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101. Calcineurin Inhibitors and Variation in the Performance of Interferon-γ Release Assays Used to Detect Tuberculosis Infection

Author

Barton, Edward, primary, Gao, Yifang, additional, Ball, Darran, additional, Fidler, Katy, additional, Klein, Nigel, additional, Curtis, Nigel, additional, Clifford, Vanessa, additional, Marshall, Ben G., additional, Chancellor, Andrew, additional, Mansour, Salah, additional, Elkington, Paul, additional, and Tebruegge, Marc, additional

Published
2019
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104. Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study

Author

Tebruegge, Marc, primary, Ritz, Nicole, additional, Donath, Susan, additional, Dutta, Binita, additional, Forbes, Benjamin, additional, Clifford, Vanessa, additional, Zufferey, Christel, additional, De Rose, Robert, additional, Robins-Browne, Roy M., additional, Hanekom, Willem, additional, Graham, Stephen M., additional, Connell, Tom, additional, and Curtis, Nigel, additional

Published
2019
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106. Performance of QuantiFERON-TBGold Plus assays in children and adolescents at risk of tuberculosis: a cross-sectional multicentre study

Author

Soler-Garcia, Aleix, Gamell, Anna, Pérez-Porcuna, Tomàs, Soriano-Arandes, Antonio, Santiago, Begoña, Tórtola, Teresa, Ruiz-Serrano, María Jesús, Korta Murua, José Javier, Bustillo-Alonso, Matilde, Garrote-Llanos, María Isabel, Rodríguez-Molino, Paula, Piqueras, Ana Isabel, Tagarro, Alfredo, Monsonís, Manuel, Tebruegge, Marc, and Noguera-Julian, Antoni

Abstract

IntroductionThe QuantiFERON-TBGold Plus (QFT-Plus) assay, which features two antigen-stimulated tubes (TB1 and TB2) instead of a single tube used in previous-generation interferon-gamma release assays (IGRAs), was launched in 2016. Despite this, data regarding the assay’s performance in the paediatric setting remain scarce. This study aimed to determine the performance of QFT-Plus in a large cohort of children and adolescents at risk of tuberculosis (TB) in a low-burden setting.MethodsCross-sectional, multicentre study at healthcare institutions participating in the Spanish Paediatric TB Research Network, including patients <18 years who had a QFT-Plus performed between September 2016 and June 2020.ResultsOf 1726 patients (52.8% male, median age: 8.4 years), 260 (15.1%) underwent testing during contact tracing, 288 (16.7%) on clinical/radiological suspicion of tuberculosis disease (TBD), 649 (37.6%) during new-entrant migrant screening and 529 (30.6%) prior to initiation of immunosuppressive treatment. Overall, the sensitivity of QFT-Plus for TBD (n=189) and for latent tuberculosis infection (LTBI, n=195) was 83.6% and 68.2%, respectively. The agreement between QFT-Plus TB1 and TB2 antigen tubes was excellent (98.9%, κ=0.961). Only five (2.5%) patients with TBD had discordance between TB1 and TB2 results (TB1+/TB2−, n=2; TB1−/TB2+, n=3). Indeterminate assay results (n=54, 3.1%) were associated with young age, lymphopenia and elevated C reactive protein concentrations.ConclusionsOur non-comparative study indicates that QFT-Plus does not have greater sensitivity than previous-generation IGRAs in children in both TBD and LTBI. In TBD, the addition of the second antigen tube, TB2, does not enhance the assay’s performance substantially.

Published
2022
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109. Does routine child health surveillance contribute to the early detection of children with pervasive developmental disorders? – An epidemiological study in Kent, U.K.

Author

Ritchie Jane, Nandini Vridhagiri, and Tebruegge Marc

Subjects
autism, Asperger's syndrome, pervasive developmental disorder, autistic spectrum disorder, child health surveillance, Pediatrics, RJ1-570
Abstract

Abstract Background Recently changed guidelines for child health surveillance in the United Kingdom (U.K.) suggest targeted checks only, instead of the previously conducted routine or universal screening at 2 years and 3.5 years. There are concerns that these changes could lead to a delay in the detection of children with autism and other pervasive developmental disorders (PDD). Recent U.K. studies have suggested that the prevalence of PDD is much higher than previously estimated. This study establishes to which extent the routine checks contributed to the early detection and assessment of cases of PDD. Simultaneously we have evaluated the process involved and estimate the prevalence of PDD in our district. Methods Retrospective study design utilising community medical files. Headteachers of schools (n = 75) within Maidstone district (Kent) were asked to report all children with an established diagnosis of autism or PDD attending year 4 (born '91 and '92 / n = 2536) in October 2000 based on educational records. Results 59 schools (78.7%) took part in the study. A total of 33 children were reported. 21 fulfilled the inclusion criteria (12 falsely reported). The prevalences were (per 10,000): PDD 82.8 (male to female ratio 6:1), childhood autism 23.7, Asperger's syndrome 11.8 and autistic spectrum disorder 47.3. Co-existing medical conditions were noted in 14.3%; 52.4% were attending mainstream schools. In 63.2% of cases concerns – mainly in the area of speech and language development (SLD) – had been documented at the 2 year check. At the 3.5 year check concerns were noted in 94.1% – the main area was again SLD (76.5%), although behavioural abnormalities were becoming more frequent (47.1%). A total of 13 children (68.4%) were referred for further assessment as a direct result of the checks. Conclusions The prevalences for different types of PDD were similar to figures published recently, but much higher than reported a few years ago. Analysis of our data suggests that routine surveillance is a valuable contributing factor for the early detection of PDD and thereby facilitates early intervention. Thus, if routine surveillance ceases, then an alternative method of early detection should be put in place.

Published
2004
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110. Current use and acceptability of novel diagnostic tests for active tuberculosis: a worldwide survey

Author

Amicosante, Massimo, D’Ambrosio, Lia, Munoz, Marcela, Mello, Fernanda Carvalho de Queiroz, Tebruegge, Marc, Chegou, Novel Njweipi, Seghrouchni, Fouad, Centis, Rosella, Goletti, Delia, Bothamley, Graham, and Migliori, Giovanni Battista

Subjects
Inquéritos e questionários, Testes sorológicos/métodos, Técnicas de diagnóstico molecular/métodos, Serologic tests/methods, Mycobacterium tuberculosis/isolation & purification, Tuberculosis/diagnosis, Income, Molecular diagnostic techniques/methods, Tuberculose/diagnóstico, Surveys and questionnaires, Renda, Mycobacterium tuberculosis/isolamento & purificação
Abstract

Objective: To determine the current use and potential acceptance (by tuberculosis experts worldwide) of novel rapid tests for the diagnosis of tuberculosis that are in line with World Health Organization target product profiles. Methods: A multilingual survey was disseminated online between July and November of 2016. Results: A total of 723 individuals from 114 countries responded to the survey. Smear microscopy was the most commonly used rapid tuberculosis test (available to 90.9% of the respondents), followed by molecular assays (available to 70.7%). Only a small proportion of the respondents in middle- and low-income countries had access to interferon-gamma-release assays. Serological and lateral flow immunoassays were used by more than a quarter (25.4%) of the respondents. Among the respondents who had access to molecular tests, 46.7% were using the Xpert assay overall, that proportion being higher in lower middle-income countries (55.6%) and low-income countries (76.6%). The data also suggest that there was some alignment of pricing for molecular assays. Respondents stated they would accept novel rapid tuberculosis tests if available, including molecular assays (acceptable to 86.0%) or biomarker-based serological assays (acceptable to 81.7%). Simple biomarker-based assays were more commonly deemed acceptable in middle- and low-income countries. Conclusions: Second-generation molecular assays have become more widely available in high- and low-resource settings. However, the development of novel rapid tuberculosis tests continues to be considered important by tuberculosis experts. Our data also underscore the need for additional training and education of end users. RESUMO Objetivo: Determinar o uso atual e a aceitação potencial (por especialistas em tuberculose em todo o mundo) de novos testes rápidos para o diagnóstico de tuberculose que estão alinhados com os perfis de produtos alvo da Organização Mundial da Saúde. Métodos: Um inquérito multilingue foi divulgado on-line entre julho e novembro de 2016. Resultados: Um total de 723 indivíduos de 114 países respondeu ao inquérito. A baciloscopia foi o teste rápido para tuberculose mais utilizado (disponível para 90,9% dos entrevistados), seguida de ensaios moleculares (disponível para 70,7%). Apenas uma pequena proporção dos entrevistados de países de renda média e baixa tinha acesso a ensaios de liberação de IFN-γ. Imunoensaios de fluxo lateral e testes sorológicos eram utilizados por mais de um quarto dos entrevistados (25,4%). Entre os entrevistados que tinham acesso a testes moleculares, 46,7% utilizavam o teste Xpert de forma geral, sendo essa proporção maior em países de renda média baixa (55,6%) e renda baixa (76,6%). Os dados também sugerem que houve algum alinhamento de preços para testes moleculares. Os entrevistados afirmaram que aceitariam novos testes rápidos para tuberculose, se disponíveis, incluindo testes moleculares (aceitáveis para 86,0%) ou testes sorológicos baseados em biomarcadores (aceitáveis para 81,7%). Testes simples baseados em biomarcadores foram mais comumente considerados aceitáveis nos países de renda média e baixa. Conclusões: Os testes moleculares de segunda geração tornaram-se mais amplamente disponíveis em locais tanto com poucos quanto com muitos recursos. No entanto, o desenvolvimento de novos testes rápidos para tuberculose continua a ser considerado importante por especialistas em tuberculose. Nossos dados também ressaltam a necessidade de maior formação e educação dos usuários finais.

Published
2017

113. Management of child MDR-TB contacts across countries in the WHO European Region: A survey of current practice

Author

Turkova, Anna, Tebruegge, Marc, Brinkmann, Folke, Tsolia, Maria, Mouchet, Françoise, Kampmann, Beate, Seddon, James Alexander, Turkova, Anna, Tebruegge, Marc, Brinkmann, Folke, Tsolia, Maria, Mouchet, Françoise, Kampmann, Beate, and Seddon, James Alexander

Abstract

The World Health Organization European Region has one of the highest rates of multidrug-resistant tuberculosis (MDR-TB) in the world, resulting in many vulnerable children being exposed each year. Evidence for preventive therapy following MDR-TB exposure is limited and current guidance is conflicting. An internetbased survey was performed to determine clinical practice in this region. Seventy-Two clinicians from 25 countries participated. Practices related to screening and decision-making were highly variable. Just over half provided preventive therapy for children exposed to MDR-TB; the only characteristic associated with provision was practice within the European Union (adjusted OR 4.07, 95%CI 1.33-12.5)., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2017

114. Diagnostic Accuracy of QuantiFERON-TB Gold Plus Assays in Children and Adolescents with Tuberculosis Disease

Author

Colino, Elena, Gómez-Pastrana, David, Montero, Maria, Peromingo, Estrella, Bustillo, Matilde, Moliner, Elisenda, Fenoy, Marina, Velásquez, Marta, Soler, Maria Queralt, GARCÍA, Lourdes, Calavia, Olga, Rius, Neus, Pascual, Maria Teresa, Soler-Palacín, Pere, Tórtola, Teresa, Lillo, Miguel, Dapena, Marta, López-Medina, Eva María, Ruiz, Marta, Santos, Maria del Mar, Hernández, Ángel, Hernández-Sanpelayo, Teresa, Tagarro, Alfredo, Méndez, Ana, Mellado, María José, Baquero-Artigao, Fernando, Sainz, Talía, García-Hortelano, Miluca, Álvarez, Javier, Villalobos, Enrique, García-García, María Luz, Garrote, María Isabel, Korta Murua, José Javier, Gundín, Nerea Azurmendi, Sánchez-Torrent, Laia, Velasco-Arnaiz, Eneritz, Fortuny, Clàudia, Soler-Garcia, Aleix, Gamell, Anna, Santiago, Begoña, Monsonís, Manuel, Calvo, Cristina, Cobo, Elvira, Espiau, María, Guerrero-Laleona, Carmelo, Lobato, Zulema, Martín-Nalda, Andrea, Pérez-Gorricho, Beatriz, Perez-Porcuna, Tomas M., Piqueras, Ana Isabel, Rodríguez-Molino, Paula, Soriano-Arandes, Antoni, Valmanya, Teresa, Tebruegge, Marc, and Noguera-Julian, Antoni

Published
2020
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115. Current use and acceptability of novel diagnostic tests for active tuberculosis: a worldwide survey

Author

Amicosante, Massimo, primary, D’Ambrosio, Lia, additional, Munoz, Marcela, additional, Mello, Fernanda Carvalho de Queiroz, additional, Tebruegge, Marc, additional, Chegou, Novel Njweipi, additional, Seghrouchni, Fouad, additional, Centis, Rosella, additional, Goletti, Delia, additional, Bothamley, Graham, additional, and Migliori, Giovanni Battista, additional

Published
2017
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116. Mycobacteria-specific cytokine responses as correlates of treatment response in active and latent tuberculosis

Author

Clifford, Vanessa, primary, Tebruegge, Marc, additional, Zufferey, Christel, additional, Germano, Susie, additional, Forbes, Ben, additional, Cosentino, Lucy, additional, McBryde, Emma, additional, Eisen, Damon, additional, Robins-Browne, Roy, additional, Street, Alan, additional, Denholm, Justin, additional, and Curtis, Nigel, additional

Published
2017
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117. D-methionine interferes with non-typeable Haemophilus influenzae peptidoglycan synthesis during growth and biofilm formation

Author

Dawe, Harriet, primary, Berger, Evelin, additional, Sihlbom, Carina, additional, Angus, Elizabeth M., additional, Howlin, Robert P., additional, Laver, Jay R., additional, Tebruegge, Marc, additional, Hall-Stoodley, Luanne, additional, Stoodley, Paul, additional, Faust, Saul N., additional, and Allan, Raymond N., additional

Published
2017
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119. Mycobacteria-specific IL-1RA response as a potential correlate of treatment success in active and latent tuberculosis infection

Author

Clifford, Vanessa, primary, Tebruegge, Marc, additional, Zufferey, Christel, additional, Germano, Susie, additional, Forbes, Ben, additional, Cosentino, Lucy, additional, Matchett, Elizabeth, additional, McBryde, Emma, additional, Eisen, Damon, additional, Robins-Browne, Roy, additional, Street, Alan, additional, Denholm, Justin, additional, and Curtis, Nigel, additional

Published
2017
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120. Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model

Author

Tezera, Liku B, primary, Bielecka, Magdalena K, additional, Chancellor, Andrew, additional, Reichmann, Michaela T, additional, Shammari, Basim Al, additional, Brace, Patience, additional, Batty, Alex, additional, Tocheva, Annie, additional, Jogai, Sanjay, additional, Marshall, Ben G, additional, Tebruegge, Marc, additional, Jayasinghe, Suwan N, additional, Mansour, Salah, additional, and Elkington, Paul T, additional

Published
2017
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121. Author response: Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model

Author

Tezera, Liku B, primary, Bielecka, Magdalena K, additional, Chancellor, Andrew, additional, Reichmann, Michaela T, additional, Shammari, Basim Al, additional, Brace, Patience, additional, Batty, Alex, additional, Tocheva, Annie, additional, Jogai, Sanjay, additional, Marshall, Ben G, additional, Tebruegge, Marc, additional, Jayasinghe, Suwan N, additional, Mansour, Salah, additional, and Elkington, Paul T, additional

Published
2016
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122. The impact of Bacille Calmette-Guérin shortage on immunisation practice and policies in Europe – A Paediatric Tuberculosis Network European Trials Group (ptbnet) survey

Author

Kontturi, Antti, primary, Santiago, Begoña, additional, Tebruegge, Marc, additional, von Both, Ulrich, additional, Salo, Eeva, additional, Ritz, Nicole, additional, Blázquez, Daniel, additional, Bogyi, Matthias, additional, Buonsenso, Danilo, additional, Dreesman, Alexandra, additional, Krivec, Uros, additional, Mouchet, Françoise, additional, Nejat, Sahar, additional, Neth, Olaf, additional, Pavić, Ivan, additional, Ruga, Ezia, additional, Schlags, Rupert, additional, Soriano-Arandes, Antoni, additional, Thee, Steffi, additional, Tsolia, Maria, additional, and Velizarova, Svetlana, additional

Published
2016
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123. Diagnostic potential of combining plasma biomarkers of tissue damage and inflammation in pediatric TB

Author

López-Suárez, Andrea, Santos-Sebastián, Mar, Hernanz-Lobo, Alicia, Rincón-López, Elena, Aguilera-Alonso, David, Saavedra-Lozano, Jesús, Ruiz Serrano, María Jesús, Hernández-Bartolomé, Ángel, Medrano de Dios, Luz María, Jiménez Fuentes, José Luis, Navarro, María Luisa, Tebruegge, Marc, and Santiago-García, Begoña

Abstract

Immune-based diagnostic tests for tuberculosis (TB) have suboptimal sensitivity in children and cannot differentiate between latent infection (LTBI) and active disease. This study evaluated the diagnostic potential of a broad range of biomarkers of tissue damage and inflammation in unstimulated plasma in children.

Published
2024
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124. Nontuberculous mycobacterial disease in children :epidemiology, diagnosis and management at a tertiary center

Author

Tebruegge, Marc, Pantazidoe, Anastasia, MacGregor, Duncan, Gonis, Gena, Leslie, David, Sedda, Luigi, Ritz, Nicole, Connell, Tom, Curtis, Nigel, Tebruegge, Marc, Pantazidoe, Anastasia, MacGregor, Duncan, Gonis, Gena, Leslie, David, Sedda, Luigi, Ritz, Nicole, Connell, Tom, and Curtis, Nigel

Abstract

Background There are limited data on the epidemiology, diagnosis and optimal management of nontuberculous mycobacterial (NTM) disease in children. Methods Retrospective cohort study of NTM cases over a 10-year-period at a tertiary referral hospital in Australia. Results A total of 140 children with NTM disease, including 107 with lymphadenitis and 25 with skin and soft tissue infections (SSTIs), were identified. The estimated incidence of NTM disease was 0.6–1.6 cases / 100,000 children / year; no increasing trend was observed over the study period. Temporal analyses revealed a seasonal incidence cycle around 12 months, with peaks in late winter/spring and troughs in autumn. Mycobacterium-avium-complex accounted for most cases (77.8%), followed by Mycobacterium ulcerans (14.4%) and Mycobacterium marinum (3.3%). Polymerase chain reaction testing had higher sensitivity than culture and microscopy for acid-fast bacilli (92.0%, 67.2% and 35.7%, respectively). The majority of lymphadenitis cases underwent surgical excision (97.2%); multiple recurrences in this group were less common in cases treated with clarithromycin and rifampicin compared with clarithromycin alone or no anti-mycobacterial drugs (0% versus 7.1%; OR:0.73). SSTI recurrences were also less common in cases treated with two anti-mycobacterial drugs compared with one or none (10.5% versus 33.3%; OR:0.23). Conclusions There was seasonal variation in the incidence of NTM disease, analogous to recently published observations in tuberculosis, which have been linked to seasonal variation in vitamin D. Our finding that anti-mycobacterial combination therapy was associated with a reduced risk of recurrences in patients with NTM lymphadenitis or SSTI requires further confirmation in prospective trials.

Published
2016

126. Stevens-Johnson Syndrome associated with thalidomide treatment in HIV infection

Author

Tebruegge, Marc and Pantazidou, Anastasia

Subjects
HIV infection -- Complications and side effects, HIV infection -- Drug therapy, Stevens-Johnson syndrome -- Case studies, Stevens-Johnson syndrome -- Drug therapy, Stevens-Johnson syndrome -- Risk factors, Stevens-Johnson syndrome -- Diagnosis, Stevens-Johnson syndrome -- Patient outcomes, Thalidomide -- Dosage and administration, Health
Abstract

Key words: HIV/AIDS * Stevens-Johnson syndrome * Toxic epidermal necrolysis * Thalidomide * Adolescence A 14-year-old boy of African origin with HIV infection presented to the emergency department complaining of [...]

Published
2008

131. Tuberculosis in young refugees

Author

Ritz, Nicole, primary, Brinkmann, Folke, additional, Garcia, Begoña Santiago, additional, Tebruegge, Marc, additional, and Kampmann, Beate, additional

Published
2015
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132. CD1b-restricted GEM T cell responses are modulated by Mycobacterium tuberculosis mycolic acid meromycolate chains.

Author

Tezera, Liku, Chancellor, Andrew, Tocheva, Anna S., Mansour, Salah, Marshall, Ben, Elkington, Paul, Tebruegge, Marc, Gadola, Stephan, Wilson, Susan, Lissini, Nikolai M., White, Andrew, Sharpe, Sally, Cave-Ayland, Chris, Skylaris, Chris-Kriton, Essex, Jonathan W., Al Dulayymi, Juma'a R., Baird, Mark S., Bridgeman, John S., Tews, Ivo, and Elliott, Tim

Subjects
TUBERCULOSIS, T cells, GRANULOMA, MYCOLIC acids, INFECTIOUS disease transmission
Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in TB granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals and meromycolate alterations modulate functional responses by GEM-TCRs. Computational simulations suggest that meromycolate chain dynamics regulate mycolate head group movement, thereby modulating GEM-TCR activity. Our findings have significant implications for the design of future vaccines that target GEM T cells. [ABSTRACT FROM AUTHOR]

Published
2017
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143. Uso atual e aceitabilidade de novos testes diagnósticos para tuberculose ativa: um inquérito mundial.

Author

Amicosante, Massimo, D'Ambrosio, Lia, Munoz, Marcela, de Queiroz Mello, Fernanda Carvalho, Tebruegge, Marc, Chegou, Novel Njweipi, Seghrouchni, Fouad, Centis, Rosella, Goletti, Delia, Bothamley, Graham, and Migliori, Giovanni Battista

Abstract

Copyright of Brazilian Journal of Pulmonology / Jornal Brasileiro de Pneumologia is the property of Sociedade Brasileira de Pneumologia e Tisiologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2017
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