalie Nakanjako, Sabine Hermans, Jessica Briggs, Lydia Nakiyingi, Jerrold J Ellner, Yukari C Manabe, Padmini Salgame
BACKGROUND: Tuberculosis (TB) is the major cause of death in Human Immunodeficiency Virus (HIV)-infected individuals. However, diagnosis of TB in HIV remains challenging particularly when HIV infection is advanced. Several gene signatures and serum protein biomarkers have been identified that distinguish active TB from latent infection. Our study was designed to assess if gene expression signatures and cytokine levels would distinguish active TB in advanced HIV. METHODS: We conducted a case-control study of whole blood RNA-Seq and plasma cytokine/chemokine analysis in HIV-infected with CD4+ T cell count of ≤ 100 cells/μl, with and without active TB...
May 15, 2018: BMC Infectious Diseases
Xuejiao Luo, Furong Wu, Jun Ma, Heping Xiao, Haiyan Cui
Objectives This study aimed to examine the change and significance of immune parameters in patients with sputum smear-positive pulmonary tuberculosis (TB) after 2 months of intensive phase anti-TB treatment. Methods The immune parameters of 232 cases of sputum smear-positive pulmonary TB were detected before and after 2 months of intensive phase anti-TB treatment and compared with 50 cases from healthy volunteers (controls). The T lymphocyte cell population in peripheral blood was detected using flow cytometry...
January 1, 2018: Journal of International Medical Research
Flonza Isa, Sean Collins, Myung Hee Lee, Diessy Decome, Nancy Dorvil, Patrice Joseph, Lauren Smith, Stephen Salerno, Martin T Wells, Steven Fischer, James M Bean, Jean W Pape, Warren D Johnson, Daniel W Fitzgerald, Kyu Y Rhee
BACKGROUND: Tuberculosis (TB) is the leading infectious cause of death worldwide. A major barrier to control of the pandemic is a lack of clinical biomarkers with the ability to distinguish active TB from healthy and sick controls and potential for development into point-of-care diagnostics. METHODS: We conducted a prospective case control study to identify candidate urine-based diagnostic biomarkers of active pulmonary TB (discovery cohort) and obtained a separate blinded "validation" cohort of confirmed cases of active pulmonary TB and controls with non-tuberculous pulmonary disease for validation...
April 22, 2018: EBioMedicine
Barry Simone E, Ellis Magda, Yang YuRong, Guan Guangyu, Wang Xiaolin, Britton Warwick J, Saunders Bernadette M
OBJECTIVE: microRNA expression profiles are of interest as a biomarker of tuberculosis (TB). How anti-TB therapy effects miRNA profiles is unknown and was examined. METHODS: We identified 87 plasma miRNAs that were significantly modified in an exploratory group of 19 Chinese pulmonary TB (PTB) patients compared to 14 healthy controls. We selected 10 of these miRNAs for analysis in a cohort of 100 PTB patients prior to, and at one, two and six months during treatment...
May 7, 2018: Journal of Infection
Shruthi Ravimohan, Kebatshabile Nfanyana, Neo Tamuhla, Caroline T Tiemessen, Drew Weissman, Gregory P Bisson
Background: Elevated inflammation is associated with early mortality among HIV/tuberculosis (TB) patients starting antiretroviral therapy (ART); however, the sources of immune activation are unclear. We hypothesized that common variation in innate immune genes contributes to excessive inflammation linked to death. As single nucleotide polymorphisms (SNPs) in inflammasome pathway genes can increase risk for inflammatory diseases, we investigated their association with early mortality among a previously described cohort of HIV/TB patients initiating ART in Botswana...
May 2018: Open Forum Infectious Diseases
Michela Terlizzi, Chiara Colarusso, Ilaria De Rosa, Nicolina De Rosa, Pasquale Somma, Carlo Curcio, Alessandro Zamparelli Sanduzzi, Pietro Micheli, Antonio Molino, Antonello Saccomanno, Rosario Salvi, Rita P Aquino, Aldo Pinto, Rosalinda Sorrentino
Late diagnosis limits therapeutic options and survival rate of non-small cell lung cancer (NSCLC) patients. Therefore the identification of biomarkers represents an emerging medical need. A highly sensitive and specific test was developed to identify/quantify a novel/selective diagnostic biomarker for NSCLC patients, caspase-4. This test was validated by using i) plasma from 125 NSCLC patients and 79 healthy (non-pathological) subjects, ii) plasma from 139 smokers and iii) from 70 chronic-obstructive pulmonary disease (COPD) patients...
April 10, 2018: Oncotarget
José W López, Maria-Cristina I Loader, Dan Smith, Dan Pastorius, Marjory Bravard, Luz Caviedes, Karina M Romero, Taryn Clark, William Checkley, Eduardo Ticona, Jon S Friedland, Robert H Gilman
To reduce transmission of tuberculosis (TB) in resource-limited countries where TB remains a major cause of mortality, novel diagnostic tools are urgently needed. We evaluated the fractional concentration of exhaled nitric oxide (FeNO) as an easily measured, noninvasive potential biomarker for diagnosis and monitoring of treatment response in participants with pulmonary TB including multidrug resistant-TB in Lima, Peru. In a longitudinal study however, we found no differences in baseline median FeNO levels between 38 TB participants and 93 age-matched controls (13 parts per billion [ppb] [interquartile range (IQR) = 8-26] versus 15 ppb [IQR = 12-24]), and there was no change over 60 days of treatment (15 ppb [IQR = 10-19] at day 60)...
April 30, 2018: American Journal of Tropical Medicine and Hygiene
Robert B Abramovitch
Reporter strains have proven to be powerful tools to study Mycobacterium tuberculosis (Mtb) physiology. Transcriptional and translational reporter strains are engineered by fusing a readout gene, encoding a fluorescent, luminescent or enzymatic protein, downstream of a promoter or in-frame with a gene of interest. When the reporter is expressed, it generates a signal that acts as a synthetic phenotype, enabling the study of physiologies that might have otherwise been hidden. This review will discuss approaches for generating reporter strains in Mtb and how they can be used as tools for high-throughput genetic and small molecule screening and as biomarkers for examining Mtb responses to drug or immune stresses during animal infections...
April 29, 2018: IUBMB Life
Fergal J Duffy, Ethan Thompson, Katrina Downing, Sara Suliman, Harriet Mayanja-Kizza, W Henry Boom, Bonnie Thiel, January Weiner Iii, Stefan H E Kaufmann, Drew Dover, David L Tabb, Hazel M Dockrell, Tom H M Ottenhoff, Gerard Tromp, Thomas J Scriba, Daniel E Zak, Gerhard Walzl
Biomarkers that predict who among recently Mycobacterium tuberculosis (MTB)-exposed individuals will progress to active tuberculosis are urgently needed. Intracellular microRNAs (miRNAs) regulate the host response to MTB and circulating miRNAs (c-miRNAs) have been developed as biomarkers for other diseases. We performed machine-learning analysis of c-miRNA measurements in the serum of adult household contacts (HHCs) of TB index cases from South Africa and Uganda and developed a c-miRNA-based signature of risk for progression to active TB...
2018: Frontiers in Immunology
Alejandro M Roncero, Ignacio E Tobal, Rosalina F Moro, David Díez, Isidro S Marcos
Covering: 1970 to 2017Diterpenes with a halimane skeleton constitute a small group of natural products that can be biogenetically considered as being between labdane and clerodane diterpenoids. Some of these compounds show biological activities, such as antitumour, mosquito repellency, germination inhibition and antimicrobial, as well as being biomarkers for tuberculosis. To the best of our knowledge, there are no reviews on these compounds. In this review, halimane skeleton diterpenoids are classified according to their biogenetic origin, characterization and/or the enzymes involved in their biosynthesis...
April 27, 2018: Natural Product Reports
Sebastian G Wicha, Oskar Clewe, Robin J Svensson, Stephen H Gillespie, Yanmin Hu, Anthony R M Coates, Ulrika S H Simonsson
A crucial step for accelerating tuberculosis drug development is bridging the gap between pre-clinical and clinical trials. In this study, we developed a pre-clinical model-informed translational approach to predict drug effects across pre-clinical systems and early clinical trials using the in vitro-based Multistate Tuberculosis Pharmacometric (MTP) model using rifampicin as an example. The MTP model predicted rifampicin biomarker response observed in (i) a hollow-fiber infection model, (ii) a murine study to determine PK/PD indices, and (iii) several clinical phase IIa early bactericidal activity (EBA) studies...
April 26, 2018: Clinical Pharmacology and Therapeutics
Yingmei Fu, Wenjing Li, Zheng Wu, Yuanmeihui Tao, Xinyang Wang, Jing Wei, Peidong Jiang, Jinyin Wu, Zhiwei Zhang, Wenli Zhang, Jizi Zhao, Fengmin Zhang
Bacterial small RNA (sRNA) has been shown to play an important role in control of bacteria virulence, stress response and physiological metabolism by post-transcriptional regulation of gene expression. However, there were few reports about bacterial sRNA as a biomarker of infection. To test the potential role of sRNA in indicating infection of Mycobacterium tuberculosis, total RNA were extracted from the filtrated bacterial cultural supernatant. After synthesis of cDNA by reverse transcription, four Mycobacterial sRNAs including ASdes, ASpks, AS1726, and AS1890, which have been experimentally confirmed by Kristine B in the year of 2009, were detected by real time PCR...
April 21, 2018: Biochemical and Biophysical Research Communications
Landry Blanc, Anne J Lenaerts, Véronique Dartois, Brendan Prideaux
MALDI mass spectrometry imaging (MALDI-MSI) is a technique capable of label-free identification and visualization of analytes in tissue sections. We have previously applied MALDI-MSI to study the spatial distribution of tuberculosis (TB) drugs in necrotic lung granulomas characteristic of pulmonary TB disease, revealing heterogeneous and often suboptimal drug distribution. To investigate the impact of differential drug distribution at the sites of infection, we sought to image mycobacterial biomarkers to co-register drugs and bacteria in lesion sections...
April 18, 2018: Analytical Chemistry
Nicholas A Owens, Lars B Laurentius, Marc D Porter, Qun Li, Sean Wang, Delphi Chatterjee
Techniques for the detection of disease biomarkers are key components in the protection of human health. While work over the last few decades has redefined the low-level measurement of disease biomarkers, the translation of these capabilities from the formal clinical setting to point-of-need (PON) usage has been much more limited. This paper presents the results of experiments designed to examine the potential utility of a handheld Raman spectrometer as a PON electronic reader for a sandwich immunoassay based on surface-enhanced Raman scattering (SERS)...
January 1, 2018: Applied Spectroscopy
Magdalena Druszczynska, Sebastian Wawrocki, Rafal Szewczyk, Wieslawa Rudnicka
Tuberculosis (TB) remains an escalating problem worldwide. The current diagnostic methods do not always guarantee reliable diagnosis. TB treatment is a time-consuming process that requires the use of several chemotherapeutics, to which mycobacteria are becoming increasingly resistant. This article focuses on the potential utility of biomarkers of mycobacterial origin with potential implications for TB diagnosis. Properly standardized indicators could become new diagnostic tools, improving and streamlining the identification of Mycobacterium tuberculosis infection and the implementation of appropriate therapy...
December 2017: Indian Journal of Medical Research
G R Kathamuthu, K Moideen, D Baskaran, G Sekar, S Rathinam, V J Bharathi, G R Ganeshan, S Babu
BACKGROUND: Angiogenic factors are important in granuloma formation and serve as biomarkers in pulmonary tuberculosis (PTB). The relationship between these markers and tuberculous lymphadenitis (TBL) is not known. OBJECTIVE AND DESIGN: To examine the association of vascular endothelial growth factor (VEGF) and angiopoietin (Ang) family molecules in TBL, we measured systemic levels of VEGF-A, C, D, R1 (VEGF-receptor 1), R2, R3, Ang-1, Ang-2 and TIE2 (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2) levels in TBL, latent tuberculous infection (LTBI) and lymph node culture supernatants (VEGF-A, C and Ang-2) of the same TBL patients...
May 1, 2018: International Journal of Tuberculosis and Lung Disease
Naveed Sabir, Tariq Hussain, Syed Zahid Ali Shah, Antonio Peramo, Deming Zhao, Xiangmei Zhou
Tuberculosis (TB) is one of the most fatal infectious diseases and a leading cause of mortality, with 95% of these deaths occurring in developing countries. The causative agent, Mycobacterium tuberculosis ( Mtb ), has a well-established ability to circumvent the host's immune system for its intracellular survival. microRNAs (miRNAs) are small, non-coding RNAs having an important function at the post-transcriptional level and are involved in shaping immunity by regulating the repertoire of genes expressed in immune cells...
2018: Frontiers in Microbiology
Milena S Espíndola, Luana S Soares, Leonardo J Galvão-Lima, Fabiana A Zambuzi, Maira C Cacemiro, Verônica S Brauer, Cleni M Marzocchi-Machado, Matheus de Souza Gomes, Laurence R Amaral, Olindo A Martins-Filho, Valdes R Bollela, Fabiani G Frantz
Monocytes are key cells in the immune dysregulation observed during human immunodeficiency virus (HIV) infection. The events that take place specifically in monocytes may contribute to the systemic immune dysfunction characterized by excessive immune activation in infected individuals, which directly correlates with pathogenesis and progression of the disease. Here, we investigated the immune dysfunction in monocytes from untreated and treated HIV + patients and associated these findings with epigenetic changes...
April 3, 2018: Scientific Reports
Yeji Han, Soo Jung Kim, Su Hwan Lee, Yun Su Sim, Yon Ju Ryu, Jung Hyun Chang, Sung Shin Shim, Yookyung Kim, Jin Hwa Lee
Background: It is difficult to predict the prognosis of miliary tuberculosis (TB). We hypothesized that blood neutrophil-lymphocyte ratio (NLR) is an indicator of inflammatory status to reflect independent prognostic significance in patients with miliary TB. The aim of this study is to investigate the relationship between NLR and outcome in miliary TB. Methods: We retrospectively collected data from patients diagnosed with miliary TB in a tertiary referral hospital between January 1995 and January 2016...
January 2018: Journal of Thoracic Disease
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