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Aspergillosis – who gets what, why and when

Aspergillosis – who gets what, why and when. David W. Denning Director, National Aspergillosis Centre University Hospital of South Manchester The University of Manchester. ABPA Severe asthma with fungal sensitisation Allergic sinusitis. Acute Invasive.

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Aspergillosis – who gets what, why and when

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  1. Aspergillosis – who gets what, why and when David W. Denning Director, National Aspergillosis Centre University Hospital of South Manchester The University of Manchester

  2. ABPA Severe asthma with fungal sensitisation Allergic sinusitis Acute Invasive Interaction of Aspergillus with the hostA unique microbial-host interaction Subacute Invasive Frequency of aspergillosis Frequency of aspergillosis Aspergilloma Chronic cavitary Chronic fibrosing Locally invasive Immune dysfunction Immune hyperactivity . After Casadevall & Pirofski, Infect Immun 1999;67:3703

  3. The anecdote

  4. General risk factors

  5. Risk factors for invasive aspergillosis Major • Neutropenia (+ monocytopenia) • Corticosteroid treatment Minor • CD4penia • Inherited immunodeficiency (ie CGD) • Lung or sinus damage/disease • Severe liver disease • Exposure to high inocula

  6. Examples of at-risk patients and pace of progression Relapsed/uncontrolled leukemia Allogeneic stem cell transplant + GVHD 25% Leukemia and profound neutropenia Risk of acquisition (and pace of progression) Solid organ transplant + rejection + CMV 20% Medical ICU, COPD + sepsis Long term glucocorticoids etc Acute respiratory infection, ie influenza 15% Short course glucocorticoids Temporary neutropenia ‘Normal immunity’, high inoculum Chronic leukaemia 10% AIDS HIV infection 5% Degree of immunocompromise

  7. Where in the hospital does invasive aspergillosis occur? Cornillet et al, Clin Infect Dis 2006;43:577

  8. Major underlying conditions

  9. IA following HSCT Pagano et al, Clin Infect Dis 2007;45:1161

  10. Probably significant underestimates Estimated number of cases of invasive fungal infectionUK [2002] Totals 5466 4120 ** no estimate for surgical patients, but some are in ICU, or have advanced cancer @ no inclusion of most chronic chest, steroid-treated patients, an increasing group # the literature figure is 6%, but felt to be autopsy selection bias, so reduced by 75%. http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1196942156347

  11. Probably significant underestimates Estimated number of cases of invasive fungal infectionUK [2002] Totals 5466 4120 ** no estimate for surgical patients, but some are in ICU, or have advanced cancer @ no inclusion of most chronic chest, steroid-treated patients, an increasing group # the literature figure is 6%, but felt to be autopsy selection bias, so reduced by 75%. http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1196942156347

  12. Invasive aspergillosis in ICU 127 of 1850 (6.9%) consecutive medical ICU admissions with IA or colonisation (micro/histol). COPD = 33 of 67 (50%) proven/probable IA Meersemann et al, Am J Resp Med Crit Care 2004;170:621.

  13. Risk factors for invasive aspergillosis in ICU Meersseman, Clin Infect Dis 2007;45:205

  14. Acute Invasive EU caseload of aspergillosis 30,000 - 70,000 cases Subacute Invasive Frequency of aspergillosis Frequency of aspergillosis Immune dysfunction Immune hyperactivity . After Casadevall & Pirofski, Infect Immun 1999;67:3703

  15. Chronic pulmonary aspergillosis Chronic cavitary pulmonary aspergillosis complicating ABPA Chronic cavitary pulmonary aspergillosis with bilateral aspergillomas complicating sarcoidosis www.aspergillus.org.uk

  16. Chronic Pulmonary Aspergillosis Underlying diseases • Classical tuberculosis * ~20% • Atypical tuberculosis * • Allergic bronchopulmonary aspergillosis * • Lung cancer survivor * • Pneumothorax * • COPD/emphysema * • Sarcoidosis (stage II/III) * • Rheumatoid arthritis • Thoracic surgery • Asthma • Chest radiotherapy • None * Common Smith, ISHAM 2009

  17. Frequency of chronic pulmonary aspergillosis after TB 25-33% of patients with TB are left with a cavity ~10% of all cases of pulmonary TB get CPA Anonymous. Tubercle 1970;51:227; Sonnenberg et al, Lancet 2001;358:1687

  18. Acute Invasive EU caseload of aspergillosis 30,000 - 70,000 cases Subacute Invasive Frequency of aspergillosis Frequency of aspergillosis Aspergilloma Chronic cavitary Chronic fibrosing Locally invasive ~7,500 cases Immune dysfunction Immune hyperactivity . After Casadevall & Pirofski, Infect Immun 1999;67:3703

  19. ABPA and severe asthma www.emphysema-copd.co.uk

  20. Likely ABPA caseload 1%+ of adult asthmatics attending clinic have ABPA In UK - ~5,000,000 with asthma, >3M adults In Europe - >17,000,000 adults with asthma ~150,000 adults with ABPA in Europe ~12% of those with CF have ABPA EU CF population ~150,000 = ~17,500 patients

  21. Likely SAFS caseload in Europe In Europe - >17,000,000 adults with asthma ~20% have severe asthma = 3,400,000 adults 20-50% of severe asthmatics have SAFS SAFS cases (EU) = 680,000 – 1,700,000 Zureik et al, Br Med J 2002;325:411

  22. Brazil survey of fungal rhinosinusitis 890 endoscopic sinus surgeries 62 (6.8%) had fungal rhinosinusitis Dall’Igna Rev Bras Otorhinolaringol 2005;71:712

  23. Prevalence of allergic rhinoconjunctivitis symptoms ISAAC Steering Committee Lancet 1998;351,1225

  24. Prevalence of chronic rhinosinusitis Global population ~6Bn If rate of allergic rhinosinusitis 15% then 900M cases, which USA = 52M Europe = 55.5M Japan = 19M ISAAC Steering Committee Lancet 1998;351,1225

  25. ABPA Severe asthma with fungal sensitisation Allergic sinusitis Acute Invasive EU caseload of aspergillosis 167,500+ ABPA cases 680,000 - 1,700,000 SAFS cases 11,200,000 CRFS cases 25,000 - 70,000 cases Subacute Invasive Frequency of aspergillosis Frequency of aspergillosis Aspergilloma Chronic cavitary Chronic fibrosing Locally invasive ~7,500 cases Immune dysfunction Immune hyperactivity . After Casadevall & Pirofski, Infect Immun 1999;67:3703

  26. www.aspergillus.org.uk

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