Aspergillus terreus
Summary
Aspergillus terreus is a thermotolerant filamentous fungus belonging to the genus Aspergillus. A relatively rare cause of aspergillosis in man, however, it is reported as an emerging pathogen in Austria and Texas, US. An important pathogen in invasive aspergillosis, A. terreus infection is associated with increased morbidity and mortality, in part due to resistance to amphotericin B. A. terreus is also a cause of allergic bronchopulmonary aspergillosis in patients with asthma and cystic fibrosis. Exposure to allergens is by inhalation and three allergens specific to Aspergillus terreus are recognized. Asp t 36 has been identified as a possible major allergen and shares molecular homology with a diverse range of phylogenetically related and unrelated allergens.
Epidemiology
Worldwide distribution
A. terreus has a global distribution and is found in a wide variety of habitats. However, there are reports of local increases of prevalence of A. terreus-associated invasive aspergillosis, such as Innsbruck in Austria and Houston, Texas. The reason for this increase is unclear. An international, multi-center surveillance study, which surveyed the prevalence of A. terreus positive isolates amongst mold positive cultures over 12 consecutive months (n = 7116) from 38 centers in 21 countries, reported A. terreus was isolated from 5.2% of cultures. The same study found that Spain and Austria hosted the highest recorded density of A. terreus isolates. The greatest proportion of A. terreus isolates (39.2%) was most commonly isolated from patients with chronic lung disease.
The estimated prevalence of sensitization to Aspergillus spp. antigens in patients with allergic respiratory diseases is between 15.3‒38.0%. Sensitization to Aspergillus is also a risk factor for more severe asthma. Up to 70% of patients with severe asthma have Aspergillus sensitized IgE, compared to 10% of patients with mild to moderate disease and 5% of the general population.
A meta-analysis has reported that the pooled prevalence of sensitization to Aspergillus spp. was 39.1% in patients with cystic fibrosis (CF). Prevalence was higher with the skin test compared to specific IgE assay (43.8% vs. 32.8%, P=0.002). ABPA occurs in approximately 9% of CF patients and 1–3% asthmatic patients. Furthermore, it has also been shown that 12.4% of patients with A. terreus isolates were diagnosed with ABPA. A terreus is the third most common filamentous fungus isolated from airway secretions of patients with CF.
Route Of Exposure
Main
The primary route of exposure to A. terreus is allergen inhalation. Aspergillus spp. have small conidiospores (2–5 µm), which means they can reach the terminal bronchial airways. However, their presence in large clusters in the upper respiratory tract can also provoke a sensitivity reaction.
Clinical Relevance
Aspergillus spp. are the causative agents of a spectrum of hypersensitivity disease in humans including allergic asthma (with or without rhinitis), allergic rhinosinusitis, hypersensitivity pneumonitis and ABPA. ABPA can cause irreversible lung damage, so there is an imperative to reach an early diagnosis.
A significant clinical implication of hypersensitivity to A. terreus is resistance to amphotericin B, where a treatment failure rate of 80-90% is reported. The aim of the treatment of ABPA is to prevent irreversible lung damage. Amphotericin B has been used in nebulized form to treat ABPA in patients with CF.
Cross-Reactivity
Several studies have demonstrated cross-reactivity of A. terreus extract with specific allergens of other Aspergillus spp. One study, which analyzed type III hypersensitivity responses, found that levels of A. fumigatus specific IgG were significantly correlated with A. terreus specific IgG, indicating cross-reactivity. Similarly, a study found that patients positive for A. terreus specific IgE were all found to be positive to A. fumigatus specific antigen, although it is thought that A. terreus is less cross-reactive with A. fumigatus than A. flavus.
TPI homologues are found in crustaceans and shellfish and are a common cause of food allergy in these species. The discovery that Asp t 36 is a homologue to crustaceans and shellfish allergens could anticipate further examples of cross-reactivity between fungal and arthropod allergens. Karmakar’s group demonstrated significant sequence homology between Asp t 36 and Der f 25, an allergen specific to the dust mite Dermatophagoides farina, as well as triosephosphate isomerases from the cockroach Blatella germanica. They also found the sequence was highly conserved, and similarities were noted with the TPI of wheat, house dust mite and the German cockroach, with conservation of IgE binding epitopes and implicating high cross-reactivity with both phylogenetically related and unrelated species.
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