Aspergillus and aspergillosis: an introduction Malcolm Richardson Director© by author Mycology Reference Centre UHSM and University of ESCMID OnlineManchester Lecture Library Aspergillus and aspergillosis © by author ESCMID Online Lecture Library Aspergillus is in the air © by author ESCMID Online Lecture Library ASPERGILLOSIS © by author ESCMID Online Lecture Library A short history of Aspergillus • First catalogued by P. Michelli in 1729 • First known case of infection: 1815 (jackdaw) • 1842 (human) • Occupational hazard amongst wig combers • (allergic disease of the lungs). © by author ESCMID Online Lecture Library Sources of Infection – Soil – Air; spores may be inhaled – Water / storage tanks in hospitals – Food – Compost and decaying vegetation – Fire proofing materials – Bedding, pillows – Ventilation and air© conditioning by author systems – Computer fans ESCMID Online Lecture Library Members of the family • Genus of around 200 fungi (moulds) worlwide • Filamentous fungus (opposed to single celled • fungus), reproduction by spores • A. fumigatus, A. flavus, A. niger, A. clavatus © by author ESCMID Online Lecture Library Where is Aspergillus found? • Natural habitat: hay and compost. • Aspergillus spores are easily airborne • (100-200 spores daily). • • Some species withstand heat (Aspergillus • fumigatus), commonly© by found author in compost. ESCMID Online Lecture Library Pulmonary Aspergillosis • Allergic Aspergillosis • Noninvasive Local Colonization © by author • Invasive Aspergillosis ESCMID Online Lecture Library © by author ESCMID Online Lecture Library Allergic Aspergillosis • Asthma bronchiale • Allergic bronchopulmonary aspergillosis ABPA (Types I, III) • Allergic Aspergillus sinusitis – AAS © by author • Allergic alveolitis ESCMID Online Lecture Library ABPA • Hypersensitivity-reaction • A. fumigatus • Bronchial collapse,© by author bronchiectasis • Lung infiltration by eosinophils ESCMID Online Lecture Library Noninvasive Local Colonization • Aspergilloma (cavities) • Otomycosis • Onchomycosis © by author • Eye infection ESCMID Online Lecture Library Aspergillus sinusitis © by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library Growth of Aspergillus 1-2 mm per hour © by author ESCMID Online Lecture Library Invasive Aspergillosis • Rare, but life-threatening • Progression speed varies • Immunocompetency© by author ESCMID• Pulmonary Online vs. Lecture disseminated Library EORTC-MSG Standards • DEFINITE • positive histology or culture • PROBABLE • © bysputum author • antigen • CT ESCMID Online Lecture Library Pulmomary aspegillosis © by author ESCMID Online Lecture Library © by author ESCMID Online Lecture Library © by authorAspergilloma ESCMID Online Lecture Library MORTALITY OF INVASIVE ASPERGILLOSIS IN RELATION TO UNDERLYING DISEASE Lin, Schranz, Teutsch Clin Infect Dis 2001;32:358 100 90 80 70 60 50 40 © by author 30 20 bone bone transplant marrow /lymphoma kidney transplant kidney AIDS liver transplant liver 10 leukemia /heart lung ESCMID Online Lecture Library transplant The Helsinki experience: adults • 1989-1995 • 22 IPA allo BMT • Diagnosis 69-466 (median 131 days post Tx) • 16 (73%) definite or probable • Lung involvement: 90% • CNS: 41% • respiratory symptoms >50% • neurological symptoms 27% • Optimal diagnosis: tissue biopsy • BAL: 8/14 ”suggestive©” by author Jantunen et al. BMT 2000; 25: 867-871 ESCMID Online Lecture Library The Helsinki experience: children Invasive fungal infections in pediatric bone marrow transplant recipients: single center experience of 10 years • 148 BMT • 12/73 (16%) infection: allogeneic • 6/75 (8%) infection: autologous • 15/18 died, in 12 IFI as cause of death • 48 suspected infections • allogeneics: severe© GVHDby author major risk factor • steroid dose associated with IFI HoviESCMID et al. Bone Marrow Online Transplantation Lecture 2000; Library 26: 999-1004. Pathophysiology of aspergillosis © by author ESCMID Online Lecture Library The life cycle of Aspergillus Spores Germination © by author Mass of hyphae Hyphal elongation (plateau phase) and branching ESCMID Online Lecture Library Gravity sedimentation © by author ESCMID Online Lecture Library Aspergillus in tea! © by author ESCMID Online Lecture Library © by authorAir sampling ESCMID Online Lecture Library Air sampling: >1300 cfu/m3! © by author ESCMID Online Lecture Library © by author Dust ESCMID Online Lecture Library © by authorDust collection ESCMID Online Lecture Library Double door entry: HYKS © by author ESCMID Online Lecture Library Ceiling tiles: HYKS © by author ESCMID Online Lecture Library Nosocomial aspergillosis © by author ESCMID Online Lecture Library Nosocomial aspergillosis © by author ESCMID Online Lecture Library Invasive aspergillosis © by author ESCMID Online Lecture Library DEVELOPMENT OF ASPERGILLOSIS INHALATION COLONIZATION INFECTION Dissemination 1 2 © by author3 ESCMID Online Lecture Library IPA: DISEASE PROGRESSION CAB CAB CAB CAB 0.3mg 0.5mg 0.8mg DC Day 1 4© by author 7 10 2cms/day in vitro ESCMID Online Lecture Library Aspergillus: Risk of aspergillosis Remission induction Consolidation Allogeneic BM SCT GVHD Complete remission Remission Remission induction induction © by author Refractory Refractory Risk of aspergillosis ESCMID Online Lecture Library Aspergillus: Time to diagnosis of aspergillosis after BMT 20 Neutropenia Graft versus host disease 18 Wald et al. J Infect Dis 16 1997;175:1459 14 12 10 Cases 8 6 © by author 4 2 0 10 ESCMID20 30 40 50 Online60 70 80 Lecture90 100 110 120 Library 130 140 150 160 170 Days after transplant Assessment of risks following HSCT PRE- ENGRAFTMENT EARLY POST- LATE POST- TRANSPLANT ENGRAFTMENT ENGRAFTMENT Disease remote possible Probable disease proven likelihood41 °C °C 40 39 38 Temperature Temperature 37 Clinical 36 /L) features 6 High risk Persistent fever Tissue 10 Host factors Mucositis evidence 1x 10 1x Mycological 10 evidence features 1 © by author treatment0.1 Prophylaxis Empirical Pre-emptive Specific Granulocytes (log Granulocytes -14 -7 0 7 14 21 28 6 8 10 12 6 9 12 ESCMIDTransplant DaysOnline LectureWeeks Library Months Risk periods for mycosis following HSCT PRE- ENGRAFTMENT EARLY POST- LATE POST- TRANSPLANT ENGRAFTMENT ENGRAFTMENT 41 °C °C 40 39 38 Temperature Temperature 37 36 /L) 6 neutropenia corticosteroids 10 1x 10 1x 10 Stem cells acute GvHD chronic GvHD low IgG 1 © by author 0.1 Granulocytes (log Granulocytes -14 -7 0 7 14 21 28 6 8 10 12 6 9 12 ESCMIDTransplant DaysOnline LectureWeeks Library Months Aspergillus: Risk factors for aspergillosis after BMT – building works 7.0 6.0 5.0 4.0 % % 3.0 2.0 1.0 © by author 0.0 Absent Present ESCMID Online Lecture LibraryWald et al. J Infect Dis 1997;175:1459 Risk factors for aspergillosis after BMT – season 5.0 4.0 3.0 2.0 1.0 © by author 0.0 Winter Spring Summer Autumn ESCMID Online Lecture LibraryWald et al. J Infect Dis 1997;175:1459 Risk factors for aspergillosis after BMT – building works 7.0 6.0 5.0 4.0 % % 3.0 2.0 1.0 © by author 0.0 Absent Present ESCMID Online Lecture LibraryWald et al. J Infect Dis 1997;175:1459 The application of a quantitative risk assessment paradigm to the acquisition of nosocomial infection caused by Aspergillus species •hazard identification •exposure assessment •dose-response relationship •risk characterisation •risk management© by author •communication Wilkinson 1998; HIS Electronic News Bulletin ESCMID Online Lecture Library Acceptable levels • HEPA filtered air: 0 • Open ward:? • General hospital areas: ? • Outdoor air: highly variable/seasonal © by author ESCMID Online Lecture Library Bioaerosols in the hospital environment • What are bioaerosols? • Can bioaerosols cause health problems • What are the sources of bioaerosols in hospital? • What measures can be taken to control bioaerosols in the hospital? • How can I control© the by cause author of bioaerosols? ESCMID Online Lecture Library Building materials Ceiling tiles, insulation, Aspergillus. painted surfaces, wallpaper Cladosporium Carpet Alternaria Stachybotrys Dust Alternaria © by author Cladosporium Penicillium ESCMID Online Lecture Library Sources of Aspergillus spp. • Environment • Food – long list! – Sharing of salt and pepper pots – autoclave pepper • standing water • ice-making machines • fomites © by author – carpets/furniture/fabrics/soft toys ESCMID Online Lecture Library Fungal contamination of food distributed to neutropenic patients Food Contaminated Fungi samples (%) Tea 100 A. fum, A. flavus Pepper 100 A. fum, A. niger Freeze-dried soup 20 A. fum, A. niger Apricot 66 A. fum, A. flavus Kiwi 50 A. fum Banana 25 © by authorA. fum Grapefruit juice 15 A. fum Bouakline et al. JCM 2000; 38: 4272-4273. ESCMID Online Lecture Library Kitchens as a source of A. niger infection • 3 cases of cutaneous infection: BMT unit • A. niger isolated: – surfaces – side vent of ice-maker – tea caddy • No isolates from ©bedroom by author • I patient infected with environmental strain Loudon et al., JHI 1996 ESCMID Online Lecture Library Aspergillosis due to carpet contamination • 13 cases of IA: July 1991 - March 1992 • construction • fire in adjacent building • open window • carpet tiles: Aspergillus spp. • shampoo cleaning replaced by water extraction: dramatic reduction in cases of IA • Carpet tiles: ?source© or by ?marker author of airborne spores Gerson et al., Infect Contr Hosp Epidemiol 1994 ESCMID Online Lecture Library Water as a source of filamentous fungi in a childhood bone marrow transplantation unit • 168 filtered water samples • 20 water-related surfaces: