by author The Interaction Between Influenza and Aspergillus Carolina Garcia-Vidal Infectious Diseases Department Hospital Clínic Barcelona

Transcription

1 The Interaction Between Influenza and Aspergillus Carolina Garcia-Vidal Infectious Diseases Department Hospital Clínic Barcelona Influenza-associated aspergillosis-eccmid April 2018

2 Relationship between influenza and aspergillus

3 New diagnostic tools have allowed us to better recognize the strong association between these infections 0

4 Garcia-Vidal C et al. Epidemiology of invasive mold infections in allogenic SCT recipients:biological risk factors for infection according to time after transplantation; Clin Infect Dis 2008; EARLY INFECTION LATE INFECTION > 40 years old Underlying disease Transplant-related factors Cytopenias Respiratory viruses CMV diseases Graft versus host diseases Corticosteroids Blood transfusion

5 Garcia-Vidal C et al. Epidemiology of invasive mold infections in allogenic SCT recipients:biological risk factors for infection according to time after transplantation; Clin Infect Dis 2008; EARLY INFECTION LATE INFECTION > 40 years old Underlying disease Transplant related factors Cytopenias Respiratory viruses CMV diseases Graft versus host diseases Corticosteroids Blood transfusion

6 Garcia-Vidal C et al. Epidemiology of invasive mold infections in allogenic SCT recipients:biological risk factors for infection according to time after transplantation; Clin Infect Dis 2008; EARLY INFECTION LATE INFECTION > 40 years old Underlying disease Transplant related factors Cytopenias Respiratory viruses CMV diseases Graft versus host diseases Corticosteroids Blood transfusion

7 Garcia-Vidal C et al. Epidemiology of invasive mold infections in allogenic SCT recipients:biological risk factors for infection according to time after transplantation; Clin Infect Dis 2008; > 40 years old Underlying disease Transplant related factors Cytopenias Respiratory viruses CMV diseases Graft versus host diseases Corticosteroids Blood transfusion Parainfluenza 3, Respiratory syncytial virus, Influenza Few days after viral infection Worsening of respiratory symptoms after patient s condition had initially improved

8 Lat A et al. Invasive Aspergillosis after pandemic influenza A (H1N1) 2009 Emerg Infect Dis 2010; 51: year-old man (college student) No prior medical history Respiratory failure -> mechanical ventilation Influenza (H1N1) pdm 09 Received high dose of methylprednisolone Necrosis of the airway wall and cartilage Extensive hyphae and A. fumingatus culture 51-year-old man (office worker) No prior medical history Respiratory failure -> mechanical ventilation Influenza (H1N1) pdm 09 Received high dose of methylprednisolone Lung bleeding Extensive hyphae and A. fumingatus culture Exitus Exitus

9 Garcia-Vidal C et al. Invasive Aspergillosis complicating pandemic influenza A (H1N1) infection in severely immunocompromised patients Clin Infect Dis 2011; 53 : e16-e19 The frequency of IA in patients with AML or in transplant recipients who have influenza A(H1N1) pdm09 was 8.8%.

10 Relationship between influenza and aspergillosis Aspergillosis pathogenesis

11 Video

12 Garcia-Vidal C et al. Pathogenesis of invasive fungal infections Curr Opin Infect Dis 2013; 26 : m 3 Spores (conidias) < 5 micras Aspergillus fumigatus A. flavus A. niger > 5-10 micras

13 Garcia-Vidal C et al. Pathogenesis of invasive fungal infections Curr Opin Infect Dis 2013; 26 : Innate immune system Germination and Hyphae production TNF-alpha Macrophages disfunction (viral infections) INF-gamma macrophage IL-10 Dendritic cell

14 Garcia-Vidal C et al. Immunopathogenesis of invasive mould infections; Rev Iberoam Micol 2014; 31: Pro-inflammatory cytokines TNF-alpha, INF-gamma IL-12, IL-15 Th 1/Th17 Protection against fungal infections Innate immune system Anti-inflammatory cytokines IL-10, IL-4 Th 2/Treg Impaired host defense against fungal infections

15 Garcia-Vidal C et al. Pathogenesis of invasive fungal infections Curr Opin Infect Dis 2013; 26 : Innate immune system leucocytes pmn TNF-alpha Macrophages disfunction (viral infections) INF-gamma macrophage IL-10 Dendritic cell

16 Garcia-Vidal C et al. Pathogenesis of invasive fungal infections Curr Opin Infect Dis 2013; 26 : Innate immune system Adaptative immune system macrophage leucocytes pmn macrophage Macrophages disfunction (viral infections) TNF-alpha INF-gamma macrophage IL-10 Chronic necrotizing aspergillosis Dendritic cell

17 TNF-alpha INF-gamma IL-10 Dendritic cell

18 Garcia-Vidal C et al. Pathogenesis of invasive fungal infections Curr Opin Infect Dis 2013; 26 : neutropenia < 100 leucocitos Macrophage disfunction (viral infections) Macrophage Dendritic Célula dendrítica cell

19 Garcia-Vidal C et al. Pathogenesis of invasive fungal infections Curr Opin Infect Dis 2013; 26 : dissemination angioinvasion

20 Garcia-Vidal C et al. Pathogenesis of invasive fungal infections Curr Opin Infect Dis 2013; 26 : Ischemic necrosis trombosis angioinvasion Halo sign Invasive aspergillosis

21 Host immune response and clinical forms of Figure from Taylor R, Clin Microbiol Rev 2009: aspergillosis and diagnostic Chronic necrotizing aspergillosis Less invasion - Cavitation forms - Need for BAL (GMN > 0,8) Invasive aspergillosis angioinvasion - Halo sign. Air crescent sign - Serum GMN > 0,5

22 Bermejo-Martin JF et al. Host adaptive immunity deficiency in severe pandemic influenza; Crit Care 2010; 14 : R167

23 Relationship between influenza and aspergillosis Aspergillosis pathogenesis Role of viral infections in facilitating fungal pathogenesis

24

25

26

27 Invasive aspergilosis IL-10

28 Lionakis M, et al. Glucocorticoids and invasive fungal infections Impaired phagocytosis, degranulation and oxidative burst Impaired formation of nitric oxide Inhibition of apoptosis Impaired phagocitosis and oxidative killing Impaired maduration of macrophages Inhibition of pro-inflammatory citokine productin Lancet : Lymphopenia Decreased proliferation and migration of lymphocytes Decreased citokine production Decreased Th1 and increased Th2 cytokine production Decreased counts of alveolar dendritic cells Impaired antigen-presenting capacity of dendritic cells Decreased cell-killing capacity

29 Relationship between influenza and aspergillosis Aspergillosis pathogenesis Role of viral infections in facilitating fungal pathogenesis Impact of respiratory viral infection in IA in real life

30 Garcia-Vidal C, et al. Environmental variables associated with an increased risk of invasive aspergillosis Clin Microbiol Infect 2014; 20: Influenza A Influenza B Adenovirus Respiratory syncytial virus HOST FUNGI Precipitation Humidity Wind Wind speed Temperature

31 Garcia-Vidal C, et al. Environmental variables associated with an increased risk of invasive aspergillosis Clin Microbiol Infect 2014; 20: Institute of Environmental Science and Technology at the Autonomous University of Barcelona determined daily median airborne mould concentrations. The estimations were based on continuous measurements taken at different points of the city. The Catalan Meteorological Service provided data on climatic conditions based on continuous measurements taken at the weather station in the urban area. Data on circulating respiratory virus were obtained from The Acute Respiratory Infection Surveillance Project of Catalonia. The distribution of admissions for IA in 3-tertiary teaching institutions.

32 Garcia-Vidal C, et al. Environmental variables associated with an increased risk of invasive aspergillosis Clin Microbiol Infect 2014; 20: No relationship between climatic conditions and airbone mould count or IA admissions was found The presence of airborne mould spores increased the risk of IA admission 6 times after the third 2-week period days Spearman Rho correlation 0.241; p=0.014 AI day 0 (dx)

33 Garcia-Vidal C, et al. Environmental variables associated with an increased risk of invasive aspergillosis Clin Microbiol Infect 2014; 20: days Day 0 dx AI 7-14 days 7 days Day 0 dx AI Day 0 dx AI During circulating respiratory virus periods we found that a lower airborne mould spore load was required for IA to occur. Moreover, time to report spore inhalation and IA was shorter

34

35 Thankatención you for your attention!