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Objectives: Allergic bronchopulmonary aspergillosis (ABPA) is a complex lung disease associated with significant morbidity. The ABPA Working Group (AWG) of the International Society for Human and Animal Mycology (ISHAM) revised their management guidelines in 2024, but there is currently no standardised tool to assess adherence to these recommendations., Methods: We extracted key recommendations from the updated 2024 ISHAM-AWG guidelines, focusing on critical areas: screening and diagnosis of ABPA, managing acute and treatment-dependent ABPA, and monitoring treatment response. Each item was assigned a score ranging from zero to three. We assigned negative scores to interventions not recommended by the guidelines., Results: We identified 38 items indicative of optimal clinical care for patients with ABPA. The score for screening asthmatics for ABPA was set at three points. For diagnosing ABPA, 16 items were included, with a score ranging from 12 to 16 points, depending on the specific components used (predisposing conditions, serum A. fumigatus-specific IgE and IgG, serum total IgE, blood eosinophil count and chest computed tomography). The management of acute ABPA comprised 11 items, with a maximum score of three points. For treatment-dependent ABPA, there were nine items (scores ranging from -3 to 6). Follow-up care comprised 10 items with a maximum score of 10-13 points, covering imaging, spirometry, testing serum total IgE levels and therapeutic drug monitoring., Conclusions: The EQUAL ABPA score has been developed as a comprehensive tool to quantify guideline adherence. Future studies will evaluate to which extent guideline adherence is associated with improved clinical outcomes for patients with ABPA., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Background: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics., Methods: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively., Results: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL -1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus -IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response., Conclusion: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research., Competing Interests: Conflict of interest: R. Agarwal has received grants from Cipla Pharmaceuticals, India for conducting research in ABPA. D.W. Denning and family hold founder shares in F2G Ltd, a University of Manchester spin-out antifungal discovery company, and share options in TFF Pharma. He acts or has recently acted as a consultant to Pulmatrix, Pulmocide, Biosergen, TFF Pharmaceuticals, Rostra Therapeutics, Mucpharma PTY and Lifemine Therapeutics. In the last 3 years, he has been paid for talks on behalf of Mundipharma, Bio-Rad, Basilea, Gilead, Avir and Pfizer. He has been involved in multiple guideline groups, primarily focused on diagnostics and aspergillosis. D. Armstrong-James holds share options in Pulmocide Ltd. K. Asano is partially supported by a research grant on allergic disease and immunology from the Japan Agency for Medical Research and Development under grant number 22ek0410097. S.H. Chotirmall has served on advisory boards for CSL Behring, Pneumagen Ltd and Boehringer Ingelheim, on data monitoring boards for Inovio Pharmaceuticals and Imam Abdulrahman Bin Faisal University, and has received personal fees from AstraZeneca and Chiesi Farmaceutici, all unrelated to this work. H.J.F. Salzer has received honoraria for lectures or consulting fees from Ismed, GlaxoSmithKline, AstraZeneca, Advanz Pharma, MSD and Chiesi, all unrelated to this work. J.D. Chalmers has received research grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis, Insmed and Trudell, and received consultancy or speaker fees from Antabio, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Insmed, Janssen, Novartis, Pfizer, Trudell and Zambon. C. Godet has received speaker fees and travel support from Pfizer and MSD, fees for board memberships from SOS Oxygène and Pulmatrix, and grant support from Ohre Pharma, Pfizer, MSD, SOS Oxygène, ISIS Medical, LVL Médical, Oxyvie, Vivisol, Elivie, CF Santé, Boehringer, Sandoz and AstraZeneca. M. Joest has received honoraria for lectures or grants from ALK-Abelló, AstraZeneca, Bencard, Berlin-Chemie, Boehringer Ingelheim, GlaxoSmithKline and HAL Allergy, all unrelated to this work. P. Nair reports grants and personal fees from AstraZeneca, Teva and Sanofi, personal fees from Equillium, Arrowhead Pharma and GlaxoSmithKline, and grants from Foresee and Cyclomedica, outside the submitted work. C.G. Baxter serves on strategic advisory board for Nob Hill Therapeutics Ltd. W.J. Calhoun is a member of the scientific advisory board of Pulmatrix, and that work is unrelated to this publication. O.A. Cornely reports grants from Cidara, F2G, Gilead, MSD, Mundipharma, Pfizer and Scynexis, consulting fees from AiCuris, Basilea, Cidara, Gilead, IQVIA, Matinas, Pfizer, PSI, Pulmocide and Scynexis, honoraria for lectures from Al-Jazeera, Gilead, Knight, MSD, Pfizer and Shionogi, and payment for expert testimony from Cidara. J.A. Douglass has received honoraria for educational presentations from AstraZeneca, GlaxoSmithKline, Novartis and CSL, has served on advisory boards for Sanofi-Aventis, Novartis, GlaxoSmithKline, AstraZeneca, Immunosis and CSL, and has undertaken contracted or investigator-initiated research on behalf of GlaxoSmithKline, Novartis, Immunosis, AstraZeneca, Sanofi-Aventis, Grifols, CSL, BioCryst and Equillium. R. Moss reports consulting fees from the Cystic Fibrosis Foundation, Astellas Pharma Inc., Nob Hill Therapeutics Inc., Pulmatrix, Mayne Pharma, Zambon Company SpA, Aridis Pharmaceuticals Inc., Regeneron Pharmaceuticals Inc. and 4D Molecular Therapeutics, royalties from UpToDate, Inc., and is a member of the board of directors for the Cystic Fibrosis Research Institute. D. Seidel received speaker fees from Pfizer, outside of the submitted work. R. Sprute has received speaker fees from Hikma and Pfizer, and travel support from Pfizer, all outside of the submitted work. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Purpose of Review: Post-tuberculosis lung disease (PTLD) is an increasingly recognized and debilitating consequence of pulmonary tuberculosis (PTB). In this review, we provide a comprehensive overview of PTLD with airflow obstruction (PTLD-AFO), focusing on its burden, pathophysiology, clinical manifestations, diagnostic methods, and management strategies., Recent Findings: The relationship between PTLD and airflow obstruction is complex and multifactorial. Approximately 60% of the patients with PTLD have some spirometric abnormality. Obstruction is documented in 18-22% of PTLD patients. The host susceptibility and host response to mycobacterium drive the pathogenic mechanism of PTLD. A balance between inflammatory, anti-inflammatory, and fibrotic pathways decides whether an individual with PTB would have PTLD after microbiological cure. An obstructive abnormality in PTLD-AFO is primarily due to destruction of bronchial walls, aberrant healing, and reduction of mucosal glands. The most common finding on computed tomography (CT) of thorax in patients with PTLD-AFO is bronchiectasis and cavitation. Therefore, the 'Cole's vicious vortex' described in bronchiectasis applies to PTLD. A multidisciplinary approach is required for diagnosis and treatment. The disability-adjusted life-years (DALYs) attributed to PTLD represent about 50% of the total estimated burden of DALYs due to tuberculosis (TB). Patients with PTLD require comprehensive care that includes psychosocial support, pulmonary rehabilitation, and vaccination against respiratory pathogens. In the absence of trials evaluating different treatments for PTLD-AFO, therapy is primarily symptomatic., Summary: PTLD with airflow obstruction has considerable burden and causes a significant morbidity and mortality. However, many aspects of PTLD-AFO still need to be answered. Studies are required to evaluate different phenotypes, especially concerning Aspergillus -related complications. The treatment should be personalized based on the predominant phenotype of airflow obstruction. Extensive studies to understand the exact burden, pathogenesis, and treatment of PTBLD-AFO are needed., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Post-tuberculosis lung disease (PTLD) has only recently been put in the spotlight as a medical entity. Recent data suggest that up to 50% of tuberculosis (TB) patients are left with PTLD-related impairment after completion of TB treatment. The presence of residual cavities in the lung is the largest risk factor for the development of chronic pulmonary aspergillosis (CPA) globally. Diagnosis of CPA is based on four criteria including a typical radiological pattern, evidence of Aspergillus species, exclusion of alternative diagnosis, and a chronic course of disease. In this manuscript, we provide a narrative review on CPA as a serious complication for patients with PTLD., Competing Interests: None declared., (Thieme. All rights reserved.)

How to identify MAC-PD patients with limited treatment options: an expert consensus https://bit.ly/3QwLQ8T., Competing Interests: Conflict of interest: A. Fløe reports participation on an advisory board for Insmed Inc., outside the submitted work. Conflict of interest: P.R. Burgel reports grants or contracts from GSK and Vertex, outside the submitted work; consulting fees from AstraZeneca, Chiesi, GSK, Insmed, MSD, Pfizer, Vertex, Viatris and Zambon, outside the submitted work. Conflict of interest: A. Calcagno reports receiving support for the present manuscript from Insmed; consulting fees from Insmed, outside the submitted work; and speakers’ honoraria from Insmed, outside the submitted work. Conflict of interest: E. Polverino reports support for the present manuscript from Lena Group; grants or contracts from Grifols, outside the submitted; consulting fees from Insmed, Chiesi, Zambon and Electromed, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Insmed, Chiesi, Zambon, Teva, Boehringer, Glaxo and Electromed, outside the submitted work; payment for expert testimony from Chiesi, outside the submitted work; support for attending meetings and/or travel from Insmed, Teva, Glaxo and Chiesi, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for Insmed, Electromed, and Chiesi, outside the submitted work. Conflict of interest: G. Rohde reports personal fees from AstraZeneca, Atriva, Boehringer Ingelheim, GSK, Insmed, MSD, Sanofi, Novartis and Pfizer for consultancy during advisory board meetings, outside the submitted work; and personal fees from AstraZeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Sanofi, Solvay, Takeda, Novartis, Pfizer and Vertex for lectures including service on speakers' bureaus, outside the submitted work. Conflict of interest: H.J.F. Salzer reports receiving support for the present manuscript from Insmed; and honoraria for lectures from Insmed, GSK, Gilead and Chiesi, outside the submitted work. Conflict of interest: A. Sánchez-Montalvá reports receiving support for the present manuscript from Insmed; and consulting fees from Insmed, outside the submitted work. Conflict of interest: M. Shteinberg reports receiving support for the present manuscript from Insmed. A. Sánchez-Montalvá reports grants or contracts from GSK, Trumed and Novartis, outside the submitted work; consulting fees from GSK, Boehringer Ingelheim, Kamada and Zambon, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Insmed, Boehringer Ingelheim, GSK, AstraZeneca, Teva, Novartis, Kamada and Sanofi, outside the submitted work; support for attending meetings and/or travel from Novartis, Actelion, Boehringer Ingelheim, GSK and Rafa, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Boards for Bonus Therapeutics, Israel, outside the submitted work; a leadership or fiduciary role in an other board, society, committee or advocacy group for EMBARC management, Israel Pulmonology Society board, and Israel society for TB and mycobacterial diseases, outside the submitted work; receipt of equipment, materials, drugs, medical writing, gifts or other services from Trudell Medical Intnl; receipt of supply to clinical trial, outside the submitted work; other financial or non-financial interests. A. Sánchez-Montalvá is Associate Editor, American Journal of Respiratory and Critical Care Medicine, with a direct stipend, outside the submitted work. Conflict of interest: E. Van Braeckel reports support for the present manuscript from Publi Creations SAM – Lenagroup; grants or contracts from Insmed, outside the submitted work; consulting fees from Insmed, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Insmed, outside the submitted work. E. Van Braeckel is Chair of the Belgian Respiratory Society working group on respiratory infections, unpaid, outside the submitted work. Conflict of interest: J. van Ingen reports grants or contracts from MannKind and AN2, outside the submitted work; patents planned, issued or pending: Inhaled tigecycline for M. abscessus treatment, outside the submitted work. Conflict of interest: N. Veziris reports receiving support for the present manuscript from Insmed; grants or contracts from Bioversys, outside the submitted work; consulting fees from Insmed and Becton Dickinson, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Insmed, outside the submitted work; payment for expert testimony from Insmed, outside the submitted work; support for attending meetings and/or travel from Insmed, outside the submitted work; and was involved in the Respiri-NTM consortium with Janssen, outside the submitted work. Conflict of interest: D. Wagner reports support for the present manuscript from Publi Creations SAM via an unrestricted grant by Insmed Inc.; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Biomerieux, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for Pfizer, outside the submitted work; and participation in clinical trials for Insmed, outside the submitted work. Conflict of interest: S. Aliberti reports grants or contracts from Insmed Incorporated, Chiesi, Fisher & Paykel and GSK, outside the submitted work; royalties or licences from McGraw Hill, outside the submitted work; consulting fees from Insmed Incorporated, Insmed Italy, Insmed Ireland Ltd, Zambon Spa, AstraZeneca UK Limited, AstraZeneca Pharmaceutical LP, CSL Behring GmbH, Grifols, Fondazione Internazionale Menarini, Moderna, Chiesi, MSD Italia S.r.l., Brahms, Physioassist SAS and GlaxoSmithKline Spa, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GlaxoSmithKline Spa, Thermofisher Scientific, Insmed Italy, Insmed Ireland Ltd, Zambon, and Fondazione Internazionale Menarini, outside the submitted work; participation on a Data Safety Monitoring Board or Advisory Board for INSMED Incorporated, INSMED Italy, AstraZeneca UK Limited, and MSD Italia S.r.l, outside the submitted work. Conflict of interest: F. Blasi reports grants or contracts from AstraZeneca, Chiesi, GlaxoSmithKline and Insmed, outside the submitted work; consulting fees from GlaxoSmithKline, Menarini and OM Pharma, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Chiesi, GlaxoSmithKline, Grifols, Insmed, Menarini, Novartis, OM Pharma, Pfizer, Sanofi, Vertex, Viatris and Zambon, outside the submitted work. Conflict of interest: A. Papavasileiou reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Insmed, outside the submitted work. Conflict of interest: M.R. Loebinger reports consulting fees from Armata, 30T, AstraZeneca, Parion, Insmed, Chiesi, Zambon, Electromed, Recode, AN2, Savara, Boehringer Ingelheim and Mannkind, outside the submitted work; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Insmed, outside the submitted work; and is chair of the ERS Respiratory Infection group, outside the submitted work. Conflict of interest: D. Grogono reports consulting fees from Insmed, outside the submitted work; and support received from Insmed for attending a consensus meeting. Conflict of interest: C. Prados has nothing to disclose., (Copyright ©The authors 2024.)

Based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB) in December 2022. The new recommendations and the latest study data made it necessary to update the existing guideline on the treatment of at least rifampicin-resistant TB (RR-TB) for the German-speaking countries, replacing the respective chapters of the treatment guidelines published in 2022. A shortened treatment of proven RR-TB and multidrug-resistant TB for at least 6 months using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Austria, Germany, and Switzerland under certain conditions considering the existing barriers for the implementation of the new treatment regimen. For the treatment of pre-extensively drug-resistant (pre-XDR-) TB, an individualized treatment for 18 months continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in selected pre-XDR-TB cases, provided that all prerequisites are met. The necessary requirements for using BPaLM and BPaL are presented in detail in this amendment to the consensus-based TB treatment guideline for adult patients., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

In December 2022, based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB). The evaluation of both, these recommendations, and the latest study data, makes it necessary to update the existing guidelines on the treatment of at least rifampicin-resistant tuberculosis for the German-speaking region, hereby replacing the respective chapters. A shortened MDR-TB treatment of at least 6 month using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Germany, Austria, and Switzerland under certain conditions. This recommendation applies to TB cases with proven rifampicin resistance, including rifampicin monoresistance. For treatment of pre-extensively drug resistant TB (pre-XDR-TB), an individualized treatment for 18 months adjusted to resistance data continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in pre-XDR TB if all prerequisites are met. The necessary prerequisites for the use of BPaLM and BPaL are presented in this amendment to the S2k guideline for 'Tuberculosis in adulthood'., Competing Interests: Informationen zu Interessenkonflikten finden Sie auf den Seiten der AWMF (http://www.awmf.org/leitlinien/awmf-regelwerk.html)., (Thieme. All rights reserved.)

Objectives: To evaluate the performance of Aspergillus-specific IgG antibodies for diagnosing chronic pulmonary aspergillosis (CPA) by using a cohort of patients with histologically proven CPA as a reference standard., Methods: We collected Aspergillus-specific IgG antibody titres from patients with histologically proven CPA in collaboration with CPAnet study sites in Denmark, Germany, Belgium, India, Moldova, and Pakistan (N = 47). Additionally, sera from diseased and healthy controls were prospectively collected at the Medical Clinic of the Research Center, Borstel, Germany (n = 303). Aspergillus-specific IgG antibody titres were measured by the ImmunoCAP® assay (Phadia 100, Thermo Fisher Scientific, Uppsala, Sweden). An Aspergillus-specific IgG antibody titre ≥50 mgA/L was considered positive., Results: Using patients with histologically proven CPA as the reference standard, the ImmunoCAP® Aspergillus-specific IgG antibody test had a sensitivity and specificity of 85.1% (95% CI: 71.7-93.8%) and 83.6% (95% CI: 78.0-88.3%), respectively. Patients with histologically proven CPA had significantly higher Aspergillus-specific IgG antibody titre with a median of 83.45 mgA/L (interquartile range 38.9-115.5) than all other cohorts (p < 0.001). False-positive test results occurred in one-third of 79 healthy controls., Discussion: Our study results confirm a high sensitivity of the Aspergillus-specific IgG antibody test for the diagnosis of CPA when using patients with histologically proven CPA as a reference standard. However, positive test results should always match radiological findings as false-positive test results limit the interpretation of the test., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Immunosuppression after chemotherapy, stem cell transplantation or solid organ transplantation are the main risk factors for invasive fungal infections in Austria. Here, we aim to describe the status of laboratory mycology and the access to antifungal treatment in Austria., Methods: Between October and November 2021, hospitals were contacted to participate in our online survey: www.clinicalsurveys.net/uc/IFI&#95;management&#95;capacity/. Centres were required to provide information on their institutional profile; self-assessment of burden of invasive fungal infections; access to microscopy, culture, serology, antigen detection and molecular testing; and availability of antifungal agents and therapeutic drug monitoring., Results: Responses were collected from university hospitals and laboratories in Graz, Innsbruck, Linz and Vienna. The four hospitals can provide tertiary care and were highly specialised, including management of patients with severe immunosuppression. All sites consider the incidence of invasive fungal infections to be moderate. Access to microscopy, culture, serology, antigen detection and molecular testing is provided regardless of laboratory. The maximum capacity to identify fungi varies from institution to institution. All currently marketed antifungal agents are available at the four sites., Conclusion: Austria is currently well equipped to deal with the emerging threat of invasive fungal infections. However, hospitals may consider preparing for the potential endemicity of certain infections in the near future., (© 2023 The Authors. Mycoses published by Wiley-VCH GmbH.)

Minimally invasive autopsies (MIAs) allow the collection of tissue samples for diagnostic and research purposes in special situations, e.g., when there is a high risk of infection which is the case in the context of COVID-19 or restrictions due to legal or personal reasons. We performed MIA to analyze lung tissue from 92 COVID-19 patients (mean age 78 years; range 48-98; 35 women, 57 men), representing 44% of all patients who died from the disease between October 2020 and April 2021. An intercostal approach was used with removal of a 5-cm rib section followed by manual collection of four lung tissue samples (5-8 cm in size). Diffuse alveolar damage (DAD) was found in 89 (97%) patients at various stages. Exudative DAD (eDAD) predominated in 18 (20%) patients, proliferative DAD (pDAD) in 43 (47%) patients, and mixed DAD (mDAD) in 31 (34%) patients. There were no significant differences in the predominant DAD pattern between tissue samples from the same patient. Additional purulent components were present in 46 (50%) cases. Fungi were detected in 11 (12%) patients. The pDAD pattern was associated with longer hospital stay including intensive care unit (p=0.026 and p<0.001) and younger age (p=0.019). Positive bronchoalveolar lavage and blood cultures were observed more frequently in pDAD patterns (p<0.001; p=0.018). In contrast, there was no significant association between intravital positive microbiological results and superimposed bronchopneumonia or fungal infection at autopsy. Having demonstrated the characteristic lung changes in a large longitudinal autopsy series, we conclude that the presented MIA approach can be considered a reliable and safe method for performing post mortem lung diagnostics in COVID-19 and other high-risk situations. The lack of correlation between histological changes indicative of bacterial or fungal superinfection and microbiology could have clinical implications for disease and treatment surveillance., (© 2023. The Author(s).)

BackgroundEuropean-specific policies for tuberculosis (TB) elimination require identification of key populations that benefit from TB screening.AimWe aimed to identify groups of foreign-born individuals residing in European countries that benefit most from targeted TB prevention screening.MethodsThe Tuberculosis Network European Trials group collected, by cross-sectional survey, numbers of foreign-born TB patients residing in European Union (EU) countries, Iceland, Norway, Switzerland and the United Kingdom (UK) in 2020 from the 10 highest ranked countries of origin in terms of TB cases in each country of residence. Tuberculosis incidence rates (IRs) in countries of residence were compared with countries of origin.ResultsData on 9,116 foreign-born TB patients in 30 countries of residence were collected. Main countries of origin were Eritrea, India, Pakistan, Morocco, Romania and Somalia. Tuberculosis IRs were highest in patients of Eritrean and Somali origin in Greece and Malta (both > 1,000/100,000) and lowest among Ukrainian patients in Poland (3.6/100,000). They were mainly lower in countries of residence than countries of origin. However, IRs among Eritreans and Somalis in Greece and Malta were five times higher than in Eritrea and Somalia. Similarly, IRs among Eritreans in Germany, the Netherlands and the UK were four times higher than in Eritrea.ConclusionsCountry of origin TB IR is an insufficient indicator when targeting foreign-born populations for active case finding or TB prevention policies in the countries covered here. Elimination strategies should be informed by regularly collected country-specific data to address rapidly changing epidemiology and associated risks.

Purpose: Lower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes., Methods: A prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups., Results: 1060 patients with LRTI (72.5% male sex, median age 64 [50-74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates., Conclusion: VHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study., (© 2023. The Author(s).)

Background: The chronic pulmonary aspergillosis network (CPAnet) has recently proposed definitions for treatment outcomes in CPA. However, these definitions need to be validated. Herein, we evaluate the agreement between the existing and the CPAnet definitions for response assessment., Methods: We enrolled consecutive treatment-naïve CPA subjects (between January 2021 and June 2021) who received six months of itraconazole therapy and followed them for an additional six months after treatment discontinuation. We retrospectively applied the CPAnet criteria and compared the agreement between the existing and the CPAnet criteria for response assessment (primary objective). We also assessed if adding weight loss (> 5% from baseline) as a component improved the performance of the CPAnet criteria., Results: We included 43 (mean age, 47.4 years) CPA subjects. The existing and the CPAnet criteria categorized 29 (67.4%) and 30 (69.8%) subjects as treatment success, respectively, at treatment completion. There was substantial (kappa = 0.73; p < 0.0001) agreement between the two definitions. However, both criteria did not identify eight subjects requiring treatment re-initiation within three months. There was an increment in the sensitivity of both criteria (by 36%) for identifying treatment failure after incorporating ≥ 5% weight loss as an element of worsening., Conclusion: The CPAnet definitions correctly categorized treatment outcomes in most cases of CPA. The addition of weight change would further enhance the performance of the CPAnet treatment outcome definitions., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Invasive fungal infections caused by Candida or Aspergillus are associated with a high mortality. Knowledge about the risk factors, diagnosis and treatment management is crucial for improving the survival of those affected., Objective: To give a practical overview about risk factors and treatment management of Candida and Aspergillus infections as well as providing an outlook on new antifungal agents., Material and Methods: Summary of the relevant literature and recommendations on candidemia and invasive candidiasis as well as invasive and chronic pulmonary aspergillosis., Results: The first line treatment of candidemia and invasive candidiasis are echinocandins including caspofungin, anidulafungin and micafungin. Regular blood cultures have to be taken to determine the duration of treatment. After the first negative control blood culture treatment should be continued for another 14 days. The first line treatment of invasive pulmonary aspergillosis is azoles including voriconazole and isavuconazole. The duration of treatment depends on disease severity and is recommended for 6-12 weeks. The duration of treatment for chronic pulmonary aspergillosis is 6-12 months. Therapeutic drug monitoring is recommended for voriconazole and for posaconazole. New antifungal agents including olorofim, fosmanogepix, opelconazole, rezafungin or ibrexafungerp will broaden the therapeutic spectrum in the foreseeable future., Conclusion: Knowledge about risk factors and the correct treatment management is crucial for the survival of patients with invasive fungal infections., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

This nationwide Austrian consensus statement summarizes the recommendations on the management of latent tuberculosis by treatment with biologic and targeted synthetic DMARDs. The essential questions with respect to screening and preventive treatment were discussed by experts from the disciplines of rheumatology, pneumology, infectious diseases, dermatology and gastroenterology, based on the available data, and then a joint consensus was formed by agreement. This involved a differentiated discussion on the various forms of treatment, and clear recommendations were formulated., (© 2022. The Author(s).)

This publication provides a thorough analysis of the most relevant topics concerning the management of latent tuberculosis when using biologic and targeted synthetic Disease Modifying Antirheumatic Drugs (DMARDs) by a multidisciplinary, select committee of Austrian physicians. The committee includes members of the Austrian Societies for Rheumatology and Rehabilitation, Pulmonology, Infectiology, Dermatology and Gastroenterology. Consensus was reached on issues regarding screening and treatment of latent tuberculosis and includes separate recommendations for each biologic and targeted synthetic DMARD., (© 2022. The Author(s).)

In Germany tuberculosis is a rare disease and usually well treatable. Worldwide it is one of the most common infectious diseases with approximately 10 million new cases every year. Even with low incidences in Germany, tuberculosis is an important differential diagnosis especially due to international developments and migration movements. With a decreasing experience there's a continuous demand on accurate and up-to-date information. This guideline covers all aspects of microbiological diagnostics, basic principles of standard therapy, treatment of extrapulmonary tuberculosis, management of side effects, special features of diagnosis and treatment of resistant tuberculosis, and treatment in TB-HIV coinfection. Also, it explains when treatment in specialized centers is required, aspects of care and legal regulations and the diagnosis and preventive therapy of latent tuberculosis infection. The update of the S2k guideline "Tuberculosis in Adults" is intended to serve as a guideline for prevention, diagnosis, and treatment of tuberculosis for all those involved in tuberculosis care and to help meet the current challenges in dealing with tuberculosis in Germany., Competing Interests: Eine Übersicht der Interessenkonflikte findet sich im Internet unter http://awmf.org; AWMF-Registriernummer 020-019, (Thieme. All rights reserved.)

Background: Gastrointestinal tuberculosis (TB) is a rare manifestation in low TB-incidence countries such as Austria. It is usually seen in immunocompromised patients or in migrants being more susceptible for extrapulmonary disease manifestations., Case Description: We report a very rare manifestation of severe gastrointestinal TB in a 49-year-old previously healthy man from Upper Austria. Endoscopy showed a large tumor mass obstructing about 2/3 of the lumen of the cecum. Positron emission tomography/computed tomography scan revealed not only a high metabolic activity in the tumor mass, but also active pulmonary lesions in both upper lung lobes. Bronchial secretion showed acid-fast bacilli in the microscopy and polymerase chain reaction was positive for M. tuberculosis complex. Phenotypic resistance testing showed no resistance for first-line anti-TB drugs. Treatment with isoniazid, rifampicin, pyrazinamide and ethambutol was initiated. Based on therapeutic drug monitoring, the standard treatment regime was adapted to rifampicin high dose. TB treatment was well tolerated and the patient achieved relapse-free cure one year after the end of treatment., Conclusion: Gastrointestinal involvement mimicking an intestinal tumor is a very rare TB manifestation in previously healthy Austrians. However, it should be kept in mind due to increasing migration from countries with higher rates of extrapulmonary TB and due to an increasing number of immunocompromised patients. TB telephone consultations can support medical professionals in the diagnosis and the management of complex TB patients. TB management is currently at a transitional stage from a programmatic to personalized management concept including therapeutic drug monitoring or biomarker-guided treatment duration to achieve relapse-free cure., (© 2021. The Author(s).)

Background: In December 2019, the new virus infection coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged. Simple clinical risk scores may improve the management of COVID-19 patients. Therefore, the aim of this pilot study was to evaluate the quick Sequential Organ Failure Assessment (qSOFA) score, which is well established for other diseases, as an early risk assessment tool predicting a severe course of COVID-19., Methods: We retrospectively analyzed data from adult COVID-19 patients hospitalized between March and July 2020. A critical disease progress was defined as admission to intensive care unit (ICU) or death., Results: Of 64 COVID-19 patients, 33% (21/64) had a critical disease progression from which 13 patients had to be transferred to ICU. The COVID-19-associated mortality rate was 20%, increasing to 39% after ICU admission. All patients without a critical progress had a qSOFA score ≤ 1 at admission. Patients with a critical progress had in only 14% (3/21) and in 20% (3/15) of cases a qSOFA score ≥ 2 at admission (p = 0.023) or when measured directly before critical progression, respectively, while 95% (20/21) of patients with critical progress had an impairment oxygen saturation (SO 2 ) at admission time requiring oxygen supplementation., Conclusion: A low qSOFA score cannot be used to assume short-term stable or noncritical disease status in COVID-19., (© 2021. The Author(s).)

The Austrian Society of Pneumology (ASP) launched a first statement on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in May 2020, at a time when in Austria 285 people had died from this disease and vaccinations were not available. Lockdown and social distancing were the only available measures to prevent more infections and the breakdown of the health system. Meanwhile, in Austria over 13,000 patients have died in association with a SARS-CoV‑2 infection and coronavirus disease 2019 (COVID-19) was among the most common causes of death; however, SARS-CoV‑2 has been mutating all the time and currently, most patients have been affected by the delta variant where the vaccination is very effective but the omicron variant is rapidly rising and becoming predominant. Particularly in children and young adults, where the vaccination rate is low, the omicron variant is expected to spread very fast. This poses a particular threat to unvaccinated people who are at elevated risk of severe COVID-19 disease but also to people with an active vaccination. There are few publications that comprehensively addressed the special issues with SARS-CoV‑2 infection in patients with chronic lung diseases. These were the reasons for this updated statement. Pulmonologists care for many patients with an elevated risk of death in case of COVID-19 but also for patients that might be at an elevated risk of vaccination reactions or vaccination failure. In addition, lung function tests, bronchoscopy, respiratory physiotherapy and training therapy may put both patients and health professionals at an increased risk of infection. The working circles of the ASP have provided statements concerning these risks and how to avoid risks for the patients., (© 2022. The Author(s).)

Chronic pulmonary aspergillosis (CPA) is a potentially life-threatening fungal lung infection, and recent research suggests CPA to be more common than previously considered. Although CPA mimics other lung diseases including pulmonary cancer, awareness of this disease entity is still sparse. This study aimed to investigate the prevalence of CPA in a population of patients under suspicion of having lung cancer. We conducted a retrospective cohort study of 1200 patients and manually collected individual health record data from previous cancer examinations, with retrospective CPA status assessment using international criteria. Among 992 included patients, 16 (1.6%) fulfilled diagnostic criteria for CPA retrospectively, of whom 15 were undiscovered at initial lung cancer examination. The prevalence of CPA in this study population was 50 times higher than the reported prevalence of the overall European population. Our findings indicate that CPA is often missed in patients suspected of malignancy in the chest. Therefore, CPA should be kept in mind as a significant differential diagnosis.

Objective: To develop and validate a prognostic model for in-hospital mortality after four days based on age, fever at admission and five haematological parameters routinely measured in hospitalized Covid-19 patients during the first four days after admission., Methods: Haematological parameters measured during the first 4 days after admission were subjected to a linear mixed model to obtain patient-specific intercepts and slopes for each parameter. A prediction model was built using logistic regression with variable selection and shrinkage factor estimation supported by bootstrapping. Model development was based on 481 survivors and 97 non-survivors, hospitalized before the occurrence of mutations. Internal validation was done by 10-fold cross-validation. The model was temporally-externally validated in 299 survivors and 42 non-survivors hospitalized when the Alpha variant (B.1.1.7) was prevalent., Results: The final model included age, fever on admission as well as the slope or intercept of lactate dehydrogenase, platelet count, C-reactive protein, and creatinine. Tenfold cross validation resulted in a mean area under the receiver operating characteristic curve (AUROC) of 0.92, a mean calibration slope of 1.0023 and a Brier score of 0.076. At temporal-external validation, application of the previously developed model showed an AUROC of 0.88, a calibration slope of 0.95 and a Brier score of 0.073. Regarding the relative importance of the variables, the (apparent) variation in mortality explained by the six variables deduced from the haematological parameters measured during the first four days is higher (explained variation 0.295) than that of age (0.210)., Conclusions: The presented model requires only variables routinely acquired in hospitals, which allows immediate and wide-spread use as a decision support for earlier discharge of low-risk patients to reduce the burden on the health care system., Clinical Trial Registration: Austrian Coronavirus Adaptive Clinical Trial (ACOVACT); ClinicalTrials.gov, identifier NCT04351724., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Heber, Pereyra, Schrottmaier, Kammerer, Santol, Rumpf, Pawelka, Hanna, Scholz, Liu, Hell, Heiplik, Lickefett, Havervall, Traugott, Neuböck, Schörgenhofer, Seitz, Firbas, Karolyi, Weiss, Jilma, Thålin, Bellmann-Weiler, Salzer, Szepannek, Fischer, Zoufaly, Gleiss and Assinger.)

Aims: Anticoagulation was associated with improved survival of hospitalized coronavirus disease 2019 (COVID-19) patients in large-scale studies. Yet, the development of COVID-19-associated coagulopathy (CAC) and the mechanism responsible for improved survival of anticoagulated patients with COVID-19 remain largely elusive. This investigation aimed to explore the effects of anticoagulation and low-molecular-weight heparin (LMWH) in particular on patient outcome, CAC development, thromboinflammation, cell death, and viral persistence., Methods and Results: Data of 586 hospitalized COVID-19 patients from three different regions of Austria were evaluated retrospectively. Of these, 419 (71.5%) patients received LMWH and 62 (10.5%) received non-vitamin-K oral anticoagulants (NOACs) during hospitalization. Plasma was collected at different time points in a subset of 106 patients in order to evaluate markers of thromboinflammation (H3Cit-DNA) and the cell death marker cell-free DNA (cfDNA). Use of LMWH was associated with improved survival upon multivariable Cox regression (hazard ratio = 0.561, 95% confidence interval: 0.348-0.906). Interestingly, neither LMWH nor NOAC was associated with attenuation of D-dimer increase over time, or thromboinflammation. In contrast, anticoagulation was associated with a decrease in cfDNA during hospitalization, and curtailed viral persistence was observed in patients using LMWH leading to a 4-day reduction of virus positivity upon quantitative polymerase chain reaction [13 (interquartile range: 6-24) vs. 9 (interquartile range: 5-16) days, P = 0.009]., Conclusion: Time courses of haemostatic and thromboinflammatory biomarkers were similar in patients with and without LMWH, indicating either no effects of LMWH on haemostasis or that LMWH reduced hypercoagulability to levels of patients without LMWH. Nonetheless, anticoagulation with LMWH was associated with reduced mortality, improved markers of cell death, and curtailed viral persistence, indicating potential beneficial effects of LMWH beyond haemostasis, which encourages use of LMWH in COVID-19 patients without contraindications., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Derailed cytokine and immune cell networks account for the organ damage and the clinical severity of COVID-19 (refs. 1-4 ). Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and is accompanied by a senescence-associated secretory phenotype (SASP), which comprises pro-inflammatory cytokines, extracellular-matrix-active factors and pro-coagulatory mediators 5-7 . Patients with COVID-19 displayed markers of senescence in their airway mucosa in situ and increased serum levels of SASP factors. In vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, which mirrored hallmark features of COVID-19 such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue 1,8,9 . Moreover, supernatant from VIS cells, including SARS-CoV-2-induced senescence, induced neutrophil extracellular trap formation and activation of platelets and the clotting cascade. Senolytics such as navitoclax and a combination of dasatinib plus quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-infected hamsters and mice. Our findings mark VIS as a pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest that senolytic targeting of virus-infected cells is a treatment option against SARS-CoV-2 and perhaps other viral infections., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as a biomarker for individualised therapy durations for patients with drug-susceptible (DS)- and multidrug-resistant (MDR)-TB., Methods: Adult patients with pulmonary TB were prospectively enrolled into five independent cohorts in Germany and Romania. Clinical and microbiological data and whole blood for RNA transcriptomic analysis were collected at pre-defined time points throughout therapy. Treatment outcomes were ascertained by TBnet criteria (6-month culture status/1-year follow-up). A whole-blood RNA therapy-end model was developed in a multistep process involving a machine-learning algorithm to identify hypothetical individual end-of-treatment time points., Results: 50 patients with DS-TB and 30 patients with MDR-TB were recruited in the German identification cohorts (DS-GIC and MDR-GIC, respectively); 28 patients with DS-TB and 32 patients with MDR-TB in the German validation cohorts (DS-GVC and MDR-GVC, respectively); and 52 patients with MDR-TB in the Romanian validation cohort (MDR-RVC). A 22-gene RNA model (TB22) that defined cure-associated end-of-therapy time points was derived from the DS- and MDR-GIC data. The TB22 model was superior to other published signatures to accurately predict clinical outcomes for patients in the DS-GVC (area under the curve 0.94, 95% CI 0.9-0.98) and suggests that cure may be achieved with shorter treatment durations for TB patients in the MDR-GIC (mean reduction 218.0 days, 34.2%; p<0.001), the MDR-GVC (mean reduction 211.0 days, 32.9%; p<0.001) and the MDR-RVC (mean reduction of 161.0 days, 23.4%; p=0.001)., Conclusion: Biomarker-guided management may substantially shorten the duration of therapy for many patients with MDR-TB., Competing Interests: Conflict of interest: J. Heyckendorf reports no conflicts of interest; the Research Center Borstel has a patent EP20158652.6. Conflict of interest: S. Marwitz has nothing to disclose. Conflict of interest: M. Reimann has nothing to disclose. Conflict of interest: K. Avsar has nothing to disclose. Conflict of interest: A.R. DiNardo has nothing to disclose. Conflict of interest: G. Günther has nothing to disclose. Conflict of interest: M. Hoelscher has nothing to disclose. Conflict of interest: E. Ibraim reports grants, personal fees and non-financial support from Deutsches Zentrum fur Infektionsforschung (DZIF), during the conduct of the study. Conflict of interest: B. Kalsdorf has nothing to disclose. Conflict of interest: S.H.E. Kaufmann has nothing to disclose. Conflict of interest: I. Kontsevaya reports grants from German Center for Infectious Research (DZIF) and German Center for Lung Research (DZL), during the conduct of the study; grants from EU Horizon 2020 AnTBiotic (733079) and CARE (825673), outside the submitted work. Conflict of interest: F. van Leth has nothing to disclose. Conflict of interest: A.M. Mandalakas has nothing to disclose. Conflict of interest: F.P. Maurer has nothing to disclose. Conflict of interest: M. Müller has nothing to disclose. Conflict of interest: D. Nitschkowski has nothing to disclose. Conflict of interest: I.D. Olaru has nothing to disclose. Conflict of interest: C. Popa has nothing to disclose. Conflict of interest: A. Rachow has nothing to disclose. Conflict of interest: T. Rolling has nothing to disclose. Conflict of interest: J. Rybniker has nothing to disclose. Conflict of interest: H.J.F. Salzer has nothing to disclose. Conflict of interest: P. Sanchez-Carballo has nothing to disclose. Conflict of interest: M. Schuhmann has nothing to disclose. Conflict of interest: D. Schaub has nothing to disclose. Conflict of interest: V. Spinu reports grants, personal fees and non-financial support from Deutsches Zentrum fur Infektionsforschung (DZIF), during the conduct of the study. Conflict of interest: I. Suárez has nothing to disclose. Conflict of interest: E. Terhalle has nothing to disclose. Conflict of interest: M. Unnewehr has nothing to disclose. Conflict of interest: J. Weiner 3rd has nothing to disclose. Conflict of interest: T. Goldmann has a patent pending. Conflict of interest: C. Lange reports personal fees for lectures from Chiesi, Gilead, Janssen, Lucane, Novartis, Oxoid, Berlin Chemie and Thermofisher, and personal fees for meeting attendance from Oxford Immunotec, outside the submitted work., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

The SARS-CoV-2 pandemic has required the development of multiple testing systems to monitor and control the viral infection. Here, we developed a PCR test to screen COVID-19 infections that can process up to ~180 samples per day without the requirement of robotics. For this purpose, we implemented the use of multichannel pipettes and plate magnetics for the RNA extraction step and combined the reverse transcription with the qPCR within one step. We tested the performance of two RT-qPCR kits as well as different sampling buffers and showed that samples taken in NaCl or PBS are stable and compatible with different COVID-19 testing systems. Finally, we designed a new internal control based on the human RNase P gene that does not require a DNA digestion step. Our protocol is easy to handle and reaches the sensitivity and accuracy of the standardized diagnostic protocols used in the clinic to detect COVID-19 infections.

Background: Chronic pulmonary aspergillosis (CPA) is a life-threatening sequel in patients with pulmonary tuberculosis (PTB). Aspergillus -specific IgG antibody is a useful diagnostic biomarker supporting CPA diagnosis, especially in countries with limited health recourses., Methods: We conducted a prospective pilot study to assess the seroprevalence of Aspergillus -specific IgG antibodies among 61 Mozambican tuberculosis patients before, during, and after the end of TB treatment. Aspergillus -specific IgG antibody levels were measured using the ImmunoCAP ® ., Results: In this study, 3 out of 21 HIV-negative PTB patients had a positive Aspergillus -specific IgG antibody level before, during, and after the end of TB treatment. Antibody levels were 41.1, 45.5, and 174 mg/L at end of treatment (EOT), respectively. Additionally, two HIV-negative PTB patients with negative Aspergillus -specific IgG antibody levels at baseline became seropositive at EOT (41.9 and 158 mg/L, respectively). Interestingly, none of the HIV-positive PTB patients (40/61) had a positive Aspergillus -specific IgG antibody level at any time, neither at baseline nor at EOT. Probable CPA was diagnosed in one HIV-negative patient (5%; 1/20)., Conclusion: Seroprevalence of Aspergillus -specific IgG antibody may differ between HIV-negative and HIV-positive Mozambican PTB patients. Future studies evaluating post-tuberculosis lung disease should integrate CPA as a life-threatening sequel to PTB.

Aims: COVID-19, a respiratory viral disease causing severe pneumonia, also affects the heart and other organs. Whether its cardiac involvement is a specific feature consisting of myocarditis, or simply due to microvascular injury and systemic inflammation, is yet unclear and presently debated. Because myocardial injury is also common in other kinds of pneumonias, we investigated and compared such occurrence in severe pneumonias due to COVID-19 and other causes., Methods and Results: We analysed data from 156 critically ill patients requiring mechanical ventilation in four European tertiary hospitals, including all n = 76 COVID-19 patients with severe disease course requiring at least ventilatory support, matched to n = 76 from a retrospective consecutive patient cohort of severe pneumonias of other origin (matched for age, gender, and type of ventilator therapy). When compared to the non-COVID-19, mortality (COVID-19 = 38.2% vs. non-COVID-19 = 51.3%, P = 0.142) and impairment of systolic function were not significantly different. Surprisingly, myocardial injury was even more frequent in non-COVID-19 (96.4% vs. 78.1% P = 0.004). Although inflammatory activity [C-reactive protein (CRP) and interleukin-6] was indifferent, d-dimer and thromboembolic incidence (COVID-19 = 23.7% vs. non-COVID-19 = 5.3%, P = 0.002) driven by pulmonary embolism rates (COVID-19 = 17.1% vs. non-COVID-19 = 2.6%, P = 0.005) were higher., Conclusions: Myocardial injury was frequent in severe COVID-19 requiring mechanical ventilation, but still less frequent than in similarly severe pneumonias of other origin, indicating that cardiac involvement may not be a specific feature of COVID-19. While mortality was also similar, COVID-19 is characterized with increased thrombogenicity and high pulmonary embolism rates., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The high clinical mortality and economic burden posed by invasive fungal infections (IFIs), along with significant agricultural crop loss caused by various fungal species, has resulted in the widespread use of antifungal agents. Selective drug pressure, fungal attributes, and host- and drug-related factors have counteracted the efficacy of the limited systemic antifungal drugs and changed the epidemiological landscape of IFIs. Species belonging to Candida , Aspergillus , Cryptococcus , and Pneumocystis are among the fungal pathogens showing notable rates of antifungal resistance. Drug-resistant fungi from the environment are increasingly identified in clinical settings. Furthermore, we have a limited understanding of drug class-specific resistance mechanisms in emerging Candida species. The establishment of antifungal stewardship programs in both clinical and agricultural fields and the inclusion of species identification, antifungal susceptibility testing, and therapeutic drug monitoring practices in the clinic can minimize the emergence of drug-resistant fungi. New antifungal drugs featuring promising therapeutic profiles have great promise to treat drug-resistant fungi in the clinical setting. Mitigating antifungal tolerance, a prelude to the emergence of resistance, also requires the development of effective and fungal-specific adjuvants to be used in combination with systemic antifungals.

The clinical relevance of newly described nontuberculous mycobacteria is often unclear. We report a case of pulmonary infection caused by Mycobacterium hassiacum in an immunocompetent patient in Austria who had chronic obstructive pulmonary disease. Antimicrobial drug susceptibility testing showed low MICs for macrolides, aminoglycosides, fluoroquinolones, tetracyclines, imipenem, and linezolid.

Since its recognition in December 2019, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread globally causing a pandemic that represents the greatest medical challenge in decades. The aim of the study was to evaluate the spectrum of cardiopulmonary pathology of COVID-19 based on (non-minimal invasive) autopsies performed on 14 COVID-19 decedents. Bilateral diffuse alveolar damage (DAD) was found in all patients. Superimposed acute bronchopneumonia was present in 11 of 14 (78.6%) patients and was considered the major cause of death in 2 patients. A key finding was the presence of thrombotic/thromboembolic vascular occlusions. We classified 5 types of pulmonary thrombi: 1. capillary microthrombi (11/14, 78.6%); 2. partially organized thrombi in mid-sized pulmonary arteries with complete vessel occlusion; 3. non-organized thrombi in mid-sized pulmonary arteries that did not completely fill out the vessel lumen and probably represented thromboemboli rather than thrombosis; 4. bone marrow emboli (1/14, 7.1%); and 5. septic pulmonary thromboemboli (1/14, 7.1%). Pulmonary thrombi in mid-sized arteries were noted in 5 of 14 (35.7%) patients, causing pulmonary infarction and/or pulmonary hemorrhage. All patients had evidence of chronic cardiac disease, including myocardial hypertrophy (13/14, 92.9%), mild to marked coronary artery atherosclerosis (14/14, 100%) and focal myocardial fibrosis (3/14, 21.4%). Acute myocardial infarction was found as concurrent cause of death in 3 (21.4%) patients, and significant cardiac hypertrophy (heart weight 750 g) was present in 1 (7.1%) patient with ATTR-positive cardiac amyloidosis. The autopsy findings confirm that COVID-19 is a systemic disease, with major involvement of the lungs, that increases the risk of cardiac and vascular complications including acute myocardial injury and thrombotic/thromboembolic events. Secondary acute bronchopneumonia is a common complication in patients with COVID-19 and may be the major cause of death., (Copyright © 2020. Published by Elsevier Inc.)

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P =0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P <0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

Chronic pulmonary aspergillosis (CPA) is a chronic fungal infection of the lung associated with high morbidity and mortality. The CPA Research network (CPAnet) registry established in 2018 is an international multicenter collaboration aiming to improve CPA knowledge and patient care. This study's aim was to describe the data collection process and content of CPAnet registry with preliminary clinical data. In the CPAnet registry, clinical data are collected through a web-based questionnaire. Data include CPA phenotype, comorbidities, treatment, outcome, and follow-up from several international centers. An exemplary descriptive analysis was performed on 74 patients, who were registered online before April 2020. CPA patients were predominantly (72%) male, 39% had chronic obstructive pulmonary disease, and 68% had a history of smoking. Chronic cavitary pulmonary aspergillosis was the most common CPA subtype (62%). In 32 patients (52%), voriconazole was the preferred first-line therapy. The multicenter multinational CPAnet registry is a valuable approach to gather comprehensive data on a large study population and reflects real-world clinical practice rather than focusing on specific patient populations in more specialized centers. Additional CPA reference centers are being encouraged to join this promising clinical research collaboration.

Chronic pulmonary aspergillosis (CPA) is an uncommon, slowly destructive pulmonary disease characterized by progressive cavitation, fibrosis, and pleural thickening. CPA is usually seen in immunocompetent individuals with underlying respiratory disorders. Estimates suggest that up to 3 million people are affected worldwide causing high rates of morbidity and mortality. Pulmonary tuberculosis (TB) seems to be the most relevant driver for the global burden of CPA with estimates suggesting about 1.2 million patients with CPA as a sequel to TB. Diagnosis of CPA is often challenging and delayed and should be based upon a combination of characteristics. The first guidelines for the diagnosis and management of CPA were published in 2016 jointly by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), the European Respiratory Society (ERS), and the European Confederation of Medical Mycology (ECMM). CPA continues to receive significant public attention, which resulted in almost 150 newly published papers during 2017. The aim of this mini-review is to highlight the most important published papers from January 2017 to April 2018 to provide an update on current developments in the field of CPA., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Introduction: The spectrum of disease caused by Aspergillus spp. is dependent on the immune system of the host, and ranges from invasive aspergillosis (IA) to chronic pulmonary aspergillosis (CPA). Early and reliable diagnosis of Aspergillus disease is important to decrease associated morbidity and mortality. Areas covered: The following review will give an update on current diagnostic strategies for the diagnosis of IA and CPA. Expert commentary: Several new diagnostics for IA (including point-of-care tests) are now available to complement galactomannan testing. In particular, immunoPET/MRI imaging may be a promising approach for diagnosing IA in the near future. Notably, nearly all new biomarkers and tests for IA have been evaluated in the hematology setting only. Validation of biomarkers and tests is therefore needed for the increasing proportion of patients who develop IA outside the hematology setting. As an important first step, reliable definitions of IA are needed for non-hematology settings as clinical presentation and radiologic findings differ in these settings. CPA diagnosis is based on a combination of radiological findings in chest CT, mycological evidence (e.g. by the Aspergillus-specific IgG assay), exclusion of alternative diagnosis and chronicity. ([18F]FDG) PET/CT and immuno PET/MRI imaging are promising new imaging approaches.

Background: Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Active cigarette smoking may have a significant impact on treatment responses to anti-tuberculosis treatment., Objective: To ascertain the effect of smoking on Mycobacterium tuberculosis sputum culture conversion rates following treatment initiation in patients with susceptible, multidrug-resistant and extensively drug-resistant TB (M/XDR-TB)., Method: Sputum cultures of smoking and non-smoking patients with pulmonary TB (PTB) treated at a referral centre in Germany were evaluated., Results: Between January 2012 and March 2017, 247 patients with PTB treated at the Medical Clinic of Research Center Borstel, Borstel, Germany, were included in the study. Of 247 patients, 65 (26.3%) were infected with multidrug-resistant strains of M. tuberculosis (MDR-TB). Sputum culture examinations were performed on a weekly basis. Active smoking ( n = 111; time to culture conversion [TCC] 50.7 days, interquartile range [IQR] 26.5-73.0) and former smoking ( n = 72; TCC 43.1 days, IQR 19.8-56.0) significantly delayed culture conversion rates ( P < 0.001) when compared with never smoking ( n = 64; TCC 33.2 days, IQR 8.0-50.3). Delay in TCC among smoking, non-MDR-TB patients ( n = 138; TCC 47.3 days, IQR 19.0-89.0) was comparable with non-smoking, MDR-TB patients ( n = 20; TCC 53.0 days, IQR 18.0-71.0). The shortest TCC was observed in non-smoking, non-MDR-TB patients ( n = 44; TCC 33.0 days, IQR 10.0-48.5), whereas the longest was seen in smoking, MDR-TB patients ( n = 45; TCC 60.7 days, IQR 33.3-89.0); P < 0.001)., Conclusion: Active cigarette smoking and, to a lesser extent, former cigarette smoking, substantially delayed culture conversion in PTB.

Background: Diagnosis of chronic pulmonary aspergillosis (CPA) is challenging. Symptoms are unspecific or missing, radiological findings are variable and proof of mycological evidence is limited by the accuracy of diagnostic tests. The goal of this study was to investigate diagnostic performance of galactomannan (GM), the newly formatted Aspergillus -specific lateral-flow-device test (LFD), and a number of cytokines in bronchoalveolar lavage fluid (BALF) samples obtained from patients with CPA, patients with respiratory disorders without CPA and healthy individuals. Methods: Patients with CPA ( n = 27) and controls ( n = 27 with underlying respiratory diseases but without CPA, and n = 27 healthy volunteers) were recruited at the Medical University of Graz, Austria and the Research Center Borstel, Germany between 2010 and 2018. GM, LFD and cytokine testing was performed retrospectively at the Research Center Borstel. Results: Sensitivity and specificity of GM testing from BALF with a cut off level of ≥0.5 optical density index (ODI) was 41 and 100% and 30 and 100% with a cut off level of ≥1.0 ODI. ROC curve analysis showed an AUC 0.718 (95% CI 0.581-0.855) for GM for differentiating CPA patients to patients with other respiratory diseases without CPA. The LFD resulted positive in only three patients with CPA (7%) and was highly specific. CPA patients did not differ significantly in the BALF cytokine profile compared to patients with respiratory disorders without CPA, but showed significant higher values for IFN-γ, IL-1b, IL-6, IL-8, and TNF-α compared to healthy individuals. Conclusion: Both GM and LFD showed insufficient performance for diagnosing CPA, with sensitivities of BALF GM below 50%, and sensitivity of the LFD below 10%. The high specificities may, however, result in a high positive predictive value and thereby help to identify semi-invasive or invasive disease.

Background: International travel has increased in the past few decades, placing more travellers at risk of acquiring systemic endemic mycoses. There are limited published data on systemic endemic mycoses among international travellers. We report epidemiological characteristics of non-migrant, international travellers who acquired systemic endemic mycoses during travel., Methods: We analysed records of non-migrant international travellers with a confirmed diagnosis of histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, blastomycosis or talaromycosis reported from 1997 through 2017 to GeoSentinel, a global surveillance network now consisting of 70 travel or tropical medicine centres in 31 countries., Results: Sixty-nine records met the inclusion criteria. Histoplasmosis was most frequently reported; the 51 travellers with histoplasmosis had the lowest median age (30 years; range: 8-85) and shortest median duration of travel (12 days; range: 5-154). Coccidioidomycosis was reported in 14 travellers; travellers with coccidioidomycosis were older (median 62 years; range: 22-78) and had the longest median number of days between return from travel and presentation to a GeoSentinel site (55 days; range: 17-273). Almost all travellers with coccidioidomycosis were exposed in the USA. Other systemic endemic mycoses were less frequently reported, including blastomycosis (three travellers) and talaromycosis (one traveller)., Conclusions: Although relatively rare, systemic endemic mycoses should be considered as potential travel-related infections in non-migrant international travellers. Epidemiological exposures should be used to guide diagnostic evaluations and treatment.

Chronic pulmonary aspergillosis (CPA) is a recognized complication of pulmonary tuberculosis (TB). In 2015, the World Health Organization reported 2.2 million new cases of nonbacteriologically confirmed pulmonary TB; some of these patients probably had undiagnosed CPA. In October 2016, the Global Action Fund for Fungal Infections convened an international expert panel to develop a case definition of CPA for resource-constrained settings. This panel defined CPA as illness for >3 months and all of the following: 1) weight loss, persistent cough, and/or hemoptysis; 2) chest images showing progressive cavitary infiltrates and/or a fungal ball and/or pericavitary fibrosis or infiltrates or pleural thickening; and 3) a positive Aspergillus IgG assay result or other evidence of Aspergillus infection. The proposed definition will facilitate advancements in research, practice, and policy in lower- and middle-income countries as well as in resource-constrained settings.

A 60-year-old man was admitted to the hospital with productive cough and yellowish sputum, severe fatigue, and weight loss of 4 kg over the past month; furthermore, he reported a slowly progressive shortness of breath on exertion over the past 6 months. Before admission, he received ampicillin/sulbactam (750 mg) orally twice daily for 7 days without significant clinical improvement., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)