Percorrer por autor "Lange, Christoph"
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- Diagnostic accuracy and predictive value of the QuantiFERON-TB gold plus assay for tuberculosis in immunocompromised individuals: a prospective TBnet studyPublication . Sester, Martina; Altet-Gomez, Neus; Andersen, Åse Bengaard; Arias-Guillén, Miguel; Avsar, Korkut; Bakken Kran, Anne-Marte; Bothamley, Graham; Nordholm Breschel, Anne Christine; Brown, James; Chesov, Dumitru; Ciobanu, Nelly; Cirillo, Daniela Maria; Crudu, Valeriu; de Souza Galvao, Malu; Dilektasli, Asli Görek; Dominguez, José; Duarte, Raquel; Dyrhol-Riise, Anne Ma; Goletti, Delia; Hoffmann, Harald; Ibraim, Elmira; Kalsdorf, Barbara; Krawczyk, Marcin; Kunst, Heinke; Lange, Berit; Lipman, Marc; Matteelli, Alberto; Milkiewicz, Piotr; Neyer, David; Nitschke, Martin; Oral, Haluk Barbaros; Palacios-Gutiérrez, Juan José; Petruccioli, Elisa; Raszeja-Wyszomirska, Joanna; Ravn, Pernille; Rupp, Jan; Spohn, Hanna-Elisa; Toader, Corina; Villar-Hernandez, Raquel; Wagner, Dirk; van Leth, Frank; Martinez, Leonardo; Pedersen, Ole Skouvig; Lange, ChristophBackground: In low tuberculosis (TB)-endemic countries, tuberculosis preventive therapy (TPT) is recommended for immunocompromised individuals with a positive immunodiagnostic test. This study aimed to assess the performance of the QuantiFERON-TB Gold Plus (QFT+) assay and predictive power for future tuberculosis in immunocompromised individuals. Methods: In this prospective observational study, immunocompromised adults ≥18 years of age including people living with HIV (PLHIV), chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, and immunocompetent adults with and without TB-disease were recruited at 21 sites in 11 European countries and tested with the QFT+ assay. Individuals without TB-disease were followed up for the development of tuberculosis. TB incidence rates (IR) were calculated, stratified by QFT+ results and acceptance of TPT. This study is registered with Clinicaltrials.gov, NCT02639936. Findings: A total of 2663 individuals (1115 female, 1548 male) were enrolled from 03/11/2015 to 29/03/2019. Persons without tuberculosis were followed up for at least two years. Among 1758 immunocompromised individuals without active tuberculosis, 13.6% had positive QFT+ results. Sensitivity and specificity for TB-disease were 70.0% (52.1-83.3%) and 91.4% (89.6-92.9%), respectively, in immunocompromised, and 81.4% (76.6-85.3%) and 96.0% (92.5-97.9%), respectively, in immunocompetent individuals. During 2457 cumulative years of follow-up among 932 individuals with chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, including 83 persons with a positive QFT+ test without TPT, no-one developed active tuberculosis. In contrast, among 642 PLHIV without TPT, one with an indeterminate QFT+ and 3/30 individuals with a positive QFT+ developed active tuberculosis; all had detectable HIV-replication and low CD4 T-cell counts (incidence 4.1 (95% CI (1.3-12.4) per 100 person-years). No individuals receiving TPT developed active tuberculosis during 269 years of follow-up. Interpretation: In immunocompromised individuals in low TB-endemic countries, the 2-year-risk for active tuberculosis was highest among PLHIV with detectable HIV-replication and low CD4-counts. In this study, the QFT+ assay did not strongly predict progression to active tuberculosis, which emphasises the need to incorporate additional risk factors.
- The importance of getting the dose right in the treatment of tuberculosisPublication . Dudnyk, Andrii; Lutchmun, Wandini; Duarte, Raquel; Lange, Christoph; Svensson, Elin M.; on behalf of the UNITE4TB ConsortiumPrescribing the optimal combination of anti-tuberculosis drugs at the right dose is a fundamental step to achieve successful treatment outcomes. To aid the decision, clinicians should consider multiple factors, such as body weight, age, results of drug susceptibility testing, risk of intolerance and potential drug-drug interactions. In this viewpoint, we outline different aspects of dose selection in the treatment of tuberculosis (TB) such as traditional pharmacokinetics/pharmacodynamics, population pharmacokinetics models, the importance of real-world evidence and clinical trial design in the development of shorter treatment regimens and the new TB drug pipeline. Therapeutic drug monitoring for rifampicin, linezolid and amikacin may significantly improve their risk-benefit profile promoting their responsible administration. Precision dosing of novel, repurposed or conventional TB drugs should ensure optimal efficacy, while minimising toxicity and the development of resistance.
- Limited Benefit of the New Shorter Multidrug-Resistant Tuberculosis Regimen in Europe [Letters to the Editor]Publication . Lange, Christoph; Duarte, Raquel; Fréchet-Jachym, Mathilde; Guenther, Gunar; Guglielmetti, Lorenzo; Olaru, Ioana D; Oliveira, Olena; Rumetshofer, Rudolf; Veziris, Nicolas; van Leth, Frank; European MDR-TB database collaborationExtract: The emergence of multidrug-resistant tuberculosis (MDR-TB), defined as bacillary resistance to at least rifampicin and isoniazid, threatens global TB control. The number of patients notified with MDR-TB worldwide has increased by 261% from 2009 to 2014, and more than one-third of these patients currently live in the European Region of the World Health Organization (WHO). Management of patients with MDR-TB is challenging owing to the long duration of therapy required to achieve a relapse-free cure, complex drug regimens, frequent drug-related adverse events, high costs, suboptimal adherence, and overall low cure rates. [...]
- A multinational Delphi consensus on tuberculosis screening of migrants in EuropePublication . Pinheiro, Marina; Aguiar, Ana; Moreira, David N.; Akkerman, Onno W.; Al-Suwaidi, Zubaida; Alffenaar, Jan-Willem C.; Arandjelović, Irena; Brito, Ulisses; de Colombani, Pierpaolo; Curcic, Radmila; Garcia-Basteiro, Alberto L.; Goletti, Delia; Günther, Gunar; Ibraim, Elmira; Kapata, Nathan; Lange, Christoph; Lipman, Marc; Jankovic Makek, Mateja; Marais, Ben J.; Mariandyshev, Andrei; Magis-Escurra, Cecile; Migliori, Giovanni Battista; Sánchez Montalvá, Adrián; Nanovic, Zorica; Palmero, Domingo Juan; Priwitzer, Martin; Raviglione, Mario C. B.; Silva, Denise Rossato; Salzer, Helmut J.F.; Schwarzbach, Christian; Spruijt, Ineke; Winthrop, Kevin L.; Udwadia, Zarir; Vasankari, Tuula; Vilaplana, Cristina; Duarte, RaquelThe disproportionate burden of tuberculosis among migrants in the World Health Organization (WHO) European Region underscores the urgent need to address the public health challenges associated with global migration. Recommendations for screening of pulmonary tuberculosis (TB) and TB infection (TBI) are highly variable across European countries, highlighting the need for standardised practices and coordinated efforts to reduce TB risk more effectively. This study aims to produce a harmonised set of recommendations to contribute to elaboration for policy action using the Delphi method. It brings together a multidisciplinary panel of 33 TB experts from academia, healthcare, non-governmental organisations and government agencies across 22 countries to formulate consensus-based recommendations. The panel created 19 consensus statements and 36 recommendations for governments, health systems and other stakeholders. The recommendations span four key domains: 1) policy, 2) health systems and health professionals, 3) screening procedures and priority populations and 4) continued treatment and care. This study recommends a unified, evidence-based approach to TB screening in migrants, with free access to diagnosis and treatment, culturally sensitive care, use of digital tools and coordinated efforts across health systems to ensure effective and equitable TB control in Europe. Thus, the experts emphasised key recommendations that strike a balance between immediate health system interventions, screening procedures and cultural inclusivity to more effectively address TB among migrants. The findings of this study offer actionable policies to address gaps and weaknesses in Europe's response to tuberculosis among migrants, advancing efforts to eliminate TB as a public health threat.
- Tuberculosis incidence in solid organ transplant recipients in Europe: A multicenter TBnet cohort studyPublication . Lange, Berit; Brehm, Thomas Theo; Arend, Sandra M.; Arias-Guillén, Miguel; Bakker, Marleen; Berastegui, Cristina; Babiker, Maaz; Charif, Rawya; Duarte, Raquel; Flick, Holger; Hofland, Regina W.; Ismail, Joanna; Kniepeiss, Daniela; Krepel, Jessica; Krishnan, Nithya; Kuijpers, Dora L.; Kunst, Heinke; van Leth, Frank; Lezaic, Visnja; Los-Arcos, Ibai; Machová, Jana; Milburn, Heather; Morais, Sandra A.; Kon, Onn Min; Osoro-Suarez, Carmen; Pessegueiro Miranda, Helena; Pesut, Dragica; Rahman, Ananna; Reischig, Tomas; Sánchez-Montalvá, Adrián; Spohn, Hanna Elisa; Stegenga, Merel T.; de Vries, Aiko P. J.; Wagner, Dirk; Wobser, Rika; Lange, Christoph; Sester, MartinaBackground: Solid organ transplant (SOT) recipients face elevated tuberculosis risk, yet optimal prevention strategies in low- to medium-incidence regions remain unclear. Methods: We conducted a multicenter retrospective cohort study of adult SOT recipients transplanted between 2007 and 2012 at 15 European centers, with follow-up through 2018. The primary outcome was microbiologically confirmed post-transplant tuberculosis. Incidence rates were calculated per 100,000 person-years; standardized incidence ratios (SIRs) used World Health Organization country-specific background rates. Cox models assessed risk factors. Results: Among 5805 patients (median age 51; 62.7% male; 73.9% renal transplants), 33.8% were tested for tuberculosis infection and 10.3% received tuberculosis preventive therapy (TPT). Over 33,785 person-years, 23 patients (0.4%) developed tuberculosis (68.0/100,000 person-years). Highest incidence occurred in patients with positive screening but no TPT (233.8/100,000). Incidence was higher in Southern vs. Central Europe (251.9 vs. 28.7/100,000), with pooled SIRs of 12.8 and 3.1, respectively. Tuberculosis risk was elevated among Southern European recipients (HR 22.9) and those with migration history (HR 2.7). Conclusion: Tuberculosis risk is increased in European SOT recipients. Regionally adapted prevention strategies, including targeted screening in low-incidence areas and universal screening in higher-incidence regions, are warranted.