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Aspergillosis: nosocomial or community acquired?

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... B unit - Before construction 4 rooms with laminar flux and HFPA 10 conventional ... . exposure outside health-care setting and infection not related to care. – PowerPoint PPT presentation

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Title: Aspergillosis: nosocomial or community acquired?


1
Aspergillosis nosocomial or community acquired?
  • Philippe Vanhems, MD, PhD, Marie-Christine
    Nicolle, MD, Nicolas Voirin, PhD, Thomas Bénet,
    MD, MSc
  • Infection Control Unit
  • Edouard Herriot University Hospital
  • Lyon, France

2
  • No conflict of interest for every author
    regarding the topic of the presentation

3
Aspergillosis nosocomial or community acquired?
Some answers but many epidemiological questions
are unresolved
4
Definition nosocomial (hospital-acquired)
infections
  • Usual definition
  • Onset of infection gt48 hours after
    hospitalization but not always (i.e. influenza
    72 hours)
  • Not in incubation at admission
  • Device related ventilator associated pneumonia,
    catheter associated infection
  • Invasive procedure surgical site infection
  • Treatments related infections chemotherapy,
    steroids, immunosuppressive drugs,
    cyclosporin,...
  • Outbreaks
  • Definition more complicated
  • Invasive aspergillosis (IA), MRSA community
    acquired but hospital diagnosed, hepatitis C
    viral infection, etc.

5
Definition community acquired
  • . exposure outside health-care setting and
    infection not related to care.

6
Aspergillosis
  • Invasive Aspergillosis (IA) a severe disease in
    immunocompromised persons and often fatal
  •  Disease IA dysfunction of host defense in
    combination with Aspergillus survival and growth
    (Dagenais, 2009)
  • Asthm and allergenic manisfestions in
    immunocompetent persons

7
Epidemiological issues for IA
  • Environmental exposure documented in the
    community
  • Environmental exposure documented in the hospital
  • Where are the most important sources of
    infections?

8
Epidemiological issues for IA
  • Environmental exposure documented in the
    community
  • Environmental exposure documented in the hospital
  • Where are the most important sources of
    infections?
  • Impact of inoculum size on colonization/infection
    is unknown in humans
  • Patients at risk inside the hospital
  • Patients at risk outside the hospital

9
Epidemiological issues for IA
  • What is the incubation period ?
  • Is a definition based on the interval time
    between hospitalization and onset a valid
    definition?

10
Risk calculation of IA
  • Relative risk
  • Attributable risk
  • Theoretical interest
  • But faisability questionnable

11
Relative risk of hospital-acquired IA
Invasive Aspergillosis Invasive Aspergillosis -
Hospital exposure N1 N2
Community exposure N3 N4
RR (OR) of hospital exposure vs community
exposure? Incidence rate in the hospital
N1/(N1N2) RR Incidence rate in
the community N3/(N3N4) Determinants of RR?
Confounders?
12
Relative risk of hospital-acquired IA
Invasive Aspergillosis Invasive Aspergillosis -
Hospital exposure N1 N2
Community exposure N3 N4
RR (OR) of hospital exposure vs community
exposure? Incidence rate in the hospital
N1/(N1N2) RR Incidence rate in
the community N3/(N3N4) Determinants
of RR? Confounders?
?
13
Attributable risk of IA related to hospitalisation
Invasive Aspergillosis Invasive Aspergillosis -
Hospital exposure N1 N2
Community exposure N3 N4
The attributable exposure to hospital regarding
the risk of IA? Or of prevented cases if
hospital exposure was eliminated compared to the
community AR N1/(N1N2)
N3/(N3N4) Determinants? Confounders ?
14
Exposures in the community
  • Air, soil, water
  • Ubiquitous
  • Common spores inhalation (200 Asp conidia/day
    (Dagenais, 2009)
  • Colonization before IA but after IA could also
    occurred
  • Impact of underlying diseases

15
Environmental exposures in the hospital
  • Sources of Aspergillus spores in the hospital air
    (VandenBergh, 1999)
  • Inadequate filtration of outside air or
    malfunctionning of ventilation (High-efficiency
    particulate air filtration, LAF)
  • Dust and places infrequently cleaned
  • Vacuum cleaning
  • Plants, flowers, etc.
  • Periods of hospital constructions, renovations,
    demolition

16
Environmental exposures in the hospital
  • Sources of Aspergillus spores in the hospital air
    (VandenBergh, 1999)
  • Inadequate filtration of outside air or
    malfunctionning of ventilation (High-efficiency
    particulate air filtration, LAF)
  • Dust and places infrequently cleaned
  • Vacuum cleaning
  • Plants, flowers, etc.
  • Periods of hospital constructions, renovations,
    demolition

17
Environmental exposures in the hospital
  • Correlation between concentration of
    Aspergillus spores in the air and the risk of
    human infection (IA) is difficult to calculate
  • Baseline measurements are needed (i.e. before
    renovation)

18
Individual risk factors
  • Diseases with major impact on immunity
  • Related to treatments as chemotherapy HSCT,
    GVHD, solid transplantation,
  • Neutropenia degree and duration
  • Acquired immunosuppression AIDS, granulomatosis
    diseases
  • Host predisposition (Bochud, 2008)
  • Drugs steroids,

19
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20
Incubation(s) of IA ?
  • At least 12 days of neutropenia (Denning , 1999)
  • Cases observed for short periods (1 week after
    hospitalization) (Carter, 1997)
  • Cases observed 3-6 months after HSCT (McWhinney,
    1993)
  • Unknown delays
  • From exposure to colonization
  • From colonization to disease
  • Migration from sup airways to the lungs
  • Impact of duration and severity of neutropenia on
    disease incubation

21
Natural history
Community Hospital
Community Hospital
Community ? Hospital
Community - Hospital
22
IA 3 stages
Colonization
Infection (IA)
Exposure
Time
23
IA 3 stages
Colonization
Infection (IA)
Exposure
Time
Distal date
Proximal date
Distal date
Proximal date
24
IA 3 stages
Colonization
Infection (IA)
Exposure
C-A
Time
Distal date
Proximal date
Distal date
Proximal date
25
IA 3 stages
Colonization
Infection (IA)
Exposure
C-A
C-A H-diag
Time
Distal date
Proximal date
Distal date
Proximal date
26
IA 3 stages
Colonization
Infection (IA)
Exposure
CA
CA H-diag
C-A H-A H-diag
Time
Distal date
Proximal date
Distal date
Proximal date
27
IA 3 stages
Colonization
Infection (IA)
Exposure
CA
CA H-diag
CA H-A? H-diag
H-A
Time
Distal date
Proximal date
Distal date
Proximal date
28
IA 3 stages
Colonization
Exposure
Infection
Time
Distal date
Proximal date
Distal date
Proximal date
29
IA at Edouard Herriot hospital
  • Prospective surveillance of IA in patients
    hospitalized in a department of haematology
  • N 235 IA
  • 17 (7) patients without neutropenia lt 0.5 G/L
  • 218 (93) patients with neutropenia lt 0.5 G/L

(Nicolle MC, unpublished data)
30
IA and neutropenia lt 0.5 G/L
Median Min Max
Delay between admission and neutropenia onset 5 days -3 56

Delay between admission and IA 20 days 0 185

Delay between neutropenia onset and IA 14 days -15 198
(Nicolle MC, unpublished data)
31
Onset of neutropenia (mean)
Date of IA (mean)
Onset of neutropenia Date of IA
(No patient with laminar flow)
32
Community vs nosocomial IAwithout laminar flow
Community
Hospital
Colonization/ Infection
Exposure
Incubation
(Nicolle MC, unpublished data)
33
Reduction of Invasive Aspergillosis Incidence
after Control of Environmental Exposure in
Immunocompromised Patients
34
Background
  • Controversial impact of environmental control
    invasive aspergillosis (IA)
  • Most studies evaluating environmental
    intervention were conducted retrospectively
    without control group
  • Objective to assess the impact of the relocation
    of an adult hematological intensive care unit on
    IA incidence

35
Methods (1)
  • Study design
  • Quasi-experimental
  • With control group
  • Pre-test and post-test evaluation
  • Setting
  • 3 adult hematological intensive care units
  • Each composed of 14 single rooms in a university
    hospital
  • Patients
  • Hospitalised 48 hours
  • Period 1 (pre-test) 14/04/2005 01/09/2005
  • Period 2 (post-test) 14/09/2005 01/02/2006

36
Methods (3)
  • Intervention
  • Relocation of a unit from the main building to an
    adjoining modular construction
  • 4 rooms equipped with laminar air flow before
    relocation
  • All rooms were equipped with positive pressure
    isolation after relocation
  • Control group
  • The 2 other units
  • Each containing 8 rooms with laminar air flow
  • No environmental modification

37
Méthodes (3)
  • Intervention, B unit
  • - Before construction
  • 4 rooms with laminar flux and HFPA
  • 10 conventional rooms
  • - Closed from september ,1er to 14
  • 2005
  • - Moving to new building
  • 14 rooms with HFPA and positive pressure
  • Units A and C, no intervention

38
Results
  • 356 hospitalized patients included
  • 7 027 patient-days
  • 21 IA diagnosed
  • 18 nosocomial
  • 3 of undetermined origin
  • Delay between hospitalisation and IA diagnosis
  • Median 22 days (15-26)

39
/ 100 hosp. stays / 1000 patient-days
40
  • Straightforward association between environmental
    modification and decreased IA incidence
  • Emphasized the utility of an environmental
    strategy, including high-efficiency air
    filtration, in IA prevention

41
Conclusion
  •  Despite the breadth of studies of Aspergillus
    pathogenesis, there are few well-defined factors
    that contribute to A. fumigatus-related IA 
    (Dagenais, 2009)

42
Epidemiology of IA some open questions and
expectations
  • Factors associated with colonization and portage?
    But difficult to assess in the community.
  • Factors associated with colonization to disease
    in the hospital.
  • Environmental data
  • Virulence and Aspergillus dependent
  • Iatrogenic/ treatment/ diseases dependant
  • Predisposing genetic factors
  • Other factors

43
  • Epidemiological studies for a detailled
    description of the sequence of the events from
    exposure before hospital admission, exposure
    after admission and the diagnosis of IA
  • Modelisation of incubations using for exemple
    parametric and non-parametric survival models
  •  Cohort of cohorts  of patients with
    documented data on exposure could be helpfull for
    incubation calculations.

44
  • Molecular typing
  • additional studies are needed which compared
    environmental and clinical isolates
  • determinants associated with similiarities and
    lack of similarities between environmental and
    clinical isolates
  • Repeated measurements of fungal exposure outside
    and inside the hospital.

45
Aknowledgments
  • Dr MC Nicolle, Dr T Bénet, N Voirin
  • Pr M. Michallet, Dr A. Thiébaut, and colleagues
    (Hematology department, Edouard Herriot
    University Hospital, Lyon)
  • Department of mycology (Pr S Picot, Dr MA Piens,
    colleagues, Lyon)

46
(No Transcript)
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