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1. A stool based qPCR for the diagnosis of TB in children and people living with HIV in Uganda, Eswatini and Mozambique (Stool4TB): a protocol for a multicenter diagnostic evaluation

Author

Carratala-Castro, Lucia, Ssengooba, Willy, Kay, Alex, Acácio, Sozinho, Ehrlich, Joanna, DiNardo, Andrew R, Shiba, Nosisa, Nsubuga, Joachim K, Munguambe, Shilzia, Saavedra-Cervera, Belén, Manjate, Patricia, Mulengwa, Durbbin, Sibandze, Busizwe, Ziyane, Mangaliso, Kasule, George, Mambuque, Edson, Sekadde, Moorine Penninah, Wobudeya, Eric, Joloba, Moses L, Heyckendorf, Jan, Lange, Christoph, Hermans, Sabine, Mandalakas, Anna, García-Basteiro, Alberto L., and Lopez-Varela, Elisa

Published
2024
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4. Update on the diagnosis of tuberculosis

Author

Kontsevaya, Irina, Cabibbe, Andrea Maurizio, Cirillo, Daniela Maria, DiNardo, Andrew R., Frahm, Nicole, Gillespie, Stephen H., Holtzman, David, Meiwes, Lennard, Petruccioli, Elisa, Reimann, Maja, Ruhwald, Morten, Sabiiti, Wilber, Saluzzo, Francesca, Tagliani, Elisa, and Goletti, Delia

Published
2024
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5. Performance of a stool-based quantitative PCR assay for the diagnosis of tuberculosis in adolescents and adults: a multinational, prospective diagnostic accuracy study

Author

Kay, Alexander, Vasiliu, Anca, Carratala-Castro, Lucia, Mtafya, Bariki, Mendez Reyes, Jose Euberto, Maphalala, Nontobeko, Munguambe, Shilzia, Mulengwa, Durbbin, Ness, Tara, Saavedra, Belen, Bacha, Jason, Maphalala, Gugu, Mejia, Rojelio, Mtetwa, Godwin, Acacio, Sozinho, Manjate, Patricia, Mambuque, Edson, Shiba, Nosisa, Kota, Nokwanda, Ziyane, Mangaliso, Ntinginya, Nyanda Elias, Lange, Christoph, Kirchner, H Lester, DiNardo, Andrew R, Garcia-Basteiro, Alberto L, and Mandalakas, Anna Maria

Published
2024
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6. Bacillus Calmette-Guérin vaccination as defense against SARS-CoV-2 (BADAS): a randomized controlled trial to protect healthcare workers in the USA by enhanced trained immune responses

Author

DiNardo, Andrew R., Arditi, Moshe, Kamat, Ashish M., Koster, Kent J., Carrero, Santiago, Nishiguchi, Tomoki, Lebedev, Maxim, Benjamin, Aaron B., Avalos, Pablo, Lozano, Marisa, Moule, Madeleine G., McCune, Brittany, Herron, Baysia, Ladki, Malik, Sheikh, Daanish, Spears, Matthew, Herrejon, Ivan A., Dodge, Courtney, Kumar, Sathish, Hutchison, Robert W., Ofili, Theresa U., Opperman, Lynne A., Bernard, Jessica A., Lerner, Seth P., Udeani, George, Neal, Gabriel, Netea, Mihai G., and Cirillo, Jeffrey D.

Published
2023
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7. Performance of a Novel Stool Quantitative Polymerase Chain Reaction Assay for Pediatric Tuberculosis Detection in Sub-Saharan Africa

Author

Vasiliu, Anca, primary, Carratala-Castro, Lucia, additional, Seeger, Abigail, additional, Ehrlich, Joanna, additional, Nkala, Babongile, additional, Ness, Tara, additional, Cumbe, Miguel Mario, additional, Mulengwa, Durbbin, additional, Munguambe, Shilzia, additional, Mtafya, Bariki, additional, Mambuque, Edson, additional, Shiba, Nosisa, additional, Acacio, Sozinho, additional, Komba, Lilian, additional, Adu-Gyamfi, Clement Gascua, additional, Kirchner, Lester H., additional, Lange, Christoph, additional, DiNardo, Andrew R., additional, Garcia-Basteiro, Alberto, additional, Mandalakas, Anna, additional, and Kay, Alexander, additional

Published
2024
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9. Trained immunity, tolerance, priming and differentiation: distinct immunological processes

Author

Divangahi, Maziar, Aaby, Peter, Khader, Shabaana Abdul, Barreiro, Luis B., Bekkering, Siroon, Chavakis, Triantafyllos, van Crevel, Reinout, Curtis, Nigel, DiNardo, Andrew R., Dominguez-Andres, Jorge, Duivenvoorden, Raphael, Fanucchi, Stephanie, Fayad, Zahi, Fuchs, Elaine, Hamon, Melanie, Jeffrey, Kate L., Khan, Nargis, Joosten, Leo A. B., Kaufmann, Eva, Latz, Eicke, Matarese, Giuseppe, van der Meer, Jos W. M., Mhlanga, Musa, Moorlag, Simone J. C. F. M., Mulder, Willem J. M., Naik, Shruti, Novakovic, Boris, O’Neill, Luke, Ochando, Jordi, Ozato, Keiko, Riksen, Niels P., Sauerwein, Robert, Sherwood, Edward R., Schlitzer, Andreas, Schultze, Joachim L., Sieweke, Michael H., Benn, Christine Stabell, Stunnenberg, Henk, Sun, Joseph, van de Veerdonk, Frank L., Weis, Sebastian, Williams, David L., Xavier, Ramnik, and Netea, Mihai G.

Published
2021
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10. Stool based qPCR for the diagnosis of TB in children and people living with HIV in Uganda, Eswatini and Mozambique (Stoo4TB): a protocol for a multicenter diagnostic evaluation

Author

Carratala-Castro, Lucia, primary, Ssengooba, Willy, additional, Kay, Alexander, additional, Acacio, Sozinho, additional, Ehrlich, Joanna, additional, DiNardo, Andrew R, additional, Shiba, Nosisa, additional, Nsubuga, Joachim K, additional, Munguambe, Shilzia, additional, Saavedra, Belen, additional, Mandjate, Patricia, additional, Mulengwa, Durbbin, additional, Sibandze, Busizwe, additional, Ziyane, Mangaliso, additional, Kasule, Gerorge, additional, Mambuque, Edson, additional, Sekadde, Moorine Penninah, additional, Wobudeya, Eric, additional, Joloba, Moses L, additional, Heyckendorf, Jan, additional, Lange, Christoff, additional, Hermans, Sabine, additional, Mandalakas, Anna, additional, Garcia-Basteiro, Alberto, additional, and Lopez-Varela, Elisa, additional

Published
2023
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11. DNA hypermethylation during tuberculosis dampens host immune responsiveness

Author

DiNardo, Andrew R., Rajapakshe, Kimal, Nishiguchi, Tomoki, Grimm, Sandra L., Mtetwa, Godwin, Dlamini, Qiniso, Kahari, Jaqueline, Mahapatra, Sanjana, Kay, Alexander, Maphalala, Gugu, Mace, Emily M., Makedonas, George, Cirillo, Jeffrey D., Netea, Mihai G., van Crevel, Reinout, Coarfa, Cristian, and Mandalakas, Anna M.

Subjects
BCG -- Health aspects, Genetic research -- Health aspects, Papillomavirus infections -- Health aspects, Mitogens -- Health aspects, Methylation -- Health aspects, Genes -- Health aspects, Medical research -- Health aspects, DNA -- Health aspects, Immune response -- Health aspects, Tuberculosis -- Health aspects, Gene expression -- Health aspects, Health care industry
Abstract

Mycobacterium tuberculosis (M. tuberculosis) has coevolved with humans for millennia and developed multiple mechanisms to evade host immunity. Restoring host immunity in order to improve outcomes and potentially shorten existing therapy will require identification of the full complement by which host immunity is inhibited. Perturbation of host DNA methylation is a mechanism induced by chronic infections such as HIV, HPV, lymphocytic choriomeningitis virus (LCMV), and schistosomiasis to evade host immunity. Here, we evaluated the DNA methylation status of patients with tuberculosis (TB) and their asymptomatic household contacts and found that the patients with TB have DNA hypermethylation of the IL-2/STAT5, TNF/NF-[kappa]B, and IFN-[gamma] signaling pathways. We performed methylation- sensitive restriction enzyme-quantitative PCR (MSRE-qPCR) and observed that multiple genes of the IL-12/IFN-[gamma] signaling pathway (IL12B, IL12RB2, TYK2, IFNGR1, JAK1, and JAK2) were hypermethylated in patients with TB. The DNA hypermethylation of these pathways was associated with decreased immune responsiveness with decreased mitogen-induced upregulation of IFN-[gamma], TNF, IL-6, CXCL9, CXCL10, and IL-1 p production. The DNA hypermethylation of the IL-12/IFN-[gamma] pathway was associated with decreased IFN-[gamma]-induced gene expression and decreased IL-12-inducible upregulation of IFN-[gamma]. This study demonstrates that immune cells from patients with TB are characterized by DNA hypermethylation of genes critical to mycobacterial immunity resulting in decreased mycobacteria-specific and nonspecific immune responsiveness., Introduction Tuberculosis (TB) continues to be a global problem, with 10 million cases and over 1 million deaths each year (1). Anti-TB therapy (ATT) requires 6 months of antibiotics, despite [...]

Published
2020
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12. Author Correction: Trained immunity, tolerance, priming and differentiation: distinct immunological processes

Author

Divangahi, Maziar, Aaby, Peter, Khader, Shabaana Abdul, Barreiro, Luis B., Bekkering, Siroon, Chavakis, Triantafyllos, van Crevel, Reinout, Curtis, Nigel, DiNardo, Andrew R., Dominguez-Andres, Jorge, Duivenvoorden, Raphael, Fanucchi, Stephanie, Fayad, Zahi, Fuchs, Elaine, Hamon, Melanie, Jeffrey, Kate L., Khan, Nargis, Joosten, Leo A. B., Kaufmann, Eva, Latz, Eicke, Matarese, Giuseppe, van der Meer, Jos W. M., Mhlanga, Musa, Moorlag, Simone J. C. F. M., Mulder, Willem J. M., Naik, Shruti, Novakovic, Boris, O’Neill, Luke, Ochando, Jordi, Ozato, Keiko, Riksen, Niels P., Sauerwein, Robert, Sherwood, Edward R., Schlitzer, Andreas, Schultze, Joachim L., Sieweke, Michael H., Benn, Christine Stabell, Stunnenberg, Henk, Sun, Joseph, van de Veerdonk, Frank L., Weis, Sebastian, Williams, David L., Xavier, Ramnik, and Netea, Mihai G.

Published
2021
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19. The Importance of Early Recognition of HHV8-mediated syndromes: A Case Report

Author

Spezia-Lindner, Nathaniel J, Kondapi, Divya, DiNardo, Andrew R, Ramaswami, Ramya, Chiao, Elizabeth, and Clark, Eva H

Subjects
Herpesviridae Infections, Syndrome, Middle Aged, Antiviral Agents, Article, Diagnosis, Differential, Early Diagnosis, Doxorubicin, Herpesvirus 8, Human, Humans, Immunologic Factors, Drug Therapy, Combination, Female, Rituximab
Abstract

Acute Kaposi sarcoma herpes virus (KSHV)-associated inflammatory diseases are under-recognized. We describe a woman with HIV presenting with disseminated KS and refractory shock, concerning for KSHV-associated inflammatory cytokine syndrome (KICS) versus multicentric Castelman’s disease (MCD). High-quality research and clinician education are needed to improve prognosis of patients with KSHV-associated diseases.

Published
2021

20. Pathogen-free diagnosis of tuberculosis

Author

Heyckendorf, Jan, primary, Reimann, Maja, additional, Marwitz, Sebastian, additional, Lange, Christoph, additional, Avsar, Korkut, additional, DiNardo, Andrew R., additional, Günther, Gunar, additional, Hoelscher, Michael, additional, Ibraim, Elmira, additional, Kalsdorf, Barbara, additional, Kaufmann, Stefan H.E., additional, Kontsevaya, Irina, additional, van Leth, Frank, additional, Mandalakas, Anna M., additional, Maurer, Florian, additional, Müller, Marius, additional, Nitschkowski, Dörte, additional, Olaru, Ioana D., additional, Popa, Cristina, additional, Rachow, Andrea, additional, Rolling, Thierry, additional, Rybniker, Jan, additional, Salzer, Helmut J.F., additional, Sanchez-Carballo, Patricia, additional, Schuhmann, Maren, additional, Schaub, Dagmar, additional, Spinu, Victor, additional, Suárez, Isabelle, additional, Terhalle, Elena, additional, Unnewehr, Markus, additional, Weiner, January, additional, and Goldmann, Torsten, additional

Published
2021
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21. Perspectives for systems biology in the management of tuberculosis

Author

Kontsevaya, Irina, Lange, Christoph, Comella-del-Barrio, Patricia, Coarfa, Cristian, DiNardo, Andrew R., Gillespie, Stephen H., Hauptmann, Matthias, Leschczyk, Christoph, Mandalakas, Anna M., Martinecz, Antal, Merker, Matthias, Niemann, Stefan, Reimann, Maja, Rzhepishevska, Olena, Schaible, Ulrich E., Scheu, Katrin M., Schurr, Erwin, Abel zur Wiesch, Pia, Heyckendorf, Jan, and Universitat Autònoma de Barcelona

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Tuberculosis, Systems biology, Respiratory Medicine and Allergy, 030106 microbiology, Genomics, Context (language use), Drug resistance, Disease, 03 medical and health sciences, Medicine, Humans, Metabolomics, Prospective Studies, Intensive care medicine, Lungmedicin och allergi, business.industry, Systems Biology, medicine.disease, Clinical trial, 030104 developmental biology, business, Systems pharmacology
Abstract

Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis. Here, we review the available evidence on the role of systems biology approaches - human and mycobacterial genomics and transcriptomics, proteomics, lipidomics/metabolomics, immunophenotyping, systems pharmacology and gut microbiomes - in the management of tuberculosis including prediction of risk for disease progression, severity of mycobacterial virulence and drug resistance, adverse events, comorbidities, response to therapy and treatment outcomes. Application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach demonstrated that at present most of the studies provide "very low" certainty of evidence for answering clinically relevant questions. Further studies in large prospective cohorts of patients, including randomised clinical trials, are necessary to assess the applicability of the findings in tuberculosis prevention and more efficient clinical management of patients. We are at the doorstep of a new era in which systems biology approaches will contribute to the management of patients with tuberculosis including prediction of risk for disease progression and severity, response to therapy and treatment outcome.

Published
2021

22. Perspectives for systems biology in the management of tuberculosis

Author

Kontsevaya, Irina, primary, Lange, Christoph, additional, Comella-del-Barrio, Patricia, additional, Coarfa, Cristian, additional, DiNardo, Andrew R., additional, Gillespie, Stephen H., additional, Hauptmann, Matthias, additional, Leschczyk, Christoph, additional, Mandalakas, Anna M., additional, Martinecz, Antal, additional, Merker, Matthias, additional, Niemann, Stefan, additional, Reimann, Maja, additional, Rzhepishevska, Olena, additional, Schaible, Ulrich E., additional, Scheu, Katrin M., additional, Schurr, Erwin, additional, Abel zur Wiesch, Pia, additional, and Heyckendorf, Jan, additional

Published
2021
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23. Prediction of anti-tuberculosis treatment duration based on a 22-gene transcriptomic model

Author

Heyckendorf, Jan, primary, Marwitz, Sebastian, additional, Reimann, Maja, additional, Avsar, Korkut, additional, DiNardo, Andrew R., additional, Günther, Gunar, additional, Hoelscher, Michael, additional, Ibraim, Elmira, additional, Kalsdorf, Barbara, additional, Kaufmann, Stefan H.E., additional, Kontsevaya, Irina, additional, van Leth, Frank, additional, Mandalakas, Anna M., additional, Maurer, Florian P., additional, Müller, Marius, additional, Nitschkowski, Dörte, additional, Olaru, Ioana D., additional, Popa, Cristina, additional, Rachow, Andrea, additional, Rolling, Thierry, additional, Rybniker, Jan, additional, Salzer, Helmut J.F., additional, Sanchez-Carballo, Patricia, additional, Schuhmann, Maren, additional, Schaub, Dagmar, additional, Spinu, Victor, additional, Suárez, Isabelle, additional, Terhalle, Elena, additional, Unnewehr, Markus, additional, Weiner, January, additional, Goldmann, Torsten, additional, and Lange, Christoph, additional

Published
2021
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26. Discerning divergent tuberculosis endotypes: A meta-analysis and systematic review of individual patient data

Author

DiNardo, Andrew R, Rajapakshe, Kimal, Gandhi, Tanmay, Grimm, Sandra, Nishiguchi, Tomoki, Heyckendorf, Jan, Kahari, Jaqueline, Dlamini, Qiniso, Lange, Christoph, Cirillo, jeffrey D, Kaufmann, Stefan, van Crevel, Reinout R, Netea, Mihai G, Mandalakas, Anna M, and Coarfa, Cristian

Abstract

Rationale: Host response is a critical factor determining susceptibility to tuberculosis (TB). A delicate balance should be maintained between intracellular immunity against Mycobacterium tuberculosis (Mtb) and minimizing detrimental immunopathology. Studies have identified incongruous immune responses that can lead to a similar TB disease phenotype. Instead of envisioning that susceptibility to TB follows a singular path, we propose the hypothesis that varied host endotypes exist within the TB clinical phenotype. Methods and Results: Unbiased clustering analysis from 12 publicly available gene expression datasets consisting of data from 717 TB patients and 527 controls, identified 4 TB patient endotypes with distinct immune responses. The two largest endotypes exhibit divergent metabolic, epigenetic and immune pathways. TB patient endotype A, comprising 333 TB patients (46.4%), is characterized by increased expression of genes important for i) glycolysis, ii) IL-2-STAT5, IL-6-STAT3, Type I and II Interferon IFN-γ and TNF signaling and iii) epigenetic-modifying genes. In contrast, TB patient endotype B, comprising 313 TB patients (43.6%), is characterized by i) upregulated NFAT and hormone metabolism, and ii) decreased glycolysis, IFN-γ and TNF signaling. In silico evaluation suggests therapies beneficial for endotype A could be detrimental to endotype B, and vice versa. Multiplex ELISA completed from an external validation cohort confirmed a TB patient sub-group with decreased immune upregulation. Conclusions: Host immunity to TB is heterogenous. Unbiased clustering analysis identified distinct TB endotypes with divergent metabolic, epigenetic and immune gene expression profiles that may enable stratified or personalized treatment management in the future.

Published
2020
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27. Perspective for Precision Medicine for Tuberculosis

Author

Lange, Christoph, Aarnoutse, Rob, Chesov, Dumitru, van Crevel, Reinout, Gillespie, Stephen H., Grobbel, Hans-Peter, Kalsdorf, Barbara, Kontsevaya, Irina, van Laarhoven, Arjan, Nishiguchi, Tomoki, Mandalakas, Anna, Merker, Matthias, Niemann, Stefan, Köhler, Niklas, Heyckendorf, Jan, Reimann, Maja, Ruhwald, Morten, Sanchez-Carballo, Patricia, Schwudke, Dominik, Waldow, Franziska, and DiNardo, Andrew R.

Subjects
mycobacterial genotypes, Mini Review, precision medicine, Immunology, Antitubercular Agents, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Mycobacterium tuberculosis, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], tailor-made regimen, endotypes, tuberculosis, Animals, Humans, Immunology and Allergy
Abstract

Contains fulltext : 229189.pdf (Publisher’s version ) (Open Access) Tuberculosis is a bacterial infectious disease that is mainly transmitted from human to human via infectious aerosols. Currently, tuberculosis is the leading cause of death by an infectious disease world-wide. In the past decade, the number of patients affected by tuberculosis has increased by ~20 percent and the emergence of drug-resistant strains of Mycobacterium tuberculosis challenges the goal of elimination of tuberculosis in the near future. For the last 50 years, management of patients with tuberculosis has followed a standardized management approach. This standardization neglects the variation in human susceptibility to infection, immune response, the pharmacokinetics of drugs, and the individual duration of treatment needed to achieve relapse-free cure. Here we propose a package of precision medicine-guided therapies that has the prospect to drive clinical management decisions, based on both host immunity and M. tuberculosis strains genetics. Recently, important scientific discoveries and technological advances have been achieved that provide a perspective for individualized rather than standardized management of patients with tuberculosis. For the individual selection of best medicines and host-directed therapies, personalized drug dosing, and treatment durations, physicians treating patients with tuberculosis will be able to rely on these advances in systems biology and to apply them at the bedside.

Published
2020

28. Trained immunity, tolerance, priming and differentiation: distinct immunological processes

Author

Divangahi, Maziar, primary, Aaby, Peter, additional, Khader, Shabaana Abdul, additional, Barreiro, Luis B., additional, Bekkering, Siroon, additional, Chavakis, Triantafyllos, additional, van Crevel, Reinout, additional, Curtis, Nigel, additional, DiNardo, Andrew R., additional, Dominguez-Andres, Jorge, additional, Duivenvoorden, Raphael, additional, Fanucchi, Stephanie, additional, Fayad, Zahi, additional, Fuchs, Elaine, additional, Hamon, Melanie, additional, Jeffrey, Kate L., additional, Khan, Nargis, additional, Joosten, Leo A. B., additional, Kaufmann, Eva, additional, Latz, Eicke, additional, Matarese, Giuseppe, additional, van der Meer, Jos W. M., additional, Mhlanga, Musa, additional, Moorlag, Simone J. C. F. M., additional, Mulder, Willem J. M., additional, Naik, Shruti, additional, Novakovic, Boris, additional, O’Neill, Luke, additional, Ochando, Jordi, additional, Ozato, Keiko, additional, Riksen, Niels P., additional, Sauerwein, Robert, additional, Sherwood, Edward R., additional, Schlitzer, Andreas, additional, Schultze, Joachim L., additional, Sieweke, Michael H., additional, Benn, Christine Stabell, additional, Stunnenberg, Henk, additional, Sun, Joseph, additional, van de Veerdonk, Frank L., additional, Weis, Sebastian, additional, Williams, David L., additional, Xavier, Ramnik, additional, and Netea, Mihai G., additional

Published
2020
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29. Correspondence on ‘Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 mimicking Kawasaki disease (Kawa-COVID-19): a multicentre cohort’ by Pouletty et al

Author

Ventura, Meredith J, primary, Guajardo, Emmanuel, additional, Clark, Eva H, additional, Bhairavarasu, Kalpana, additional, Kherallah, Riyad Y, additional, DiNardo, Andrew R, additional, Ye, Xunyan, additional, Piedra, Pedro A, additional, Atmar, Robert L, additional, and Agarwal, Sandeep K, additional

Published
2020
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31. Persistent DNA Hyper-methylation Dampens Host Anti-Mycobacterial Immunity

Author

DiNardo, Andrew R., primary, Rajapakshe, Kimal, additional, Nishiguchi, Tomoki, additional, Mtetwa, Godwin, additional, Dlamini, Qiniso, additional, Kahari, Jaqueline, additional, Mahapatra, Sanjana, additional, Kay, Alexander, additional, Maphalala, Gugu, additional, Mace, Emily, additional, Grimm, Sandra L., additional, Makedonas, George, additional, Cirillo, Jeffrey D, additional, Netea, Mihai G., additional, van Crevel, Reinout, additional, Coarfa, Cristian, additional, and Mandalakas, Anna M., additional

Published
2019
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32. Reversing Post-Infectious Epigenetic-Mediated Immune Suppression.

Author

Abhimanyu, Ontiveros, Carlos O., Guerra-Resendez, Rosa S., Nishiguchi, Tomoki, Ladki, Malik, Hilton, Isaac B., Schlesinger, Larry S., and DiNardo, Andrew R.

Subjects
IMMUNOSUPPRESSION, PROTEIN kinases, CELL-mediated cytotoxicity, MORTALITY, HEPATITIS B, HEPATITIS C
Abstract

The immune response must balance the pro-inflammatory, cell-mediated cytotoxicity with the anti-inflammatory and wound repair response. Epigenetic mechanisms mediate this balance and limit host immunity from inducing exuberant collateral damage to host tissue after severe and chronic infections. However, following treatment for these infections, including sepsis, pneumonia, hepatitis B, hepatitis C, HIV, tuberculosis (TB) or schistosomiasis, detrimental epigenetic scars persist, and result in long-lasting immune suppression. This is hypothesized to be one of the contributing mechanisms explaining why survivors of infection have increased all-cause mortality and increased rates of unrelated secondary infections. The mechanisms that induce epigenetic-mediated immune suppression have been demonstrated in-vitro and in animal models. Modulation of the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR), nuclear factor of activated T cells (NFAT) or nuclear receptor (NR4A) pathways is able to block or reverse the development of detrimental epigenetic scars. Similarly, drugs that directly modify epigenetic enzymes, such as those that inhibit histone deacetylases (HDAC) inhibitors, DNA hypomethylating agents or modifiers of the Nucleosome Remodeling and DNA methylation (NuRD) complex or Polycomb Repressive Complex (PRC) have demonstrated capacity to restore host immunity in the setting of cancer-, LCMV- or murine sepsis-induced epigenetic-mediated immune suppression. A third clinically feasible strategy for reversing detrimental epigenetic scars includes bioengineering approaches to either directly reverse the detrimental epigenetic marks or to modify the epigenetic enzymes or transcription factors that induce detrimental epigenetic scars. Each of these approaches, alone or in combination, have ablated or reversed detrimental epigenetic marks in in-vitro or in animal models; translational studies are now required to evaluate clinical applicability. [ABSTRACT FROM AUTHOR]

Published
2021
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36. Pathogen-free diagnosis of tuberculosis

Author

Avsar, Korkut, DiNardo, Andrew R., Günther, Gunar, Hoelscher, Michael, Ibraim, Elmira, Kalsdorf, Barbara, Kaufmann, Stefan H.E., Kontsevaya, Irina, van Leth, Frank, Mandalakas, Anna M., Maurer, Florian, Müller, Marius, Nitschkowski, Dörte, Olaru, Ioana D., Popa, Cristina, Rachow, Andrea, Rolling, Thierry, Rybniker, Jan, Salzer, Helmut J.F., Sanchez-Carballo, Patricia, Schuhmann, Maren, Schaub, Dagmar, Spinu, Victor, Suárez, Isabelle, Terhalle, Elena, Unnewehr, Markus, Weiner, January, 3rd, Goldmann, Torsten, Heyckendorf, Jan, Reimann, Maja, Marwitz, Sebastian, and Lange, Christoph

Published
2021
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38. Diagnostic and Treatment Monitoring Potential of A Stool-Based Quantitative Polymerase Chain Reaction Assay for Pulmonary Tuberculosis

Author

DiNardo, Andrew R., primary, Kay, Alexander W., additional, Maphalala, Gugu, additional, Harris, Nadine M., additional, Fung, Celia, additional, Mtetwa, Godwin, additional, Ustero, Pilar, additional, Dlamini, Sindisiwe, additional, Ha, Ngan, additional, Graviss, Edward A., additional, Mejia, Rojelio, additional, and Mandalakas, Anna M., additional

Published
2018
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39. Schistosomiasis Induces Persistent DNA Methylation and Tuberculosis-Specific Immune Changes

Author

DiNardo, Andrew R., primary, Nishiguchi, Tomoki, additional, Mace, Emily M., additional, Rajapakshe, Kimal, additional, Mtetwa, Godwin, additional, Kay, Alexander, additional, Maphalala, Gugu, additional, Secor, W. Evan, additional, Mejia, Rojelio, additional, Orange, Jordan S., additional, Coarfa, Cristian, additional, Bhalla, Kapil N., additional, Graviss, Edward A., additional, Mandalakas, Anna M., additional, and Makedonas, George, additional

Published
2018
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50. 1, 2, 3 (Years) ... and You're Out: The End of a 123-year Historic Era.

Author

DiNardo, Andrew R., Lange, Christoph, and Mandalakas, Anna M.

Subjects
*TUBERCULOSIS diagnosis, *MYCOBACTERIUM tuberculosis, *DIAGNOSTIC imaging research, *MICROFLUIDIC analytical techniques, *NUCLEIC acid amplification techniques, *TUBERCULOSIS treatment, *DIAGNOSIS
Abstract

The article focuses on the study on the development of the diagnosis of tuberculosis. Topics include the introduction of the diagnostic method for Mycobacterium tuberculosis under the microscope, the development of the molecular acid-fast bacilli (AFB) microscopy techniques, and the aspect of the Gene Xpert System (Xpert), a method which uses microfluidic technology and nucleic acid amplification techniques (NAT).

Published
2016
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