Aspergillosis in AIDS David W Denning Director National
- Slides: 51
Aspergillosis in AIDS David W. Denning Director, National Aspergillosis Centre University Hospital South Manchester [Wythenshawe Hospital] The University of Manchester Myconostica Ltd
New manifestations of aspergillosis Aspergillosis in AIDS Denning et al, New Engl J Med 1991: 324: 654
Frequency
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 167, 500 ABPA cases 680, 000 -1, 700, 000 SAFS cases 11, 200, 000 CFRS cases ABPA Severe asthma with fungal sensitisation Allergic sinusitis ~7, 500 cases Immune dysfunction Immune hyperactivity . After Casadevall & Pirofski, Infect Immun 1999; 67: 3703
Trends over time in IFDs in AIDS – autopsy series 1630 autopsies in 2101 deaths (77. 6%) IFD found in 297 (18. 2%) IA was diagnosed during life in only 12% Antinori et al, Am J Clin Pathol 2009; 132: 221
CDC surveillance National survey in US 35, 252 patients 1990 - 1998 IA diagnosed in 228 patients Incidence of 3. 5/1000 person years Holding et al, Clin Infect Dis 2000; 31: 1253
Mumbai autopsy series Lanjewar & Duggal, HIV Med 2001; 2: 266
Risk factors
CDC surveillance Holding et al, Clin Infect Dis 2000; 31: 1253
Italian experience of aspergillosis in AIDS Libanore et al, Infection 2002; 30: 341
Risk factors for invasive aspergillosis in AIDS Stage of AIDS CDC Group II CDC Group IV Neutropenia <1000 x 106/L Corticosteroid therapy Prior pulmonary infection 4 (1%) 289 (72%) 92/202 (46%) 79/202 (39%) 124/169 (73%) Khoo & Denning, Clin Infect Dis 1994; 19 (S 1) 541
Clinical suspicion
Missed IFDs in AIDS – autopsy series Antinori et al, Am J Clin Pathol 2009; 132: 221
Aspergillosis in AIDS Site of disease in 293 published cases Respiratory Sinuses Otomastoiditis Larynx Tracheobronchitis Obstructing bronchial Invasive Pulmonary Empyema/pleural mass Aspergilloma 9 5 2 11 5 208 5 4 Other CNS Cardiac Renal Thyroid Miscellaneous 30 10 12 4 16 ≥ 2 organs involved = 47 Khoo & Denning, Clin Infect Dis 1994; 19 (S 1) 541
Invasive pulmonary aspergillosis in AIDS Presenting features (in 78 patients) Cough 92 % Fever 91 % Dypsnoea 65 % Chest pain 24 % Haemoptysis 9% Khoo & Denning, Clin Infect Dis 1994; 19 (S 1) 541
Italian experience of aspergillosis in AIDS Libanore et al, Infection 2002; 30: 341
Invasive Pulmonary Aspergillosis in AIDS Patient JJ Late stage AIDS, unresponsive to ITZ (Af 90 and Af 91) Patient JB Denning et al, New Engl J Med 1991; 324: 654
Invasive Pulmonary Aspergillosis, with dissemination, in AIDS Patient JA 31 st May Patient JA 25 th June, 3 days before death Denning et al, New Engl J Med 1991; 324: 654
Invasive pulmonary aspergillosis in AIDS, showing nodules with cavitation WWW. aspergillus. org. uk
Invasive pulmonary aspergillosis in AIDS, showing upper lobe cavities Denning et al, New Engl J Med 1991; 324: 654
Invasive pulmonary aspergillosis in AIDS Patient DF A. niger grown 5 x from sputum WWW. aspergillus. org. uk;
Italian experience of aspergillosis in AIDS Libanore et al, Infection 2002; 30: 341
Radiology and diagnostic accuracy 8 radiologists compared with 8 internists 25 IPA and 25 other diagnoses in AIDS Analysed with and without clinical information Zaspel et al, Eur Radiol 2004; 14: 2030
Radiology and diagnostic accuracy Zaspel et al, Eur Radiol 2004; 14: 2030
AUC = 0. 84 AUC = 0. 75 Radiology and diagnostic accuracy Zaspel et al, Eur Radiol 2004; 14: 2030
Obstructing bronchial aspergillosis Patient ML Pre-bronchscopy Patient ML After bronchoscopy Denning et al, New Engl J Med 1991; 324: 654
Invasive Aspergillus tracheobronchitis in AIDS Lortholary et al, Am J Med 1993; 95: 177
Ear and sinus aspergillosis in AIDS Sinusitis • Headache, facial, neck or ear pain; • Nasal discharge • Often chronic Invasive fungal otomastoiditis Ear pain (often severe), otorrhoea, without fever
Sphenoid sinusitis leading to local spread to the brain and cerebral aspergillosis Presented with headache over the vertex of the skull www. aspergillus. man. ac. uk
Establishing a diagnosis
Significance of positive respiratory cultures 45/972 (4. 6%) incidence of positive cultures 5/45 (11%) invasive aspergillosis 4/13 (23%) neutropenic AIDS patients had invasive aspergillosis if positive sputum culture for Aspergillus Pursell et al. Clin Infect Dis 1992; 14: 141
Aspergillus in AIDS Species isolated (n = 82) A. fumigatus 69 (84%) A. flavus 7 (9%) A. niger 4 (5%) A. terreus 2 (2%) Khoo & Denning, Clin Infect Dis 1994; 19 (S 1) 541
Early French experience of aspergillosis in AIDS “The mycologic culture from BAL was the method of choice for the diagnosis of invasive pulmonary disease” Of 28 patients with a positive BAL culture for Aspergillus, 15 underwent a biopsy or autopsy and 14 were positive at histology. Serum antigen detection was positive in only 4 of 16 tested patients. Lortholary et al, Am J Med 1993; 95: 177
Italian experience of aspergillosis in AIDS Libanore et al, Infection 2002; 30: 341
Would PCR help?
Myc. Assay™: Aspergillus Myc. Assay™: Pneumocystis Real-time molecular based in vitro diagnostic tests for Aspergillus spp. and Pneumocystis jirovecii d re a le c § Aspergillus based on 18 S r. RNA A D F § Pneumocystis based on mitochondrial LSU ot CE rk a m , d e b n t u
Myc. Assay™: Aspergillus Establishing a tentative clinical cut-off, for use in prospective regulatory studies
Treatment
Choice of antifungal for aspergillosis Priority sequence • Voriconazole (unless drug interaction) • Am. Bisome 3 mg/Kg (if not ‘nephro-critical’) OR caspofungin/micafungin (if not neutropenic) 3. Posaconazole (oral only, if no drug interactions) 4. Itraconazole
When not to use voriconazole as primary therapy? Absolute contraindications • Drug interactions (ie rifampicin, carbamazepine, phenytoin etc) • Voriconazole used as prophylaxis (but not itraconazole or posaconazole) • Resistance to voriconazole (esp zygomycosis, A. lentulus or azole resistance) Relative contraindications • Renal failure (IV only) • Young children (need higher dose ? + other agent) • Severe hepatic dysfunction • Interacting drugs (ie sirolimus)
HIV therapy and azole interactions Beware!
IRIS
Immune reconstitution in invasive pulmonary aspergillosis, in AIDS Patient HB Day +14, CD 4 cells 84/u. L Patient HB Day +42, after Am. B and ITZ Sambatakou, Eur J Clin Microbiol Infect Dis 2005; 24: 628
Immune reconstitution in invasive pulmonary aspergillosis, in AIDS Patient HB Day +64, CD 4 cells 340/u. L, on VRC Patient HB Day +87, day of death Sambatakou, Eur J Clin Microbiol Infect Dis 2005; 24: 628
Azole resistance
Chronic cavitary pulmonary aspergillosis (CCPA) in HIV February 2005 32 yr old from Malawi, on HAART Rx - haemoptysis - Aspergillus precipitin titre 1/16 CT scan shows 2 large cavities with aspergillomas, with additional lesions (October 2005) Surgical removal would require a pneumonectomy So treated with itraconazole
CCPA in HIV February 2007 On HAART Rx, with low viral load, CD 4 count >200 - New haemoptysis - Aspergillus precipitin titre 1/32 MICs A. fumigatus Feb 2007 CXR & CT scan showed expansion of inferior cavity Itraconazole = >8. 0 mg/m. L Voriconazole = 0. 5 mg/m. L Posaconazole = 1. 0 mg/m. L February 2007 April 2007
CCPA in HIV - low itraconazole concentrations Itraconazole concentrations Nov 05 2. 5 mg/L Dec 05 3. 4 mg/L March 06 4. 5 mg/L July 06 6. 7 mg/L Feb 07 8. 4 mg/L Do low concentrations of antifungal predispose to the development of resistance?
Azole resistance in Manchester in A. fumigatus 11% 5% 17% 5% 3% 7% 0% 0% 5% 7% 0% 0% Howard et al, Emerg Infect Dis 2009; 15: 1068
www. aspergillus. org. uk
- Professor david denning
- Doc for invasive aspergillosis
- Aspergillosis
- Aspergillosis
- Aspergillosis
- Aspergillosis symptoms
- Objective of interpretation
- Phil denning
- Graham-denning model
- Patricia denning stars in a sad movie
- Nikki denning
- Lattice based access control example
- Kathryn denning
- Graham denning model
- David warren director
- National aids control council tenders
- National unification and the national state
- The text-based director, also known as the
- Responsabilidades de un director de escuela
- Miercurea ciuc penitenciar
- Tugas director syarikat
- Director of operations org chart
- Procolombia organigrama
- Oliver stone
- Salaam bombay! nominations
- Directors brief
- Types of span of control in organization
- Nuh management structure
- Usana commission payout
- Floor manager hand signals
- Fashion show staff positions
- Importance of audience in theatre
- Electron donating groups examples
- Ciclo de micenas
- Musica de la pelicula el pianista
- Director regional de alajuela
- Director of technical education hp
- Managing director message for company profile
- Class director
- Images of change management
- Bartholomew cubbins jared leto
- Traffic director triage
- Qualification of a director
- Cisco threat intelligence director
- Director comercial organigrama
- Orange county ems protocols
- Discussion director examples
- What is an associate director
- Juniper nms
- Que es desarrollo profesional
- Shaalarth
- Defination of secretary