Aspergillosis

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Aspergillosis who gets what, why and when

• David W. Denning
• Director, National Aspergillosis Centre
• University Hospital of South Manchester
• The University of Manchester

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Interaction of Aspergillus with the hostA unique
microbial-host interaction
Subacute Invasive
Frequency of aspergillosis
Frequency of aspergillosis
Aspergilloma Chronic cavitary Chronic
fibrosing Locally invasive
Immune dysfunction
Immune hyperactivity
.
After Casadevall Pirofski, Infect Immun
1999673703
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The anecdote
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General risk factors
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Risk factors for invasive aspergillosis

• Major
• Neutropenia ( monocytopenia)
• Corticosteroid treatment
• Minor
• CD4penia
• Inherited immunodeficiency (ie CGD)
• Lung or sinus damage/disease
• Severe liver disease
• Exposure to high inocula

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Examples of at-risk patients and pace of
progression
Relapsed/uncontrolled leukemia
Allogeneic stem cell transplant GVHD
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Leukemia and profound neutropenia
Risk of acquisition (and pace of progression)
Solid organ transplant rejection CMV
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Medical ICU, COPD sepsis
Long term glucocorticoids etc
Acute respiratory infection, ie influenza
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Short course glucocorticoids
Normal immunity, high inoculum
Temporary neutropenia
Chronic leukaemia
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AIDS
HIV infection
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Degree of immunocompromise
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Where in the hospital does invasive aspergillosis
occur?
Cornillet et al, Clin Infect Dis 200643577
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Major underlying conditions
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IA following HSCT
Pagano et al, Clin Infect Dis 2007451161
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Estimated number of cases of invasive fungal
infection UK 2002
Patient group Number of patients Invasive candidosis/ candidaemia risk estimates Expected number invasive candidosis/ candidaemia Invasive aspergillosis risk estimates_at_ Expected number invasive aspergillosis
AlloBMTx 793 4 32 10 79
Solid organ Tx 2953 5 148 1.9 56
Leukaemia 16269 3 488 6 976
Solid tumour (neutropenic) 28955 3 869 2 579
Advanced cancer 131678 1 1316 1.5 1975
ICU 210130 1 2101 0.2 420
Burns 378 5.6 21 1.9 7
Renal dialysis 24536 0.2 490 0.02 5
HIV/AIDS 661 0.2 1 4 26
Totals 5466
4120
no estimate for surgical patients, but some
are in ICU, or have advanced cancer _at_ no
inclusion of most chronic chest, steroid-treated
patients, an increasing group the literature
figure is 6, but felt to be autopsy selection
bias, so reduced by 75.
http//www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1196
942156347
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Estimated number of cases of invasive fungal
infection UK 2002
Patient group Number of patients Invasive candidosis/ candidaemia risk estimates Expected number invasive candidosis/ candidaemia Invasive aspergillosis risk estimates_at_ Expected number invasive aspergillosis
AlloBMTx 793 4 32 10 79
Solid organ Tx 2953 5 148 1.9 56
Leukaemia 16269 3 488 6 976
Solid tumour (neutropenic) 28955 3 869 2 579
Advanced cancer 131678 1 1316 1.5 1975
ICU 210130 1 2101 0.2 420
Burns 378 5.6 21 1.9 7
Renal dialysis 24536 0.2 490 0.02 5
HIV/AIDS 661 0.2 1 4 26
Totals 5466
4120
no estimate for surgical patients, but some
are in ICU, or have advanced cancer _at_ no
inclusion of most chronic chest, steroid-treated
patients, an increasing group the literature
figure is 6, but felt to be autopsy selection
bias, so reduced by 75.
http//www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1196
942156347
15
Invasive aspergillosis in ICU

• 127 of 1850 (6.9) consecutive medical ICU
  admissions with IA or colonisation
  (micro/histol).
• COPD 33 of 67 (50) proven/probable IA

Meersemann et al, Am J Resp Med Crit Care
2004170621.
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Risk factors for invasive aspergillosis in ICU
Meersseman, Clin Infect Dis 200745205
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EU caseload of aspergillosis
30,000 - 70,000 cases
Subacute Invasive
Frequency of aspergillosis
Frequency of aspergillosis
Immune dysfunction
Immune hyperactivity
.
After Casadevall Pirofski, Infect Immun
1999673703
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Chronic pulmonary aspergillosis
Chronic cavitary pulmonary aspergillosis
complicating ABPA
Chronic cavitary pulmonary aspergillosis with
bilateral aspergillomas complicating sarcoidosis
www.aspergillus.org.uk
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Chronic Pulmonary Aspergillosis Underlying
diseases

• Classical tuberculosis 20
• Atypical tuberculosis
• Allergic bronchopulmonary aspergillosis
• Lung cancer survivor
• Pneumothorax
• COPD/emphysema
• Sarcoidosis (stage II/III)
• Rheumatoid arthritis
• Thoracic surgery
• Asthma
• Chest radiotherapy
• None

Common
Smith, ISHAM 2009
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Frequency of chronic pulmonary aspergillosis
after TB
25-33 of patients with TB are left with a
cavity 10 of all cases of pulmonary TB get CPA
Anonymous. Tubercle 197051227 Sonnenberg et
al, Lancet 20013581687
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EU caseload of aspergillosis
30,000 - 70,000 cases
Subacute Invasive
Frequency of aspergillosis
Frequency of aspergillosis
Aspergilloma Chronic cavitary Chronic
fibrosing Locally invasive
7,500 cases
Immune dysfunction
Immune hyperactivity
.
After Casadevall Pirofski, Infect Immun
1999673703
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ABPA and severe asthma
www.emphysema-copd.co.uk
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Likely ABPA caseload
1 of adult asthmatics attending clinic have
ABPA In UK - 5,000,000 with asthma, gt3M
adults In Europe - gt17,000,000 adults with
asthma 150,000 adults with ABPA in Europe 12
of those with CF have ABPA EU CF population
150,000 17,500 patients
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Likely SAFS caseload in Europe
In Europe - gt17,000,000 adults with asthma 20
have severe asthma 3,400,000 adults 20-50 of
severe asthmatics have SAFS SAFS cases (EU)
680,000 1,700,000
Zureik et al, Br Med J 2002325411
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Brazil survey of fungal rhinosinusitis
890 endoscopic sinus surgeries 62 (6.8) had
fungal rhinosinusitis
DallIgna Rev Bras Otorhinolaringol 200571712
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Prevalence of allergic rhinoconjunctivitis
symptoms
ISAAC Steering Committee Lancet 1998351,1225
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Prevalence of chronic rhinosinusitis
Global population 6Bn If rate of allergic
rhinosinusitis 15 then 900M cases, which USA
52M Europe 55.5M Japan 19M
ISAAC Steering Committee Lancet 1998351,1225
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EU caseload of aspergillosis
167,500 ABPA cases 680,000 - 1,700,000 SAFS
cases 11,200,000 CRFS cases
25,000 - 70,000 cases
Subacute Invasive
Frequency of aspergillosis
Frequency of aspergillosis
Aspergilloma Chronic cavitary Chronic
fibrosing Locally invasive
7,500 cases
Immune dysfunction
Immune hyperactivity
.
After Casadevall Pirofski, Infect Immun
1999673703
29
www.aspergillus.org.uk