Aspergillus Infections

Aspergillus infections are caused by members of the genus Aspergillus. Aspergilli are cosmopolitan fungi that are important causes of nosocomial infections. Infections occur mainly in immunocompromised patients and can be fatal.

Aspergillosis
The term aspergillosis includes a group of diseases that result from infection by one of the members of the genus Aspergillus.

There are four basic types of aspergillosis:


 * Invasive aspergillosis (IPA), which occurs primarily in patients with severe immunodeficiency.
 * Allergic bronchopulmonary aspergillosis (ABPA), common in patients with atopy, asthma or cystic fibrosis.
 * Chronic necrotizing pulmonary aspergillosis, described in patients with chronic lung disease and mild immunodeficiency.
 * Aspergilloma, which can be found to a greater extent in patients with pre-existing cavities in the lungs.

= Invasive aspergillosis = It is an infectious disease with high morbidity and mortality in immunocompromised patients caused by fungi of the genus Aspergillus, most often A. fumigatus.

Epidemiology
Aspergils are ubiquitous, occurring in the air, soil, dust, building materials, some foods, and water. The main route of entry for aspergillus is the respiratory tract. After inhalation, conidiospores mature in the lungs and can also penetrate other tissues through blood vessels if they are not controlled by the body's defense mechanisms.

However, most people are naturally immune to the development of the disease because alveolar macrophages have the ability to absorb and destroy conidia. However, in patients treated with corticosteroids and in immunodeficient patients (patients with leukemia, AIDS, COPD, patients after chemotherapy or transplantation, etc.), this ability is reduced.

Risk factors
The main risk factors for the development of IPA are neutropenia, solid organ transplantation (especially lung), stem cell haematopoietic stem cell transplantation (HSCT), chronic obstructive pulmonary disease (COPD), systemic corticosteroid therapy and haematological malignancies.

Other risk factors such as liver and renal failure, HIV, diabetes mellitus, malnutrition, autoimmune diseases and extensive burns have also been described.

In most cases, aspergilli are trapped in the lower respiratory tract by inhalation of infectious spores. Less often, IPA can start from other sites, namely the paranasal sinuses, gastrointestinal tract and skin. The infection can spread through the bloodstream to other organs such as the brain, kidneys, liver, heart, pleura, etc.

Symptomatics
The symptoms are non-specific and resemble bronchopneumonia: fever, cough, sputum formation, dyspnoea, chest pain of pleural origin due to vascular invasion leading to thrombosis and small pulmonary infarction, hemoptysis.

Diagnostics
The gold standard in the diagnosis of IPA is histopathological examination - samples of lung tissue obtained by thoracoscopy or open lung biopsy for the presence of septated, branched hyphae and positive cultures. Other options are sputum examination, BAL fluid, chest CT examination (presence of nodules and halo sign - weakening zone around the lung nodules caused by hemorrhage and typical for neutropenic patients), ELISA test for detection of aspergillus antigens in body fluids ( galactomannan - polysaccharide released from aspergillus after growth time) and PCR.

Therapy
Due to the possible progression of the disease, it is recommended to start treatment when IPA is suspected, before the diagnosis is confirmed by laboratory tests. Commonly used drugs are liposomal amphotericin B, voriconazole and echinocandin derivatives such as caspofungin or micafungin.

= Allergic bronchopulmonary aspergillosis = It is a disease that develops in hypersensitivity to aspergillus antigens, mainly A. fumigatus. Most cases occur in people with asthma and cystic fibrosis. The incidence is also higher in people with atopy.

Clinical picture


In ABPA, the lungs show reversible obstructive changes, which, however, may progress to irreversible changes at more advanced stages. Restrictive lung disease with reduced diffusion capacity due to mucus and hyphae compression and central bronchiectasis (CB) develops.

ABPA is divided into five stages:


 * acute - initial phase characterized by asthma, elevated IgE levels, eosinophilia, pulmonary infiltrates and IgG and IgE antibodies against A. fumigatus,
 * remission phase - symptoms weakened (reduced),
 * exacerbation - recurrence of initial symptoms, IgE levels double,
 * phase occurring in patients with asthma dependent on regular use of corticosteroids - asthma worsens, bronchiectasis develops,
 * fibrotic phase - development of fibrosis in the upper lobes of the lungs.

Symptomatics
Patients experience episodic wheezing, sputum coughing with brown coatings, chest pain of pleural origin, and fever.

Diagnostics
Diagnostic criteria for ABPA are asthma, immediate skin reaction to Aspergillus, presence of IgG and IgE against A. fumigatus in the blood, IgE level higher than 1000 IU/ml, incidence of pulmonary infiltrates on the CT of the chest, eosinophilia (1000 cells/µl).

Therapy
Most cases require treatment with systemic corticosteroids. Corticosteroids (suppression of hypersensitivity and inflammatory response). The drug of choice is mainly prednisone. In some cases, itraconazole is also used.

= Chronic necrotizing pulmonary aspergillosis = Chronic necrotizing aspergillosis (chronic necrotizing pulmonary aspergillosis, CNPA, semi-invasive or subacute invasive aspergillosis) is an infectious process of the lung parenchyma that develops in response to local invasion commonly A. fumigatus.

Clinical picture
This is a rare syndrome and, unlike IPA, CNPA develops slowly, over several weeks to months, and vascular invasion or dissemination to other organs usually does not occur. It can be difficult to distinguish from aspergilloma. However, in the case of CNPA, this is a local invasion of the lung parenchyma, and a cavity filled with Aspergilus may form secondarily as a result of fungal tissue damage. CNPA is characterized by necrosis of lung tissue, acute or chronic inflammation of the cavity wall, and the presence of hyphae.

Risk factors
It mainly affects the older part of the population with chronic lung diseases such as COPD, pulmonary TB, pneumoconiosis, cystic fibrosis, sarcoidosis, pulmonary infarction.

Symptomatics
Patients often complain of fever, malaise, fatigue, weight loss, chronic productive cough and hemoptysis. However, the course of CNPA can also be asymptomatic.

Diagnostics
Chest CT is used in the diagnosis of CNPA, on which pleural thickening is visible, which can lead to the formation of broncho-pleural fistula and cavity lesions in the upper lung lobes. In most patients we also find serum IgG antibodies against A. fumigatus. Histopathological examination and cultivation are essential to confirm the diagnosis.

Therapy
Voriconazole or itraconazole are most commonly used to treat mild to moderate forms of CNPA, with severe forms being treated with amphotericin B and intravenous voriconazole.

= Aspergilloma = It is the most common form of aspergilloma. It consists of a conglomerate of hyphae, mucus, fibrin and inflammatory cells in a pre-existing cavity in the lungs.

Clinical picture
The conglomerate can move within the cavity, but usually does not penetrate the surrounding parenchyma or blood vessels. The lesions usually remain permanent, sometimes they may shrink or disappear spontaneously, rarely they may enlarge. In some cases, they can cause heavy bleeding by damaging the bronchial vessels or the vessels surrounding the cavities. Predisposing factors for the development of aspergilloma may be previously established pathological cavities, such as conditions after tuberculosis, sarcoidosis, bronchiectasis, bronchial cysts, ankylosing spondylitis or lung infections.

Symptomatics
Most patients develop hemoptysis, which can be mild but also life-threatening. Other symptoms include cough, dyspnoea and fever.

Diagnostics
The diagnosis is based on an X-ray or CT of the chest, which shows the site of the lesion on the lungs. Sputum culture is positive in only 50% of cases, whereas IgG antibodies against A. fumigatus are present in most cases.

Therapy
Treatment is started when the patient is symptomatic, especially after the development of haemoptysis. The drug of choice is itraconazole. Surgical resection of aspergilloma is commonly indicated for recurrent hemoptysis. Bronchial artery embolization is recommended in patients with life-threatening hemoptysis.

Related articles

 * Invasive fungal infections

Použitá literatura

 * VOTAVA, Miroslav, et al. Lékařská mikrobiologie speciální. 1. vydání. Brno : Neptun, 2003. 495 s. ISBN 80-902896-6-5.


 * WILLEY, Joanne M, Linda M SHERWOOD a Christopher J WOOLVERTON, et al. Prescott,Harley, and Klein’s Microbiology. 7. vydání. New York : McGraw-Hill Hogher Education, 2008. 0 s. ISBN 978–0–07–299291–5.


 * KOUSHA, M, R TADI a A.O SOUBANI. Pulmonary aspergillosis: a clinical review. European Respiratory review [online]. 2011, roč. 2011, vol. 20, no. 121, s. 156-162, dostupné také z . ISSN 1600-0617. DOI: 10.1183/09059180.00001011.


 * WILLEY, Joanne M, Linda M SHERWOOD a Christopher J WOOLVERTON, et al. Prescott,Harley, and Klein’s Microbiology. 7. vydání. New York : McGraw-Hill Hogher Education, 2008. 0 s. ISBN 978–0–07–299291–5.


 * EDITOR, Moselio, Moselio Schaechter; consulting SCHAECHTER a Joshua LEDERBERG. The desk encyclopedia of microbiology. - vydání. Amsterdam : Elsevier, 2004. ISBN 0-12-621361-5.