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

Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi

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

Page 2: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

The fungi: What a team!The fungi: What a team!

Page 3: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

The background: Children’s HospitalThe 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%

Page 4: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Double door entryDouble door entry

Page 5: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Ceiling tilesCeiling tiles

Page 6: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Aspergillus fumigatusAspergillus fumigatus

BlankophorBlankophor

© G. Armstrong, © G. Armstrong, Hope Hospital, Hope Hospital, Manchester Manchester © O. Zimmerman and R. Ruchel, Gottingen, Germany© O. Zimmerman and R. Ruchel, Gottingen, Germany

Page 7: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Growth of Aspergillus

1-2 mm per hour1-2 mm per hour

EORTC EORTC IFICGIFICG

Page 8: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

DEVELOPMENT OF ASPERGILLOSISDEVELOPMENT OF ASPERGILLOSIS

11 22 33

INHALATIONINHALATION INFECTIONINFECTIONCOLONIZATIONCOLONIZATION Dissemination

Dissemination

Page 9: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Invasive Aspergillus infectionsInvasive Aspergillus infections

Page 10: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Sources of Aspergillus spp.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

Page 11: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Aspergillus is in the air Aspergillus is in the air

Page 12: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Aspergillus is in the airAspergillus is in the air

Page 13: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Aspergillosis and building worksAspergillosis and building works

Wald et al. J Infect Dis 1997;175:1459

0.00.0

1.01.0

2.02.0

3.03.0

4.04.0

5.05.0

6.06.0

7.07.0

AbsentAbsent PresentPresent

%%

Page 14: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Acceptable levelsAcceptable 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

Page 15: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Invasive aspergillosis related to construction and the utility of air samplingInvasive 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

cleaningLai 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

cleaningLai et al., 39th ICAAC, San Francisco 1999

Page 16: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Assessment Assessment

Structural survey Air Surfaces Dust Water analysis Fabrics Carpets Relative humidity

Structural survey Air Surfaces Dust Water analysis Fabrics Carpets Relative humidity

Page 17: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Air samplingAir sampling

Page 18: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Objectives of air sampling 1Objectives 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

Page 19: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Objectives of air sampling 2Objectives 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

Page 20: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Dust!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

Page 21: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Dust collection

Page 22: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Ward 9, Dust

0

2

4

6

8

1 2 3 4 5 6 7Weeks

CFU

K9/1 K9/2 K9/3 K9/4 K9/5K9/6 K9/7 K9/8 K9/9 K9/10

Page 23: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Is invasive aspergillosis community-acquired?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

Page 24: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Days after transplantDays after transplant

1010 2020 3030 4040 5050 6060 7070 8080 9090 100100 110110 120120 130130 140140 150150 160160 170170

Cases

Cases

2020

1818

1616

1414

1212

1010

88

66

44

22

00

Wald et al. J Infect Dis 1997;175:1459(modified by J.P. Donnelly)

Aspergillus: Time to diagnosis of aspergillosis after BMTAspergillus: Time to diagnosis of aspergillosis after BMTNeutropeniaNeutropenia

Graft versus host Graft versus host diseasedisease

Page 25: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Late onset of IA in BMT patients at a university hospitalLate 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

Page 26: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Surveillance of the home environmentSurveillance of the home environment

Page 27: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Patients live in mouldy houses:exposure to Aspergillus and morePatients live in mouldy houses:exposure to Aspergillus and more

Page 28: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

ConclusionsConclusions

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

Page 29: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

A deadly dust may be blowing in the wind during renovationsA 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

Page 30: Longitudinal Risk Assessment of a Paediatric Bone Marrow Transplant Unit for Pathogenic Fungi Malcolm Richardson PhD, FIBiol, FRCPath University of Helsinki.

Prevention is better than cureAvoid exposure in the hospital and in the homePrevention is better than cureAvoid exposure in the hospital and in the home


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