1. Hospital-acquired Invasive Aspergillosis: How Big is the Problem?
Michael Phillips, MD
NYU Medical Center
New York, NY

2. Disclaimer & Disclosure
The views expressed here are my own, and not necessarily those of NYU Medical Center
Financial disclosures: none

3. Objectives Review the epidemiology of invasive Aspergillosis (IA)
Discuss the extent IA is a nosocomial infection
Present a surveillance system for hospital-associated IA

4. Image: Fungal Research Trust
Aspergillus –
38 species cause disease
Common in the environment:
Soil
Plants
Dust
Building materials
Food
Water
Over 200 species worldwide
Spore forming head of Asp. Fumigatus
Inhale spores daily
Image: Fungal Research Trust

5. Is Aspergillus an Emerging Pathogen? Images: Fungal Research Trust
Aspergillus flavus on left
Aspergillus fumigatus on right
Both: malt extract agar
Images: Fungal Research Trust

6. Prevalence of IA at Autopsy
Fungus
No. of Patients (%) P
(n=2956)
(n=2718)
(n=2450)
Candida
51 (1.7)
47 (1.7)
31 (1.3)
0.3
Aspergillus
11 (0.4)
32 (1.2)
76 (3.1)
<0.001
Mucor
4 (0.1) --
1 (<0.1)
0.1
Unclassified
2 (<0.1)
8 (0.3)
0.002
Groll AH, J of Infection 1996;33:23-32

7. Prevalence of IA at Autopsy
Fungus
No. of Patients (%) P
(n=2956)
(n=2718)
(n=2450)
Candida
51 (1.7)
47 (1.7)
31 (1.3)
0.3
Aspergillus
11 (0.4)
32 (1.2)
76 (3.1)
<0.001
Mucor
4 (0.1) --
1 (<0.1)
0.1
Unclassified
2 (<0.1)
8 (0.3)
0.002
Groll AH, J of Infection 1996;33:23-32

8. Changing Incidence of Invasive Fungal Disease in Patients without HIV
0.6
0.4
0.2
Rate per 100,000
1981
1986
1991
1996
Year
Candida species
Aspergillus species
McNeil et al, Clin Infect Dis 2001;33:641

9. Solid Organ Transplantation: United States, 1985 – 2005
Source: Organ Procurement and Transplantation Network

10. IA Incidence and Risk Factors in Solid Organ Transplant Recipients
Type
% Incidence (mean, range)
Risk Factor
Lung
8, 3–14
Allograph rejection,
CMV infection
Heart
6, 0–11
No data
Liver
1.7, 1–8
Allograph rejection, dialysis,
Kidney
0.7, 0–0.9
Allograph rejection, augmented immunosuppression
Singh, JAC 2000;45:

11. IA Incidence and Risk Factors in Solid Organ Transplant Recipients
Type
% Incidence (mean, range)
Risk Factor
Lung
8, 3–14
Allograph rejection,
CMV infection
Heart
6, 0–11
No data
Liver
1.7, 1–8
Allograph rejection, dialysis,
Kidney
0.7, 0–0.9
Allograph rejection, augmented immunosuppression
Singh, JAC 2000;45:

12. Hematopoietic Stem Cell Transplantation: United States, 2000 – 2007
Source: US Department of Health and Human Services

13. Incidence of IA: Allogeneic HSCT
Figure 1. One-year cumulative incidence of proven or probable IA among allogeneic graft recipients through the 1990s. Data for years 1990 through 1992 were abstracted from a previously published study.2 Diagnoses established after second transplantation, relapsed malignancy, or death are not included.
MR = HLA matched related
MM = mismatched; UR = unrelated
Marr, K. A. et al. Blood 2002;100:
Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.

14. IA in Patients after HSCT
Cases: 187
Controls: 1495
Marr, K. A. et al.
Blood 2002;100:
Copyright ©2002 American Society of Hematology. Copyright restrictions may apply.

15. IA in Patients with Hematologic Malignancies
Invasive Aspergillosis
Control
(n=133) P
Proven
(n=9)
Probable
(n=3)
Possible
(n=33)
Age
(mean years)
46.8
50.3
45.3
44.9
0.65
Female
(%)
33%
54%
50%
0.86
Comorbidity score (mean)
0.22
0.24
0.25
0.74
Neutropenia (mean days)
18.7
37.6
19.6
9.9
<0.001
Mulemann K, et al, Leukemia 2005;19:

16. IA in Patients with Hematologic Malignancies
Invasive Aspergillosis
Control
(n=133) P
Proven
(n=9)
Probable
(n=3)
Possible
(n=33)
Age
(mean years)
46.8
50.3
45.3
44.9
0.65
Female
(%)
33%
54%
50%
0.86
Comorbidity score (mean)
0.22
0.24
0.25
0.74
Neutropenia (mean days)
18.7
37.6
19.6
9.9
<0.001
Mulemann K, et al, Leukemia 2005;19:

17. Is IA a Nosocomial Infection?

18. Is IA a Nosocomial Infection?
Difficult question!

19. Is IA a Nosocomial Infection?
Difficult question!
Incubation period unknown

20. Is IA a Nosocomial Infection?
Difficult question!
Incubation period unknown
Role of colonization

21. Is IA a Nosocomial Infection?
Difficult question!
Incubation period unknown
Role of colonization
Community associated infections

22. Is there a correlation between: environmental Aspergillus concentrations and incidence of invasive Aspergillosis?

23. Alberti C, et al J. Hospital Infection 2001,48:198-206
Measurement of Environmental Fungal Contamination and IA in Hematology Patients
Prospective study over a 4 years
3 units (BMT, 2 hematology wards)
Alberti C, et al J. Hospital Infection 2001,48:

24. Alberti C, et al J. Hospital Infection 2001,48:198-206
Measurement of Environmental Fungal Contamination and IA in Hematology Patients
Prospective study over a 4 years
3 units (BMT, 2 hematology wards)
Inclusion: allogenic HSCT, acute leukemia
Alberti C, et al J. Hospital Infection 2001,48:

25. Alberti C, et al J. Hospital Infection 2001,48:198-206
Measurement of Environmental Fungal Contamination and IA in Hematology Patients
Prospective study over a 4 years
3 units (BMT, 2 hematology wards)
Inclusion: allogenic HSCT, acute leukemia
Probable and definite IA case definition
Systematic air and surface sampling
Alberti C, et al J. Hospital Infection 2001,48:

26. Alberti C, et al J. Hospital Infection 2001,48:198-206
Results
64 hospital-acquired IA cases identified
No clusters or seasonal variation
Alberti C, et al J. Hospital Infection 2001,48:

27. Alberti C, et al J. Hospital Infection 2001,48:198-206
Results
64 hospital-acquired IA cases identified
No clusters or seasonal variation
Incidence rate: 0 – 2.59 per 1000 pt-days
Alberti C, et al J. Hospital Infection 2001,48:

28. Alberti C, et al J. Hospital Infection 2001,48:198-206
Results
64 hospital-acquired IA cases identified
No clusters or seasonal variation
Incidence rate: 0 – 2.59 per 1000 pt-days
Increase in environmental fungal cultures prior to hospital-acquired IA case
Statistically significant in non-protected areas
Alberti C, et al J. Hospital Infection 2001,48:

29. Efficacy of Protective Measures during Outbreaks
10 A. flavus infections in a hematology patients during 6 month period
Hahn TH, Inf Cont Hosp Epi 2002, 23;525

30. Efficacy of Protective Measures during Outbreaks
10 A. flavus infections in a hematology patients during 6 month period
Construction project
Comment on air sampling results (HEPA filtered unit: <4 CFU/m3, nonHEPA unit: >100 CFU/m3)
Hahn TH, Inf Cont Hosp Epi 2002, 23;525

31. Efficacy of Protective Measures during Outbreaks
10 A. flavus infections in a hematology patients during 6 month period
Construction project
9 cases in 35 patients on unit without HEPA filtration
1 case in 20 patients on unit with HEPA filtration
Comment on air sampling results (HEPA filtered unit: <4 CFU/m3, nonHEPA unit: >100 CFU/m3)
Hahn TH, Inf Cont Hosp Epi 2002, 23;525

32. CDC Recommendations
Enhanced protective measures HSCT recipients during construction
Specific steps at construction site to reduce risk of exposure to dust
Consider HEPA air filtration for high risk patients
Surveillance for IA
CDC, MMWR 2000,49(rr10);1-128

33. Surveillance: Autopsy Pathology specimens Unit surveillance
Microbiology
Culture results
Galactomannan EIA
Aspergillus PCR
Radiology
Chest CT scan

34. 2002: International Consensus Statement
Standardized definition for invasive fungal disease
Host factors
Clinical manifestations
Mycological evidence

35. 2002: International Consensus Statement
Standardized definition for invasive fungal disease
Host factors
Clinical manifestations
Mycological evidence
Proven, probable, possible categories

36. 2002: International Consensus Statement
Standardized definition for invasive fungal disease
Host factors
Clinical manifestations
Mycological evidence
Proven, probable, possible categories
Ascioglu S, Clin Inf Dis 2002;34,7

37. 2002: International Consensus Statement
Standardized definition for invasive fungal disease
Host factors
Clinical manifestations
Mycological evidence
Proven, probable, possible categories
Ascioglu S, Clin Inf Dis 2002;34,7
Recent revision: DePauw B, Clin Inf Dis 2008;46,1813

38. Microbiological Surveillance

39. Methods Surveillance criteria:
Inpatient  7 days with any of the following :
Mycological evidence of Aspergillus sp.
CT scan (CT) report containing specific key word(s)
Pathology reports consistent with invasive fungal infection
Excluded: prior diagnosis of Aspergillosis

40. Methods Surveillance criteria:
Inpatient  7 days with any of the following :
Mycological evidence of Aspergillus sp.
CT scan (CT) report containing specific key word(s)
Pathology reports consistent with invasive fungal infection
Excluded: prior diagnosis of Aspergillosis
Investigated using consensus case definition

41. Results 45 patients met surveillance criteria 10 case-patients
5 possible
2 probable
3 proven
Test type
Test results meeting
surveillance criteria (%)
Test results
in HIA case-patients
possible
probable1
proven
all
Microbiology
20 (36) 2 4
Pathology
4 (7) 1
Chest CT
31 (56) 5 6
Total
55 (100) 3 11
Test type
Test results meeting
surveillance criteria (%)
Test results
in HIA case-patients
possible
probable1
proven
all
Microbiology
20 (36) 2 4
Pathology
4 (7) 1
Chest CT
31 (56) 5 6
Total
55 (100) 3 11

42. Epidemic curve 2006 2007 Education and work site practices to
minimize construction dust enhanced
2006
2007

43. Summary
Incidence of IA is increasing

44. Summary Incidence of IA is increasing
IA is a healthcare-associated infection 44

45. Summary Incidence of IA is increasing
IA is a healthcare-associated infection
Implementation of protective measures can be successful 45

46. Summary Incidence of IA is increasing
IA is a healthcare-associated infection
Implementation of protective measures can be successful
Systematic, ongoing surveillance for IA is needed 46

47. Thank you!

48. 48

49. Patient with specific host factors plus Positive microbiology results
Proven:
Hyphae on histopathology or cytopathology from a specimen with evidence of tissue damage or
Positive culture from a normally sterile site with clinical or radiographic evidence of infection
Probable:
Patient with specific host factors plus
Positive microbiology results
and
1 major or 2 minor clinical features
Possible:
Patient with specific host factors and attending physician documentation that invasive Aspergillosis likely plus: 49