Fungal diagnostics update: urine tests, oral-wash PCR, lateral flow and AI
Several recent papers point in the same direction for fungal diagnostics: faster testing, less invasive sampling and better use of molecular and computational methods.
This week’s most interesting studies include a new urine-based test for invasive aspergillosis, oral-wash PCR for Pneumocystis jirovecii pneumonia, a prototype lateral-flow test for Candida auris, and a timely review of anti-Aspergillus serology in chronic pulmonary aspergillosis (CPA).
A urine test for invasive aspergillosis
One of the most striking papers is a study by Datta and colleagues describing a new urine assay for invasive aspergillosis.
The test, called MycoMEIA-Aspergillus, uses monoclonal antibodies to detect galactofuranose-containing fungal antigens associated with Aspergillus extracellular vesicles in urine.
In the reported study, the assay achieved a per-patient sensitivity of approximately 91% and specificity of approximately 89%.
This is important because diagnosing invasive aspergillosis remains difficult. Current diagnosis usually relies on a combination of clinical assessment, imaging, fungal culture, galactomannan, PCR and sometimes invasive procedures such as bronchoscopy.
Urine is particularly attractive as a diagnostic sample because it can be collected repeatedly and non-invasively.
The underlying idea is not entirely new. Previous work has shown that shorter-chain galactofuranose-containing fungal antigens can be detected in urine and may be associated with extracellular vesicles. The new study appears to move this approach further towards a practical diagnostic assay.
However, this remains a development and validation study. Larger prospective studies in different patient populations will be needed before such a test could replace or substantially alter established diagnostic pathways.
Could oral-wash PCR reduce the need for bronchoscopy in Pneumocystis?
A second important study evaluated PCR on oropharyngeal wash samples for diagnosing Pneumocystis jirovecii pneumonia (PJP) in non-HIV immunocompromised patients.
The study included 134 patients with suspected PJP.
This is clinically important because the most reliable respiratory samples for PJP are usually obtained from the lower respiratory tract, often by bronchoalveolar lavage. Bronchoscopy may be difficult or risky in severely unwell patients.
Oral wash is much easier to obtain.
The concept has been investigated previously, but a major difficulty is that non-HIV immunocompromised patients often have lower fungal burdens than people with HIV-associated PJP. Highly sensitive PCR can also detect colonisation rather than active infection.
A 2025 systematic review concluded that the diagnostic performance of oral-wash PCR in this particularly important patient group remained incompletely defined.
The new study therefore addresses a genuine evidence gap rather than simply demonstrating that Pneumocystis DNA can be detected in the mouth.
If sufficiently reliable thresholds and diagnostic algorithms can be established, oral-wash PCR could potentially become part of a less invasive diagnostic pathway alongside clinical findings, imaging and blood biomarkers such as beta-D-glucan.
Aspergillus IgG remains central to diagnosing CPA — but interpretation matters
A new narrative review examines the strengths and weaknesses of anti-Aspergillus antibody testing in chronic pulmonary aspergillosis.
Culture and direct microscopy are useful but frequently insensitive in CPA, which is why anti-Aspergillus IgG has become a cornerstone of diagnosis.
Published studies of commercial Aspergillus IgG ELISAs generally report sensitivities in the region of 86–98% and specificities around 90–99%, although performance varies between assays and populations.
That variability matters.
Different laboratories may use different commercial assays, antigens and cut-off values. Geographic variation, the infecting Aspergillus species and the patient’s underlying lung disease can also affect results.
A separate 2026 study from the same research group examined optimisation of an Aspergillus IgG ELISA and the performance of Western blot testing. It also highlighted that antibody results obtained during an unrelated respiratory exacerbation may sometimes be difficult to interpret.
The practical message remains important: Aspergillus IgG is a powerful diagnostic test, but it should be interpreted alongside symptoms, CT imaging and other mycological evidence rather than as a stand-alone diagnosis.
A prototype lateral-flow test for Candida auris
Researchers have also reported an interesting new approach to rapid detection of Candida auris.
The team created a synthetic beta-mannan epitope representing part of the fungal cell wall. Antibodies raised against this defined structure could recognise multiple C. auris strains.
One of these antibodies was then used to build a prototype lateral-flow assay for rapid detection of the fungus.
This approach is attractive because C. auris can spread within healthcare environments and may be resistant to multiple antifungal drugs. Rapid identification is therefore important both for individual patient management and infection control.
However, this remains early-stage technology. A prototype laboratory assay is not the same as a clinically validated bedside diagnostic test.
Further work will need to determine sensitivity, specificity, performance with real clinical samples and whether the test can distinguish colonisation from invasive disease where necessary.
What else is emerging?
CRISPR diagnostics for Candida tropicalis
Ye and colleagues developed a rapid molecular assay combining multiple cross-displacement amplification with CRISPR/Cas12a for detecting Candida tropicalis.
CRISPR-based diagnostics are attractive because they can combine highly specific sequence recognition with simple visual or fluorescence-based readouts.
At present, however, many CRISPR fungal diagnostic systems remain at the assay-development stage. Their eventual clinical value will depend on reproducibility, sample preparation, contamination control, cost and performance in real-world patient samples.
Metagenomic sequencing is moving into routine respiratory diagnostics
A real-world study examined the clinical utility of metagenomic next-generation sequencing (mNGS) in lower respiratory tract infections.
The study included a broad range of pathogens rather than focusing specifically on fungi, but fungi including Candida were frequently detected.
mNGS is particularly useful when conventional testing fails or when several different pathogens are plausible.
The challenge is increasingly not whether sequencing can detect microbial DNA, but whether the detected organism is actually causing disease. Colonisation, contamination and clinically irrelevant organisms must be distinguished from true infection.
Machine learning for earlier recognition of invasive aspergillosis
Several groups are exploring machine-learning models to identify patients at high risk of invasive pulmonary aspergillosis.
Ding and colleagues developed an interpretable model for patients with severe fever with thrombocytopenia syndrome, a group at particularly high risk of IPA.
Another recent study developed machine-learning models and a bedside risk score for critically ill non-neutropenic immunocompromised patients.
These systems do not detect the fungus directly. Instead, they combine clinical and laboratory information to estimate the probability of infection and potentially identify patients who should undergo targeted fungal testing earlier.
Such models are promising, but they require external validation in independent hospitals and patient populations before they can safely influence routine diagnostic decisions.
Extracellular vesicles may become a new class of fungal biomarker
The urinary Aspergillus study also fits into a broader area of fungal research involving extracellular vesicles.
These tiny membrane-bound particles are released by fungal cells and can contain proteins, carbohydrates, lipids and nucleic acids.
A new review discusses their potential as biomarkers in invasive candidiasis and other fungal infections.
For many years extracellular vesicles were primarily studied as part of fungal biology and host-pathogen interactions. The important development now is that some of their contents are beginning to be investigated as measurable diagnostic targets.
The bigger picture: fungal diagnosis is becoming less invasive
The strongest theme running through this week’s papers is not any single technology.
It is the attempt to obtain useful diagnostic information from easier and safer samples.
- Urine instead of invasive respiratory sampling for invasive aspergillosis.
- Oral wash instead of bronchoalveolar lavage for Pneumocystis.
- Lateral-flow devices that could potentially move fungal testing closer to the patient.
- Molecular amplification and CRISPR systems designed to produce results rapidly.
- Machine-learning systems that may help identify which patients need fungal investigation earlier.
None of these technologies eliminates the need for clinical judgement. Fungal disease is particularly difficult because the same organism may represent environmental contamination, airway colonisation, allergic disease, chronic infection or invasive infection depending on the patient and clinical context.
The future is therefore unlikely to be one universal fungal test.
More likely, diagnosis will increasingly combine non-invasive biomarkers, molecular detection, imaging and clinical probability — with each component contributing a different piece of evidence.