Urine and blood tests could help detect a life-threatening fungal infection

Invasive aspergillosis is a serious disease, particularly in patients with blood cancers. An international team led by scientists at the Institute of Microbiology of the Czech Academy of Sciences has developed a minimally invasive diagnostic approach that combines three biomarkers in urine and blood to detect up to 80% of cases. The approach could be particularly valuable when samples cannot be collected from the lungs safely or promptly.

Infections caused by microscopic fungi pose a far greater threat to human health than most people realise. Current global estimates suggest that approximately 6.5 million people develop invasive fungal infections each year, and up to 2.5 million die as a result.

One of the most dangerous forms is invasive aspergillosis, caused by fungi of the genus Aspergillus. People routinely inhale their spores from the air, and a healthy immune system can usually deal with them. The situation is very different, however, for people whose immune defences have been severely weakened by leukaemia, haematopoietic stem cell transplantation or intensive cancer treatment. Invasive aspergillosis affects approximately one in ten patients in the highest-risk group with blood cancers and can cause life-threatening infections of the lungs and other organs.

These vulnerable patients were the focus of an international study published in the leading journal Clinical Microbiology and Infection. The findings represent an important step towards simpler, less invasive diagnosis of invasive aspergillosis. For patients whose treatment outcomes may depend on a matter of days - or even hours - rapid, non-invasive detection could allow targeted treatment to begin sooner and improve their chances of survival.

Diagnostic challenges in the most vulnerable patients

Diagnosing invasive aspergillosis quickly and accurately remains a major challenge. A key procedure for confirming the infection is bronchoscopy, during which fluid is collected from the lower airways. This allows the pathogen to be detected directly by microscopy and culture, and its susceptibility to antifungal drugs to be determined.

Yet the patients who need this procedure most may also be those in whom it is most difficult to perform. They may have very low platelet counts, be critically ill or have other complications. Bronchoscopy may therefore have to be postponed, and in some cases cannot be performed at all. The international team led by Czech scientists is seeking a way to obtain additional diagnostic information from urine and blood alone in precisely these circumstances.

“We are not seeking to replace bronchoscopy. Whenever it is feasible, it remains an invaluable diagnostic tool. The difficulty arises when we cannot perform it promptly, yet cannot afford to wait several days for the information needed to make a treatment decision,” says Vladimír Havlíček of the Institute of Microbiology of the Czech Academy of Sciences, the study’s corresponding author.

One disease, three different biomarkers

The proposed approach combines three biomarkers that reflect different aspects of the same infection: triacetylfusarinine C (TafC) in urine, and galactomannan and the protein pentraxin-3 in blood.

“We can think of this in terms of three layers: the fungus is metabolically active and growing; it releases a substance that activates our immune system; and the patient’s body responds to the infection. Each test therefore measures something different. We believe this biological independence is the greatest strength of the concept,” explains Vladimír Havlíček.

The study included 138 high-risk patients with haematological malignancies and proven or probable invasive aspergillosis.

Urinary TafC and blood galactomannan alone detected approximately half of the cases of invasive aspergillosis. Adding pentraxin-3 increased detection to 83.8%, but at the cost of substantially lower specificity. Pentraxin-3 therefore cannot serve as standalone evidence of aspergillosis; its value lies in providing additional information about the patient’s response. When bronchoscopy is feasible, it remains the preferred method for obtaining direct evidence of infection. When it is contraindicated, however, non-invasive biomarkers may provide valuable information to support timely clinical decisions.

“This is where we see the greatest potential benefit for patients. We have not shown that our panel, on its own, reduces mortality - that will need to be established in a further prospective study. But it could provide diagnostic information in situations where that information is currently difficult to obtain or comes too late. And in invasive aspergillosis, time can be critical,” says Vladimír Havlíček.

A step towards changes in international diagnostic criteria?

The study also proposes a practical diagnostic pathway. At the first suspicion of invasive aspergillosis, clinicians would assess whether bronchoscopy is feasible while collecting blood and urine samples in parallel. The authors now aim to validate the approach in further independent patient cohorts. Only then will it be possible to assess whether the principle could inform wider diagnostic practice.

“It would clearly be premature to suggest that a single study will change international diagnostic criteria. But if this three-component approach is confirmed in further prospective cohorts, it could become part of the evidence underpinning future revisions. That is the direction we would like to pursue,” says Vladimír Havlíček.

The next goal: testing on equipment already familiar to hospitals

The long-term aim is to bring this type of testing onto a platform that clinical microbiology laboratories already have and know how to use. The researchers confirmed that TafC remains stable under standard conditions for storing clinical samples, supporting its potential future use in routine laboratory diagnostics.

“If we could combine sufficiently sensitive detection with the equipment hospitals already use, we could significantly shorten the time from collecting a patient’s sample to obtaining a result. But that is the next technological step, rather than something this study has already achieved,” Vladimír Havlíček emphasises.

Media contact:

Professor Vladimír Havlíček, Ing., Dr.
Head of the Laboratory of Molecular Structure Characterization
Institute of Microbiology of the Czech Academy of Sciences
vladimir.havlicek@mbu.cas.cz

Publication

https://doi.org/10.1016/j.cmi.2026.10.002

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