ORCID Profile
0000-0003-4007-0807
Current Organisations
University of Southampton
,
University College London
,
Guy's and Saint Thomas' NHS Foundation Trust
,
University of Melbourne
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Publications
Preventing tuberculosis in paediatric kidney transplant recipients: is there a role for BCG immunisation pre-transplantation in low tuberculosis incidence countries?
Publisher: Springer Science and Business Media LLC
Date: 27-11-2020
DOI: 10.1007/S00467-020-04844-5
Abstract: The risk of tuberculosis (TB) disease is increased in children with chronic kidney disease (CKD), even higher in stage 5 CKD/kidney failure and especially high after kidney transplantation due to immunosuppression. TB disease may follow recent primary infection, or result from reactivation of latent infection. Reactivation is more common in adults, while progression following primary infection makes up a greater proportion of disease in children. Recommendations for preventing TB disease in some low TB incidence countries have previously included offering Bacillus Calmette-Guérin (BCG) vaccine to all children listed for kidney transplant if they had not received this as part of previous national immunisation programmes. Based on the available evidence, we recommend modifying this practice, focusing instead on awareness of risk factors for TB exposure, infection and disease and the use of appropriate testing strategies to identify and treat TB infection and disease.
Corticosteroids and infliximab impair the performance of interferon-γ release assays used for diagnosis of latent tuberculosis
Publisher: BMJ
Date: 03-02-2017
DOI: 10.1136/THORAXJNL-2016-209397
Abstract: The impact of immunosuppression on interferon-γ release assays and novel cytokine biomarkers of TB infection, mycobacteria-specific IL-2, IP-10 and TNF-α responses was investigated in an ex vivo model. Cytokine responses in standard QuantiFERON-TB Gold in-Tube (QFT-GIT) assays were compared with duplicate assays containing dexamethasone or infliximab. Dexamethasone converted QFT-GIT results from positive to negative in 30% of participants. Antigen-stimulated interferon-γ, IL-2 and TNF-α responses were markedly reduced, but IP-10 responses were preserved. Infliximab caused QFT-GIT result conversion in up to 30% of participants and substantial reductions in all cytokine responses. Therefore, corticosteroids and anti-TNF-α agents significantly impair interferon-γ release assay performance. IP-10 may be a more robust TB biomarker than interferon-γ in patients receiving corticosteroids.
Accuracy of Xpert Ultra for the diagnosis of paediatric tuberculosis in a low TB burden country: a prospective multicentre study
Publisher: BMJ
Date: 09-2022
DOI: 10.1136/THORAX-2021-218378
Abstract: Childhood pulmonary tuberculosis (TB) remains a diagnostic challenge. This study aimed to evaluate the performance of Xpert Ultra for the diagnosis of pulmonary TB in children in a low TB prevalence setting. Prospective, multicentre, diagnostic accuracy study. Children with clinical or radiological suspicion of pulmonary TB were recruited at 11 paediatric units in Spain. Up to three gastric or sputum specimens were taken on 3 consecutive days, and analysed by Xpert MTB/RIF, Xpert Ultra and culture in parallel. 86 children were included (median age 4.9 years, IQR 2.0–10.0 51.2% male). The final diagnosis was pulmonary TB in 75 patients (87.2%) 33 (44.0%) were microbiologically confirmed. A total of 219 specimens, comprising gastric aspirates (n=194 88.6%) and sputum specimens (n=25 11.4%), were analysed. Using culture as reference standard and comparing in idual specimens, the sensitivity was 37.8% (14/37) for Xpert MTB/RIF and 81.1% (30/37) for Xpert Ultra (p .001) specificity was 98.4% (179/182) and 93.4% (170/182), respectively (p=0.02). In the per-patient analysis, considering positive results on any specimen, the sensitivity was 42.9% (9/21) for Xpert MTB/RIF and 81.0% for Xpert Ultra (17/21, p=0.01) specificity was 96.9% (63/65) and 87.7% (57/65, p=0.07), respectively. In children with pulmonary TB in a low burden setting, Xpert Ultra has significantly higher sensitivity than the previous generation of Xpert assay and only marginally lower specificity. Therefore, in children undergoing evaluation for suspected pulmonary TB, Xpert Ultra should be used in preference to Xpert MTB/RIF whenever possible.
Cytokine diagnosis of pleural TB: will it stand the test of time?
Publisher: BMJ
Date: 20-12-2018
Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis
Publisher: American Society for Clinical Investigation
Date: 17-09-2020
Calcineurin Inhibitors and Variation in the Performance of Interferon-γ Release Assays Used to Detect Tuberculosis Infection
Publisher: American Thoracic Society
Date: 06-2019
Bacillus Calmette-Guérin Skin Reaction Predicts Enhanced Mycobacteria-Specific T-Cell Responses in Infants: A Post Hoc Analysis of a Randomized Controlled Trial
Publisher: American Thoracic Society
Date: 04-2022
Seasonal variation in the performance of QuantiFERON-TB Gold In-Tube assays used for the diagnosis of tuberculosis infection
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.TUBE.2018.03.002
Abstract: This study aimed to determine whether there are seasonal changes in the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) assays, an interferon-gamma release assay widely used for the diagnosis of tuberculosis infection. Results of 31,932 QFT-GIT assays performed at a large independent, accredited diagnostic service provider in London, UK over a 4.5-year-period were analysed. The proportion of positive results was significantly lower in autumn (14.8%) than in spring (16.0% p = 0.0366) and summer (17.5% p < 0.0001), but similar to winter (15.2% p = 0.4711). The proportion of indeterminate results was significantly higher in autumn (8.2%) than in spring (6.2% p < 0.0001), summer (4.8% p < 0.0001), and winter (6.2% p < 0.0001). The highest proportions of indeterminate results were observed in October (8.4%) and November (8.8%), the lowest in June (4.5%). Our data show that significant seasonal variation occurs in the performance of QFT-GIT assays in a temperate climate setting. Potential underlying mechanisms, including host and environmental factors, are discussed.
Cytokine biomarkers for the diagnosis of tuberculosis infection and disease in adults in a low prevalence setting
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.TUBE.2018.08.011
Abstract: Accurate and timely diagnosis of tuberculosis (TB) is essential to control the global pandemic. Currently available immunodiagnostic tests cannot discriminate between latent tuberculosis infection (LTBI) and active tuberculosis. This study aimed to determine whether candidate mycobacterial antigen-stimulated cytokine biomarkers can discriminate between TB-uninfected and TB-infected adults, and additionally between LTBI and active TB disease. 193 adults were recruited, and categorised into four unambiguous diagnostic groups: microbiologically-proven active TB, LTBI, sick controls (non-TB lower respiratory tract infections) and healthy controls. Whole blood assays were used to determine mycobacterial antigen (CFP-10, ESAT-6, PPD)-stimulated cytokine (IL-1ra, IL-2, IL-10, IL-13, TNF-α, IFN-γ, IP-10 and MIP-1β) responses, measured by Luminex multiplex immunoassay. The background-corrected mycobacterial antigen-stimulated cytokine responses of all eight cytokines were significantly higher in TB-infected participants compared with TB-uninfected in iduals, with IL-2 showing the best performance characteristics. In addition, mycobacterial antigen-stimulated responses with IL-1ra, IL-10 and TNF-α were higher in participants with active TB compared those with LTBI, reaching statistical significance with PPD stimulation, although there was a degree of overlap between the two groups. Mycobacterial antigen-stimulated cytokine responses may prove useful in future immunodiagnostic tests to discriminate between tuberculosis-infected and tuberculosis-uninfected in idual, and potentially between LTBI and active tuberculosis.
Related Organisations
University Of Southampton
Location: United Kingdom of Great Britain and Northern Ireland
University College London
Location: United Kingdom of Great Britain and Northern Ireland
Guy's And Saint Thomas' NHS Foundation Trust
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Marc Tebruegge.