Aspergillus and Aspergillosis
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Direct answer
Aspergillus is a ubiquitous mould whose septate hyphae branch at acute angles, causing disease from allergy to invasive infection. Aspergillus fumigatus is the commonest species, and the host decides the form: allergic bronchopulmonary aspergillosis in asthma, aspergilloma in an old lung cavity and invasive disease in profound neutropenia. Diagnosis combines imaging, serum galactomannan and culture, and invasive disease is treated first with voriconazole.
What you must remember
- Species profile: Aspergillus fumigatus is commonest, Aspergillus flavus produces aflatoxin and causes fungal sinusitis and keratitis (A. niger is the usual cause of otomycosis), and Aspergillus terreus is intrinsically resistant to amphotericin B.
- Morphology: septate hyphae that branch at roughly 45 degrees, with a vesicle bearing phialides and small round conidia.
- ABPA: a hypersensitivity response in asthma or cystic fibrosis, marked by eosinophilia, markedly raised total IgE, Aspergillus-specific IgE or IgG and central bronchiectasis.
- ABPA treatment: oral corticosteroids to suppress the response, with itraconazole added to reduce steroid dependence.
- Aspergilloma: a fungal ball in a pre-existing cavity, often left by tuberculosis, whose classic presentation is haemoptysis.
- Halo and air-crescent signs: a ground-glass halo around a nodule suggests early invasive disease in neutropenia, and an air-crescent appears later as neutrophils recover.
- Invasive aspergillosis: voriconazole is first-line, with isavuconazole as an alternative and liposomal amphotericin B used in some settings.
A nodule in a neutropenic patient
A patient on chemotherapy for acute leukaemia has fever that persists after five days of antibiotics, and a new nodule appears on chest computed tomography.
- Recognise the host: neutropenia, prolonged corticosteroids and transplantation raise suspicion of invasive disease well before the culture result.
- Image the chest: a nodule surrounded by a halo of ground glass is typical early, while an air-crescent sign suggests recovery of neutrophils.
- Send the markers: serum galactomannan and a bronchoalveolar lavage specimen are sent, since a positive galactomannan supports the diagnosis.
- Confirm the diagnosis: culture of lavage or tissue, with histology showing septate hyphae branching at acute angles, provides the definitive evidence.
- Start the right drug: voriconazole is started promptly, and isavuconazole or liposomal amphotericin B is an alternative when the azole cannot be used.
- Monitor the response: serial imaging and galactomannan levels show whether the infection is controlled, and drug levels guide voriconazole dosing.
The steps run in parallel rather than in strict sequence, because the imaging and the markers are needed together.
Where the exam tries to catch you
Aspergillus questions usually test the link between host, form of disease and drug.
- Trap: treating ABPA with antifungal alone Correct: ABPA is a hypersensitivity state that needs corticosteroids, with itraconazole as the steroid-sparing agent.
- Trap: attributing a fungal ball to invasive disease Correct: aspergilloma sits in a pre-existing cavity in a non-neutropenic host, so surgery or observation is typical rather than urgent antifungal therapy.
- Trap: expecting a positive culture alone to confirm invasive disease Correct: Aspergillus colonises airways, so diagnosis needs the host risk, imaging and galactomannan or histology together.
Frequently asked questions
What is the halo sign in invasive aspergillosis?
The halo sign is a ground-glass zone surrounding a pulmonary nodule on chest computed tomography, typical of early invasive aspergillosis in neutropenic patients. It reflects haemorrhage around the infected focus. The air-crescent sign appears later as neutrophils recover.
Which antifungal treats invasive aspergillosis first?
Voriconazole is the first-line agent for invasive aspergillosis, with isavuconazole as an alternative and liposomal amphotericin B used in some settings. Treatment continues according to clinical and radiological response. The choice is adjusted for drug interactions and toxicity.
How is allergic bronchopulmonary aspergillosis treated?
Allergic bronchopulmonary aspergillosis is treated with oral corticosteroids that suppress the hypersensitivity response. Itraconazole is added to reduce steroid dependence and control exacerbations. Diagnosis rests on raised total IgE, Aspergillus-specific IgE or IgG, eosinophilia and central bronchiectasis.
What is the role of galactomannan in aspergillosis?
Serum galactomannan is an antigen from the Aspergillus cell wall, and a positive assay supports invasive aspergillosis, particularly in haematological patients. Its sensitivity is lower in patients receiving mould-active prophylaxis. Serial testing and imaging together give the most reliable picture.