Allergic bronchopulmonary aspergillosis
This condition presents as a form of asthma that is resistant to conventional treatment. It also affects people with cystic fibrosis.
Treatment is based on the use of corticosteroids, sometimes in combination with an oral antifungal drug.
The fungus can develop in a pre-existing lung cavity resulting from a previous illness such as tuberculosis or sarcoidosis. Spores germinate in the cavity to form a ball known as a mycetoma. The disease can go unnoticed, especially in the early stages. It can lead to weight loss, chronic cough, fatigue and blood-streaked sputum. Treatment depends on the size and location of the lesions. Hemoptysis (coughing up blood) is a warning sign that may lead to surgical resection, where possible.
The fungus can develop in the sinuses. In patients with an effective immune system, infection gives rise to chronic headaches and nasal obstruction, and sinus drainage is generally an effective treatment. If the sphenoid sinuses are affected, surgery and an antifungal treatment are required. Aspergillus sinusitis is much more serious in patients with a weakened immune system caused by leukemia, a bone marrow transplant, etc., who often present with an invasive form requiring immediate antifungal treatment.
This is the third leading cause of invasive fungal infection in France. Mainly caused by the species Aspergillus fumigatus, it affects immunocompromised individuals, especially those who have had a bone marrow transplant, patients undergoing long-term cancer and neutropenia treatment or immunosuppressive therapy following an organ transplant, and patients in hospital intensive care units, in particular for severe influenza or COVID-19 infection. Symptoms are fever, cough, thoracic pain, hemoptysis and breathing difficulties.
The condition is diagnosed by culture, detection of particular fungal antigens or DNA from a blood or deep respiratory sample (using a galactomannan antigen test or Aspergillus PCR), and the appearance of thoracic lesions in a CT scan. Antifungal treatment must be administered at an early stage.
Antifungal treatment with voriconazole or isavuconazole is started immediately. The emergence of Aspergillus resistant to these azole drugs is a growing problem in some countries as a result of widespread azole use in agriculture. Azole resistance in treatment for invasive infections is not currently a major problem in France.
At the Institut Pasteur
The Molecular Mycology Unit and the National Reference Center (CNR) for Invasive Mycoses & Antifungals, both led by Françoise Dromer, have been involved in major international multi-center studies on the criteria used to define invasive aspergillosis and the treatment of aspergillosis infection. They are responsible for monitoring invasive fungal infections, including aspergillosis, via a network of hospital laboratories.
The Molecular Mycology Unit also conducts projects to elucidate the mechanisms involved in immune defense, especially soluble factors in the pulmonary alveoli that offer protection against the development of Aspergillus fungi. The scientists aim to develop new diagnostic and therapeutic approaches by analyzing how these factors interact with the characteristic sugars present in the fungal wall.
A. fumigatus prefers high temperatures, corresponding to a high level of fever in humans. This property contributes to its pathogenicity. The Fungal Epigenomics G5, led by Eugene Gladyshev, seeks to understand the molecular mechanisms used by A. fumigatus to adapt to high temperatures. The team led by Eugene Gladyshev, in collaboration with the Institut Pasteur's Spatial Regulation of Genomes Unit, has observed that the three-dimensional organization of the A. fumigatus genome is more ordered at temperatures between 37°C and 55°C than at 20°C. Research is currently under way in the laboratory to identify the molecular players involved in this adaptation of the A. fumigatus genome to high temperatures.
Surveillance and public health : National Reference Center for Invasive Mycoses & Antifungals led by Françoise Dromer