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Article: Bovine Tuberculosis: A Re-emerging Zoonotic Infection

Quadri, Nasreen S. / Brihn, Auguste / Shah, Javeed A. / Kirsch, Jonathan D

Journal of agromedicine. 2021 July 03, v. 26, no. 3

2021

Abstract: Bovine tuberculosis is caused by Mycobacterium bovis (M. bovis), which infects both humans and cattle. In 2018, a dairy farm in Wisconsin was affected by M. bovis, including a farmworker with exposure to the affected herd. Largely eradicated by effective ...

Abstract	Bovine tuberculosis is caused by Mycobacterium bovis (M. bovis), which infects both humans and cattle. In 2018, a dairy farm in Wisconsin was affected by M. bovis, including a farmworker with exposure to the affected herd. Largely eradicated by effective public health strategies in the United States, most cases are now associated with risk factors including occupational hazards, food consumption, and iatrogenic infections. M. bovis continues to cause disease worldwide affecting certain at-risk populations in the United States. Infections more often result in extrapulmonary sequelae and resistance to pyrazinamide is universal. Thus, successful treatment depends on early and correct identification of the mycobacterium species. A One Health approach to control this re-emerging disease is crucial.
Keywords	Mycobacterium bovis ; One Health initiative ; agromedicine ; bovine tuberculosis ; cattle ; complications (disease) ; dairy farming ; farm labor ; food consumption ; herds ; public health ; zoonoses ; Wisconsin
Language	English
Dates of publication	2021-0703
Size	p. 334-339.
Publishing place	Taylor & Francis
Document type	Article
ZDB-ID	1289325-0
ISSN	1545-0813 ; 1059-924X
ISSN (online)	1545-0813
ISSN	1059-924X
DOI	10.1080/1059924X.2020.1771497
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Bovine Tuberculosis: A Re-emerging Zoonotic Infection.

Quadri, Nasreen S / Brihn, Auguste / Shah, Javeed A / Kirsch, Jonathan D

Journal of agromedicine

2020 Volume 26, Issue 3, Page(s) 334–339

Abstract: Bovine tuberculosis is caused ... ...

Abstract	Bovine tuberculosis is caused by
MeSH term(s)	Animals ; Cattle ; Farmers ; Humans ; Mycobacterium bovis ; Public Health ; Tuberculosis, Bovine/epidemiology ; Zoonoses/epidemiology
Language	English
Publishing date	2020-06-01
Publishing country	England
Document type	Journal Article
ZDB-ID	1289325-0
ISSN	1545-0813 ; 1059-924X
ISSN (online)	1545-0813
ISSN	1059-924X
DOI	10.1080/1059924X.2020.1771497
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Article ; Online: Nontuberculous Mycobacteria and Heterologous Immunity to Tuberculosis.

Shah, Javeed A / Lindestam Arlehamn, Cecilia S / Horne, David J / Sette, Alessandro / Hawn, Thomas R

The Journal of infectious diseases

2019 Volume 220, Issue 7, Page(s) 1091–1098

Abstract: Development of an improved tuberculosis (TB) vaccine is a high worldwide public health priority. Bacillus Calmette-Guerin (BCG), the only licensed TB vaccine, provides variable efficacy against adult pulmonary TB, but why this protection varies is ... ...

Abstract	Development of an improved tuberculosis (TB) vaccine is a high worldwide public health priority. Bacillus Calmette-Guerin (BCG), the only licensed TB vaccine, provides variable efficacy against adult pulmonary TB, but why this protection varies is unclear. Humans are regularly exposed to non-tuberculous mycobacteria (NTM) that live in soil and water reservoirs and vary in different geographic regions around the world. Immunologic cross-reactivity may explain disparate outcomes of BCG vaccination and susceptibility to TB disease. Evidence supporting this hypothesis is increasing but challenging to obtain due to a lack of reliable research tools. In this review, we describe the progress and bottlenecks in research on NTM epidemiology, immunology and heterologous immunity to Mtb. With ongoing efforts to develop new vaccines for TB, understanding the effect of NTM on vaccine efficacy may be a critical determinant of success.
MeSH term(s)	Adult ; Animals ; BCG Vaccine/immunology ; Humans ; Immunity, Cellular ; Immunity, Heterologous ; Mycobacterium Infections, Nontuberculous/diagnosis ; Mycobacterium Infections, Nontuberculous/epidemiology ; Mycobacterium tuberculosis/immunology ; Nontuberculous Mycobacteria/immunology ; Tuberculosis, Pulmonary/immunology ; Vaccination
Chemical Substances	BCG Vaccine
Language	English
Publishing date	2019-06-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiz285
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Article ; Online: TOLLIP inhibits lipid accumulation and the integrated stress response in alveolar macrophages to control Mycobacterium tuberculosis infection.

Venkatasubramanian, Sambasivan / Plumlee, Courtney R / Dill-McFarland, Kimberly A / Cohen, Sara B / Gern, Benjamin H / Rane, Divya A / Meyer, Mackenzie K / Saha, Aparajita / Hinderstein, Sarah A / Pearson, Gemma L / Lietzke, Anne C / Pacheco, Amanda / Chow, Yu-Hua / Hung, Chi F / Soleimanpour, Scott A / Altman, Matthew / Urdahl, Kevin B / Shah, Javeed A

Nature microbiology

2024 Volume 9, Issue 4, Page(s) 949–963

Abstract: A polymorphism causing deficiencies in Toll-interacting protein (TOLLIP), an inhibitory adaptor protein affecting endosomal trafficking, is associated with increased tuberculosis (TB) risk. It is, however, unclear how TOLLIP affects TB pathogenesis. Here ...

Abstract	A polymorphism causing deficiencies in Toll-interacting protein (TOLLIP), an inhibitory adaptor protein affecting endosomal trafficking, is associated with increased tuberculosis (TB) risk. It is, however, unclear how TOLLIP affects TB pathogenesis. Here we show that TB severity is increased in Tollip
MeSH term(s)	Animals ; Mice ; Macrophages, Alveolar/microbiology ; Tuberculosis/microbiology ; Mycobacterium tuberculosis/physiology ; Macrophages/microbiology ; Lipids ; Intracellular Signaling Peptides and Proteins/metabolism
Chemical Substances	Lipids ; Tollip protein, mouse ; Intracellular Signaling Peptides and Proteins
Language	English
Publishing date	2024-03-25
Publishing country	England
Document type	Journal Article
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-024-01641-w
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Article ; Online: Molecular detection of pre-ribosomal RNAs of Mycobacterium bovis bacille Calmette-Guérin and Mycobacterium tuberculosis to enhance pre-clinical tuberculosis drug and vaccine development.

Chang, Ming / Venkatasubramanian, Sambasivan / Barrett, Holly / Urdahl, Kevin B / Weigel, Kris M / Cangelosi, Gerard A / Shah, Javeed A / Saha, Aparajita / Feng, Libing / Adams, Kristin N / Sherman, David R / Smith, Nahum / Seshadri, Chetan / Kublin, James G / Murphy, Sean C

Diagnostic microbiology and infectious disease

2023 Volume 108, Issue 1, Page(s) 116106

Abstract: Efforts are underway globally to develop effective vaccines and drugs against M. tuberculosis (Mtb) to reduce the morbidity and mortality of tuberculosis. Improving detection of slow-growing mycobacteria could simplify and accelerate efficacy studies of ... ...

Abstract	Efforts are underway globally to develop effective vaccines and drugs against M. tuberculosis (Mtb) to reduce the morbidity and mortality of tuberculosis. Improving detection of slow-growing mycobacteria could simplify and accelerate efficacy studies of vaccines and drugs in animal models and human clinical trials. Here, a real-time reverse transcription PCR (RT-PCR) assay was developed to detect pre-ribosomal RNA (pre-rRNA) of Mycobacterium bovis bacille Calmette-Guérin (BCG) and Mtb. This pre-rRNA biomarker is indicative of bacterial viability. In two different mouse models, the presence of pre-rRNA from BCG and Mtb in ex vivo tissues showed excellent agreement with slower culture-based colony-forming unit assays. The addition of a brief nutritional stimulation prior to molecular viability testing further differentiated viable but dormant mycobacteria from dead mycobacteria. This research has set the stage to evaluate pre-rRNA as a BCG and/or Mtb infection biomarker in future drug and vaccine clinical studies.
MeSH term(s)	Animals ; Mice ; Humans ; Mycobacterium bovis/genetics ; Mycobacterium tuberculosis/genetics ; BCG Vaccine ; RNA Precursors ; Tuberculosis/diagnosis ; Tuberculosis/prevention & control ; Vaccine Development ; Biomarkers
Chemical Substances	BCG Vaccine ; RNA Precursors ; Biomarkers
Language	English
Publishing date	2023-10-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	604920-5
ISSN	1879-0070 ; 0732-8893
ISSN (online)	1879-0070
ISSN	0732-8893
DOI	10.1016/j.diagmicrobio.2023.116106
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Article ; Online: TOLLIP Optimizes Dendritic Cell Maturation to Lipopolysaccharide and

Venkatasubramanian, Sambasivan / Pryor, Robyn / Plumlee, Courtney / Cohen, Sarah B / Simmons, Jason D / Warr, Alexander J / Graustein, Andrew D / Saha, Aparajita / Hawn, Thomas R / Urdahl, Kevin B / Shah, Javeed A

Journal of immunology (Baltimore, Md. : 1950)

2022 Volume 209, Issue 3, Page(s) 435–445

Abstract: TOLLIP is a central regulator of multiple innate immune signaling pathways, including TLR2, TLR4, IL-1R, and STING. Human TOLLIP deficiency, regulated by single-nucleotide polymorphism rs5743854, is associated with increased tuberculosis risk and ... ...

Abstract	TOLLIP is a central regulator of multiple innate immune signaling pathways, including TLR2, TLR4, IL-1R, and STING. Human TOLLIP deficiency, regulated by single-nucleotide polymorphism rs5743854, is associated with increased tuberculosis risk and diminished frequency of bacillus Calmette-Guérin vaccine-specific CD4
MeSH term(s)	Animals ; Humans ; Mice ; BCG Vaccine ; CD40 Antigens ; Dendritic Cells ; Interleukin-12/metabolism ; Intracellular Signaling Peptides and Proteins/metabolism ; Lipopolysaccharides/metabolism ; Mice, Inbred C57BL ; Mycobacterium tuberculosis ; Tuberculosis
Chemical Substances	BCG Vaccine ; CD40 Antigens ; Interleukin-12 (187348-17-0) ; Intracellular Signaling Peptides and Proteins ; Lipopolysaccharides ; TOLLIP protein, human ; Tollip protein, mouse
Language	English
Publishing date	2022-07-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2200030
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Article ; Online: New tricks for old dogs: countering antibiotic resistance in tuberculosis with host-directed therapeutics.

Hawn, Thomas R / Shah, Javeed A / Kalman, Daniel

Immunological reviews

2014 Volume 264, Issue 1, Page(s) 344–362

Abstract: Despite the availability of Mycobacterium tuberculosis (Mtb) drugs for over 50 years, tuberculosis (TB) remains at pandemic levels. New drugs are urgently needed for resistant strains, shortening duration of treatment, and targeting different stages of ... ...

Abstract	Despite the availability of Mycobacterium tuberculosis (Mtb) drugs for over 50 years, tuberculosis (TB) remains at pandemic levels. New drugs are urgently needed for resistant strains, shortening duration of treatment, and targeting different stages of the disease, especially for treatment during human immunodeficiency virus co-infection. One solution to the conundrum that antibiotics kill the bacillus yet select for resistance is to target the host rather than the pathogen. Here, we discuss recent progress in so-called 'host-directed therapeutics' (HDTs), focusing on two general mechanistic strategies: (i) HDTs that disrupt Mtb pathogenesis in macrophages and (ii) immunomodulatory HDTs that facilitate protective immune responses that kill Mtb or reduce deleterious responses that exacerbate disease. HDTs hold significant promise as adjunctive therapies in that they are less likely to engender resistance, will likely have efficacy against antibiotic-resistant strains, and may have activity against non-replicating Mtb. However, TB is a complex and variegated disease, and human populations exhibit significant diversity in their immune responses to it, which presents a complicated landscape for HDTs to navigate. Nevertheless, we suggest that a detailed mechanistic understanding of drug action, together with careful selection of disease stage targets and dosing strategies may overcome such limitations and allow the development of HDTs as effective adjunctive treatment options for TB.
MeSH term(s)	Animals ; Antitubercular Agents/pharmacology ; Antitubercular Agents/therapeutic use ; Autophagy ; Carbohydrate Metabolism/drug effects ; Cytokines/metabolism ; Drug Resistance, Bacterial ; Eicosanoids/metabolism ; Host-Pathogen Interactions ; Humans ; Immunity, Innate/drug effects ; Lipid Metabolism/drug effects ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/physiology ; Precision Medicine ; Tuberculosis/drug therapy ; Tuberculosis/immunology ; Tuberculosis/microbiology
Chemical Substances	Antitubercular Agents ; Cytokines ; Eicosanoids
Language	English
Publishing date	2014-10-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.12255
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Article ; Online: Mycobacterium tuberculosis infection, immune activation, and risk of HIV acquisition.

Bender Ignacio, Rachel A / Long, Jessica / Saha, Aparajita / Nguyen, Felicia K / Joudeh, Lara / Valinetz, Ethan / Mendelsohn, Simon C / Scriba, Thomas J / Hatherill, Mark / Janes, Holly / Churchyard, Gavin / Buchbinder, Susan / Duerr, Ann / Shah, Javeed A / Hawn, Thomas R

PloS one

2022 Volume 17, Issue 5, Page(s) e0267729

Abstract: Background: Although immune activation is associated with HIV acquisition, the nature of inflammatory profiles that increase HIV risk, which may include responses to M. tuberculosis (Mtb) infection, are not well characterized.: Methods: We conducted ... ...

Abstract	Background: Although immune activation is associated with HIV acquisition, the nature of inflammatory profiles that increase HIV risk, which may include responses to M. tuberculosis (Mtb) infection, are not well characterized. Methods: We conducted a nested case-control study using cryopreserved samples from persons who did and did not acquire HIV during the multinational Step clinical trial of the MRKAd5 HIV-1 vaccine. PBMCs from the last HIV-negative sample from incident HIV cases and controls were stimulated with Mtb-specific antigens (ESAT-6/CFP-10) and analyzed by flow cytometry with intracellular cytokine staining and scored with COMPASS. We measured inflammatory profiles with five Correlates of TB Risk (CoR) transcriptomic signatures. Our primary analysis examined the association of latent Mtb infection (LTBI; IFNγ+CD4+ T cell frequency) or RISK6 CoR signature with HIV acquisition. Conditional logistic regression analyses, adjusted for known predictors of HIV acquisition, were employed to assess whether TB-associated immune markers were associated with HIV acquisition. Results: Among 465 participants, LTBI prevalence (21.5% controls vs 19.1% cases, p = 0.51) and the RISK6 signature were not higher in those who acquired HIV. In exploratory analyses, Mtb antigen-specific polyfunctional CD4+ T cell COMPASS scores (aOR 0.96, 95% CI 0.77, 1.20) were not higher in those who acquired HIV. Two CoR signatures, Sweeney3 (aOR 1.38 (1.07, 1.78) per SD change) and RESPONSE5 (0.78 (0.61, 0.98)), were associated with HIV acquisition. The transcriptomic pattern used to differentiate active vs latent TB (Sweeney3) was most strongly associated with acquiring HIV. Conclusions: LTBI, Mtb polyfunctional antigen-specific CD4+ T cell activation, and RISK6 were not identified as risks for HIV acquisition. In exploratory transcriptomic analyses, two CoR signatures were associated with HIV risk after adjustment for known behavioral and clinical risk factors. We identified host gene expression signatures associated with HIV acquisition, but the observed effects are likely not mediated through Mtb infection.
MeSH term(s)	Antigens, Bacterial ; CD4-Positive T-Lymphocytes ; Case-Control Studies ; HIV Infections/complications ; Humans ; Latent Tuberculosis ; Mycobacterium tuberculosis ; Tuberculosis/complications
Chemical Substances	Antigens, Bacterial
Language	English
Publishing date	2022-05-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0267729
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Article ; Online: A CD4+ TNF+ monofunctional memory T-cell response to BCG vaccination is associated with Mycobacterium tuberculosis infection in infants exposed to HIV.

Warr, Alex J / Anterasian, Christine / Shah, Javeed A / De Rosa, Stephen C / Nguyen, Felicia K / Maleche-Obimbo, Elizabeth / Cranmer, Lisa M / Matemo, Daniel / Mecha, Jerphason / Kinuthia, John / LaCourse, Sylvia M / John-Stewart, Grace C / Hawn, Thomas R

EBioMedicine

2022 Volume 80, Page(s) 104023

Abstract: Background: The immunologic correlates of risk of Mycobacterium tuberculosis (Mtb) infection after BCG vaccination are unknown. The mechanism by which BCG influences the tuberculin skin test (TST) remains poorly understood. We evaluated CD4+ T-cell ... ...

Abstract	Background: The immunologic correlates of risk of Mycobacterium tuberculosis (Mtb) infection after BCG vaccination are unknown. The mechanism by which BCG influences the tuberculin skin test (TST) remains poorly understood. We evaluated CD4+ T-cell responses in infants exposed to HIV and uninfected (HEU) who received BCG at birth and examined their role in susceptibility to Mtb infection and influence on TST induration. Methods: HEU infants were enrolled in a randomised clinical trial of isoniazid (INH) to prevent Mtb infection in Kenya. We measured mycobacterial antigen-specific Th1 and Th17 cytokine responses at 6-10 weeks of age prior to INH randomisation and compared responses between Mtb infected and uninfected infants. Outcomes at 14 months of age included TST, QuantiFERON-Plus (QFT-Plus), and ESAT-6/CFP-10-specific non-IFN-γ cytokines measured in QFT-Plus supernatants. Findings: A monofunctional mycobacterial antigen-specific TNF+ CD4+ effector memory (CCR7-CD45RA-) T-cell response at 6-10 weeks of age was associated with Mtb infection at 14 months of age as measured by ESAT-6/CFP-10-specific IFN-γ and non-IFN-γ responses (Odds Ratio 2.26; Confidence Interval 1.27-4.15; P = 0.006). Mycobacterial antigen-specific polyfunctional effector memory Th1 responses at 6-10 weeks positively correlated with TST induration in infants without evidence of Mtb infection at 14 months, an association which was diminished by INH therapy. Interpretation: Induction of monofunctional TNF+ CD4+ effector memory T-cell responses may be detrimental in TB vaccine development. This study also provides mechanistic insight into the association of BCG-induced immune responses with TST induration and further evidence that TST-based diagnoses of Mtb infection in infants are imprecise. Funding: Thrasher Research Fund.
MeSH term(s)	Antitubercular Agents/administration & dosage ; BCG Vaccine/administration & dosage ; BCG Vaccine/immunology ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/immunology ; Cytokines/immunology ; HIV Infections/immunology ; HIV Infections/microbiology ; Humans ; Infant ; Infant, Newborn ; Isoniazid/administration & dosage ; Memory T Cells/drug effects ; Memory T Cells/immunology ; Mycobacterium tuberculosis ; Tuberculosis/diagnosis ; Tuberculosis/immunology ; Tuberculosis/prevention & control ; Tuberculosis/virology ; Tumor Necrosis Factor-alpha/immunology
Chemical Substances	Antitubercular Agents ; BCG Vaccine ; Cytokines ; Tumor Necrosis Factor-alpha ; Isoniazid (V83O1VOZ8L)
Language	English
Publishing date	2022-05-06
Publishing country	Netherlands
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2022.104023
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Article ; Online: BMI and Outcomes of SARS-CoV-2 Among US Veterans.

Eastment, McKenna C / Berry, Kristin / Locke, Emily / Green, Pamela / O'Hare, Ann / Crothers, Kristina / Dominitz, Jason A / Fan, Vincent S / Shah, Javeed A / Ioannou, George N

Obesity (Silver Spring, Md.)

2021 Volume 29, Issue 5, Page(s) 900–908

Abstract: Objective: The purpose of this study is to examine the associations of BMI with testing positive for severe acute respiratory coronavirus 2 (SARS-CoV-2) and risk of adverse outcomes in a cohort of Veterans Affairs enrollees.: Method: Adjusted ... ...

Abstract	Objective: The purpose of this study is to examine the associations of BMI with testing positive for severe acute respiratory coronavirus 2 (SARS-CoV-2) and risk of adverse outcomes in a cohort of Veterans Affairs enrollees. Method: Adjusted relative risks/hazard ratios (HRs) were calculated for the associations between BMI category (underweight, normal weight, overweight, class 1 obesity, class 2 obesity, and class 3 obesity) and testing positive for SARS-CoV-2 or experiencing hospitalization, intensive care unit admission, mechanical ventilation, and death among those testing positive. Results: Higher BMI categories were associated with higher risk of a positive SARS-CoV-2 test compared with the normal weight category (class 3 obesity adjusted relative risk: 1.34, 95% CI: 1.28-1.42). Among 25,952 patients who tested positive for SARS-CoV-2, class 3 obesity was associated with higher risk of mechanical ventilation (adjusted HR [aHR]: 1.77, 95% CI: 1.35-2.32) and mortality (aHR: 1.42, 95% CI: 1.12-1.78) compared with normal weight individuals. These associations were present primarily in patients younger than 65 and were attenuated or absent in older age groups (interaction P < 0.05). Conclusion: Veterans Affairs enrollees with higher BMI were more likely to test positive for SARS-CoV-2 and were more likely to be mechanically ventilated or die if infected with SARS-CoV-2. Higher BMI contributed relatively more to the risk of death in those younger than 65 years of age as compared with other age categories.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Body Mass Index ; COVID-19/complications ; COVID-19/epidemiology ; COVID-19/mortality ; Cohort Studies ; Female ; Hospitalization ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Obesity/complications ; Proportional Hazards Models ; Respiration, Artificial ; Risk Factors ; Veterans/statistics & numerical data ; Young Adult
Language	English
Publishing date	2021-03-17
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2230457-5
ISSN	1930-739X ; 1071-7323 ; 1930-7381
ISSN (online)	1930-739X
ISSN	1071-7323 ; 1930-7381
DOI	10.1002/oby.23111
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