By: Ibrahim M. Ibrahim

By: Ibrahim M. Ibrahim  Definition: is a spectrum of diseases that may be caused by number of aspergillus species, and occur worldwide. Aspergillus fumigatus is the most common human pathogen but A. flavus, A. Niger, A. nidulans and A. terreus can cause disease. The manifestations of the disease can only appear in case of the immunosuppressed patient principally corticosteroid-treated individuals. The disease usually develops allergic bronchopulmonary aspergillosis, aspergilloma, and invasive aspergillosis.

 Morphology and properties: The aspergillus species exist as molds. They have septate hyphae that form V-shaped branches. The conidia of the Aspergillus form radiating chains. In laboratory the tissue containing the fungi is stained by Grocott’s methenamine silver (GMS).

Microscopic morphology of Aspergillus fumigatus showing typical conidial heads.

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- Grocott’s methenamine silver (GMS) stained tissue sections: Shows Aspergillus fumigatus in lung tissue, note conidial heads.

 Etiology and transmission: It was believed that cases infected are because the environmental and occupational factors, for example, a farmer living in farms in trees, plants, decaying leaves, and using compost. But because of the isolation of the fungi from air conditioning systems, carpets, and surprisingly computers; the previous etiological factors are no longer the only concerns. The way of transmission is through inhalation of readily distributed spores in the atmosphere (mainly in autumn). Then the alveolar macrophages are able to engulf the conidia before spread, but for one reason or another, the defence is weakened and infection occurs.

 Pathogenesis: in immunocompetent individuals the macrophages takes hold of this and eradicate the invading conidia. However, in corticosteroid-treated and immunocompromised patients there is a diminished ability to defend, so in the lung the conidia swell and germinate to produce hyphae that have tendency to invade surrounding tissues.

In case of allergic bronchopulmonary aspergillosis (ABPA), there is growth of aspergillus in the wall of the bronchi and eventually produces proximal bronchiectasis. There are episodes of eosinophilic pneumonia usually in asthmatic

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subjects and if left untreated may progress into pulmonary fibrosis that affect the upper zone. The peripheral blood eosinophil count is raised and total number of IgE in high. ABPA is known to be present in more than 20% of all asthmatics in tropical countries.

In case of aspergilloma, the fungus usually finds a comfortable area to grow like damaged or scarred pulmonary tissue, for example, pre-existing cavities or bronchiectatic areas. The mycelia grow to form ball-like mass. Some predisposing factors are tuberculosis and sarcoidosis.

In case of invasive aspergillosis (chronic necrotizing), this implies the aggressive aspergillus invasion into viable tissues and blood vessels resulting in necrosis. Invasion of blood vessels leads to dissemination into distant organs usually in immunocompromised individuals.

 Clinical findings, diagnosis, and radiography: -

Allergic forms: in Atopic individuals, development of IgE Abs to surface antigens of aspergillus conidia elicits immediate asthmatic reaction. In others, the conidia germinate and hyphae colonize the bronchial tree and invade the lung parenchyma. This clinical asthma is the allergic bronchopulmonary aspergillosis.

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Chest infiltrates eosinophilia, both type Ι immediate & ΙΙΙ Arthur skin test hypersensitivity, and high temperature. Many patients produce sputum with aspergillus and serum precipitin. -

Aspergilloma: occurs when inhaled conidia enter existing cavity, so patient with previous cavity diseases like tuberculosis, sarcoidosis, bronchiectasis, emphysema are at risk. It sometimes stays asymptomatic and some times complicate into severe hemoptysis. Cough and dyspnea, unexplained weight loss if developed into chronic necrotizing aspergillosis. X-ray and CT scan show a dark mass.

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Invasive pulmonary aspergillosis: usually diagnosed by asking about the systemic symptoms, x-ray and CT scan imaging of the lung shows cloudiness. Samples of blood and mucus may also be checked for antibodies and fungal spores. Symptoms include high temperature, cough with mucus, hemoptysis, wheeze, headache, fatigue, and chest pain.

 laboratory identification: -

Specimen: sputum or other respiratory tract specimen, lung biopsy is a good specimen, and blood samples are rarely positive.

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Microscopic examination: on direct examination of sputum or histological sections, the hyphae of aspergillus are hyaline, septate, and uniform in width, and branch dichotomously.

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Culture: aspergillus species grow within few days on most media at room temperature, then identified according to their conidial morphology.

Aspergillus fumigatus on Czapek dox agar showing typical blue-green surface pigmentation with a suede-like surface consisting of a dense felt of conidiophores.

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Serology: the ID test for precipitin to A. fumigatus is positive in over 80% of aspergilloma and ABPA, but antibody tests are not helpful in diagnosis of invasive aspergillosis. However, a serologic test for circulating cell wall galactomannan is diagnostic.

 Treatment and prognosis: –

ABPA: with prednisolone 30mg daily, this causes rapid clearing of pulmonary infiltrates. Several antifungal agents can be administered but itraconazole seems to be the most helpful.

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Aspergilloma: first by amphotericin B injection directly into the lung (fungus ball) and that can stop hemoptysis. When the hemoptysis is controlled additional antifungal treatment is introduced like itraconazole. But usually surgical removal is required with safety margins.

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Invasive aspergillosis: intravenous amphotericin B, and itraconazole or the powerful variconazole if amphotericin is ineffective. Additional administration of caspofungin may be effective.

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Prognosis: is good when no dissemination.

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 Prevention: The main way to prevent aspergillosis is to avoid exposure to the aspergillus fungus. Chiefly, if you have asthma, a suppressed immune system, or a history of lung disease, you should avoid places where the aspergillus fungus is likely to be, such as: forests, compost heaps, grain stores, rotting vegetation, and piles of dead leaves. Moreover, avoid dusty environments like building constructions, and keep your house disinfected, temperature maintained, good ventilation should ensured as well.

 References: 1. Review of medical microbiology and immunology by Warren Levinson. Ninth edition 2006. 2. Textbook of the practice of medicine by Sir Ronald Scott. Twelfth edition. 3. Clinical medicine by Kumar & Clark. Sixth edition 2005. 4. Jawetz, Melnick, & Adelberg's Medical Microbiology, 24th edition 2007. 5. Cecil’s textbook of internal medicine. 22 nd edition. 6. http://www.nhs.uk/Conditions/Aspergillosis/Pages/References.aspx Indian journal of tuberculosis (research papers presented in Mumbai conference of tuberculosis and chest diseases) 2004.

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