Transcript Interaction of Aspergillus with the host A unique

Aspergillosis – who gets what, why
and when
David W. Denning
Director, National Aspergillosis Centre
University Hospital of South Manchester
The University of Manchester
Interaction of Aspergillus with the host
Acute Invasive
Subacute Invasive
ABPA
Severe asthma with
fungal sensitisation
Allergic sinusitis
Aspergilloma
Chronic cavitary
Chronic fibrosing
Locally invasive
Immune dysfunction
Frequency of aspergillosis
Frequency of aspergillosis
A unique microbial-host interaction
Immune hyperactivity
.
After Casadevall
& Pirofski, Infect Immun 1999;67:3703
The anecdote
General risk factors
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
Risk of acquisition (and pace of progression)
Examples of at-risk patients and pace of progression
25%
20%
15%
10%
5%
Degree of immunocompromise
Where in the hospital does invasive
aspergillosis occur?
Cornillet et al, Clin Infect Dis 2006;43:577
Major underlying conditions
IA following HSCT
Pagano et al, Clin Infect Dis 2007;45:1161
Estimated number of cases of invasive
fungal infection UK [2002]
Patient group
Number of
Invasive candidosis/ Expected number
patients
candidaemia
invasive
risk estimates**
candidosis/
candidaemia
AlloBMTx
Invasive
Expected number
aspergillos
invasive
is risk
aspergillosis
@
estimates
4%
32
10%
79
5%
148
1.9%
56
3%
488
6%
976
3%
869
2%
579
1%
1316
1.5%#
1975
1%
2101
0.2%
420
5.6%
21
1.9%
7
793
Solid organ Tx
2953
Leukaemia
16269
Solid tumour
(neutropenic)
Advanced cancer
ICU
28955
131678
210130
Burns
378
Renal dialysis
0.2%
24536
HIV/AIDS
490 significant
0.02% underestimates
5
Probably
0.2%
1
4%
26
661
Totals
5466
4120
** no estimate for surgical patients, but some are in ICU, or have advanced cancer
@ 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/1196942156347
Estimated number of cases of invasive
fungal infection UK [2002]
Patient group
Number of
Invasive candidosis/ Expected number
patients
candidaemia
invasive
risk estimates**
candidosis/
candidaemia
AlloBMTx
Invasive
Expected number
aspergillos
invasive
is risk
aspergillosis
@
estimates
4%
32
10%
79
5%
148
1.9%
56
3%
488
6%
976
3%
869
2%
579
1%
1316
1.5%#
1975
1%
2101
0.2%
420
5.6%
21
1.9%
7
793
Solid organ Tx
2953
Leukaemia
16269
Solid tumour
(neutropenic)
Advanced cancer
ICU
28955
131678
210130
Burns
378
Renal dialysis
0.2%
24536
HIV/AIDS
490 significant
0.02% underestimates
5
Probably
0.2%
1
4%
26
661
Totals
5466
4120
** no estimate for surgical patients, but some are in ICU, or have advanced cancer
@ 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/1196942156347
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 2004;170:621.
Risk factors for invasive aspergillosis in ICU
Meersseman, Clin Infect Dis 2007;45:205
EU caseload of aspergillosis
Frequency of aspergillosis
Frequency of aspergillosis
30,000 - 70,000 cases
Acute Invasive
Subacute Invasive
Immune dysfunction
Immune hyperactivity
.
After Casadevall
& Pirofski, Infect Immun 1999;67:3703
Chronic pulmonary aspergillosis
Chronic cavitary
pulmonary
aspergillosis
complicating ABPA
Chronic cavitary pulmonary
aspergillosis with bilateral
aspergillomas complicating
sarcoidosis
www.aspergillus.org.uk
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
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 1970;51:227; Sonnenberg et al, Lancet 2001;358:1687
EU caseload of aspergillosis
Frequency of aspergillosis
Acute Invasive
Subacute Invasive
Aspergilloma
Chronic cavitary
Chronic fibrosing
Locally invasive
Frequency of aspergillosis
30,000 - 70,000 cases
~7,500 cases
Immune dysfunction
Immune hyperactivity
.
After Casadevall
& Pirofski, Infect Immun 1999;67:3703
ABPA and severe asthma
www.emphysema-copd.co.uk
Likely ABPA caseload
1%+ of adult asthmatics attending clinic have
ABPA
In UK - ~5,000,000 with asthma, >3M adults
In Europe - >17,000,000 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
Likely SAFS caseload in Europe
In Europe - >17,000,000 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 2002;325:411
Brazil survey of fungal
rhinosinusitis
890 endoscopic sinus surgeries
62 (6.8%) had fungal rhinosinusitis
Dall’Igna Rev Bras Otorhinolaringol 2005;71:712
Prevalence of
allergic
rhinoconjunctivitis
symptoms
ISAAC Steering Committee Lancet 1998;351,1225
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 1998;351,1225
EU caseload of aspergillosis
Frequency of aspergillosis
Acute Invasive
Subacute Invasive
Aspergilloma
Chronic cavitary
Chronic fibrosing
Locally invasive
Frequency of aspergillosis
25,000 - 70,000 cases
167,500+ ABPA cases
680,000 - 1,700,000 SAFS cases
11,200,000 CRFS cases
ABPA
Severe asthma with
fungal sensitisation
Allergic sinusitis
~7,500 cases
Immune dysfunction
Immune hyperactivity
.
After Casadevall
& Pirofski, Infect Immun 1999;67:3703
www.aspergillus.org.uk