Aspergillus terreus

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Code: m36
Latin name: Aspergillus terreus
Source material: Spores and mycelium
Family: Trichocomaceae

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Mould

A mould, which may result in allergy symptoms in sensitised individuals.

Allergen Exposure

Aspergillus species are widely distributed in nature; they have been isolated predominantly from soils, decaying vegetation and a wide variety of organic matter. (1) Although the genus Aspergillus contains over 150 species, only a few are considered to be pathogenic for humans. More than 30 species have been implicated in different human and animal infections. (1) 

Aspergillus terreus is a fungus that is widespread throughout the world and found in warm arable soils; and found more commonly in cultivated soils than the forest. It is rarely found in the acidic forest soils from the colder temperate zone. A. terreus is distinguished from the more common Aspergillus species by its compactly columnar, cinnamon to tan (sometimes yellowish to orange-brown) conidial heads, and tan to yellow colouration. (Cited in 2) A. terreus, A. carneus, A. flavipes, and A. niveus are unique among Aspergillus species, as they produce morphologically distinct lateral conidia (aleurioconidia) in infected tissue. These conidia are usually attached directly to a very short lateral extension of the hyphae and are generally borne singly, although multiple conidia can be formed from a single locus. (Cited in 2)

A. terreus is also commonly found in aerobiological surveys, and has been demonstrated to occur in air-conditioned rooms. (3, 4)

A. terreus is commonly used in industry to produce important organic acids, such as itaconic acid and cis-aconitic acid. It was also the initial source for the drug mevinolin (lovastatin), a drug for lowering serum cholesterol. A. terreus may cause opportunistic infection in people with deficient immune systems, but may also cause disease in immunocompetent individuals. It is refractory to amphotericin B therapy.

Infection with A. terreus is more likely to result in invasive, disseminated disease than infection with other Aspergillus species; importantly, this species appears to be less susceptible to the antifungal drug amphotericin B. Unique to this species is the ability to produce specialised structures – denoted accessory conidia (AC) – directly on hyphae, both in vitro and in vivo. (5)

Allergen Description

No allergens have been characterised.

A number of proteins (including heat shock protein 90 (6) and heat shock protein 60 (7) that have been shown to have allergenic potential in other fungi have been isolated, but their allergenic potential has not yet been elucidated. An alkaline protease enzyme has been isolated which is related to that of Aspergillus fumigatus. (8)

Importantly, A. terreus does not appear to contain an allergen related to Asp f 1, a major 18 kDa allergen of A. fumigatus and a member of the mitogillin family of cytotoxins, which is also 99% homologous to mitogillin from Aspergillus restrictus. (9)

Potential Cross-Reactivity

A. terreus, A. flavus and A. nidulans hydrolyse collagen and were found to secrete an alkaline protease related to that of A. fumigatus. In contrast, A. niger, A. glaucus, A. versicolor and A. clavatus were unable to degrade collagen in vitro, suggesting a possible pathogenic role for the secreted alkaline proteases of the Aspergillus species.(8) The allergenic potential of this alkaline protease was not evaluated, but may be similar to that of other alkaline proteases that are recognised allergens in other fungal species.

Clinical Experience

IgE-mediated reactions

Anecdotal evidence suggests that Aspergillus terreus may induce symptoms of hypersensitivity, including asthma, allergic alveolitis and hypersensitivity pneumonitis in sensitised individuals. (10) However, few studies have been reported to date; it is possible that the allergy occurs more frequently than has been reported. A. terreus has been recognised as a cause of allergic bronchopulmonary aspergillosis. (11, 12)

A farmer who had developed severe respiratory as well as systemic symptoms upon exposure to hay dust was shown by inhalation challenge (utilising his own hay) to experience peripheral and central airway obstruction beginning immediately after challenge, as well as the development of symptoms of typical hypersensitivity pneumonitis reaction several hours later. Immunodiffusion studies demonstrated serum precipitins to antigenic components of this hay, which were identified as antigens of several Aspergillus species. Further analysis isolated ten relevant antigens of A. terreus and four of A. fumigatus. Only minimal Aspergillus-specific IgE antibodies were found in the patient's serum. The authors concluded that this case demonstrates that hay dust can cause bronchial obstruction as well as hypersensitivity pneumonitis in the same individual, with symptoms beginning immediately and lasting up to 2 days. (10)

Farmer’s lung as a result of A. fumigatus, A terreus and Nocardiopsis alba has been documented in a farmer and his son. (13)

A 16-year-old male with a history of asthma and recurrent pneumonia was diagnosed with allergic bronchopulmonary aspergillosis (ABPA), based upon the typical clinical presentation of peripheral eosinophilia, elevated IgE and positive immediate skin tests to Aspergillus. Sputum cultures grew A. terreus. Precipitins against A. terreus (but not against A. fumigatus) were detected in the patient's serum. His lymphocytes proliferated markedly in vitro when exposed to soluble A. terreus antigen, but not when exposed to A. fumigatus antigen. (14)

In patients with allergic respiratory diseases, there is heterogeneity of immune response to different species of Aspergillus. (15) In a study of the allergenic significance of 13 species of Aspergillus and their allergenic and antigenic relationship, after skin-prick testing on 289 patients with allergic respiratory diseases, 627 (20.7%) were positive and 12.8% significantly positive. Of the 64 patients eliciting a positive cutaneous response to at least one species, 42 (65.6%) were positive to 5 or fewer species while others showed a broad spectrum of positive skin reactivity to different Aspergillus extracts. The presence of both species-specific allergenic components and those shared between different Aspergillus species was demonstrated. (15)

Other reactions

A. terreus has been recognised as a cause of aspergilloma, (16, 17) onychomycosis, (18, 19) aural cavity disease, (20, 21, 22, 23, 24, 25) subcutaneous abscesses, (26, 27) and keratitis. (28, 29)

Invasive fungus infections caused by Aspergillus spp. may occur in immuno-competent hosts, but occur most frequently in immunocompromised patients. (30) A high infection-associated death rate of up to and over 50% is attributed to these fungi. Although disease in humans is caused mainly by A. fumigatus, A. flavus and A. niger, other species (such as A. terreus and A. nidulans) occur but are less prevalent. (31) A retrospective single-centre study of invasive fungal infections in 1 095 patients with haematological malignancies found that A. fumigatus (n = 46) and A. terreus (n = 41) were the predominant causes. (32)

However, an increase in the rates of infection caused by A. terreus has been observed, including in Japan. (33) A. terreus appears to have become an increasingly frequent cause of opportunistic infections at the University Hospital of Innsbruck, Austria, (34) and has been implicated even in dryer climates such as that of Kuwait. (35)

A 12-year retrospective study identified 13 cases of invasive aspergillosis caused by A. terreus, of which 11 were primary pulmonary infections and 2 were primary peritoneal infections; all patients had malignancy. (36) In another study (1997-2002), 83 cases of A. terreus infection from three medical centres were described. (37) Cases of infective endocarditis, (38, 39, 40) myocarditis, (41) meningitis, (42) brain abscess, (43) osteomyelitis, (44) discitis, lymphadenitis, (45) endophthalmitis, (46) mycotic aortic aneurysm and peritonitis (47, 48) due to A. terreus have been reported. (49, 50, 51, 52, 53)

Other conditions reported to occur as a result of A. terreus include granulomatosis (54) or infection of the ear, nose and throat, (55) following transplantation of organs (56) or in patients who are receiving immunosuppressive drugs. (57)

Infection of patients with cystic fibrosis with A. terreus has been reported. (58) A. fumigatus, Scedosporium apiospermum and A. terreus (for filamentous fungi) and Candida albicans (for yeasts) are reported to be the main fungal species associated with cystic fibrosis. (59) Similarly, this organism may infect patients with COPD who are receiving corticoids. (60)

Significantly, invasive infections caused by this organism are often disseminated with increased lethality compared to infections caused by other Aspergillus species, and tend to be resistant to treatment with the antifungal drug amphotericin B. (61)

A Japanese study reported that in fungal infections of the ear and nose, A. terreus was the most common pathogen of otomycosis, followed by A. niger and A. flavus; aspergillosis was the most common fungal disease in the paranasal sinuses. (62)

Although cutaneous infections due to A. terreus are rare they may occur, as described in a paediatric patient with cutaneous infections who had undergone surgical treatment for an open tibial fracture secondary to an agricultural accident. (47) Keratitis has been described. (63)

Compiled by Dr Harris Steinman.

References

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As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.