Aspergillosis

Aspergillosis is an umbrella term for a series of infections caused by the Aspergillus fungus. The spores of this fungus are in the air around us and we are constantly breathing them in. While they are totally harmless for most people, they can cause various forms of mycosis. The species Aspergillus fumigatus is responsible for more than 80% of human aspergillosis cases.

 

 

 

Allergic bronchopulmonary aspergillosis

This disease is relatively common in asthma sufferers – around 20% may be affected at some point in their life. It also affects cystic fibrosis patients in their late teens and early twenties. The symptoms are similar to those associated with asthma (intermittent episodes of feeling unwell, coughing, and wheezing). If left untreated, the disease can result in irreversible damage to the lungs (fibrosis).

Treatment is based on the use of corticosteroids by aerosol or oral administration, especially during attacks. An orally administered antifungal agent (itraconazole) can also be used in conjunction with steroid therapy. Patients on waiting lists for lung transplants should be tested for bronchial colonization by Aspergillus spp., which requires antifungal treatment.

 

Aspergilloma

The fungus can develop in a pre-existing cavity in the lung resulting from a previous disease such as tuberculosis or sarcoidosis. The spores germinate in this cavity and form a fungus ball. The disease can remain undetected, especially in its early stages. Advanced mycosis is characterized by weight loss, a chronic cough, tiredness, and coughing up blood (in 50 to 80% of infected people). Treatment depends on the size of the lesions and the affected area. Hemoptysis (coughing up blood) implies a poor prognosis and often requires surgical resection, if possible, combined with antifungal treatment. In some cases, local antifungal treatment is a possibility.

 

Aspergillus sinusitis

The fungus can develop in the sinuses. In patients with a healthy immune system, infection leads to chronic headaches and nasal congestion, and sinus drainage treatment is usually enough to clear up the problem. If the sphenoid sinuses are affected, surgery and antifungal treatment are required. In patients with a deficient immune system (as a result of leukemia or a bone marrow transplant, etc.), aspergillus sinusitis is far more serious and often develops into an invasive form. It requires immediate antifungal treatment; surgery is not usually performed in this case.

 

Invasive aspergillosis

This is the second leading cause of death by fungal infection in hospitals. It is mainly caused by Aspergillus fumigatus and affects immunodeficient patients, particularly those who have had a bone marrow transplant, those undergoing treatment for cancer and who are neutropenic for long periods, or undergoing immunosuppressive therapy following an organ transplant, and more rarely patients with AIDS or in intensive care units. The symptoms are fever, a cough, chest pains, and breathing difficulties.

Diagnosis is confirmed by culture, the detection of specific antigens (the galactomannan antigen or beta-glucan) in serum, and the characteristic appearance of thoracic lesions on a scan. Antifungal treatment must be started early. Only 60% of patients are cured at best, and this depends on whether the diagnosis is suspected at an early stage and also on the other disease the patient is suffering from. Infection can also affect other regions, particularly the brain, and the prognosis in this case is very poor.

 

At the Institut Pasteur

The Aspergillus Unit, led by Jean-Paul Latge, specializes in research into Aspergillus fumigatus. It focuses on invasive aspergillosis (diagnosis and pathophysiology) and also on the biosynthesis of the Aspergillus cell wall, which is a key stage in the development of all fungi and represents a unique source of therapeutic targets for the development of new antifungal drugs. The laboratory is also involved in annotating the Aspergillus fumigatus genome and developing large-scale biological experiments on this fungus.

The National Reference Center for Mycology and Antifungals, led by Françoise Dromer, has taken part in major international multi-center studies on the criteria for defining invasive aspergillosis and on how to treat such infections. It organizes in vitro studies and uses experimental models to test the efficacy of antifungal combinations against A. fumigatus and Aspergillus terreus, which are known for their low susceptibility to some antifungal drugs. The center is responsible for monitoring unusual manifestations of Aspergillus spp. infections (in the bones or brain, for example) and any infections by rare species that may be resistant to the usual antifungal treatment, via a network of hospital laboratories. The National Reference Center carries out epidemiological surveillance of invasive aspergillosis in several regions, in cooperation with the French Institute for Public Health Surveillance and the microbiologists and mycologists concerned.

 

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Illustration - Copyright Institut Pasteur

Caption – The filamentous fungus Aspergillus fumigatus in scanning electron microscopy.

 

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February 2014

 

The Institut Pasteur teams

 

Research units

 

> Aspergillus Unit
led by Jean-Paul Latge

Surveillance and public health

 

> National Reference Center for Invasive Mycoses and Antifungals

led by Françoise Dromer