Rapid Urine Test for Invasive Aspergillosis Wins FDA Clearance After Clinical Validation

Invasive aspergillosis has long been one of the most feared diagnoses in hospitals that care for patients with weakened immune defenses. The infection is caused by Aspergillus, a mold so common in the environment that most people breathe in its spores every day without consequence. In individuals whose immune systems have been devastated by blood cancers, bone marrow transplantation or critical illness, however, those same spores can seed a progressive, frequently fatal infection of the lungs and beyond. Now, researchers at Johns Hopkins Medicine have published the clinical data behind a diagnostic advance that could shorten the dangerous interval between suspicion and certainty: a rapid urine-based assay for the disease, cleared by the U.S. Food and Drug Administration in late 2025 and believed to be the first of its kind.

The study, published in the journal Clinical Infectious Diseases, was supported through long-standing funding from the National Institutes of Health and describes the analytical and clinical performance data that underpinned the FDA clearance of the assay for use in adults with suspected invasive aspergillosis. Sean X. Zhang, M.D., Ph.D., the senior study author, an associate professor of pathology and director of the Medical Mycology Laboratory at Johns Hopkins Medicine, emphasized what is at stake in the speed of diagnosis. “Having an early diagnosis is critical; it can initiate appropriate and timely treatment to help prevent disease progression and increase the odds of survival,” Zhang said in the announcement accompanying the publication.

The clinical problem the test addresses is stark. Invasive aspergillosis is generally rare in people with healthy immune systems, but its prevalence within vulnerable populations is substantial. Studies have estimated that the infection develops in 5 to 15 percent of patients with acute myeloid leukemia, or in those receiving bone marrow transplants for conditions such as sickle cell disease. It has also been identified in 5 to 20 percent of patients admitted to the intensive care unit with severe influenza or COVID-19, a category of cases that gained renewed attention during the pandemic. Despite the availability of antifungal treatment, up to half of some high-risk populations may die from the infection, a mortality figure that reflects both the aggressiveness of the disease and the difficulty of diagnosing it in time.

Historically, establishing a diagnosis of invasive aspergillosis has required a laborious combination of evidence. Clinicians have relied on chest imaging, blood tests, respiratory samples obtained during bronchoscopy and, in some cases, tissue biopsy. Several of these approaches are invasive, demanding procedures that can be risky for patients who are already profoundly ill, neutropenic or recovering from major transplantation. Even after such workups, uncertainty often remains, and antifungal therapy may be started empirically in patients who ultimately turn out not to have the infection, exposing them to toxicity, drug interactions and unnecessary cost. The newly cleared assay takes a different approach: rather than requiring bronchoscopic or tissue sampling, it directly detects Aspergillus antigens in urine and can return a laboratory result within several hours, using a specimen that can be collected noninvasively at the bedside. The test is intended to be used alongside clinical findings, imaging and other laboratory tests, not to replace them.

The core of the publication is a rigorous validation study of the assay’s ability to detect Aspergillus galactofuranose-containing antigens, proteins that signal the body’s response to this infection. The investigators analyzed frozen urine samples from 290 study participants who had been enrolled in studies in the United States and Belgium at various times between 2009 and 2022. Of these participants, 50 had a confirmed case of invasive aspergillosis and 240 served as controls, giving the analysis a substantial body of true-positive and true-negative material against which the test could be measured. The frozen-sample design allowed the investigators to evaluate the assay blindly, on specimens collected years before the test existed, which is a meaningful advantage in a disease where prospective enrollment of large numbers of confirmed cases is difficult.

The performance figures reported from that retrospective cohort are striking. Among the 50 participants with confirmed invasive aspergillosis, the urine test correctly identified 46 cases, a sensitivity of 92 percent; only four cases produced false negative results. On the negative side, the test correctly identified 218 of 249 samples as negative, a specificity of 88 percent. To guard against site-specific artifacts, the urine samples were tested at laboratories in Baltimore, Maryland; Pittsburgh, Pennsylvania; and Raleigh, North Carolina, providing a multi-center assessment of reproducibility. For a noninvasive test that yields results within hours, those operating characteristics compare favorably with the diagnostic pathways it is designed to complement, which often involve invasive procedures and delays of days.

Retrospective accuracy alone does not establish a test’s usefulness in the messy reality of clinical medicine, where patients suspected of infection frequently turn out to have something else. To address this, the investigators conducted a second phase of research examining how the assay performs in real time among people suspected of having invasive aspergillosis who were receiving care at The Johns Hopkins Hospital for conditions such as blood cancer or autoimmune diseases between January 2023 and February 2024. Of the 210 participants suspected of having the infection who provided samples, 168 were eligible for analysis, and 171 fresh urine samples were analyzed in real time in the hospital laboratory. In this prospective component, a small portion of the participants had confirmed results: seven confirmed positive and 39 confirmed negative. Against those confirmed outcomes, the test correctly identified six of the seven positive cases, or 86 percent, and 35 of the 39 negative cases, or 90 percent.

Perhaps the most clinically revealing finding came from the large group of patients in whom the diagnosis remained uncertain. Among the 210 people suspected of having invasive aspergillosis, about half lacked a confirmed diagnosis, a proportion that captures the everyday diagnostic ambiguity of the disease. Yet among those suspected cases without confirmation, the urine test produced a positive result in roughly one in four. The researchers say this pattern demonstrates the benefit of having such a diagnostic tool available in a hospital setting, because it can begin to stratify an uncertain population into those with evidence of infection and those in whom alternative explanations should be pursued, all without subjecting patients to additional invasive procedures.

Nitipong Permpalung, M.D., M.P.H., director of mycology research and associate director for clinical trials at the Johns Hopkins Transplant Research Center, framed the value of the test in terms of the clinical decision-making it enables. “For patients with blood cancers or stem cell transplants, the hardest part is often the gap between suspecting invasive aspergillosis and having enough evidence to act,” Permpalung said. “This urine test is not a stand-alone answer, but it can provide another piece of evidence quickly and noninvasively, which could help us move faster for patients most likely to benefit from treatment while avoiding unnecessary antifungal exposure when infection is less likely.” That dual promise, faster treatment for true infections and less gratuitous antifungal use for everyone else, is precisely the calculus that determines outcomes and toxicity in immunocompromised wards.

The work is not finished. The investigators are currently studying how the assay performs when incorporated into routine clinical care, and whether it may provide value in other high-risk settings, including among immunocompromised patients evaluated for fungal complications following respiratory viral infections, a population that grew in prominence during the influenza and COVID-19 pandemics. The research also aligns with global priorities set by the World Health Organization, which in 2022 named Aspergillus fumigatus to its list of critical-priority fungal pathogens as part of its program to better diagnose, treat and prevent invasive aspergillosis. The published study, titled “Performance of the Urinary MycoMEIA Aspergillus Assay as an Aid to Diagnose Invasive Aspergillosis,” appears in Clinical Infectious Diseases with the DOI 10.1093/cid/ciag522. Additional authors include Irina Baburina, Kieren Marr, Yuri Vanbiervliet, Chiung-Yu Huang, Robina Aerts, Patricia Marques, Andrew Shorr, M. Hong Nguyen, Binghua Hao, John Wingard and Johan Maertens. The study was funded by Pearl Diagnostics, Inc., and NIH grant R44AI157572. Disclosures note that Kieren Marr started Pearl Diagnostics in 2014 and is a shareholder of the company, and that several authors, including Permpalung and Zhang, have received consulting income or sponsored research support from Pearl Diagnostics and a range of other diagnostics and therapeutics companies. For a disease that kills up to half of some high-risk groups, the arrival of a validated, hours-fast, urine-based diagnostic marks one of the most consequential additions to the invasive aspergillosis toolkit in years.

Subject of Research: Clinical validation of a rapid urine-based antigen assay for diagnosing invasive aspergillosis

Article Title: Johns Hopkins Medicine researchers publish clinical data for rapid diagnostic urine test to detect invasive aspergillosis

Article References: Johns Hopkins Medicine researchers publish clinical data for rapid diagnostic urine test to detect invasive aspergillosis. (n.d.). Original publication

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Keywords: invasive aspergillosis, Aspergillus, urine antigen test, FDA clearance, diagnostic assay, galactofuranose antigens, immunocompromised patients, bone marrow transplant, Clinical Infectious Diseases, Johns Hopkins Medicine, antifungal therapy, WHO fungal priority list