The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology and the European Respiratory Society Joint Clinical Guidelines focus on diagnosis and management of aspergillosis. Of the numerous recommendations, a few are summarized here. Chest computed tomography as well as bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis (IA) are strongly recommended. For diagnosis, direct microscopy, preferably using optical brighteners, histopathology and culture are strongly recommended. Serum and BAL galactomannan measures are recommended as markers for the diagnosis of IA. PCR should be considered in conjunction with other diagnostic tests. Pathogen identification to species complex level is strongly recommended for all clinically relevant Aspergillus isolates; antifungal susceptibility testing should be performed in patients with invasive disease in regions with resistance found in contemporary surveillance programmes. Isavuconazole and voriconazole are the preferred agents for first-line treatment of pulmonary IA, whereas liposomal amphotericin B is moderately supported. Combinations of antifungals as primary treatment options are not recommended. Therapeutic drug monitoring is strongly recommended for patients receiving posaconazole suspension or any form of voriconazole for IA treatment, and in refractory disease, where a personalized approach considering reversal of predisposing factors, switching drug class and surgical intervention is also strongly recommended. Primary prophylaxis with posaconazole is strongly recommended in patients with acute myelogenous leukaemia or myelodysplastic syndrome receiving induction chemotherapy. Secondary prophylaxis is strongly recommended in high-risk patients. We strongly recommend treatment duration based on clinical improvement, degree of immunosuppression and response on imaging.

Chronic pulmonary aspergillosis (CPA) is an uncommon and problematic pulmonary disease, complicating many other respiratory disorders, thought to affect ∼240 000 people in Europe. The most common form of CPA is chronic cavitary pulmonary aspergillosis (CCPA), which untreated may progress to chronic fibrosing pulmonary aspergillosis. Less common manifestations include: Aspergillus nodule and single aspergilloma. All these entities are found in non-immunocompromised patients with prior or current lung disease. Subacute invasive pulmonary aspergillosis (formerly called chronic necrotising pulmonary aspergillosis) is a more rapidly progressive infection (<3 months) usually found in moderately immunocompromised patients, which should be managed as invasive aspergillosis. Few clinical guidelines have been previously proposed for either diagnosis or management of CPA. A group of experts convened to develop clinical, radiological and microbiological guidelines. The diagnosis of CPA requires a combination of characteristics: one or more cavities with or without a fungal ball present or nodules on thoracic imaging, direct evidence of Aspergillus infection (microscopy or culture from biopsy) or an immunological response to Aspergillus spp. and exclusion of alternative diagnoses, all present for at least 3 months. Aspergillus antibody (precipitins) is elevated in over 90% of patients. Surgical excision of simple aspergilloma is recommended, if technically possible, and preferably via video-assisted thoracic surgery technique. Long-term oral antifungal therapy is recommended for CCPA to improve overall health status and respiratory symptoms, arrest haemoptysis and prevent progression. Careful monitoring of azole serum concentrations, drug interactions and possible toxicities is recommended. Haemoptysis may be controlled with tranexamic acid and bronchial artery embolisation, rarely surgical resection, and may be a sign of therapeutic failure and/or antifungal resistance. Patients with single Aspergillus nodules only need antifungal therapy if not fully resected, but if multiple they may benefit from antifungal treatment, and require careful follow-up. @ERSpublications ERS and ESCMID guideline for the management of chronic pulmonary aspergillosis released

Abstract Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.

No abstract

Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. A panel of experts was carefully selected by leading international respiratory medicine and infectious diseases societies (ATS, ERS, ESCMID, IDSA) and included specialists in pulmonary medicine, infectious diseases and clinical microbiology, laboratory medicine, and patient advocacy. Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. This guideline is intended for use by healthcare professionals who care for patients with NTM pulmonary disease, including specialists in infectious diseases and pulmonary diseases.

American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB).Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-c release assays or, as an alternative in individuals without a history of bacille Calmette-Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis.Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test and an interferon-c release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistent M. tuberculosis-specific immune responses undergoing TNF antagonist therapy as it significantly reduces the risk of progression to TB. This TBNET consensus statement summarises current knowledge and expert opinions and provides evidence-based recommendations to reduce the TB risk among candidates for TNF antagonist therapy.KEYWORDS: Interferon-c release assay, tuberculin skin test, tuberculosis, tumour necrosis factor T umour necrosis factor (TNF) and TNF receptors play a key role in mediating immune responses in acute and chronic inflammation [1][2][3]. Over the past decade, TNF antagonists in the form of anti-TNF monoclonal antibodies or TNF fusion protein have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, psoriasis and psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis and inflammatory bowel disease [4][5][6][7]. Tuberculosis (TB) is a granulomatous disease caused by infection with Mycobacterium tuberculosis.Most of the individuals who are thought to have become infected with M. tuberculosis will never develop TB due to the control exercised by the host immune system [8,9]. One of the key cytokines in the immune response against infection with M. tuberculosis is TNF, which is also critical for the integrity of the granuloma [10]. Individuals who are being treated with anti-TNF therapies are at increased risk of developing TB. Following TNF antagonist therapy, the relative risk for TB is increased 1.6-25.1 times, depending on the clinical setting and the TNF antagonist used [4,7,11,12]. The majority of cases of TB related to TNF antagonist therapies occur in close temporal proximity to

IntroductionImmunity to infections depends on the successful integration of innate and adaptive defense strategies. 1 Cells of the innate immune system, such as macrophages and dendritic cells, recognize pathogen-associated molecular patterns shared by many microbes but not found in higher eukaryotes, via members of the Toll-like receptor (TLR) family. 2,3 TLR-dependent signaling pathways can directly induce macrophage antimicrobial programs but also initiate inflammatory cell recruitment and help prime cells of the adaptive immune system to amplify bactericidal effector mechanisms. Experimental infections with microorganisms have been used successfully to uncover the intricacies governing the interplay between innate and adaptive immunity. 4,5 For example, cell-wall components of Mycobacterium tuberculosis, the causative organism of tuberculosis, critically depend on TLR2 and TLR4 to induce secretion of the proinflammatory cytokines tumor necrosis factor alpha (TNF-␣) and interleukin (IL-12, necessary for differentiating T-helper 1 cells). 6 Subsequently, mycobacteria-primed T cells secrete interferon gamma (IFN-␥) as a critical macrophageactivating agent. Eradication of mycobacteria is achieved only when both arms of the immune system are fine-tuned for full antimicrobial potency.Functionally, the Toll-mediated induction of antimicrobial effector systems is highly conserved between Drosophila melanogaster (D melanogaster) and Homo sapiens. 7,8 Another example for human evolutionarily ancient effector mechanisms is granulysin (a granule-stored bactericidal molecule), which is homologous to the amoebapores of Entamoeba histolytica. 9,10 Thus, there is ample precedence for evolutionarily conserved signatures governing individual facets of the immune response. To uncover novel regulatory pathways in innate responses to infection, we performed a microarray-based gene-expression screen with human macrophages infected with mycobacteria or conserved bacterial structures. We found mRNA for WNT5A, a homolog of Wingless in Drosophila species, to be consistently up-regulated in response to all stimuli.Wingless was originally characterized as a segment polarity gene in D melanogaster, which is essential in embryonic segmentation and patterning (reviewed in Klingensmith and Nusse 11 ). Various homologs of the Wingless protein, termed WNT, are involved in embryonic development of nonvertebrates and vertebrates, 12,13 where WNT signaling determines cell motility, differentiation, and apoptosis. 14 In mammalian hematopoiesis, WNT signaling is essential for stem-cell homeostasis 15 and lymphocyte differentiation. 16,17 Most recently, one member of the WNT family of proteins, WntD, was shown to be involved in regulating antibacterial defenses in Drosophila. 18 To date, however, WNT Center Borstel, Germany), phorbol-12-myristate13-acetate (PMA), calcium ionophore A23187 (both Sigma Aldrich, Taufkirchen, Germany), and phytohemagglutinin (PHA) were used for stimulation. To rule out the presence of lipopolysaccharides (LPSs) in the...