Image created by Dr. Michael J. Miller
Through long-standing research, which has been supported by the National Institutes of Health, investigators at Johns Hopkins Medicine have advanced insights into ways to better detect invasive aspergillosis (IA). Caused by mold, the infection is uncommon in the general population but can create significant health risks for people with underlying conditions that affect or weaken their immune system. The researchers published data in the journal Clinical Infectious Diseases that led to the FDA clearance of what is believed to be the first rapid urine-based assay to aid in the diagnosis of the condition.
“Having an early diagnosis is critical; it can initiate appropriate and timely treatment to help prevent disease progression and increase the odds of survival,” says 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.
IA, which is generally rare in people with healthy immune systems, is a potentially life-threatening infection caused by Aspergillus, a common environmental mold. It most often affects people whose immune defenses have been severely weakened by certain cancers and medicines used to suppress rejection of transplanted bone marrow, among other conditions.
The prevalence of IA varies, but studies have estimated that IA develops in 5% to 15% of patients with acute myeloid leukemia or those receiving bone marrow transplants for conditions like sickle cell disease. It has also been identified in 5% to 20% of patients admitted to the intensive care unit with severe influenza or COVID-19. Despite antifungal treatment, up to half of some high-risk populations may die from the infection.
The urine assay, which was cleared by the FDA in late 2025 for use in adults with suspected IA, is intended to be used alongside clinical findings, imaging and other laboratory tests. Historically, IA has been diagnosed through a combination of chest imaging, blood tests, respiratory samples obtained during bronchoscopy and, in some cases, tissue biopsy. However, some of these approaches are invasive and still leave uncertainty. This assay directly detects Aspergillus antigens in urine and can provide a laboratory result within several hours.
As part of research to determine the assay’s value and reliability, the investigators analyzed its ability to detect Aspergillus galactofuranose-containing antigens, proteins signaling the body’s response to this infection. They used frozen urine samples from 290 study participants enrolled in studies in the United States and Belgium at various times between 2009 and 2022.
Among the 290 study participants, 50 had a confirmed case of IA. (There were 240 controls.) Among the 50 people who had IA, 46 cases (92%) were correctly identified through the urine test. Four had false negative test results. The test correctly identified 218 out of 249 (88%) samples as negative. The urine samples were tested at laboratories in Baltimore, Maryland, Pittsburgh, Pennsylvania, and Raleigh, North Carolina.
To further assess the test’s value, the investigators studied how the assay may help predict cases among people suspected to have IA who were receiving care at The Johns Hopkins Hospital for conditions like blood cancer or autoimmune diseases between January 2023 and February 2024.
Among 210 study participants in that part of the research and who provided samples, 168 were eligible for analysis. Among the 168 participants, 171 fresh urine samples were analyzed in “real time” at the hospital laboratory. A small portion were confirmed positive (7) or negative (39). The test correctly identified 6/7 (86%) positive and 35/39 (90%) negative cases.
Among the 210 people suspected to have invasive aspergillosis, about half lacked a confirmed diagnosis. Among those suspected to have IA but without confirmation, the test identified about 1 in 4 having a positive test result. The researchers say this shows the benefit of having this type of diagnostic tool available in a hospital setting.
“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,” says Nitipong Permpalung, M.D., M.P.H., director of mycology research and associate director for clinical trials at the Johns Hopkins Transplant Research Center. “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.”
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.
This ongoing research also supports goals the World Health Organization established in 2022 to better diagnose, treat and prevent IA by naming Aspergillus fumigatus to its list of critical-priority fungal pathogens.
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.
This study was funded by Pearl Diagnostics, Inc., and NIH grant R44AI157572.
Reference
Irina Baburina, Kieren A Marr, Yuri Vanbiervliet, Nitipong Permpalung, Chiung-Yu Huang, Robina Aerts, Patricia X Marques, Andrew F Shorr, M Hong Nguyen, Binghua Hao, John R Wingard, Johan Maertens, Sean X Zhang, Performance of the Urinary MycoMEIA Aspergillus Assay as an Aid to Diagnose Invasive Aspergillosis, Clinical Infectious Diseases, 2026;, ciag522, https://doi.org/10.1093/cid/ciag522.
Abstract
Background: Invasive aspergillosis (IA) is difficult to diagnose, contributing to poor clinical outcomes and unnecessary antifungal therapies. The MycoMEIA Aspergillus assay (MycoMEIA), which detects Aspergillus glycans in urine, does not require invasive specimens. We report data that supported regulatory approval.
Methods: A case-control study and prospective cohort study were conducted to evaluate MycoMEIA as an aid to diagnose IA. Performance was assessed using consensus criteria of "proven" or "probable" IA and controls. Additional analyses evaluated positivity in "possible" IA, agreement with serum galactomannan (GM EIA), cross-reactivity, and timing of positivity relative to clinical diagnosis. Reproducibility was assessed across three laboratories.
Results: In brief, 469 urine samples from 50 IA cases and 240 controls demonstrated MycoMEIA 92% (95% CI 80.8-97.8) sensitivity and 87.6% (95% CI 82.8-91.8) specificity. All cases with positive serum GM EIA were positive by MycoMEIA. Urine testing identified 19/24 (79.2%) IA cases diagnosed by bronchoalveolar lavage (BAL) but negative by serum GM EIA and provided lead-time positivity of 5 days (range -21 to +14) before clinical diagnosis. Prospective testing confirmed a specificity of 89.7% (95% CI 75.8-97.1) and identified IA in 28/102 (27.5%) people with suspected "possible" IA. Some cross-reactivity was observed with other Ascomycetes fungi. Results were reproducible across sites.
Conclusions: MycoMEIA shows strong performance as an aid to diagnose IA. Its high sensitivity and negative predictive value may help reduce unnecessary empirical antifungals. Further studies are needed to define its role in screening and broader patient populations.