1. Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki MoBiAir Diagnostics Ltd Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki MoBiAir Diagnostics Ltd

2. The fungi: What a team!

3. The background: Children’s Hospital Before renovation: incidence of IFI: allogeneic stem cell Tx recipients: 16% autologous stem cell Tx recipients: 8% Renovation/interventions: air ventilation improvements two-door isolation rooms HEPA filtration After renovation: allogeneic SCT: 3.2% incidence autologous SCT: 0% Before renovation: incidence of IFI: allogeneic stem cell Tx recipients: 16% autologous stem cell Tx recipients: 8% Renovation/interventions: air ventilation improvements two-door isolation rooms HEPA filtration After renovation: allogeneic SCT: 3.2% incidence autologous SCT: 0%

4. Double door entry

5. Ceiling tiles

6. Aspergillus fumigatus Blankophor © G. Armstrong, Hope Hospital, Manchester © O. Zimmerman and R. Ruchel, Gottingen, Germany

7. Growth of Aspergillus 1-2 mm per hour

8. DEVELOPMENT OF ASPERGILLOSIS 1 1 2 2 3 3 INHALATION INFECTION COLONIZATION Dissemination

9. Invasive Aspergillus infections

10. Sources of Aspergillus spp. Environment: air, dust Food Long list! Sharing of salt and pepper pots Standing water Showers Ice-making machines Fomites Carpets/furniture/fabrics/soft toys Environment: air, dust Food Long list! Sharing of salt and pepper pots Standing water Showers Ice-making machines Fomites Carpets/furniture/fabrics/soft toys

11. Aspergillus is in the air

13. Aspergillosis and building works Wald et al. J Infect Dis 1997;175:1459 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 Absent Present %

14. Acceptable levels HEPA filtered air: 0 Open ward:? General hospital areas: ? Outdoor air: highly variable/seasonal HEPA filtered air: 0 Open ward:? General hospital areas: ? Outdoor air: highly variable/seasonal

15. Invasive aspergillosis related to construction and the utility of air sampling 8-bedded BMT unit 2 cases of IPA 5 cases of colonisation Coincided with major construction project on floor directly below unit High air counts before cleaning No isolation after construction stopped and deep cleaning Lai et al., 39th ICAAC, San Francisco 1999 8-bedded BMT unit 2 cases of IPA 5 cases of colonisation Coincided with major construction project on floor directly below unit High air counts before cleaning No isolation after construction stopped and deep cleaning Lai et al., 39th ICAAC, San Francisco 1999

16. Assessment Structural survey Air Surfaces Dust Water analysis Fabrics Carpets Relative humidity Structural survey Air Surfaces Dust Water analysis Fabrics Carpets Relative humidity

17. Air sampling

18. Objectives of air sampling 1 Correlation of outbreaks with hospital construction/demolition Identification of potential sources of nosocomial aspergillosis Prediction of contamination from outside sources Identification of defects/breakdown in ventilation/filtration systems Correlation of outbreaks with hospital construction/demolition Identification of potential sources of nosocomial aspergillosis Prediction of contamination from outside sources Identification of defects/breakdown in ventilation/filtration systems

19. Objectives of air sampling 2 Monitoring of cleaning procedures Efficacy of HEPA filters in LAF rooms Monitoring of procedures to contain hospital building work from hospital wards/single-bedded units Monitoring of cleaning procedures Efficacy of HEPA filters in LAF rooms Monitoring of procedures to contain hospital building work from hospital wards/single-bedded units

20. Dust! Indoor dust: Deposited over long periods of time Will reflect long-term exposure history easy and cheap to collect Indoor dust: Deposited over long periods of time Will reflect long-term exposure history easy and cheap to collect

21. Dust collection

23. Is invasive aspergillosis community- acquired? Up to 70% of cases community-acquired? Hospital environmental control measures will not influence community-acquired cases Control/preventative measures Surveillance of home environments Prophylaxis with antifungal drugs Up to 70% of cases community-acquired? Hospital environmental control measures will not influence community-acquired cases Control/preventative measures Surveillance of home environments Prophylaxis with antifungal drugs

24. Days after transplant 102030405060708090100110120130140150160170 Cases 20181614121086420 Wald et al. J Infect Dis 1997;175:1459 (modified by J.P. Donnelly) Aspergillus: Time to diagnosis of aspergillosis after BMT Neutropenia Graft versus host disease

25. Late onset of IA in BMT patients at a university hospital 93 allogeneic and 149 autologous pts 20 month period 0% IA autologous 15.1% allogeneic: overall incidence 5.8% Median time to occurrence: 92 days No de novo cases prior to engraftment Survival 100 days from diagnosis 29% Conclusions shift towards late occurrence outpatient environment surveillance Grow et al., BMT 2002; 29: 15-19 93 allogeneic and 149 autologous pts 20 month period 0% IA autologous 15.1% allogeneic: overall incidence 5.8% Median time to occurrence: 92 days No de novo cases prior to engraftment Survival 100 days from diagnosis 29% Conclusions shift towards late occurrence outpatient environment surveillance Grow et al., BMT 2002; 29: 15-19

26. Surveillance of the home environment

27. Patients live in mouldy houses: exposure to Aspergillus and more

28. Conclusions Strong association between building renovation and an increase in environmental contamination Many studies confirm the value of the high efficacy of laminar airflow plus HEPA filtration and a high air- exchange rate HEPA filtration alone did not prevent contamination during renovation A standard protocol for aerobiological surveillance is needed Strong association between building renovation and an increase in environmental contamination Many studies confirm the value of the high efficacy of laminar airflow plus HEPA filtration and a high air- exchange rate HEPA filtration alone did not prevent contamination during renovation A standard protocol for aerobiological surveillance is needed

29. A deadly dust may be blowing in the wind during renovations Hospital infection control Deaths – despite aggressive control measures ??Community-acquired aspergillosis Put guidelines in the contract One death should prompt inquiry Water may be source of Aspergillus Conduct regular walk-throughs Hospital infection control Deaths – despite aggressive control measures ??Community-acquired aspergillosis Put guidelines in the contract One death should prompt inquiry Water may be source of Aspergillus Conduct regular walk-throughs

30. Prevention is better than cure Avoid exposure in the hospital and in the home