New insights into diagnosing and treating invasive fungal infections will help save lives

Thousands of patients suffering from invasive fungal infections in intensive-care units or after organ transplantation will benefit from the latest insights into diagnostic and therapeutic interventions, published today in the prestigious journal The Lancet Infectious Diseases.

Fungal infections invading the bloodstream, lungs or other organs can cause prolonged illness and in extreme cases can lead to permanent disability or even death.

A new review paper has outlined the gold standard for identifying at-risk patients who are critically ill, or in receipt of organ transplants, for preventing, diagnosing and treating invasive fungal infections, potentially saving countless lives across both the developed and developing world.

Senior author, Professor Tania Sorrell from the Westmead Institute for Medical Research and the Marie Bashir Institute for Infectious Diseases and Biosecurity, said that invasive fungal infections can have serious consequences for patients and their families.

“These new insights into diagnosing and treating invasive fungal infections are significant because early and correct treatment clearly leads to better outcomes for the patient.

“These infections are uncommon but potentially life-threatening. Blood infections such as candidaemia and lung infections such as aspergillosis have high mortality rates of up to 85% in critically ill and immune-compromised patients,” Professor Sorrell said.

Professor Sorrell added that invasive fungal infections, overall, are a major problem in both developed and developing nations, killing more than 1.5 million people annually. The cost to the global healthcare system runs into billions of dollars each year.

“This is an important problem in Australia, but an even more serious issue in developing countries where mortality is unacceptably high despite the best available therapies and care.

“The research that has informed the recommendations in this paper will play an important role in educating doctors in both developed and developing countries about these diseases and outlining available diagnostic and therapeutic options in different medical contexts.

“It will allow clinicians to tailor their approach to managing these infections in different countries or when working with specific at-risk populations.

“This is vital, because rapid and accurate diagnosis, together with the right treatment, will significantly increase the chances of recovery for a patient.

“A significant proportion of these infections are preventable. We are also working to improve capability to identify patients at high risk of contracting these infections.

The Westmead team is now expanding their research in prevention, new diagnostic strategies, and therapeutic approaches towards infectious diseases of significant public health importance

Researchers Find Fungus-Fighting Compound in Drug Discovery Center Library

Researchers with the Virginia Tech Center for Drug Discovery have identified a compound that blocks the growth of a fungus that causes deadly lung infections and allergic reactions in people with compromised immune systems.

The research team targeted the switch that allows the fungus Aspergillus fumigatus to survive in iron-deficient conditions like the human body. Specifically, they targeted an enzyme known as SidA, which is essential for the synthesis of molecules called siderophores that are made during infection to steal iron from human proteins.

Furthermore, by performing high-throughput screening in the center’s Drug Discovery Screening Laboratory, they found a compound called Celastrol that blocks the growth of iron-producing organelles in the fungus.

The results were published in the journal ACS Chemical Biology.

“This project shows what an asset the screening lab is to the community,” said Pablo Sobrado, a professor of biochemistry in the College of Agriculture and Life Sciences and director of the screening laboratory. “Without the robots and chemical libraries available at the screening lab, this work would not have been possible. We are very fortunate at Virginia Tech to have this facility.”

Aspergillus fumigatus is common and is typically found in soil and decaying organic matter. Most people are exposed to it daily with little consequence, but it can cause lung damage in people with compromised immune systems, such as organ transplant recipients and people with AIDS or leukemia. The mortality rate of this population, when exposed to the fungus, is more than 50 percent, according to the authors.

“Growing antibiotic resistance is demanding the development of target-directed therapies,” said Julia S. Martin del Campo, a postdoctoral research scientist in Sobrado’s lab. “This approach requires the discovery of enzyme inhibitors that block essential pathogen pathways. The discovery of Celastrol as a SidA inhibitor represents the first building block in the development of drugs against A. fumigatus and related pathogens.”