Saturday, 28 January 2012

5th Advances Against Aspergillosis - Day 3

Saturday 28 January 2012 – Day 3 

08.00 – 08.45      Meet the Professor
                          Stump the Professor – Interesting clinical dilemmas
                          John E. Bennett, MD
                          Souha Kanj, MD

Session 9: Diagnostics and Imaging
Chairs: Dimitrios P. Kontoyiannis, MD & Malcolm Richardson, PhD

09.15 – 09.40      Application of diagnostic markers for IA in children
                          Emmanuel Roilides, MD

09.40 – 10.05      Impact of prophylaxis on galactomannan, beta-D-glucan and PCR
                          J. Peter Donnelly, PhD

10.05 – 10.30      Which antigens are important and why?
                          Max S. Topp, MD

10.30 – 10.40      Oral Poster Presentation: Impact of current antifungal therapy on PCR based investigation of bronchoalveolar lavage samples for diagnosing pulmonary aspergillosis in patients with hematologic malignanciesMark Reinwald, MD

Session 10: Pfizer Symposium
The Treatment Options Strategies for IA
Chairman: J. Peter Donnelly, PhD

11.10 – 11.15      Welcome and introduction
                          J. Peter Donnelly, PhD

11.15 – 11.30      Stratification of risk for IA in immunocompromised patients
                          Raoul Herbrecht, MD

11.20 – 11.45      Pre-emptive versus empirical anti-fungal therapy in neutropenic hematologic patients
                          Omrum Uzun, MD

11.45 – 12.00      Combination therapy: who benefits?
                          Keiren Marr, MD

12.00 – 12.10      Panel discussion

Session 11: Antifungal Resistance
Chairs: David A. Stevens, MD & Beyza Ener, MD

14.10 – 14.35      Global status of azole resistance in Europe and Asia
                          Sevtap Arikan-Akdagli, MD

14.35 – 15.00      Update on resistance mechanisms
                          David S. Perlin, PhD

15.00 – 15.10      Oral Poster Presentation: Aspergillus fumigatus biofilms releases extracellular DNA which plays a role in phase dependant antifungal resistance
                          Ranjith Rajendran, MSc

15.10 – 15.35      Current section and species complex concepts: recommendations for routine daily practice
                          Manuel Cuenca-Estrella, MD, PhD

15.35 – 16.00      Implications of resistance in Aspergillus treatment guidelines
                          Dimitrios P. Kontoyiannis, MD

16.00 – 16.10      Farewell
                          David A. Stevens, MD

16.20                  Farewell Drinks and Discussion about the next AAA Meeting

Friday, 27 January 2012

5th Advances Against Aspergillosis Conference: Day 2

Go directly to a day's programme Thursday | Friday | Saturday

Friday 27 January 2012 – Day 2  

Session 6: Astellas Symposium
Chair: Katsuhiko Kamei, MD, PhD

08.00 – 09.00      Controversies in management: prophylaxis or diagnostics
                          Andrew Ullman, MD
                          Drosos E. Karageorgopoulos, MD

Session 7: Genomics and Proteomics
Chairs: Elaine Bignell, PhD & David S. Perlin, PhD

09.15 – 09.40      Aspergillus adhesions
                          Don Sheppard, MD

09.40 – 10.05      mRNAs in Aspergillus
                          Michelle Momany, PhD

10.05 – 10.30      RNAseq
                          Antonis Rokas, PhD

10.30 – 10.55      Alternative approaches to drug discovery in Aspergillus fumigatus
                          Michael Bromley, PhD

10.55 – 11.20      Targets for broad spectrum antifungal vaccines? Quantitative proteomic comparisons of Aspergillus & Co.
                          Markus Kalkum, PhD

11.20 – 11.50      Coffee / Tea Break

Session 8: Management of Aspergillosis
Chairs: John E. Bennett, MD & Volkan Korten, MD

11.50 – 12.15      Management of chronic pulmonary aspergillosis
                          Koichi Izumikawa, MD, PhD

12.15 – 12.40      Update on biologicals for ABPA and asthma
                          Richard B. Moss, MD

12.40 – 13.05      Paediatric aspergillosis
                          Andreas Groll, MD

13.05 – 13.15      Aspergillus bronchitis in non-immunocompromised patients – case series, response to treatment and criteria for diagnosisTimothy Felton, MD

13.15 – 14.15      Lunch

14.15                  CONFERENCE SOCIAL EVENT: Tours followed by Dinner

Thursday, 26 January 2012

5th Advances Against Aspergillosis Conference: Day 1


Go directly to a day's programme
Thursday | Friday | Saturday

Wednesday 25 January 2012

08.30 – 18.00      Pre-Meeting Workshop
                          Masterclass in the management of chronic and allergic pulmonary aspergillosis
                          Open to 35 clinicians
                          Lead by Professor David Denning and other colleagues.

Thursday 26 January 2012 – Day 1

08.00 – 08.45      Meet the Professor Session
                          Controversies in immunology: Excessive inflammation in aspergillosis
                          Luigina Romani, MD, PhD

09.00 – 09.10      Opening Remarks
                          William J. Steinbach, MD

Session 1: Cutting Issues in the Pathogenesis of Aspergillosis
Chairs: William J. Steinbach, MD & Jean-Paul Latgé, PhD

09.15 – 09.40      Angiogenesis at the mold-host interface: a potential key to understanding and treating invasive aspergillosis
                          Ronen Ben-Ami, MD

09.40 – 10.05      Aspergillus fumigatus survival in the lung environment
                          Elaine Bignell, PhD

10.05 – 10.30      Visualising phagosomal killing of Aspergillus fumigatus
                          Jatin M. Vyas, MD

10.30 – 10.55      Vitamin D and OX40L interaction
                          Jay K. Kolls, MD

10.55 – 11.05      Oral Poster Presentation: Aspergillus fumigatus supermaters: genome comparison and genetic recombinationJanyce Sugui, PhD

Session 2: Emerging Clinical Associations with Aspergillosis
Chairs: David W. Denning, FMedSci & Omrum Uzun, MD

11.35 – 12.00      COPD and aspergillosis
                          Jesús V. Guinea OrtegaPharmD, PhD

12.00 – 12.25      Aspergillosis in cystic fibrosis – insights from new and old diagnostics
                          Caroline Baxter, MD

12.25 – 12.50      Invasive aspergillosis in ICU – are we moving forward?
                          George Dimopoulos, MD

12.50 – 13.15      Immune regulation in idiopathic bronchiectasis
                          Rosemary Boyton, PhD

Session 3: Top Six Papers in Aspergillosis in 2011
Chair: Sevtap Arikan-Akdagli, MD & Jay K. Kolls, MD

13.45 – 14.45 and concurrent with lunch
Murat Akova, MD and Nir Osherov, PhD

Session 4: Novel Immunological Insights into Aspergillosis
Chairs: Richard B. Moss, MD & Emmanuel Roilides, MD

14.45 – 15.10      Innate immunity to Aspergillus
                          Mihai G. Netea, PhD

15.10 – 15.35      Neutrophil extracellular traps and A. fumigatus
                          Matthias Gunzer, PhD

15.35 – 15.45      Control of neutrophil ROS responses to A. fumigatus
                          Keith Boyle, PhD

15.45 – 15.55      Oral Poster Presentation: T-cell responses to several Aspergillus antigens may be detected in patients with invasive Aspergillosis and may be exploited for diagnostic and therapeutic purposes: a multicenter study Leonardo Potenza, MD, PhD

Session 5: Portraits of Non-Fumigatus Aspergilli – What is so Special About:
Chairs: Paul Bowyer, PhD & Karl V. Clemons, PhD

16.25 – 16.50      Specification of polarity sites during growth and development ofAspergillus nidulans
                          Steven D. Harris, PhD

16.50 – 17.15      Aspergillus niger a perfect host for industrial biotechnology: systems biology approaches for the production of building block chemicals
                          Peter J. Punt, PhD

17.15 – 17.40      Diversity of Aspergillus flavus on crops and in the environment can be exploited to reduce aflatoxin exposure and improve environmental health
                          Peter J. Cotty, PhD

17.40 – 17.50      Oral Poster Presentation: Unique polysaccharide cell-wall composition responsible for dysregulated inflammation of A. nidulans infections in chronic granulomatous diseaseStefanie Henriet, MD

Wednesday, 25 January 2012

Defensin Mimetics Show Antifungal Activity

It is a fairly well-established fact that many of the antibiotics that have been developed in the past are starting to become less effective as the microbes they are designed to attack gradually become resistant. This is a slow process and can be managed quite effectively by limiting use of our current antibiotics to the more severe cases of infection - this slows the rate at which resistance can occur.

Despite precautions there is still a need to develop new antibiotics to replace those that become useless. Antibiotic-resistance mechanisms can affect more than one antibiotic at a time - a microbe can sometimes become resistant to several similar antibiotics at the same time - so ideally we need new antibiotics that attack microbes in different ways (i.e. new targets) to that which have already been developed.

How can we find new antibiotics that work on new targets? One new strategy is to look at our own immune systems for inspiration. Defensins are naturally occurring small proteins found in some of the cells in our immune systems - in particular neutrophils.

Neutrophils line our lungs and engulf spores (see movie above) to destroy them. Once engulfed it is defensin proteins that attack the spore, punch holes in the cell membrane and literally 'burst' the cells wide open.

Scientists have now found how to synthesis artificial defensin proteins and are investigating how we can use them to directly attack microbes - much like a totally new type of antibiotic. One company have discovered that these molecules are effective when used against diverse infectious agents including fungi (Candida) and malaria (an insect!) - albeit only in mice at the moment. They are shown to be far more effective against Candida than nystatin, an existing antifungal drug.

The fact that Candida can be treated with defensin with such efficacy at least in one clinical context (the mouth) raises the possibility that they may also be effective against Aspergillus infections. They seem highly effective in the laboratory - let us hope that this is the dawn of an new era of highly effective drugs that can be used to treat a much wider range of infectious agents compared with older antibiotics, and one that resistance is very slow to develop against.

Friday, 20 January 2012

5th Advances Against Aspergillosis

Newsbite: The 5th Advances against Aspergillosis conference opens in Istanbul next week on the 26th January 2012. AAA5 is the main conference focussing entirely on Aspergillosis, its causes, diagnosis, treatment, clinical research, clinical management and more. The conference will be reporting back to this blog every day and will be using Twitter @AAA5Conference. more...

Tuesday, 17 January 2012

Invasive Aspergillosis Outbreak in Intensive Care Unit - Contaminated Air Identified As Cause

Though it may appear to be obvious few studies have convincingly demonstrated that the source of an outbreak of invasive aspergillosis is unclean air in the hospital environment. It is not generally enough to show that  there are spores present in the air of a hospital as spores can also be present prior to the entry of a patient into the hospital, in their airways, on their clothes or in their food

In this study patients undergoing open heart surgery in a dedicated unit suffered an outbreak (December 2006 to April 2008) with seven becoming infected during this time and mortality was high (86%). The authors were able to look at the monthly surveillance records for the air in the heart surgery unit over this time and correlate the species found in the air with those found to be infecting the patients.

Aspergillus fumigatus was the main infecting species (6/7) and no spores were found during the periods prior to and after the outbreak. However during the outbreak a series of six abnormal air tests were recorded showing from 50 to 400 viable A. fumigatus spores per cubic metre of air in the intensive care units where patients spent time recovering from surgery - there was clearly a correlation between the presence of these spores in the air of ICU and the seven cases of invasive aspergillosis. The air in the operating theatres was clean throughout this time.

However there was still the problem of proving whether or not these spores caused the infections - perhaps the infecting spores were present prior to the operations?

To address this problem the authors have genotyped the strains of A.fumigatus found in the air of ICU and compared them with those found growing in infected patients and found them to be the same strains in half the patients - strongly indicating that in at least half of the cases the source of the infection was indeed the spores found in the air of ICU.

This is strong evidence for the importance of maintaining clean air for patients throughout their time in hospital after major surgery, during the operation and afterwards.

Wednesday, 11 January 2012

Newsbite: Chinese Add Mycotoxin Screening to Milk Production Testing

Testing of milk produced by the company Mengniu  found it to be contaminated with unacceptably high levels of aflatoxin (occasionally found in cattle feed) after testing was carried out before Christmas 2011. New tests show the levels of aflatoxin are now much lower and are at levels deemed safe to drink. Regular routine screening for aflatoxins in milk has now been introduced in China

Tuesday, 10 January 2012

Anti-arthritis Drugs Carry a Risk of Aspergillosis

There are a number of new drugs coming into use which are intended to correct the immune system response of the patient to specific challenges. These drugs hold high promise for the treatment of auto-immune diseases where our immune systems mistake their own host tissues as an invading organism and attack tham as if they were eliminating a bacterium or other micro-organism.

First defined by Ernst Witebsky(1957) autoimmune diseases are common and take many forms, attacking particular tissues. There are hundreds of different types of autoimmune disease and they include familiar diseases such as rheumatoid arthritis. They are traditionally treated by suppressing the immune system of the patient using glucocorticoid drugs which are very effective.

Unfortunately glucocorticoids have many unpleasant side effects so many efforts are made to minimise their usage. It is beginning to be possible to manufacture drugs that will selectively inhibit parts of our immune systems and prevent painful inflammation caused by an overactive immune system e.g. Certolizumab. These are antibodies that can very precisely eliminate proteins causing particular types of inflammation.
The amazing trick this new generation of antibodies can perform is to fool our bodies into thinking that the injected antibody is a human antibody (humanised antibody) which allows them to persist in our bodies for longer period of time. They then have a much larger effect.

These humanised antibody drugs are achieving success in treating many people who are having difficulty with inflammation - arthritis being one group but other groups are also being treated e.g. omalizumab (Xolair) to treat those with severe asthma and in some cases Allergic Bronchopulmonary Aspergillosis (ABPA). Many can reduce or eliminate their dose of steroid while taking the antibody - different antibodies are used in each case.

Revolutionary though they may be, there is a small risk with some of these medications. If you adjust parts of the immune system there is a risk that you can also reduce the ability of that person to fight off infection. Using Certolizumab on its own doesn't seem to cause a problem but if that patients is immunocompromised by taking a steroid drug at the same time as the antibody then there can be a small increased change of getting a number of infections including aspergillosis.

 This article is a summary of a research project into the use of Certolizumab to treat arthritis. It gives a warning for users of Certolizumab  to be cautious if they have had or still have tuberculosis, aspergillosis and other infections and are taking steroids at the same time. One outcome of this study may well be to investigate this risk more carefully.

NOTE: It is worth reiterating that there is no data suggesting that treating ABPA with Omalizumab can trigger more aggressive aspergillosis, this study only refers to Certolizumab - a quite different medication.

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