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Research Collaboration To Detect Life-Threatening Fungus

Hear the word fungus, and mushrooms and mold might leap to mind. But the University of Florida is about to house the nation's first research repository for one species that has nothing to do with pizza toppings or marbling blue cheese: Aspergillus, which increasingly poses a major health threat to cancer patients and transplant recipients.

The National Institutes of Health has awarded $9 million over the next seven years to the effort. UF researchers are collaborating with colleagues at Duke University, Brigham and Women's Hospital in Boston and the Dana-Farber Cancer Institute, who will funnel patients' respiratory, urine and blood samples to UF. The repository will support research aimed at learning more about the fungus and efforts to develop more accurate tests to detect it in patients.

"Aspergillus is everywhere, particularly in the air we breathe; all of us breathe it in all the time," said principal investigator John Wingard, M.D., director of UF's blood and marrow transplant program and deputy director of the UF Shands Cancer Center. "On a windy day, especially in a dusty environment or every time some dirt gets moved around, lots of these organisms get aerosolized."

The number of people contracting Aspergillus infections jumped enormously in the 1990s, Wingard said, and those with weakened immune systems are particularly susceptible. Aspergillosis is the leading cause of death from infection in bone marrow transplant and leukemia patients, as well as among those who receive certain other solid organ transplants, he said. About 15 percent of all bone marrow transplant patients, for example, will develop an infection from Aspergillus; of those, about two-thirds die.

"We haven't had good treatments, we haven't had good prevention methods and, most importantly, we haven't had good diagnostic methods to identify which patients have these infections," Wingard said. "Since we often don't recognize that patients have aspergillosis until very late in the course of the infection, by the time we try to treat the infection it is often so advanced we have very poor prospects of bringing it under control."

A number of hospitals undergoing renovations have experienced outbreaks, in many cases after the organism contaminated ventilation systems or fireproofing materials. Despite hospitals' infection control measures aimed at minimizing risks, including special air filtration systems designed to filter out Aspergillus and other infectious agents, facilities can still have problems and sometimes have even had to temporarily close their patient-care units.

"You and I have a good healthy defense, so while we may be colonized by the organisms, we rarely get serious infections," Wingard said. "But if we become immunocompromised, those organisms can be deposited on the mucosal surface of nasal passages, the sinuses and the bronchi, and they can start invading and can cause very serious, deadly infections."

Complicating the picture is that aspergillosis is frequently mistaken for bacterial pneumonia, and tests for the infection often are initially negative.

"Historically, our only means of diagnosing these infections has been by growing the organism from patient's specimens in the laboratory and then having it identified by an experienced mycologist," said Barbara D. Alexander, M.D., the project's co-principal investigator and director of transplant infectious diseases services and the clinical mycology laboratory at Duke University Medical Center. "These conventional methods for diagnosing fungal disease are slow and lack sensitivity. Furthermore, many times the patients are too sick to tolerate the invasive procedures, such as lung biopsy, in order to obtain the samples for laboratory testing."

Wingard said two-thirds of the time tests are negative even though patients have the infection.

"That's the biggest challenge - we may suspect patients have the infection but we can't really know with certainty from currently available tests whether they truly are infected or not," he said. "We end up making clinical decisions about using drugs that may be toxic or using the wrong drugs in patients when we are not sure whether they have this deadly infection."

Officials are hoping to collect samples from about 200 patients a year for the next seven years to better characterize the fungus and improve the diagnostic accuracy and speed of tests used to detect aspergillosis. The repository will include samples from patients with confirmed infections that will be compared with samples from patients whose diagnosis is less clear and with samples from patients who are at high-risk but not infected.

Researchers also will work with Emory University, Indianapolis-based MiraVista Diagnostics, and the University of Manchester in England to evaluate existing tests and develop new, more accurate and less invasive ones.

While more potent treatment regimens are improving prospects for patients, so-called emerging pathogens -- viruses, bacteria and fungi -- are a growing medical problem, Wingard said.

"With advancing medical technology and more powerful antibiotics, patients are living longer," he said. "We have a growing population of patients who are susceptible to very serious infections by viruses, bacteria and fungi that in years past were not medical problems."

University of Florida. August 2007.

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