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Drug-Resistance Fears for Deadly Fungal Disease

Deadly human fungal infections caused by certain strains of Aspergillus fungi appear to be developing resistance to current drug treatments at an alarming rate according to findings reported by research teams from UMDNJ-New Jersey Medical School and the University of Manchester, United Kingdom.

The investigators have used a new ultra-sensitive test that employs technology developed at UMDNJ that not only can better diagnose Aspergillus infections, but also can spot signs of antifungal resistance to azoles - the class of drugs used to treat patients with aspergillosis.

“This innovative approach to drug resistance detection was made possible because of the application of molecular beacon technology, which was invented by scientists at New Jersey Medical School,” said study co-author David Perlin, Executive Director and Professor at New Jersey Medical School, whose laboratory designed and performed the advanced tests. Perlin is a world-renowned expert in fungal research.

Using the new test, which uses direct molecular detection rather than culturing the fungus in a Petri dish, the team found that 55% of aspergillosis patients had telltale signs known as 'markers' that indicated they had developed resistance to azoles. The findings compare to resistance rates of 28% carried out by the team just two years ago using traditional culturing methods. The analysis was conducted on phlegm from patients with allergic and chronic lung disease caused by Aspergillus.

Furthermore, the study - published in the prestigious journal Clinical Infectious Diseases - discovered azole-resistance markers in three-quarters of the small number of aspergillosis patients (eight) who had never been treated with an azole, suggesting widespread dissemination of resistance.

"Aspergillus significantly worsens asthma symptoms and causes life-threatening infections in those with long-term lung infections or damaged immune systems, such as chemotherapy and transplant patients or people with HIV," said study co-author David Denning, Professor of Medicine and Medical Mycology at The University of Manchester and Director of the National Aspergillosis Centre at the University Hospital of South Manchester NHS Foundation Trust. "This is an extraordinarily high rate of resistance, so the findings have major implications for the sustainability of azoles for human antifungal therapy." Dr. Denning notes that one possible source of the resistance may be the frequent use of azoles as agricultural pesticides. The azoles itraconazole (Johnson & Johnson), voriconazole (Pfizer) and posaconazole (Merck) have annual sales of more than $1 billion.

Professor Denning added, "Not only is molecular testing much more sensitive than conventional culture for diagnosis, but it enables testing for resistance, which until now has been impossible if cultures are negative. Given the rising frequency of resistance in Aspergillus in northern Europe, China and the United States, this study provides key data for doctors to shift antifungal therapy in the face of resistance."

Notes to media:

A copy of the paper, Denning DW, Park S, Lass-Florl C, Fraczek MG, Kirwan M, Gore R, Smith J, Bueid A, Bowyer P, Perlin DS. 'High frequency triazole resistance found in non-culturable Aspergillus fumigatus from lungs of patients with chronic fungal disease.' Clin Infect Dis 2011;52:1123-9, is available on request.

Molecular beacons are licensed by the University of Medicine and Dentistry of New Jersey (UMDNJ), with offices at 1 World’s Fair Drive, Suite 2100, Somerset, New Jersey 08873.

The primary molecular detection test is Myconostica’s MycAssay Aspergillus, commercialized through Myconostica, a spin-out company founded by Professor David Denning. Patents were licensed to Myconostica by UMDNJ.

About UMDNJ:
The University of Medicine and Dentistry of New Jersey (UMDNJ) is the nation's largest free-standing public health sciences university with more than 6,000 students on five campuses attending the state's three medical schools, its only dental school, a graduate school of biomedical sciences, a school of health related professions, a school of nursing and New Jersey’s only school of public health. UMDNJ operates University Hospital, a Level I Trauma Center in Newark, and University Behavioral HealthCare, which provides a continuum of healthcare services with multiple locations throughout the state.

Rob Forman | Newswise Science News
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