What is aspergillus?

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, can damage the immune and nervous systems, and can increase the risk for developing asthma and sinus problems.

Natural Habitat and Features

Aspergillus is a ubiquitous aerobic mold that is found on vegetation, decomposing matter, soil, food, water, and feces, and in outdoor and indoor air. The asexual spores (conidia) are small (2 to 5 microns) and are 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 telemorphic phase and produce ascospores. Some of the more common Aspergillus ascospore forms include Eurotium amstelodami, which is the teleomorph of A. vitis, and E. herbariorum, which is the teleomorph of A. glaucus.

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

Pathogenicity and Clinical Significance

Aspergillus can adversely affect humans by 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 five thousand deaths
annually in the United States. 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 32 to 99 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 who are recovering in rooms that are 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, hemoptypsis, 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,
verrucologen, fumitremorgin, and strerigmatocystin.

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 are 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 usually will show a halo sign in images of early-stage infection (infections beginning less than five days before 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

Chandrasekar, Pranatharthi. “Diagnostic Challenges and Recent Advances in the Early Management of Invasive Fungal Infections.” European Journal of Haematology 84 (2009): 281-290. This article discusses the challenges of getting an early diagnosis for invasive Aspergillus and other fungal infections.

Gullo, Antonio. “Invasive Fungal Infections.” Drugs 69 (2009): 65-73. This paper reports on twenty-first century advances in the development of antifungal drugs.

Marr, Kieren, Thomas Patterson, and David Denning. “Aspergillosis: Pathogenesis, Clinical Manifestations, and Therapy.” Infectious Disease Clinics of North America 16 (2002): 875-894. This article provides a good overview of Aspergillus infections, lung-imaging studies, early diagnosis, and treatments.

Patridge-Hinckley, Kimberly, et al. “Infection Control Measures to Prevent Invasive Mould Diseases in Hematopoietic Stem Cell Transplant Recipients.” Mycopathologica 168 (2009): 329-337. This article discusses the use of air filters and other environmental controls to reduce the risk of Aspergillus infections in immunocompromised persons.

Patterson, Thomas F. “ Aspergillus Species.” In Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, edited by Gerald L. Mandell, John F. Bennett, and Raphael Dolin. 7th ed. New York: Churchill Livingstone/Elsevier, 2010. A thorough review of Aspergillus species in a respected text on infectious diseases.

Samson, Robert, Ellen Hoesktra, and Jens Frisvad. Introduction to Food and Airborne Fungi. 7th ed. Utrecht, the Netherlands: Central Bureau for Fungal Cultures, 2004. This guide has much useful information about Aspergillus, common indoor fungi, and their identification. Includes useful photos and diagrams.