What is Aspergillus?

The term Aspergillus refers to a group of mould fungi which are found world-wide and are especially known for decaying fruit and vegetables.  They are very common  in the autumn and winter in the Northern hemisphere. Only a few of these moulds can cause illness in humans and animals, most commonly these are Aspergillus fumigatus Aspergillus niger Aspergillus terreus and Aspergillus flavus. Most people are naturally immune and do not develop disease caused by Aspergillus.

What diseases does Aspergillus cause?

Allergic bronchopulmonary aspergillosis (ABPA)

This is a condition which produces an allergy to the spores of the aspergillus moulds. It is quite common in asthmatics; up to 20% of asthmatics might get this at some time during their lives. ABPA is also common in cystic fibrosis patients, as they reach adolescence and adulthood. The symptoms are similar to those of asthma: intermittent episodes of feeling unwell, coughing and wheezing. Some patients cough up brown-coloured plugs of mucus. The diagnosis can be made by X-ray or by sputum, skin and blood tests. In the long term ABPA can lead to permanent lung damage (fibrosis) if untreated.

The treatment is with steroids by aerosol or mouth (prednisolone), especially during attacks. Itraconazole (an oral antifungal drug) is useful in reducing the amount of steroids required in those needing medium or high doses. This is beneficial as steroids have side-effects like thinning of the bones (osteoporosis) and skin and weight gain, especially when used for a long time.

Aspergilloma

This is a very different disease from ABPA also caused by the Aspergillus mould. The fungus grows within a cavity of the lung, which was previously damaged during an illness such as tuberculosis or sarcoidosis. Any lung disease which causes cavities can leave a person open to developing an aspergilloma. The spores penetrate the cavity and germinate, forming a fungal ball within the cavity. The fungus secretes toxic and allergic products which may make the person feel ill.

The person affected may have no symptoms (especially early on). Weight loss, chronic cough and feeling rundown are common symptoms later. Coughing of blood (haemoptysis) can occur in up to 50-80 % of affected people.

The diagnosis is made by X-rays, scans of lungs and blood tests.

Treatment depends on many factors including whether the patient is coughing blood and how much lung disease there is. Oral itraconazole (usually 400 mg daily) helps symptoms in many patients but rarely kills the fungus in the cavity. Sometimes surgical removal is possible, especially if the patient is coughing blood. Sometimes other antifungal drugs (especially amphotericin B) can be injected directly into the cavity by a tube which is put into position under local anaesthesia. Up to 10 % of cases get better without treatment, especially if there are no symptoms.

Aspergillus sinusitis
Aspergillus disease can happen in the sinuses leading to Aspergillus sinusitis. This happens in a similar way to aspergilloma. In those with normal immune systems, stuffiness of the nose, chronic headache or discomfort in the face is common. Drainage of the sinus, by surgery, usually cures the problem, unless the Aspergillus has entered the sinuses deep inside the skull. Then antifungal drugs and surgery are usually successful.

When patients have damaged immune systems - if, for example they have had leukaemia or have had a bone marrow transplant- Aspergillus sinusitis is more serious. In these cases the sinusitis is a form of invasive aspergillosis (see below). The symptoms include fever, facial pain, nasal discharge and headaches. The diagnosis is made by finding the fungus in fluid or tissue from the sinuses and with scans. Treatment with powerful antifungal medicines is essential (e.g. amphotericin). Surgery is done in most cases as it is important to find out what exactly is wrong and it is often helpful in eradicating the fungus.

Invasive aspergillosis

Many people with a damaged or impaired immune system die from invasive aspergillosis. Their chances of living are improved the earlier the diagnosis is made but unfortunately there is no good diagnostic test. Often treatment has to be started when the condition is only suspected.

This condition is usually clinically diagnosed in a person with low defences such as after a bone marrow transplant, low white cells after cancer treatment, AIDS or major burns. There is also a rare inherited condition that gives people low immunity (chronic granulomatous disease) which puts affected people at moderate risk. People with invasive aspergillosis usually have a fever and symptoms from the lungs (cough, chest pain or discomfort or breathlessness) which do not respond to standard antibiotics. X-rays and scans are usually abnormal and help to localise the disease. Bronchoscopy (inspection of the inside of the lung with a small tube inserted via the nose) is often used to help to confirm the diagnosis.

Sometimes the fungus can transfer from the lung through the blood stream to the brain and to other organs, including the eye, the heart, the kidneys and the skin. Usually this is a bad sign as the condition is more severe and the person sicker with higher risk of death. However, sometimes infection of the skin enables the diagnosis to be made earlier and treatment to be started sooner.

Treatment is with antifungal drugs usually amphotericin B and/or itraconazole. The antifungal drug Diflucan (fluconazole) is not effective against Aspergillus.  Amphotericin B has to be given by vein in large doses. In some patients the treatment can damage kidney and other organs. Newer forms of amphotericin B (Amphotec or Amphocil, Abelcet or AmBisome) are useful, especially when the patient experiences side-effects, as they are less toxic. Itraconazole is generally given orally (also in large doses, e.g. at least 400 mg daily). The earlier treatment is started the better the chances of survival. In patients with low numbers of white cells (infection fighters), recovery of these cells can be important in stopping the growth of the fungus. Sometimes surgery is also required. Overall, about a third of patients survive invasive aspergillosis if treated and none survive if they are not treated. Click here to obtain antifungal drug data sheets.

How do people contract Aspergillus diseases?

Aspergillus spores are found everywhere in the environment including the air we breathe. The spores can therefore enter everyone's lungs and can also enter wounds. This is how all Aspergillus diseases are contracted, although the underlying reasons for the different types of Aspergillus diseases differ. Invasive aspergillosis occurs almost exclusively in people with a damaged immune system. Most people's natural immunity to Aspergillus means that they easily kill Aspergillus spores that enter their body. However, if someone has a damaged immune system, (for example due to leukaemia) they lose their natural protection and may develop invasive aspergillosis. Aspergilloma, sinus disease and ABPA often occur in people with an apparently healthy immune system. Individuals with ABPA are allergic to the Aspergillus spores that enter their lungs and they "overreact" to small numbers of Aspergillus spores that most people happily tolerate. This may happen with sinus disease as well. Normally, in sinus disease and Aspergilloma, Aspergillus becomes lodged in the lung or sinus often due to a cavity in these organs. Occasionally individuals with a healthy immune system are infected with Aspergillus. This is rare, however exposure to very large numbers of spores can lead to severe allergic lung disease called extrinsic allergic alveolitis. The most famous example of this is Farmers Lung, where farmers are exposed to massive numbers of Aspergillus spores in silage.

Why are the new forms of Amphotericin B safer?

There are several safer forms of amphotericin B which are mixtures of the drug with various fats.  These are called liposomal, lipid complex and colloidal dispersion forms of amphotericin B  and are sold under the names Ambisome, Abelcet and Amphocil/Amphotec respectively.

These drugs are all given intravenously and are less toxic because amphotericin B is tightly bound to the fat mixtures and will not leave these mixtures unless it meets something it is more attracted to. The fats in human cells cannot attract amphotericin B away from the fat mixtures very easily, but the fats in fungal cells can. They particularly reduce kidney dysfunction, compared with conventional amphotericin B.

Is oral amphotericin B used to treat Aspergillus diseases?

Oral amphotericin B may be used to treat intestinal infections and does not have unpleasant side-effects like intravenous amphotericin B simply because it is not absorbed into the blood stream from the gut. Since oral  amphotericin B is not absorbed from the gut, it can only be used to treat infections in the gut and not invasive aspergillosis.

Can you get Aspergillus from a wound?

Yes you can get Aspergillus in a wound although it is quite rare. The first report of infection of a skin wound with   Aspergillus was following accidental injury in a farmer. Other reports are from people who have had operations or people with traumatic wounds. Sometimes Aspergillus can get into artificial heart valves during surgery.  

What new drugs are being tested for the treatment of invasive aspergillosis?

There are several drugs in clinical trials that have activity against Aspergillus. Two of these are triazoles and are related to Sporanox (itraconazole) - a drug already used to treat aspergillosis. These are voriconazole made by Pfizer and posaconazole made by Schering Plough. Both these drugs can be given orally, are better tolerated by patients when compared with Sporanox and there is some evidence to suggest they are more potent. Three of the new drugs are candins - a completely new class of drug. These are Cancidas made by Merck and two other drugs developed by Versicor and Fujisawa. All these drugs are given intravenously. A lipid preparation of nystatin (Nyotran) is also undergoing trials. Nystatin has been used topically to treat fungal skin infections for 30 years, but is very toxic when administered intravenously. The lipid preparation is less toxic. Click here for further information about some of the clinical trials

What is sick building syndrome?

A sick building is a term tha can be used to describe a building which has the presence of unusally large quantities of multiple fungi such as Aspergillus. Individuals who would normally not experience ill effects from contact with normal levels of these fungi become reactive to the large quantities in the sick building and are said to have "sick building syndrome". Many other causes of sick buildings have been described, most without any involvement of fungi.

What is IgE?

Antibodies are also known as immunoglobulins (Ig) - IgE therefore stands for type E antibodies. IgE plays a key role in allergies and is thought to be involved in protection against parasites. People with certain forms of allergy have high IgE levels typically up to 200 x normal for asthmatics. Those with ABPA can have levels as high as 6000 x normal - as can those with serious parasite infections. IgE is a marker for an immune response called the Th2 response. This immune response damps down the bodies response to infection - sometimes too much.

What is the relationship between IgE, and ABPA?

Individuals with ABPA have very elevated levels of IgE. This level fluctuates and can go up in periods of poor health and down in periods of relatively good health.

Everyone is continually exposed to Aspergillus spores as they are ubiquitous in the environment. In addition, often ABPA sufferers are colonised with Aspergillus and react to the Aspergillus growing in their lung as well as spores they breathe in. For these reasons it is logical to assume the particular environmental level of Aspergillus spores will not predict the health of individuls with ABPA. However, no scientific study has been undertaken to investigate this and there is anecdotal evidence to suggest that exposure to high levels of spores can exacerbate symptoms. It may be sensible for ABPA sufferers to avoid high levels of spores found in dust, soil and compost. HEPA filters are used in hospitals to reduce spore concentrations in the atmosphere, again there is no scientific evidence that these could help individuals with ABPA, but it could be worth trying.

Does Prednisone suppress the immune system?

Yes it does when used long term. Even short courses (7 days or longer) can precipitate invasive aspergillosis, although this is rare.

No, individuals with invasive aspergillosis usually have a suppressed immune system and prednisone does suppress the immune system. However, ABPA sufferers taking prednisone very rarely contract invasive aspergillosis. It is thought that the overreaction of their immune system to Aspergillus protects them against invasive disease.

No. People usually contract Aspergillus diseases by breathing in the spores as Aspergillus is everywhere in the environment. In addition someone must have an underlying disease for Aspergillus to be a problem. On one occasion a silent Aspergillus infection in an organ donor passed the infection on to the recipients of his/her organs, but this is exceptional.

How can someone get onto a drug trial?

Usually doctors sign up to participate in a drug trial at the beginning of the trial, so a patient would need to be under one of these doctors in order to obtain a trial drug. However, if a patient is very ill and not under a participating doctor, often a drug company will give that patient a trial drug on compassionate grounds. The Aspergillus web site has contact addresses for the coordinators of some drug trials for invasive aspergillosis. Click here to find out more about drug trials for aspergillosis.

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