Invasive Aspergillus Tracheobronchitis Emerging as a Highly Lethal Complication of Severe Influenza.
Ontology highlight
ABSTRACT:
SUBMITTER: van de Veerdonk FL
PROVIDER: S-EPMC7462390 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
Invasive <i>Aspergillus</i> Tracheobronchitis Emerging as a Highly Lethal Complication of Severe Influenza.
van de Veerdonk Frank L FL Wauters Joost J Verweij Paul E PE
American journal of respiratory and critical care medicine 20200901 5
Similar Datasets
Project description:We report a bronchoscopic image of a 36-year-old with significant airway obstruction from obstructive tracheobronchitis secondary to invasive pulmonary aspergillosis. It is rare to see such a severe form of obstructive tracheobronchitis, likely caused by the patient'sp immunocompromised status and rapid progression nature of influenza-associated pulmonary aspergillosis.
| S-EPMC11311288 | biostudies-literature
Project description:Invasive pulmonary aspergillosis is emerging as a secondary infection in patients with COVID-19, which can present as alveolar disease, airway disease (ie, invasive Aspergillus tracheobronchitis), or both. Histopathology of invasive Aspergillus tracheobronchitis in patients with severe COVID-19 confirms tracheal ulcers with tissue invasion of Aspergillus hyphae but without angioinvasion, which differs from patients with severe influenza, where early angioinvasion is observed. We argue that aggregation of predisposing factors (eg, factors that are defined by the European Organisation for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium or genetic polymorphisms), viral factors (eg, tropism and lytic effects), immune defence factors, and effects of concomitant therapies will determine whether and when the angioinvasion threshold is reached. Management of invasive Aspergillus tracheobronchitis should include reducing viral lytic effects, rebalancing immune dysregulation, and systemic and local antifungal therapy. Future study designs should involve approaches that aim to develop improved diagnostics for tissue invasion and airways involvement and identify the immune status of the patient to guide personalised immunotherapy.
| S-EPMC8153840 | biostudies-literature
Project description:We describe a novel heterothallic species in Aspergillus section Fumigati, namely A. felis (neosartorya-morph) isolated from three host species with invasive aspergillosis including a human patient with chronic invasive pulmonary aspergillosis, domestic cats with invasive fungal rhinosinusitis and a dog with disseminated invasive aspergillosis. Disease in all host species was often refractory to aggressive antifungal therapeutic regimens. Four other human isolates previously reported as A. viridinutans were identified as A. felis on comparative sequence analysis of the partial β-tubulin and/or calmodulin genes. A. felis is a heterothallic mold with a fully functioning reproductive cycle, as confirmed by mating-type analysis, induction of teleomorphs within 7 to 10 days in vitro and ascospore germination. Phenotypic analyses show that A. felis can be distinguished from the related species A. viridinutans by its ability to grow at 45°C and from A. fumigatus by its inability to grow at 50°C. Itraconazole and voriconazole cross-resistance was common in vitro.
| S-EPMC3683053 | biostudies-literature
Project description:Influenza outbreaks are associated with substantial morbidity, mortality and economic burden. Next generation antivirals are needed to treat seasonal infections and prepare against zoonotic spillover of avian influenza viruses with pandemic potential. Having previously identified oral efficacy of the nucleoside analog 4'-Fluorouridine (4'-FlU, EIDD-2749) against SARS-CoV-2 and respiratory syncytial virus (RSV), we explored activity of the compound against seasonal and highly pathogenic influenza (HPAI) viruses in cell culture, human airway epithelium (HAE) models, and/or two animal models, ferrets and mice, that assess IAV transmission and lethal viral pneumonia, respectively. 4'-FlU inhibited a panel of relevant influenza A and B viruses with nanomolar to sub-micromolar potency in HAE cells. In vitro polymerase assays revealed immediate chain termination of IAV polymerase after 4'-FlU incorporation, in contrast to delayed chain termination of SARS-CoV-2 and RSV polymerase. Once-daily oral treatment of ferrets with 2 mg/kg 4'-FlU initiated 12 hours after infection rapidly stopped virus shedding and prevented transmission to untreated sentinels. Treatment of mice infected with a lethal inoculum of pandemic A/CA/07/2009 (H1N1)pdm09 (pdmCa09) with 4'-FlU alleviated pneumonia. Three doses mediated complete survival when treatment was initiated up to 60 hours after infection, indicating a broad time window for effective intervention. Therapeutic oral 4'-FlU ensured survival of animals infected with HPAI A/VN/12/2003 (H5N1) and of immunocompromised mice infected with pdmCa09. Recoverees were protected against homologous reinfection. This study defines the mechanistic foundation for high sensitivity of influenza viruses to 4'-FlU and supports 4'-FlU as developmental candidate for the treatment of seasonal and pandemic influenza.
| S-EPMC10138230 | biostudies-literature
Project description: Not available
| S-EPMC9068972 | biostudies-literature
Project description:Compounds that target the cellular factors essential for influenza virus replication represent an innovative approach to antiviral therapy. Sp2CBMTD is a genetically engineered multivalent protein that masks sialic acid-containing cellular receptors on the respiratory epithelium, which are recognized by influenza viruses. Here, we evaluated the antiviral potential of Sp2CBMTD against lethal infection in mice with an emerging A/Anhui/1/2013 (H7N9) influenza virus and addressed the mechanistic basis of its activity in vivo. Sp2CBMTD was administered to mice intranasally as a single or repeated dose (0.1, 1, 10, or 100 ?g) before (day -7, -3, and/or -1) or after (6 or 24 h) H7N9 virus inoculation. A single Sp2CBMTD dose (10 or 100 ?g) protected 80% to 100% of the mice when administered 7 days before the H7N9 lethal challenge. Repeated Sp2CBMTD administration conferred the highest protection, resulting in 100% survival of the mice even at the lowest dose tested (0.1 ?g). When treatment began 24 h after exposure to the H7N9 virus, a single administration of 100 ?g of Sp2CBMTD protected 40% of the mice from death. The administration of Sp2CBMTD induced the pulmonary expression of proinflammatory mediators (interleukin-6 [IL-6], IL-1?, RANTES, monocyte chemotactic protein-1 [MCP-1], macrophage inflammatory protein-1? [MIP-1?], and inducible protein [IP-10]) and recruited neutrophils to the respiratory tract before H7N9 virus infection, which resulted in less pronounced inflammation and rapid virus clearance from mouse lungs. Sp2CBMTD administration did not affect the virus-specific adaptive immune response, which was sufficient to protect against reinfection with a higher dose of homologous H7N9 virus or heterologous H5N1 virus. Thus, Sp2CBMTD was effective in preventing H7N9 infections in a lethal mouse model and holds promise as a prophylaxis option against zoonotic influenza viruses.
| S-EPMC4325779 | biostudies-other
Project description:Invasive pulmonary aspergillosis (IPA) is a severe fungal disease caused by Aspergillus spp. (particularly A. fumigatus or Af) that may spread hematogenously to extrapulmonary organs. IPA is typically associated with a broad spectrum of immunocompromised conditions and immunologic disorders and constitutes a high mortality rate. While the association of influenza as a risk for secondary bacterial infections is well appreciated, emerging evidence indicates that influenza-hospitalized patients demonstrate increased susceptibility to severe aspergillosis infection. In this study, we developed a murine Influenza A Virus (IAV)-Af co-infection model and investigated the role of IAV host response in promoting severe Af infection. Our data show that in a co-infection setting, while IAV suppresses Af-induced CXCL1 and early neutrophil recruitment, no defects in neutrophil phagocytic responses were observed. On the contrary, despite similar fungal burdens and conidial germination between single Af and co-infected lungs, there was greater fungal invasiveness in the early phase of IAV-Af co-infection. These findings suggest that enhanced lung inflammation, vascular injury, and loss of tissue protection in IAV-infecetd lung likely contribute to severe secondary Af infection.
2025-07-16 | GSE276049 | GEO
Project description:Since December 2014, Eurasian-origin, highly pathogenic avian influenza H5 viruses including H5N1, H5N2, and H5N8 subtypes (called H5Nx viruses), which belong to the H5 clade 2.3.4.4, have been detected in U.S. wild birds. Subsequently, highly pathogenic H5N2 and H5N8 viruses have caused outbreaks in U.S. domestic poultry. Vaccination is one of the most effective ways to control influenza outbreaks and protect animal and public health. Newcastle disease virus (NDV)-based influenza vaccines have been demonstrated to be efficacious and safe in poultry. Herein, we developed an NDV-based H5 vaccine (NDV-H5) that expresses a codon-optimized ectodomain of the hemagglutinin from the A/chicken/Iowa/04-20/2015 (H5N2) virus and evaluated its efficacy in chickens. Results showed that both live and inactivated NDV-H5 vaccines induced hemagglutinin inhibition antibody titers against the H5N2 virus in immunized chickens after prime and booster, and both NDV-H5 vaccines completely protected chickens from lethal challenge with the highly pathogenic H5N2 A/turkey/Minnesota/9845-4/2015 virus. No clinical signs and only minimal virus shedding was observed in both vaccinated groups. In contrast, all mock-vaccinated, H5N2-infected chickens shed virus and died within 5 days post challenge. Furthermore, one dose of the live NDV-H5 vaccine also provided protection of 90% chickens immunized by coarse spraying; after exposure to H5N2 challenge, sera from vaccinated surviving chickens neutralized both highly pathogenic H5N1 and H5N8 viruses. Taken together, our results suggest that the NDV-based H5 vaccine is able to protect chickens against intercontinental highly pathogenic H5Nx viruses and can be used by mass application to protect the poultry industry.
| S-EPMC5714955 | biostudies-literature
Project description:Eleven highly pathogenic avian influenza H5N8 viruses (clade 2.3.4.4b) were detected in migratory birds in Central China between November and December 2020, which were highly homologous to strains isolated in Europe from October to December 2020. Phylogenetic analysis indicated that the strains in the study possibly spread from Siberia by migratory birds. In this study, we found H5N8 virus infection in migratory birds could cause severe pathological damage and high viral load in multiple organs.
| S-EPMC8330791 | biostudies-literature
Project description: Not available
| S-EPMC3216443 | biostudies-literature