Diseases / Research

Opportunistic Infections - Fungal

Aspergillus

Histology special stains containing silver can be used to identify aspergillus organisms (black) in lung tissue (green).

Photo by Fred Hutch Experimental Histopathology

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Fred Hutch scientists are reducing the risk of mortality due to opportunistic fungal infections for patients with compromised immune systems by improving prevention, treatment and clinical care options.

Researchers have developed a more effective method for detecting deadly mold infections in the lungs of bone marrow transplant patients.  Our researchers have also identified risk factors, including genetic risk, for aspergillus patients undergoing transplant.  

Fast Facts

  • There are several types of fungi, including yeasts and molds, that are pathogenic and can cause disease in humans. Although these fungi are common in our daily lives they pose little risk to healthy populations. However, they can lead to serious or even deadly complications in patients with compromised immune systems.

  • Fungal infections can be contracted by inhalation of airborne fungal spores or by breaches in the integrity of the skin. Infections give rise to superficial (surface), locally invasive (occurring in a single, contained location) or disseminated infections (entering the body at a single point and spreading from there). Respiratory infections are the most common in cancer patients, and symptoms can include fever, cough, pain, bloody sputum and shortness of breath.

  • There are a variety of antifungal drugs for immunosuppressed patients to prevent fungal infections or to treat them once they occur. Surgery is also an option in some instances. However, treatment options for some fungal infections are limited.

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Prevention & Causes

New aspergillosis risk factors in transplant patients – Drs. Michael Boeckh, Paul Martin and Lawrence Corey identified risk factors of Aspergillus infection before and after hematopoietic stem cell transplantation (including bone marrow transplantation). Aspergillus is a common mold that infects the lungs and can spread quickly in transplant patients. The new risk factors include age at transplantation, underlying disease, type of transplant and more. Accurate risk factors can help health care providers identify high-risk patients and even prevent infections from occurring.

Fluconazole as a prevention strategy – Candidiasis (yeast infection) can be prevented in bone marrow transplant recipients by administering the anti-fungal medication as a prophylaxis (prevention) for 75 days after transplantation. The prevention regimen is also associated with decreased graft versus host disease in the gastrointestinal tract, according to two randomized trials conducted by Drs. Boeckh, Corey and collaborators.

Genetic risk factors for Aspergillus infection – Different inherited changes in a patient’s genetic code may predict whether that patient is more likely to develop Aspergillus infections following hematopoietic cell transplantation, according to research by Dr. Boeckh and collaborators. Using techniques to screen for specific genetic differences in the immune system, scientists demonstrated that a specific subset of people with unique immune genes were more likely to develop aspergillosis. This data has led to further research and in the future may help identify ways to prevent these infections in high-risk patients.

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Detection & Diagnosis

Earlier detection of deadly mold infections - Researchers have developed a more effective method for detecting deadly mold infections in the lungs of bone marrow transplant patients. A study by Drs. David Fredricks and Wendy Leisenring and collaborators found that by analyzing samples from a common test of lung fluid (BAL) for a key enzyme and the DNA of Aspergillus (mold), the mold infection can be detected earlier – particularly among high-risk patients – and allow for an optimal treatment regimen.

Detecting Aspergillus DNA - By testing for Aspergillus DNA using a quantitative PCR (qPCR) analysis, Aspergillus infection was detected in 76.9 percent of subjects with proven or probable aspergillosis (disease), according to a study by Dr. Fredricks and colleagues. The study developed both extraction and amplification controls as methods for assessing quality and optimizing the interpretation qPCR results.

A better way to diagnose invasive aspergillosis – Diagnosis of invasive aspergillosis is enhanced by analyzing serum and airway fluid samples for traces of fungal galactomannan, a polysaccharide antigen released during fungal growth. The discovery was based on research by Drs. Tobias Hohl, Michael Boeckh and Steve Pergam.

Reduced mortality from fungal infections – A study examining mortality rates among hematopoietic stem cell transplant patients over a 10-year period found that death due to invasive mold infections fell by 51 percent among patients receiving transplants. The study compared patients receiving transplants between the period of 2003-2007 as compared to 1993-1997. The drop was attributed to improved antifungal drugs, prevention regimens and diagnostic tests.

The landmark study, published in 2010, was authored by a dozen Fred Hutch researchers who applied their individual expertise to examining improved survival rates among transplant recipients. Learn more >

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Treatment & Prognosis

Predicting mortality risk to inform treatment options – Levels of the serum galactomannan, a polysaccharide antigen released during fungal growth, at the time of diagnosis correlates with patient mortality, according to a study conducted by Drs. Tobias Hohl, Michael Boeckh and Steve Pergam. Understanding this relationship assists researchers in formulating treatment decisions and strategies.

Immunobiology of fungal infections – Dr. Hohl has developed an animal model of respiratory fungal infection with Aspergillus fumigatus that permits researchers to monitor fungal uptake and killing by host infection-fighting cells using fluorescence as a read-out. This novel and innovative approach, published in 2012, is providing researchers with the opportunity to study host factors and molecules that shape antifungal immunity in the lung.

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