Leslee’s Story – A Life with Aspergillosis

I smiled when Jill Fairweather asked us to write a few words on how aspergillosis affects us. I am sure most of us could write a novel on the effects it has had on our lives, before and after being diagnosed. I could write a novel on applying, fighting and winning my personal independence payment (PIP) allowance with this disease alone.

Before I was diagnosed, I thought I had lung cancer. It has been five years since the start of my symptoms and about two and a half years since being positively diagnosed with allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA). Worst part for me was the initial feeling of isolation and loneliness. I didn’t know anyone else who had this disease. My GP didn’t know anything about it, my friends had never heard of it. After a few months the phone calls to go to different events in my local area began to stop. I would say I could go and then on the actual day feel so unwell I used to cancel. So after lots of cancellations the requests to go became fewer and fewer.

I had to have a stair lift fitted because I was too breathless to climb the stairs. I experienced numerous episodes of bleeding from the lungs, two of them were life threatening. I was on 40mg prednisone daily and put on four stone. I had become very withdrawn. Apart from GP, respiratory appointments or hospital inpatient stays I didn’t go anywhere. I had become very frustrated and angry because I couldn’t get any answers as to what was wrong with me.

Since being diagnosed and put on the right medication for me personally, I have got my life back. Yes, I have bad days, i.e. pneumonia last year and more recently a collapsed lung but I can breathe, I can go out, I can socialise, I can exercise.

I know I am one of the lucky ones with this disease who has had some remission from it. I had tried voriconazole, but I was still getting bleeding and other side effects. Once under Professor Denning’s care my medication was changed to posaconazole, I stopped the prednisone gradually and went on a 6 week pulmonary rehabilitation course. I have since lost the four stone I put on, partly through diet and partly by exercising.

I also have a wonderful and understanding respiratory consultant who referred me to Professor Denning. I wasn’t keen to go as it is a 600+ mile round trip for me, but I am now so happy that I made the decision to attend the National Aspergillosis Centre (NAC) in Manchester.

I know for some Aspergillosis can be successfully managed, I am one of those. When I see how far we have come with raising awareness of this condition, from the five years that I first started with the symptoms, it is amazing. Who would have thought that we’d have an Aspergillosis Awareness poster on the back of some London buses for World Aspergillosis Day on 1st February 2019?!

My hope/dream is to arrive into A&E on one of my bad flare-ups and when they ask me what is wrong and I reply ‘Aspergillosis’, nobody asks me “what is that?”…

@aspertrust
#WorldAspergillosisDay

Better diagnostics with minimal equipment

In many parts of the world there is poor diagnosis of fungal infections. Part of the problem is a lack of expertise and equipment in the many diagnostic labs that already exist and in some there is a lack of a reliable electricity supply so sophisticated machines are not going to help the situation. This is a significant barrier to getting the right treatment to many millions of people worldwide.

The Fungal Infection Trust has designed and built a series of online courses that are intended to train people to diagnose all fungal infections using nothing more than a light microscope and a few simple stains.

A microscopy training course for mycologists in 4 key modules.

Microfungi.net is a series of four modules translated into four languages (English, Spanish, Portuguese and French) with more to come in Chinese. Participating is free of charge and qualifies the participant to receive a certificate accredited by the University of Manchester, UK.

Module 1 – Teaches basic microscopy, stain preparations and staining techniques

Module 2 – How to use basic microscopy methods on wet mounted samples from a wide diversity of human tissues

Module 3 – An introduction to Histology and identification of fungal elements in many human tissues

Module 4 – An advanced course to learn skills in microscopy and histology for the identification of uncommon and very rare fungal pathogens

This course has been available for 18 months and hundreds of people have visited the site and started a course, but much more needs to be done and many more people need to become aware of this resource.
In addition large parts of the world do not speak any of the languages we have mentioned so far, so we need to add more translations to make this valuable resource more widely available.

New Genetics

The National Aspergillosis Centre and the Manchester Fungal Infection Group (MFIG) are at the forefront of the investigation of why some people get chronic aspergillosis when most of use do not. We are all breathing the same air and the source of the infection can only be the fungal spores in the air as most infection affect the lungs and sinuses!

Genetic studies looking at the entire genome of groups of patients who have chronic aspergillosis have started to reveal a small group of genes that seem to be consistently associated with aspergillosis. Perhaps unsurprisingly many of these appear to play a part in different parts of our defence mechanisms to resist infection. Fungi offer particular challenges for our bodies to solve – they are made up of strong threads that can force their way through membranes that would stop a bacterium for example, and fungal threads (hyphae) are far to large for a single neutrophil to engulf.

A recent study released by MFIG & NAC characterised a single gene named ZNF77 which, when carrying a particular mutation, causes Aspergillus fumigatus spores to stick more easily and strongly to the walls of an airway, and to germinate and grow faster! It isn’t difficult to realise that people carrying such a mutation will be more vulnerable to infection by Aspergillus, however even that change on its own is not thought to be enough to cause CPA or ABPA. There is much more to learn but it could certainly be useful to screen people thought to be at risk of chronic aspergillosis for this mutation. If someone has the mutation doctors could provide increased protection e.g. by giving antifungal drugs prior to and during a planned medical procedure such as a transplant.

#WorldAspergillosisDay

New Diagnostics

It is highly important that we are able to diagnose someone with aspergillosis as quickly as possible as the outcome of treatment is improved if we can begin earlier. Currently diagnosis is a complicated process that takes up a lot of time and that has a particular impact on people who have an acute invasive aspergillosis as that infection can progress rapidly, however there is also a large population of people who have chronic forms of aspergillosis such as Chronic Pulmonary Aspergillosis (CPA) and Allergic Pulmonary Aspergillosis (ABPA) and it is likely that many cases of severe asthma (SAFS) are also caused by Aspergillus sensitisation.

People who have chronic forms of aspergillosis are typically very difficult to diagnose. Centres such as the National Aspergillosis Centre (NAC) in Manchester are dedicated to detecting aspergillosis in patients who are struggling to manage severe asthma for example. Doctors throughout the UK send their patients to NAC as there is no local expertise, a situation that is repeated in many countries throughout the world. Only the worst patients tend to be referred, many fewer than predicted numbers of how many people there should be with ABPA/SAFS and other chronic aspergillosis in the UK. A simple test is badly needed to identify the ‘missing patients’, a test that must be sensitive and simple to use.

LD Bio, a company based in Lyon, France have developed a solution that may have far reaching consequences. Using this device doctors at the bedside of a patient who they suspect may have chronic aspergillosis can now simply put a drop of blood into the sample well at the top of the device and wait for a few minutes for the result to develop. If the patient has aspergillosis two bands will appear, if not one band will appear.

The National Aspergillosis Centre in Manchester, UK has tested the device (results to be presented at ECCMID 2019 in April 2019)  and found it to be accurate, identifying 91% of cases of Chronic Pulmonary Aspergillosis in 30min. The manufacturers claim that this test is equally as useful to detect cases of Allergic Bronchopulmonary Aspergillosis (ABPA) and Aspergillus colonisation, suggesting that many more ‘missing’ patients could now be identified quickly and cheaply. If the same technology could be used to detect cases of SAFS then even more patients could receive the correct treatment more quickly.

The test is cheap and accurate enough to use when resources are low (potentially even in developing countries) and a rapid result is desired.

 

The Impact of Aspergillus Worldwide

Research on Aspergillosis is gradually revealing that the fungus Aspergillus reaches into far more of our lives that we previously thought. Far from earlier assumptions that our airways are usually sterile places that contain no microbes, the latest research suggests that Aspergillus and many other microbes reside in many of our lungs as part of our normal micro/mycobiome and causes no health problems at all.  In fact many bacterial & fungal species found in our microbiome are thought to protect us from infection by pathogens. This harmless growth is sometimes referred to as colonisation.

Paradoxically there are large numbers of people in the world who have serious fungal infections caused by Aspergillus colonisation of their airways and lungs which suggests that either something is different about the fungus or the infected person in each case.

In some cases the cause is clearer for example someone who receives a transplant (solid organ or bone marrow) usually experiences a period of several days when they are less able to fight off infections. People who have an impaired immune system due to having AIDS are similarly affected (estimated 300 000 cases of invasive aspergillosis worldwide). Those people are often kept in sterile rooms until they recover enough of a functional immune system to cope with our normal air which contains many potential pathogens. Despite these precautions some will get an infection such as aspergillosis and it is easy to speculate that such cases may be caused by an Aspergillus pathogen  that had up to that point been harmlessly colonising their lungs.

What then of people with severe asthma with fungal sensitivity (SAFS: 6.5 million cases worldwide) who have a fungus growing in their lungs and they have become sensitive to its allergens, exacerbating their respiratory symptoms? How are they different to other asthmatics and non-asthmatics?

There are also 3 million cases of Aspergillus slowly eroding cavities into the lungs of people who apparently have a normal immune system (Chronic Pulmonary Aspergillosis CPA). Why are they so infected when many more have Aspergillus growing in their lungs with no ill effects?

We need to be able to identify individual at risk from infection as early as possible so that treatment outcomes are the best possible. To do that we need to understand why some people become infected or sensitised when most do not even though they have Aspergillus growing in their lungs.

World Aspergillosis Day is a great time to think about helping the Aspergillosis Trust and the Fungal Infection Trust fund more research into aspergillosis.

#WorldAspergillosisDay

Aspergillosis Trust Activities WAD 2019

#WorldAspergillosisDay

Aspergillosis Trust Activities

The Aspergillosis Trust has several activities planned for WAD 2019, one of which is already in operation!

This banner features two of their patrons; Dr Emily Grossman and Alan Titchmarsh and can be seen on the back of 15 buses in the Hyde Park/South Kensington/Fulham/Richmond Park area of London, which includes a route going past the Brompton Hospital. The buses will run throughout January 2019 up to Feb 1st, World Aspergillosis Day itself.

Global health improvement targets announced on World Aspergillosis Day

Aspergillosis, lung and sinus disease caused by the fungus Aspergillus, affects around 15 million people  and kills over 1 million each year.  Announced today at the 8th biennial Advances against Aspergillosis international conference in Lisbon starting on February 1st (World Aspergillosis Day), are the 5 Aspirational targets for aspergillosis to be achieved by 2030:

  1. Survival in invasive aspergillosis increased to 90% (up from under 50%)
  2. New antifungal agents licensed for all major forms of pulmonary aspergillosis (invasive, chronic and allergic) and for all age groups (only 3 classes currently available)
  3. The biological, immunological and genetic basis of aspergillosis understood (major gaps in our understanding currently)
  4. Diagnostics (standardised and clinically validated) for disease widely available and simple screening tests developed (most countries, including all of Africa have no diagnostic capability at all)
  5. At least one vaccine against aspergillosis in clinical trials or approved (none currently).

At the conference opening session, Professor David Denning, President of the Global Action Fund for Fungal Diseases (GAFFI) and the University of Manchester spoke on behalf of patients, doctors, and researchers in calling for radical improvements. Because diagnostics are not available in so many countries and cities, hundreds of thousands of people unknowingly die or are disabled by aspergillosis, yet could be saved or cured. He said:

“I have been looking after patients with aspergillosis for over 35 years, and yet we still lose patients and see too many people severely affected by this common fungus. I contributed to many clinical studies bringing the first effective oral drugs to patients (itraconazole and voriconazole), and yet the burden and deaths remain huge. Nothing less than a concerted international effort is required to address huge disparities in aspergillosis frequency.”

2018 marks the 20th anniversary of The Aspergillus Website www.aspergillus.org..uk), which the Fungal Infection Trust has been supporting. It provides a truly encyclopedic resource (>100,000 pages)  and news feed to the world at no cost to the user, thanks to its many supporters over decades. Together with its sister Website for Patients (www.nacpatients.org.uk), they attract over 125,000 users per month, indicative of the need for information. In 2012, the Fungal Infection Trust launched a global educational website Life Worldwide (www.LIFE-Worldwide.org), in English and Spanish, which is also highly utilised.

The Advances in Aspergillosis conference series held alternate years, is the premier forum for detailed and dedicated discussion of all aspects of aspergillosis, attracting over 350 delegates from 35+ countries. Topical issues include: pan-azole and echinocandin resistance has emerged and requires unique approaches, new opportunities for both antifungal agents and immunotherapies in chronic and allergic aspergillosis, better molecular and low-cost strategies for diagnosis and publication of several recent clinical guidelines for clinicians offer detailed guidance.

Other major needs for health improvements in aspergillosis include:

  • Keeping homes free from excessive Aspergillus and other moulds, related to dampness, and therapy reduce asthma cases and severity
  • Hospital environments for vulnerable patients free of Aspergillus
  • Improvement in the public’s awareness of fungal diseases and specifically aspergillosis
  • Reduction in azole resistance with reduced use of azole fungicides in non-essential crops
  • Prevention of a new epidemic of resistance with any new classes of antifungal used for aspergillosis by not allowing such chemical class to be used as a fungicide
  • Need for better surveillance and detailed epidemiology data
  • Development of immunotherapies as well as vaccines

Patients’ Stories

Patients are often diagnosed with one of the several different types of aspergillosis after a considerable time spent being treated for different medical problems for example tuberculosis or asthma. Aspergillosis is often only considered when treatment for their pre-existing condition becomes ineffective, and by that time aspergillosis can be well established. There is a pressing need for tests that may diagnose aspergillosis in all its forms more quickly. As we discover more about the genetics of vulnerability to aspergillosis it may also be possible to start screening high-risk populations for early treatment.

Nasilele describes her experience of living with CPA after a prior diagnosis of Tuberculosis and then having a severe cough that did not respond to antibiotics.

This patient describes his experiences with childhood asthma and Allergic Bronchopulmonary Aspergillosis (ABPA). After persistent chest infections and continuous steroids and a bad productive cough, Aspergillus was cultured from his sputum in 2002. His difficulties with adverse effects caused by his antifungal treatment illustrate the need for new, alternative medication.

Notes for Editors

Resources mentioned

World Aspergillosis Day Feb 1st www.aspergillosisday.org

Advances Against Aspergillosis www.AAA2018.org

Fungal Infection Trust www.fungalinfectiontrust.org.uk

Aspergillus Website www.aspergillus.org.uk

Aspergillosis Patients website www.nacpatients.org.uk

LIFE-Worldwide (Fungal disease education & awareness) www.LIFE-Worldwide.org

World Aspergillosis Day is Feb 1st, click here for more details

The Fungal Infection Trust (www.fungalinfectiontrust.org) Is a UK Company limited by Guarantee approved as a charity by the Charity Commissioners. Since 1991, the Fungal Infection Trust (FIT) has made a unique contribution to advancing the science and medicine of fungal diseases, in the UK and internationally.

GAFFI is a registered International Foundation based in Geneva and UK Charity and is focused on 4 major tasks related to serious fungal infections. These are:

  • Universal access to diagnostics for serious fungal disease
  • Universal access to antifungal agents www.gaffi.org/why/burden-of-disease-maps/
  • Accurate data on the number and severity of fungal infections
  • Health professional education related to better recognition and care for patients with serious fungal disease

GAFFI issued its 10 year Roadmap ’95-95 by 2025’ in 2015 calling on all governments and international health agencies to ensure 95% of the global population have access to fungal diagnostics and antifungal therapies by 2025: http://www.gaffi.org/roadmap/ GAFFI has enabled several antifungal drugs to be listed on the World Health Organisation’s Essential Medicine List, including those used for aspergillosis.

The Aspergillus Website (www.aspergillus.org.uk) was set up in 1998 by the Fungal Infection Trust. It is the most comprehensive source of information about Aspergillus and the diseases it causes available on the internet. An estimated 125,000 distinct visitors log on monthly and over 18,000 other websites link to the Aspergillus Website. Users are in over 140 countries. Over 3000 patients are currently registered with the support discussion groups on Facebook with over 500 LinkedIn members (Aspergillus and Aspergillosis Group). The Website for Patients supports the patient and carer community (www.nacpatients.org.uk),

LIFE is the international health professional education brainchild of the Fungal Infection Trust.  LIFE’s goal is to improve the health of patients suffering from serious fungal infections primarily through health professional education and increased awareness internationally (www.LIFE-Worldwide.org). Summary information on fungi, fungal diseases, diagnostic tests and treatments are provided free in English and in Spanish.