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Aspergillosis Patient Support Meeting July 2011 - Sue Howard

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2 hour support meeting for patients & carers that live with aspergillosis.
Main speaker is Dr Sue Howard of Manchester University and the National Aspergillosis Centre

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Aspergillosis Patient Support Meeting July 2011 - Sue Howard

  1. 1. Aspergillosis Patients Support Meeting – July 2011<br />National Aspergillosis Centre<br />Manchester, UK<br />Led by Dr Graham Atherton,<br />Specialist Nurse Georgina Powell<br />Main speaker Dr Sue Howard, Researcher at the National Aspergillosis Centre & Manchester University<br />Funding assisted by the Fungal Research Trust <br />www.fungalresearchtrust.org<br />
  2. 2. Programme<br />2pm Graham Atherton: Welcome & Introduction<br />2.05 Sue Howard: Aspergillus resistance – it’s on the increase<br />3.00 Break: Tea & Coffee – your opportunity to chat with fellow patients and staff members<br />3.15 Graham Atherton: Report on Fungal Research Trust Anniversary meeting, London Patients Support meeting and feedback on progress with various projects. Need comments on 2 new patients information leaflets<br />Complications with ABPA<br />SAFS<br />4.00 Close<br />
  3. 3. Aspergillus resistance <br />– it's on the increase<br />Dr Susan J Howard<br />The University of Manchester<br />Manchester Academic Health Science Centre<br />NIHR Translational Research Facility in Respiratory Medicine <br />University Hospital of South Manchester NHS Foundation Trust<br />
  4. 4. Aspergillus fumigatus<br />Aspergillus flavus<br />Aspergillus terreus<br />Aspergillus niger<br />
  5. 5. Other Aspergillus species<br />Klick MA. Identification of common Aspergillus species. CBS.<br />
  6. 6. Acquired resistance development<br />Intrinsicresistance in Aspergillus<br /> FLU ITR VOR POS RAV AMB 5FC CANDINS<br />fumigatus -++ ++ ++ + ++ +/- ++<br />terreus-++ ++ ++ +--++<br />flavus-++ ++ ++ + ++ - ++<br />niger-++ ++ ++ + ++ - ++<br />
  7. 7. Acquired resistance<br /><ul><li>Mostly azole resistance in A. fumigatus reported</li></ul> 1) most common species<br /> 2) primary therapy (itra, vori, posa)<br /><ul><li>Standardised methodology
  8. 8. First resistant case late 1980s</li></ul> but most >2000<br />Denning et al, 1997. AAC 41:1364-8 <br />
  9. 9. Agenda<br />How common are resistant infections?<br />What are the clinical risk factors?<br />How does resistance occur?<br />Is cross-resistance a clinical problem?<br />How can we detect resistance?<br />
  10. 10. Agenda<br />How common are resistant infections?<br />What are the clinical risk factors?<br />How does resistance occur?<br />Is cross-resistance a clinical problem?<br />How can we detect resistance?<br />
  11. 11. Clinical azole resistance reported<br />Frequency ~2% (0-15%)<br />
  12. 12. overall<br />10%<br />Significant increase since 2004<br />(Fishers exact test P<0.0001)<br />
  13. 13. Manchester as a centre<br />-> Specialist service for the management of aspergillosis2009National Aspergillosis Centre<br /> www.nationalaspergillosiscentre.org.uk<br />-> Susceptibility testing is routinely conducted <br /> may explain high frequency of itra resistance<br /> but does not explain the change in frequency<br />why?<br />
  14. 14. Denning AAC 1997;41:1364-8 VerweijDRU2009;12:141-7<br />
  15. 15. Agenda<br />How common are resistant infections?<br />What are the clinical risk factors?<br />How does resistance occur?<br />Is cross-resistance a clinical problem?<br />How can we detect resistance?<br />
  16. 16. Clinical data<br />Clinical data were available for 14 patients<br />2 invasive aspergillosis (IA)<br /> 9 chronic pulmonary aspergillosis (CPA)<br /> 2 allergic bronchopulmonary aspergillosis (ABPA)<br /> 1 Aspergillus bronchitis <br />Highest frequency in those with aspergillomas<br />13 had prior azole exposure (1 – 30 months)<br /> 6 had low drug exposures<br />8 patients failed therapy and 5 failed to improve <br /> (1 not treated)<br />Howard EID 2009;15:1068-76 Howard CMI 2010;16:683-8<br />
  17. 17. Agenda<br />How common are resistant infections?<br />What are the clinical risk factors?<br />How does resistance occur?<br />Is cross-resistance a clinical problem?<br />How can we detect resistance?<br />
  18. 18. Lanosterol Ergosterol<br />E<br />Resistance mechanism<br />Azole drug<br />
  19. 19. stop codon<br />start codon<br />intron<br />The cyp51A gene<br />
  20. 20. stop codon<br />start codon<br />intron<br />The cyp51A gene<br />54<br />98<br />220<br />“hot-spots”<br />
  21. 21. Holland<br />297<br />495<br />98<br />220<br />Snelders PLoS M 2009;5:e219<br />
  22. 22. Holland<br />297<br />495<br />98<br />220<br />Spain<br />98<br />54<br />220<br />Rodriguez-Tudela AAC 2008;52:2468-72<br />
  23. 23. 94%<br />3%<br />Holland<br />297<br />495<br />98<br />220<br />28%<br />19%<br />53%<br />Spain<br />98<br />14%<br />6%<br />11%<br />54<br />54<br />98<br />220<br />220<br />Manchester<br />216<br />138<br />448<br />284<br />219<br />147<br />431<br />495<br />434<br />Bueid JAC 2010; 65:2116-8 Howard EID 2009;15:1068-76<br />
  24. 24. Manchesterfindings<br />Striking variety of cyp51A mutations<br />Including previously reported mutations (including the hot-spots) <br />Some novel (147, 216, 431 & 434) – as yet uncharacterised<br />Of 7 patients with multiple resistant isolates, 4 revealed different mutations over time<br />Howard EID 2009;15:1068-76<br />
  25. 25. Patient case<br />64 M<br />COPD, bronchiectasis, Mycobacterium avium pulmonary infection<br />Chronic pulmonary aspergillosis 2003<br />Azole susceptible A. fumigatus<br />Itra therapy <br />Low itra drug exposure (rifabutin)<br />Ambisome twice for 2wk - some clinical improvement <br />4 mo itra resistant isolate (G54R)<br />4 mo later, another itra res isolate (G54E)<br />Increased precipitins titre, radiological progression<br />
  26. 26.
  27. 27. Patient case<br />Oct 2004 vori, 500 > 400 mg daily<br />Good levels (0.72-1.66mg/L)<br />Radiological and serological improvement<br />
  28. 28.
  29. 29. Patient case<br />Oct 2004 vori, 500 > 400 mg daily<br />Good levels (0.72-1.66mg/L)<br />Radiological and serological improvement<br />
  30. 30. Patient case<br />Oct 2004 vori, 500 > 400 mg daily<br />Good levels (0.72-1.66mg/L)<br />Radiological and serological improvement<br />20 mo isolate vori resistant (G448S), posa MIC 1mg/L<br /><ul><li>Sept 2006 posa therapy 800mg daily
  31. 31. Good levels (1.18-1.9mg/L)
  32. 32. Slow continued improvement</li></ul>keep checking MICs!<br /><ul><li>?same/different genetic type -> microsatellite typing</li></li></ul><li>Howard EID 2009;15:1068-76<br />
  33. 33. Evolution in the lung!<br />
  34. 34. ?agricultural <br />azole use<br />Environmental <br />sampling<br />Snelders PLoS M 2008;5:e219<br />
  35. 35. cyp51A mutation identified<br />no cyp51A mutation<br />Harrison E ICAAC 2009 M-1720<br />
  36. 36. Agenda<br />How common are resistant infections?<br />What are the clinical risk factors?<br />How does resistance occur?<br />Is cross-resistance a clinical problem?<br />How can we detect resistance?<br />
  37. 37. Azole cross-resistance<br />Itra resistance = almost all<br />Posa resistance = 74%<br />Vori resistance = 65%<br />Amb resistance = 0%<br />Howard EID 2009;15:1068-76<br />
  38. 38. 20%<br />14%<br />5%<br />17%<br />7%<br />5%<br />3%<br />0%<br />0%<br />5%<br />7%<br />0%<br />0%<br />Bueid JAC 2010; 65:2116-8<br />
  39. 39. Agenda<br />How common are resistant infections?<br />What are the clinical risk factors?<br />How does resistance occur?<br />Is cross-resistance a clinical problem?<br />How can we detect resistance?<br />
  40. 40. Detection options<br />MICs slow<br />Cultures frequently falsely negative in all forms of aspergillosis<br />Direct cyp51A mutation from primary specimen<br /> by real-time PCR<br />  most common mutations = G54, L98, M220, TR<br />55.1% cyp51A mutations (culture –ve)<br />Pro’s and con’s <br /> (other/no mutations & cost vs. -ve cultures & speed)<br />Need to do MICs still!<br />Denning CID 2011; 52:1123-9<br />
  41. 41. Conclusions<br />Resistance is clinically significant<br />Evidence of both environmental acquisition and emergence of resistance in the lung<br />Increasing frequency<br />Risk of cross-resistance is high/limited options<br />Need to monitor susceptibility routinely<br />
  42. 42. Thank you<br />
  43. 43. Graham Atherton<br />National aspergillosis centre<br />UHSM<br />Manchester<br />Support Meeting for Aspergillosis Patients<br />Fungal Research Trust<br />
  44. 44. Current ideas for fundraising<br />Campaign ribbons – cost us 75p each, donate what you can<br />Cook book<br />FUNGUIDE patient’s cookery book<br />Combining your recipes with ‘good news’ about fungi, how useful they can be<br />Any of your recipes including the use of any of the following:<br />Mushrooms, soy sauce, Quorn, Marmite, Stilton, Brie, camembert and so on<br />
  45. 45. New Fungal Research Trust website<br />
  46. 46. New FRT fundraising campaign<br />To fund a Postdoctoral scientist who will carry out work to increase our understanding of fungal diseases<br />1. Why Aspergillus causes disease, especially slowly progressive disease such as ABPA, bronchiectasis, chronic pulmonary aspergillosis and/or lung scarring.<br />2. What are protective factors for fungal infection? Why do some people with the same risk factors not get colonised or infected?<br />3. Why do fungi become resistant to antifungal drugs?<br />Target £150 000 which will fund research for 3 years<br />
  47. 47. Raising the money<br />Lewis Fraser Himalayan run (100 miles) in memory of Steph Smith. Target £10 000<br />Gem’s little Gems. Target £10 000 this year<br />Christmas raffle 2010 raised £1500<br />A patient raised £250 last year making and selling greetings cards <br />2010 raised approx £13 000<br />Can you help?<br />Your ideas & time will be the lifeblood of this challenge<br />Sign up for our newsletter<br />http://www.aspergillus.org.uk/newpatients/donations.php<br />
  48. 48. Drug Interactions database<br />
  49. 49. Drug Interactions database<br />
  50. 50. Drug Interactions database<br />
  51. 51. Current ideas for fundraising<br />Campaign ribbons – cost us 75p each, donate what you can<br />Cook book<br />FUNGUIDE patient’s cookery book<br />Combining your recipes with ‘good news’ about fungi, how useful they can be<br />Any of your recipes including the use of any of the following:<br />Mushrooms, soy sauce, Quorn, Marmite, Stilton, Brie, camembert and so on<br />
  52. 52. Involving you in our work<br />The Fungal Research Trust have appointed a new trustee who is a patient<br />Derek Stewart is to put forward the patients’ point of view to the board on a regular basis, eg with regard to research interests<br />Elisabeth Kershaw is working on behalf of patients by assisting with the formulation of future research proposals<br />
  53. 53. Thank You<br />“The best chance we have of beating this illness is to work together”<br />Living with it, Working with it, Treating it <br />Fungal Research Trust<br />
  54. 54. What is this meeting for?<br />For you to socialise with fellow patients<br />For you to receive support from NAC staff<br />We are here to answer your questions, feel free to approach any one of us<br />We are here to listen about what we can do better<br />We can use these meeting to assess our service, to ask for more help with research<br />We occasionally feedback results of the research already in progress<br />Fundraising for research (Fungal Research Trust)<br />
  55. 55. What can you do for us?<br />Feedback comments & suggestions on what we already do. <br />What isn’t working?<br />What is working?<br />What do you need to know more about?<br />How can we improve?<br />What more can we do?<br />Help us with fundraising<br />The Fungal Research Trust<br />

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