Aspergillus

  • TRANSMISSION ROUTE: Blood, direct contact, inhalation

Definition

Aspergillus is a common fungus (mold) that frequently causes life-threatening infections in immunocompromised persons. Aspergillus species also produce many mycotoxins and allergens that can cause cancer, damage the immune and nervous systems, and increase the risk of developing asthma and sinus problems.

94416780-89001.jpg94416780-89002.jpg

Natural Habitat and Features

Aspergillus is a ubiquitous aerobic mold found on vegetation, decomposing matter, soil, food, water, feces, and outdoor and indoor air. The asexual spores (conidia) are small (2 to 5 microns) and borne in chains formed on spherical or oblong vesicles. Aspergillus is often fast-growing and can sporulate in a few days after germination.

Aspergillus is present mainly in the anamorphic or asexual phase. Some Aspergillus species also have a teleomorphic phase and produce ascospores. Some more common Aspergillus ascospore forms include Eurotium amstelodami, the teleomorph of A. vitis, and E. herbariorum, the teleomorph of A. glaucus.

Aspergillus is often involved in plant and food spoilage and plays an important role in the decomposition of leaves and other organic matter. It is also involved in the production of certain enzymes, pharmaceuticals, and organic acids.

Pathogenicity and Clinical Significance

Aspergillus can adversely affect humans through three mechanisms that include infection and the production of mycotoxins (fungal toxins) and allergens. Both superficial and disseminated invasive Aspergillus infections are common. Invasive Aspergillus infections cause a minimum of 15,000 hospitalizations annually in the United States. This number appeared to be increasing, and there was evidence to suggest that COVID-19 played a role in the rise of infections. The most common species that causes infection is fumigatus, with flavus, niger, and terreus also causing many infections. Even with hospitalization and antifungal drugs, invasive Aspergillus infections have a 40 to 90 percent fatality rate.

Aspergillus infections are especially common in people with compromised immune systems, including persons with human immunodeficiency virus infection, lymphoma, or leukemia; malnourished persons; and persons on immunosuppressive drugs following bone or organ transplantation. Aspergillus infections are also more common in hospitalized persons recovering in rooms close to water damage or building construction. As many as 2 to 15 percent of persons with bone marrow transplants, 6 to 13 percent of persons with a lung transplant, and up to 8 percent of persons with leukemia or lymphoma develop Aspergillus infections. Disseminated Aspergillus infections usually begin in the respiratory tract and can cause breathing troubles, coughing, hemoptysis, high fever, growth of lung fungal balls, and death. Aspergillus can also produce localized infections, especially in the lungs and nasal sinuses. Exposure to Aspergillus during heart surgery can produce serious heart valve infections.

Aspergillus also produces dozens of mycotoxins. The strongly carcinogenic aflatoxin mycotoxins are produced by flavus and parasiticus. Aspergillus frequently produces aflatoxins on damp or otherwise poorly stored crops, especially peanuts and corn (maize). Eating aflatoxin-contaminated food has been associated with significantly higher levels of liver cancer. Other common mycotoxins produced by Aspergillus include ochratoxin, patulin, gliotoxin, verruculogen, fumitremorgin, and sterigmatocystin.

Aspergillus produces dozens of allergens that can worsen asthma, sinusitis, and allergies. A number of studies have reported that exposure to high airborne levels of Aspergillus and other fungi is associated with higher levels of asthma and sinus problems. Exposure to airborne Aspergillus can also produce a serious hypersensitivity condition called allergic bronchopulmonary aspergillosis.

The best way to prevent Aspergillus infection is to limit exposure in persons with compromised immune systems. Many studies have reported that housing bone and organ transplant patients in rooms with air filtration significantly reduces the incidence of Aspergillus infections and mortality from these infections. Using positive-pressure hospital rooms, adequately cleaning the patient’s room, having walls covered in antifungal paint, promptly cleaning up water damage, and avoiding construction areas can also significantly reduce Aspergillus infection rates.

Invasive Aspergillus infections are often hard to diagnose in the early stages, as persons may not exhibit obvious symptoms until the infection is advanced and life-threatening. High resolution computed tomography (CT) scans are often useful in detecting invasive fungal infections. The CT scan will usually show a halo sign in images of early-stage infection (infections beginning less than five days before the scan) and an air crescent sign in images of late-stage infection.

Serological tests are often used to detect the presence of invasive Aspergillus infections, with the most common test being the galactomannan assay. A meta-analysis of twenty-five galactomannan studies reported that the overall sensitivity and specificity were found to be 71 and 89 percent, respectively. Polymerase chain reaction (PCR) assays can also be used to detect deoxyribonucleic acid (DNA) from various Aspergillus species.

Drug Susceptibility

Traditionally, the drugs used most often for Aspergillus infections include amphotericin B and azole drugs, such as fluconazole and itraconazole. These drugs have only modest success in persons with invasive Aspergillus infections. Systemic amphotericin B also has many serious side effects, including fever, vomiting, and headache, and damage to the kidneys, liver, and heart. These side effects often force the discontinuation of amphotericin B.

A newer class of drugs, echinocandins, has been developed. This class blocks cell-wall synthesis in Candida and Aspergillus. Echinocandin drugs include anidulafungin, caspofungin, and micafungin. Studies have reported that the echinocandin drugs are about as effective in treating invasive Aspergillus infections as amphotericin B but have a much lower risk of side effects.

Bibliography

"Aspergillosis." Cleveland Clinic, 16 Jan. 2023, my.clevelandclinic.org/health/diseases/14770-aspergillosis. Accessed 26 Oct. 2024.

"Aspergillosis." Mayo Clinic, 6 June 2022, www.mayoclinic.org/diseases-conditions/aspergillosis/symptoms-causes/syc-20369619. Accessed 26 Oct. 2024.

"Aspergillosis." National Organization for Rare Disorders, 31 Mar. 2023, rarediseases.org/rare-diseases/aspergillosis/. Accessed 26 Oct. 2024.

"Aspergillosis Basics." CDC, 24 Apr. 2024, www.cdc.gov/aspergillosis/about/index.html. Accessed 26 Oct. 2024.

Chandrasekar, Pranatharthi. "Diagnostic Challenges and Recent Advances in the Early Management of Invasive Fungal Infections." European Journal of Haematology, vol. 84, 2009, pp. 281–290.

Dall, Chris. "US Data Show Rise in Hospitalizations for Fungal Infections during COVID-19." CIDRAP, 13 June 2023, www.cidrap.umn.edu/covid-19/us-data-show-rise-hospitalizations-fungal-infections-during-covid-19. Accessed 26 Oct. 2024.

Gullo, Antonio. "Invasive Fungal Infections." Drugs, vol. 69, 2009, pp. 65–73.

Marr, Kieren, Thomas Patterson, and David Denning. "Aspergillosis: Pathogenesis, Clinical Manifestations, and Therapy." Infectious Disease Clinics of North America, vol. 16, 2002, pp. 875–894.

Patridge-Hinckley, Kimberly, et al. "Infection Control Measures to Prevent Invasive Mould Diseases in Hematopoietic Stem Cell Transplant Recipients." Mycopathologica, vol. 168, 2009, pp. 329–337.

Patterson, Thomas F. "Aspergillus Species." Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, edited by Gerald L. Mandell, John F. Bennett, and Raphael Dolin. 7th ed., Churchill Livingstone/Elsevier, 2010.

Samson, Robert, Ellen Hoesktra, and Jens Frisvad. Introduction to Food and Airborne Fungi. 7th ed., Central Bureau for Fungal Cultures, 2004.

Tong, Xiang, et al. "Clinical Characteristics and Prognostic Risk Factors of Patients with Proven Invasive Pulmonary Aspergillosis: A Single-Institution Retrospective Study." Frontiers in Medicine, vol. 8, 23 Dec. 2021, doi.org/10.3389/fmed.2021.756237. Accessed 16 Sept. 2022.