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Aspergillus sp.

Fungal cutaneous vasculitis in systemic invasive aspergillosis Fungal cutaneous vasculitis in systemic invasive aspergillosis

Aspergillus is common and widespread in nature and are most often found when crops are exposed to a high humidity environment over a long period of time or are damaged in stressful conditions such as drought, a condition which lowers the barrier to entry.

The native habitat of Aspergillus is in soil, decaying vegetation, hay, and grains undergoing microbiological deterioration and it invades all types of organic substrates whenever and wherever the conditions are favorable for its growth. Favorable conditions include high moisture content (at least 7%) and high temperature.

Crops which are frequently affected include cereals (maize, sorghum, pearl millet, rice, wheat), oilseeds (peanut, soybean, sunflower, cotton), spices (chile peppers, black pepper, coriander, turmeric, ginger), and tree nuts (almond, pistachio, walnut, coconut).

The toxin can also be found in the milk of animals which are fed contaminated feed.

Aspergillus is a ubiquitous mold that causes allergies (brewer’s lung) in otherwise healthy people and serious sinusitis, pneumonia, and fungemia in immunocompromised individuals. The major factors that predispose to Aspergillus infection are neutropenia and corticosteroids. This saprophytic fungus sporulates and produces abundant conidia (asexual spores) that are readily aerosolized.

Molecular epidemiologic studies of Aspergillus isolated from opportunistic infections show many different strains of Aspergillus, suggesting that the immune status of the host is more important than fungal pathogenicity. Aspergillus fumigatus is the most common species to cause disease, and it produces severe invasive infections in immunocompromised individuals.

Pathogenesis. Aspergillus species are transmitted by airborne conidia, and the lung is the major portal of entry. The small size of Aspergillus fumigatus spores, approximately 2 to 3 μm, enables them to reach alveoli. In the lung, Aspergillus conidia are encountered initially by alveolar macrophages, which can engulf and kill the germinating conidia and secrete cytokines and chemokines to elicit adaptive immune responses.

Germinating conidia and hyphae that evade unactivated alveolar macrophages are killed mainly by activated macrophages. T lymphocytes confer protective immunity, but little is known about the effector cells and defense mechanisms.

Aspergillus produces several virulence factors, including adhesins, antioxidants, enzymes, and toxins.

Conidia can bind to fibrinogen, laminin, complement, fibronectin, collagen, albumin, and surfactant proteins, but receptor-ligand interactions are not well defined.

Aspergillus produces several antioxidant defenses, including melanin pigment, mannitol, catalases, and superoxide dismutases. This fungus also produces phospholipases, proteases, and toxins, but their roles in pathogenicity are not yet clear. Restrictocin and mitogillin are ribotoxins that inhibit host-cell protein synthesis by degrading mRNAs.

The carcinogen aflatoxin is made by Aspergillus species growing on the surface of peanuts and may be a major cause of liver cancer in Africa.137 Sensitization to Aspergillus spores produces an allergic alveolitis by TH2 reactions.

Allergic bronchopulmonary aspergillosis, which is associated with hypersensitivity arising from superficial colonization of the bronchial mucosa and often occurs in asthmatic patients, may eventually result in chronic obstructive lung disease.

Morphology. Colonizing aspergillosis (aspergilloma) usually implies growth of the fungus in pulmonary cavities with minimal or no invasion of the tissues (the nose also is often colonized). The cavities usually result from preexisting tuberculosis, bronchiectasis, old infarcts, or abscesses. Proliferating masses of fungal hyphae called fungus balls form brownish masses lying free within the cavities. The surrounding inflammatory reaction may be sparse, or there may be chronic inflammation and fibrosis. Patients with aspergillomas usually have recurrent hemoptysis.

Invasive aspergillosis is an opportunistic infection that is confined to immunosuppressed and debilitated hosts. The primary lesions are usually in the lung, but widespread hematogenous dissemination with involvement of the heart valves, brain, and kidneys is common. The pulmonary lesions take the form of necrotizing pneumonia with sharply delineated, rounded, gray foci with hemorrhagic borders, often referred to as target lesions.

Aspergillus forms fruiting bodies (particularly in cavities) and septate filaments, 5 to 10 μm thick, branching at acute angles (40 degrees).

Aspergillus has a tendency to invade blood vessels; therefore, areas of hemorrhage and infarction are usually superimposed on the necrotizing, inflammatory tissue reactions. Rhinocerebral Aspergillus infection in immunosuppressed individuals resembles that caused by Zygomycetes (e.g., mucormycosis).

Pathology

- aspergilloses (aspergillosis)

  • cavitary aspergillosis (aspergilloma)
  • invasive aspergillosis
  • Aspergillus-associated bronchiocentric granuloma

References

- Scazzocchio C. Aspergillus genomes: secret sex and the secrets of sex. Trends Genet. 2006 Oct;22(10):521-525. PMID: 16911845

- Bialek R, Konrad F, Kern J, Aepinus C, Cecenas L, Gonzalez GM, Just-Nubling G, Willinger B, Presterl E, Lass-Florl C, Rickerts V. PCR based identification and discrimination of agents of mucormycosis and aspergillosis in paraffin wax embedded tissue. J Clin Pathol. 2005 Nov;58(11):1180-4. PMID: 16254108