Article
Immunology
Evangeline Ann Daniel, Kannan Thiruvengadam, Anuradha Rajamanickam, Padmapriyadarsini Chandrasekaran, Sathyamurthi Pattabiraman, Brindha Bhanu, Amsaveni Sivaprakasam, Mandar Paradkar, Vandana Kulkarni, Rajesh Karyakarte, Shri Vijay Bala Yogendra Shivakumar, Vidya Mave, Amita Gupta, Subash Babu, Luke Elizabeth Hanna
Summary: The study identified novel biomarkers with high predictive accuracy for progression to active tuberculosis, paving the way for the development of a more targeted intervention.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Respiratory System
Rupak Shivakoti, John W. Newman, Luke Elizabeth Hanna, Artur T. L. Queiroz, Kamil Borkowski, Akshay N. Gupte, Mandar Paradkar, Pattabiraman Satyamurthi, Vandana Kulkarni, Murugesh Selva, Neeta Pradhan, Shri Vijay Bala Yogendra Shivakumar, Saravanan Natarajan, Ramesh Karunaianantham, Nikhil Gupte, Kannan Thiruvengadam, Oliver Fiehn, Renu Bharadwaj, Anju Kagal, Sanjay Gaikwad, Shashikala Sangle, Jonathan E. Golub, Bruno B. Andrade, Vidya Mave, Amita Gupta, Chandrasekaran Padmapriyadarsini
Summary: This study investigated the association between host lipids and treatment failure in tuberculosis (TB) using unbiased lipidomics. The results showed that treatment failure was associated with lower levels of cholesteryl esters and oxylipin, and higher levels of ceramides and triglycerides at the baseline. A lipid signature with predictive accuracy for TB treatment failure was also identified.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Review
Immunology
Lucinda Baatjies, Andre G. Loxton, Monique J. Williams
Summary: Mycobacterium tuberculosis manipulates the host immune response and expresses specific genes during infection. Current immunodiagnostics lack the ability to detect progression from latent infection to active disease, highlighting the need for new tuberculosis biomarkers that can accurately diagnose TB infection and monitor treatment efficacy. Iron regulation by the host plays a crucial role in the susceptibility and outcome of Mtb infection, with certain genes being induced during iron limitation and intracellular growth of Mtb.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Harriet D. Gliddon, Myrsini Kaforou, Mary Alikian, Dominic Habgood-Coote, Chenxi Zhou, Tolu Oni, Suzanne T. Anderson, Andrew J. Brent, Amelia C. Crampin, Brian Eley, Robert Heyderman, Florian Kern, Paul R. Langford, Tom H. M. Ottenhoff, Martin L. Hibberd, Neil French, Victoria J. Wright, Hazel M. Dockrell, Lachlan J. Coin, Robert J. Wilkinson, Michael Levin
Summary: The study identified four-transcript and three-transcript signatures that can distinguish tuberculosis patients from those with other diseases or latent tuberculosis infection, offering strong quantitative support for their use as diagnostic biomarkers for tuberculosis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Bih H. Chendi, Candice I. Snyders, Kristian Tonby, Synne Jenum, Martin Kidd, Gerhard Walzl, Novel N. Chegou, Anne M. Dyrhol-Riise
Summary: Multiple host markers showed diagnostic potential for TB in both the Norwegian and South African cohorts, with a site-independent 5-marker biosignature identified as having high accuracy for diagnosing TB, regardless of geographical setting. This suggests that the 5-marker host plasma biosignature may have diagnostic potential for TB disease across different TB settings.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Microbiology
Renuga Devi Kanabalan, Le Jie Lee, Tze Yan Lee, Pei Pei Chong, Latiffah Hassan, Rosnah Ismail, Voon Kin Chin
Summary: The Mycobacterium tuberculosis complex (MTBC) consists of nine closely related species that cause tuberculosis in animals and humans, with Mycobacterium tuberculosis being the primary causative agent for human tuberculosis globally. The pathogenesis of human tuberculosis involves complex interactions between host factors and bacterial determinants. Research indicates the potential of host biomarkers in early diagnosis, disease differentiation, and treatment monitoring for tuberculosis.
MICROBIOLOGICAL RESEARCH
(2021)
Review
Immunology
Pavithra Sampath, Krisna Moorthi Periyasamy, Uma Devi Ranganathan, Ramalingam Bethunaickan
Summary: The utilization of miRNA as essential biomarkers in early diagnosis and treatment of tuberculosis highlights their importance in studying disease progression and immune regulation. The research on monocytes provides valuable insight into tuberculosis pathogenesis and biomarker efficiency.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Critical Care Medicine
Matthew J. Cummings, Barnabas Bakamutumaho, Adam Price, Nicholas Owor, John Kayiwa, Joyce Namulondo, Timothy Byaruhanga, Moses Muwanga, Christopher Nsereko, Stephen Sameroff, Rafal Tokarz, Wai Wong, Shivang S. Shah, Michelle H. Larsen, W. Ian Lipkin, Julius J. Lutwama, Max R. O'Donnell
Summary: This study identified two immune subtypes among 288 adults hospitalized with sepsis in Uganda, characterized by differential activation of pro-inflammatory innate and adaptive immune pathways, T-cell exhaustion, metabolic reprogramming, and association with severe HIV-associated tuberculosis, extensive organ dysfunction, worse functional outcomes, and higher 30-day mortality. These results emphasize the unique features of sepsis immunopathology in sub-Saharan Africa and highlight the importance of developing more biologically-informed treatment strategies incorporating immunomodulation in the region.
Article
Biochemistry & Molecular Biology
Atiqa Ambreen, Aasia Khaliq, Syed Zeeshan Haider Naqvi, Amna Tahir, Manal Mustafa, Safee Ullah Chaudhary, Shaper Mirza, Tehmina Mustafa
Summary: This study aimed to explore the utility of inflammatory biomarkers in predicting treatment response in extrapulmonary tuberculosis (EPTB). The change in levels of MIG, IP-10, MIF, CCL22 and CCL23 correlated with successful treatment response, with a biosignature defined by any significant decrease in these five biomarkers indicating treatment success in a high percentage of patients.
Article
Veterinary Sciences
Jorge Luis Mazorra-Carrillo, Omar Antonio Alcaraz-Lopez, Gonzalo Lopez-Rincon, Bernardo Villarreal-Ramos, Jose A. Gutierrez-Pabello, Hugo Esquivel-Solis
Summary: The study discovered certain proteins in the serum of Holstein-Friesian cows that may serve as biomarkers for resistance to bovine tuberculosis, offering a novel avenue for future research.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Microbiology
Sebastian Schirmer, Lucas Rauh, Sogol Alebouyeh, Mario Delgado-Velandia, Vivian C. Salgueiro, Laura Lerma, Jose L. Serrano-Mestre, Mikel Azkargorta, Felix Elortza, Jose L. Lavin, Maria Jesus Garcia, Maria Teresa Tortola Fernandez, Susanne Gola, Rafael Prados-Rosales
Summary: Tuberculosis (TB) remains a major global health problem, and there is a need for improved diagnostic methods. This study analyzed the composition of extracellular vesicles produced by Mycobacterium tuberculosis and identified three new antigens with specific biomarker capacity for TB diagnosis. This research provides potential new methods for diagnosing TB.
FRONTIERS IN MICROBIOLOGY
(2022)
Review
Immunology
Nan Wang, Yongliang Yao, Yingfen Qian, Dewen Qiu, Hui Cao, Huayuan Xiang, Jianjun Wang
Summary: Exosomes are double-membrane vesicles containing various lipids, proteins, mRNAs, and non-coding RNAs, and are involved in multiple physiological processes such as intercellular communication and immunomodulation. Studies have found that the components of exosomes released from host cells are altered following Mycobacterium tuberculosis infection. The contents of exosomes provide excellent biomarkers for the diagnosis, efficacy evaluation, and prognosis of tuberculosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Medicine, Research & Experimental
Betania M. F. Nogueira, Sonya Krishnan, Beatriz Barreto-Duarte, Mariana Araujo-Pereira, Artur T. L. Queiroz, Jerrold J. Ellner, Padmini Salgame, Thomas J. Scriba, Timothy R. Sterling, Amita Gupta, Bruno B. Andrade
Summary: Tuberculosis is a preventable and curable infectious disease, but the lack of early and accurate diagnosis leads to a high number of cases. The World Health Organization has proposed biomarker-based diagnostics using easily accessible specimens, but faced challenges in developing universal diagnostic biomarkers for specific patient populations. Additionally, there are limitations to widespread validation and utilization of published biomarkers. Proposed solutions are provided to enhance TB diagnostic biomarker validation and uptake.
EMBO MOLECULAR MEDICINE
(2022)
Article
Multidisciplinary Sciences
Patricia Comella-del-Barrio, Jose Luis Izquierdo-Garcia, Jacqueline Gautier, Mariette Jean Coute Doresca, Ramon Campos-Olivas, Clara M. Santiveri, Beatriz Muriel-Moreno, Cristina Prat-Aymerich, Rosa Abellana, Tomas M. Perez-Porcuna, Luis E. Cuevas, Jesus Ruiz-Cabello, Jose Dominguez
Summary: In this study, differences in metabolic response in children with different diagnostic certainty of TB were identified using urine nuclear magnetic resonance-based metabolomics. This could help improve the accuracy of TB diagnosis and prediction in pediatric populations.
SCIENTIFIC REPORTS
(2021)
Article
Immunology
Hygon Mutavhatsindi, Gian D. van der Spuy, Stephanus T. Malherbe, Jayne S. Sutherland, Annemieke Geluk, Harriet Mayanja-Kizza, Amelia C. Crampin, Desta Kassa, Rawleigh Howe, Adane Mihret, Jacob A. Sheehama, Emmanuel Nepolo, Gunar Gunther, Hazel M. Dockrell, Paul L. A. M. Corstjens, Kim Stanley, Gerhard Walzl, Novel N. Chegou
Summary: The development of a non-sputum-based, point-of-care diagnostic test for tuberculosis is a global priority. A study conducted in six African countries identified a two-marker bio-signature with a sensitivity of 94% and specificity of 69% for diagnosing TB in patients with no prior history of the disease.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Paula Ruibal, Ian Derksen, Marjolein van Wolfswinkel, Linda Voogd, Kees L. M. C. Franken, Angela F. El Hebieshy, Thorbald van Hall, Tom A. W. Schoufour, Ruud H. Wijdeven, Tom H. M. Ottenhoff, Ferenc A. Scheeren, Simone A. Joosten
Summary: There is growing interest in HLA-E-restricted T-cell responses as a potential vaccination target. This study developed a method for efficient peptide thermal exchange on HLA-E monomers and multimers, allowing high-throughput production. The optimized conditions for detection and analysis of peptide-specific T cells revealed new insights into the interaction between HLA-E and NKG2A/CD94 receptors.
Article
Immunology
Caroline M. Williams, Abdul K. Muhammad, Basil Sambou, Adama Bojang, Alhaji Jobe, Georgetta K. Daffeh, Olumuyiwa Owolabi, Daniel Pan, Manish Pareek, Michael R. Barer, Jayne S. Sutherland, Pranabashis Haldar
Summary: Mask sampling is a sensitive and noninvasive tool for evaluating the infectiousness of individuals in high tuberculosis (TB) burden settings. It provides better insight into community transmission and can inform public health interventions more reliably than sputum bacillary load.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Louise Pierneef, Anouk van Hooij, Danielle de Jong, Elisa M. Tjon Kon Fat, Krista E. van Meijgaarden, Elisa Petruccioli, Valentina Vanini, Anna H. E. Roukens, Delia Goletti, Paul L. A. M. Corstjens, Simone A. Joosten, Annemiek Geluk, BEAT COVID Study Grp
Summary: Diagnostic services for TB and COVID-19 are not easily accessible in low-resource settings. This study demonstrates the potential of non-sputum lateral flow assays as adjunct diagnostics and treatment monitoring for both diseases based on quantitative detection of multiple host biomarkers.
Article
Biochemical Research Methods
Marjolein van Wolfswinkel, Krista E. van Meijgaarden, Tom H. M. Ottenhoff, Paula Niewold, Simone A. Joosten
Summary: Characterization of immune cells is crucial for advancing our understanding of immunology and flow cytometry plays a vital role in this. By simultaneously analyzing cellular phenotype and antigen-specific functional responses, we can gain a more comprehensive understanding of immune cell behavior. Recent developments in (spectral) flow cytometry have made it possible to use panels with 30(+) markers, allowing for advanced integrated analyses. In this study, we optimized immune phenotyping using a 32-color panel, enabling the analysis of cellular phenotypes and markers associated with immune response quality and contributing to our understanding of the immune system.
Article
Biochemistry & Molecular Biology
Julia Figl, Heike Koehler, Nadine Wedlich, Elisabeth M. Liebler-Tenorio, Leander Grode, Gerald Parzmair, Gopinath Krishnamoorthy, Natalie E. Nieuwenhuizen, Stefan H. E. Kaufmann, Christian Menge
Summary: A more effective vaccine against tuberculosis is urgently needed. The recombinant vaccine VPM1002 has been found to be safer and more efficacious than the existing vaccine BCG in mice models. In this study, the safety and immunogenicity of VPM1002 and its derivatives, PDX and NUOG, were assessed in juvenile goats. The results showed that VPM1002 and NUOG induced anti-tuberculous immunity with a comparable safety profile to BCG.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Statistics & Probability
Anna Vesely, Livio Finos, Jelle J. Goeman
Summary: In this paper, a general closed testing procedure for sum tests is proposed, which provides lower confidence bounds for the proportion of true discoveries (TDP) simultaneously over all subsets of hypotheses. The proposed method allows for exploratory approaches and adapts to the unknown joint distribution of the data through permutation testing. An iterative shortcut based on the branch and bound algorithm is presented for the closed testing procedure, which achieves convergence to the full closed testing results.
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY
(2023)
Article
Mathematical & Computational Biology
Angela Andreella, Jesse Hemerik, Livio Finos, Wouter Weeda, Jelle Goeman
Summary: We propose a permutation-based method for testing a large collection of hypotheses simultaneously. The method provides lower bounds for the number of true discoveries in any selected subset of hypotheses, while maintaining high confidence levels. This method is particularly useful in functional Magnetic Resonance Imaging cluster analysis, addressing the spatial specificity paradox and accounting for cluster selection in a data-driven manner. The method is advantageous over parametric approaches due to its ability to adapt to the spatial correlation structure in fMRI data.
STATISTICS IN MEDICINE
(2023)
Article
Microbiology
Juana Claus, Thijs ten Doesschate, Cheyenne Gumbs, Cornelis H. van Werkhoven, Thomas W. van der Vaart, Axel B. Janssen, Gaby Smits, Rob van Binnendijk, Fiona van der Klis, Debbie van Baarle, Fernanda L. Paganelli, Helen Leavis, Lilly M. Verhagen, Simone A. Joosten, Marc J. M. Bonten, Mihai G. Netea, Janneke H. H. M. van de Wijgert
Summary: Although BCG vaccination has been hypothesized to reduce SARS-CoV-2 infection, severity, and/or duration, our study found that BCG vaccination did not reduce SARS-CoV-2 infections nor infection duration or severity in healthcare workers. However, it may enhance SARS-CoV-2 antibody production during the first 3 months after vaccination.
Article
Infectious Diseases
Tracy R. Richardson, Bronwyn Smith, Stephanus T. N. Malherbe, Jane Alexandra Shaw, Firdows Noor, Candice MacDonald, Gian D. van der Spuy, Kim Stanley, Alida Carstens, Tarryn-Lee Fisher, Ilana van Rensburg, Marika Flinn, Candice Snyders, Isaac Johnson, Bernadine Fransman, Hazel Dockrell, Guy Thwaites, Nguyen Thuy Thuong Thuong, Claudia Schacht, Harriet Mayanja-Kizza, Mary Nsereko, Elisa M. Tjon Kon Fat, Paul L. A. M. Corstjens, Annemieke Geluk, Morton Ruhwald, Adam Penn-Nicholson, Novel Chegou, Jayne Sutherland, Gerhard Walzl
Summary: To improve TB diagnosis, WHO is calling for a non-sputum based triage test to focus testing on high-risk individuals. The TriageTB study aims to assess the accuracy of diagnostic test candidates and validate a multi-biomarker point-of-care test. By targeting confirmatory testing to those with a positive triage test, diagnostic costs can be reduced and TB care improved.
BMC INFECTIOUS DISEASES
(2023)
Letter
Immunology
Caroline M. Williams, Michael R. Barer, Jayne S. Sutherland, Pranabashis Haldar
CLINICAL INFECTIOUS DISEASES
(2023)
Letter
Infectious Diseases
O. A. Owolabi, A. K. Sillah, I. Loum, A. Touray, M. D. Genekah, F. Sathar, O. Ivanova, A. Rachow, D. Evans, J. S. Sutherland
INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
(2023)
Article
Statistics & Probability
Jelle J. Goeman, Pawel Gorecki, Ramin Monajemi, Xu Chen, Thomas E. Nichols, Wouter Weeda
Summary: Cluster inference based on spatial extent thresholding is a popular method for analyzing multiple testing in spatial data, commonly used in neuroimaging to identify activated brain areas. This paper addresses some limitations of the method by introducing a closed testing procedure that allows for inference of signal presence and quantification of activation percentage in regions of interest. The proposed method does not require adjustment of alpha-level and maintains family-wise error control.
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY
(2023)
Article
Multidisciplinary Sciences
Simone A. Joosten, Mark J. R. Smeets, M. Sesmu Arbous, Judith Mannien, Sander Laverman, Merijn M. G. Driessen, Suzanne C. Cannegieter, Anna H. E. Roukens
Summary: The Severity of COronavirus Disease Assessment (SCODA) score is developed to track the disease severity of hospitalized COVID-19 patients. It includes parameters related to breathing and oxygenation, and has been applied to the BEAT-COVID cohort to describe the severity of COVID-19 and determine the timing of clinical recovery. This score enhances understanding of the pathophysiology of COVID-19 and evaluation of interventions.
Article
Immunology
Tessa R. Cornell, Dawda Jobe, Simon Donkor, Daniel G. Wootton, Gina Pinchbeck, Jayne S. Sutherland, Claire Elizabeth Scantlebury
Summary: This baseline study provides evidence of Histoplasma seropositivity in TB patients in The Gambia and explores risk factors for exposure. The small sample size and use of the LAT in TB and HIV-positive patient groups are significant study limitations. Future research directions are proposed to ascertain the burden of Histoplasma in general and patient populations and explore the context-specific risk factors for exposure and infection in The Gambia.
OPEN FORUM INFECTIOUS DISEASES
(2023)