UMDNJ develops rapid detection test for Exserhilum rostratum

Jan 10 2013

A rapid detection test for Exserhilum rostratum, the fungus primarily responsible for 39 deaths among patients injected last year with a contaminated steroid medication, has been developed by a research team led by David S. Perlin, PhD, Executive Director of the Public Health Research Institute (PHRI) at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School. Details of the test have been published online by the Journal of Clinical Microbiology.

To date, clinicians and public health officials have been limited in their ability to detect the fungus in clinical samples such as cerebrospinal fluid, because the fungus tends not to be free-floating in the samples. The newly developed test improves on existing detection methods by using molecular beacon technology in a real-time polymerase chain reaction (PCR) assay. Through this approach, investigators have been able to detect a wide range of genomic DNA from E. rostratum, even in samples where abundant human DNA was also present. Fungal DNA has been reliably detected in amounts as small as 100 fg (femtograms, which are quadrillionths of a gram). The assay also detected DNA sequences from several related species of fungi, while tests of lab samples containing other species of fungi produced negative results, indicating a high level of specificity for the assay.

Perlin says, "The assay is a highly sensitive and robust method for early detection of the fungus in patients who might be infected but do not yet show symptoms, and also to monitor the progress of ongoing medical treatment." For critically ill patients, rapid diagnosis is essential and this assay has the potential to detect the presence of infecting fungus in less than two hours. "It is estimated that some 13,534 people received injections that might have exposed them to this fungus during the recent outbreak," notes Perlin. "We don't know the exact timeline for development of disease, and so we are not sure whether these patients are still are at risk. Using an assay such as this to detect possible infection in those patients could ease their minds if results are negative, or lead them to receive therapy in time to prevent future illness if results are positive."

The assay also can detect the fungus in vials of medication such as the steroid preparation that was the source of infection in the more than 600 patients who were sickened by the tainted injections. With that ability, drug manufacturers, health officials and even clinical practitioners could potentially check medication samples for presence of the fungus, says Dr. Perlin. In addition, the assay can be a valuable tool for future research on fungal infections.

Dr. Perlin and Yanan Zhao, PhD, developed the assay at PHRI in collaboration with Thomas J. Walsh, MD, Professor of Medicine, Pediatrics, and Microbiology & Immunology at Weill Cornell Medical Center, and his colleague Ruta Petraitiene, MD, Senior Research Associate. Dr. Walsh is coordinating a multicenter collaborative consortium to advance understanding of the diagnosis, treatment, host pathogenesis, and treatment of Exserohilum meningitis. Led by Dr. Perlin, this study is the first publication from this consortium.

Earlier molecular assays produced by Dr. Perlin and colleagues detect a wide range of fungal infections including Candida and Aspergillus species and drug resistant variants. The investigators have published research on these assays, and several have been commercialized.