Beyond guidelines: what do I need to know when dealing with fungal diagnostics?

Cornelia Lass-Flörl. Clinical Microbiology and Infection (2025)

PIIS1198743X2500357X

Why this paper matters

Diagnosing invasive fungal infections (including aspergillosis) remains difficult in real-world practice. Guidelines exist, but patients and clinicians often experience confusing or apparently conflicting test results. This narrative review explains why that happens and how results should be interpreted in context, particularly for Aspergillus infections.

Key messages relevant to aspergillosis

1. Your immune system strongly affects test results

The paper clearly explains that diagnostic tests behave very differently depending on immune status:

• In neutropenic or heavily immunosuppressed patients, antigen tests such as galactomannan tend to perform better, while antibody tests often fail.

• In immunocompetent or non-neutropenic patients, including many with chronic pulmonary aspergillosis (CPA), Aspergillus IgG antibody tests are often positive and clinically useful.
  This helps explain why some patients are told their blood tests are “negative” despite ongoing disease.

2. Where the sample comes from matters

For lung aspergillosis:

• Bronchoalveolar lavage (BAL) samples are far more informative than blood.

• Blood cultures are usually unhelpful for Aspergillus, as the fungus rarely circulates in the bloodstream.

• A positive sputum culture may represent colonisation rather than infection, especially in people without severe immune suppression.

This reinforces an important patient message: a single test result is rarely enough.

3. Antifungal treatment can hide infection

Starting antifungal therapy early can:

• Make cultures negative

• Reduce antigen levels (e.g. galactomannan)

• Complicate microscopy interpretation

This explains why some patients experience false reassurance from negative tests after treatment has already begun. Serial testing and clinical judgement are often more informative than a single result.

4. False positives and cross-reactivity are common

The review highlights important pitfalls:

• β-D-glucan can be positive due to bacterial infections or medical materials, not just fungi

• Galactomannan can cross-react with other fungi (e.g. Fusarium)

• Mixed infections can occur in immunosuppressed patients

This supports a cautious interpretation of “positive” results and explains why clinicians may hesitate to diagnose aspergillosis based on one test alone.

5. Colonisation vs infection is a central challenge

A particularly relevant section for aspergillosis patients explains:

• Aspergillus can live in airways without causing invasive disease

• Diagnosis relies on combining symptoms, imaging, risk factors, and multiple tests
  This reflects the lived experience of many patients with bronchiectasis, asthma, or chronic lung disease.

Strengths of the paper

• Written by a leading international mycology expert

• Pragmatic and clinically grounded

• Explains why guidelines don’t always fit individual patients

• Particularly strong on Aspergillus diagnostics, including CPA and invasive disease

Limitations

• Focuses mainly on invasive fungal infections; allergic and chronic syndromes are discussed less

• Aimed primarily at clinicians and laboratories, not patients

Take-home message for patients

There is no single “definitive” test for aspergillosis. Results depend on immune status, sample type, timing, and prior treatment. Negative tests do not always mean absence of disease, and positive tests do not always mean active infection.

This paper strongly supports the multidisciplinary, experience-based approach used in specialist centres such as the National Aspergillosis Centre.