Dangers of desert dust: new diagnostic tool for valley fever

July 22, 2014

On July 5, 2011, a massive wall of dust blanketed Phoenix, creating an awesome spectacle – or stubborn nuisance, depending on your perspective. Dust storms are a common occurrence in the arid desert environments of the American Southwest.

But windborne dust can be a serious health risk, lofting spores of a sometimes-lethal fungus known as Coccidioides. The resulting ailment, known as coccidioidomycosis, or valley fever, has been perplexing researchers since it was first described in 1892. It is currently on an alarming ascent in the United States. ASU Biodesign reseracher Krupa Navalkar Download Full Image

Stephen Albert Johnston, Krupa Navalkar and their colleagues at Arizona State University’s Biodesign Institute have been investigating valley fever. Navalkar is the lead author of a new study describing a promising strategy known as immunosignaturing, which can provide clinicians with an accurate identification of valley fever, a potentially serious affliction that is often misdiagnosed.

“The incidence of this disease is seemingly low due to non-sensitive diagnostic assays,” Navalkar says. As Johnston further notes, “Immunosignatures could easily change those false assumptions if made available in the clinical setting.”

Navalkar is a researcher in Biodesign’s Center for Innovations in Medicine under the direction of Stephen Albert Johnston, who is also a co-author of the new study and a professor in ASU's School of Life Sciences.

The group’s findings appear in the current issue of the journal ASM Clinical and Vaccine Immunology.

Valley fever is a fungal respiratory infection. It can be acquired when microscopic spores of the soil-dwelling fungus are inhaled. Two forms of the fungus exist, Coccidioides immitis and Coccidioides posadasii. They are endemic to regions of Arizona, New Mexico, California, Nevada, Utah, Texas and northern Mexico.

<>During extended periods of dryness, the fungal spores remain dormant. With rainfall, the spores, or arthroconidia, develop elongated filaments, which break off and can be lofted into the air by soil disruption due to farming, construction, earthquakes or dust storms.

Most individuals inhaling Coccidioides particles are assumed to be able to naturally resolve the infection, developing immunity to future spore infections. Often, such non-symptomatic individuals are unaware they have been exposed. Others are not so fortunate, however.

In around 40 percent of cases, valley fever causes flu-like symptoms, including cough, headache, muscle and joint pain, and rash. For reasons still unclear, those of Filipino, African American and Native American descent are more vulnerable to the severe disseminated form of the infection. The disease is also more severe in people with weakened immune systems, as well as pregnant women.

Infection with Coccidioides can progress through three stages of increasing severity. Valley fever is the acute form of the disease, which, if left untreated, can develop into a second-stage chronic infection, lasting months or years. This form affects roughly 40 percent of those exposed. The third stage of the disease, known as disseminated Coccidioides, occurs when the infection spreads throughout the body, affecting skin, bones and nervous system, and causing skin ulcers, swollen joints, severe pain, abscesses, bone lesions, heart inflammation, urinary tract infection and (potentially lethal) meningitis. Disseminated Coccidioides affects 5-10 percent of those with chronic infection.

The rapid rise in valley fever cases in the arid southwest has become a serious health concern, as human habitation has pushed further into desert areas where the soil spores are widespread. Currently, valley fever affects an estimated 150,000 people a year, with most cases occurring in Arizona, California, Nevada, New Mexico and Utah. The disease has no cure at present and is notoriously tricky to diagnose; one reason is that valley fever is readily confused with other community-acquired pneumonias.

Currently, diagnosis is carried out through a technique known as immunodiffusion, which tests the blood for antibodies against Coccidioidal antigens. As the authors note, such tests are less than satisfactory, with a false negative rate as high as 50-70 percent. Around 5 percent of symptomatic patients display no measurable antibody levels to valley fever by immunodiffusion.

The current study describes an alternate method used to address the poor accuracy of immunodiffusion, applying an innovative new technique known as "immunosignaturing." The technique can produce a detailed profile of system-wide immune activity from a small droplet of blood – typically less than a microliter.

To produce its detailed immune portrait, or immunosignature, the technique uses a microarray platform. This consists of a glass slide imprinted with 10,000 peptides. Each peptide consists of a string of 20 amino acids, randomly arranged. The power of the technology resides in the fact that the randomly generated peptides are not based on natural antigens to Coccidioides or, indeed, any disease. They are “unbiased” to the nature of particular disease antibodies, and can therefore act as a sort of universal diagnostic.

When a droplet of antibody-containing blood is smeared across the microarray, the random peptides behave like naturally occurring antigens, binding with blood antibodies in a specific pattern. Global analysis of the resulting immunosignature is used to establish disease-specific blueprints of immune activity.

The method potentially offers much higher resolution and sensitivity to disease, compared with diagnostic tests measuring a single antibody-antigen binding event or a small ensemble of molecules.

In the first round of experiments in the current study, the group used immunosignatures to determine if valley fever-infected individuals could be accurately distinguished from three other patient groups afflicted with bacterial or fungal infections.

Once an immunosignature for valley fever was established using the 10K-peptide microarray, a smaller diagnostic array was composed from relevant diagnostic peptides. This smaller, 96-peptide array was then tested for accuracy against the current immunodiffusion diagnostic standard.

The 10K-peptide array successfully distinguished valley fever from three other infections, with 98 percent accuracy. Impressively, the method was also able to classify false negative valley fever patients in a blinded test with 100 percent accuracy, easily outpacing existing immunodiffusion methods, which could only identify 28 percent of false negatives.

The smaller, 96-peptide diagnostic array showed less specificity than the 10K-peptide array in terms of identifying false negatives. The authors propose that the larger 10K-peptide array be used in initial screenings, followed by subarrays with reduced complements of carefully selected peptides, used for clinical diagnosis.

Immunosignaturing holds the promise for rapid, cost-effective and highly accurate diagnosis of valley fever. The versatile platform has the potential to separate valley fever patients from those afflicted with other bacterial or fungal infections. Making use of the same microarray, researchers can also identify false negatives with 100 percent accuracy.

Professors Phillip Stafford and Neal Woodburry of the Biodesign Institute also contributed to this study along with John Galgiani from the Valley Fever Center for Excellence.

Richard Harth

Science writer, Biodesign Institute at ASU


ASU Wrigley Institute board member to chair economic council

July 22, 2014

William McDonough, member of the board of directors of the Julie Ann Wrigley Global Institute of Sustainability at Arizona State University and world renowned architect, educator and author, has been appointed chair of the World Economic Forum’s Meta-Council on the Circular Economy.

The meta-council represents the forum’s multi-sector initiative to accelerate business-driven innovation to scale the circular economy – an industrial economy that is restorative in principle by using renewable energy, minimizing the use of toxic chemicals, and eliminating waste through thoughtful design. portrait of ASU Wrigley Institue board member William McDonough Download Full Image

A sustainable growth pioneer, McDonough is known internationally for his revolutionary Cradle to Cradle design framework developed with Michael Braungart, an approach that relies on restorative and sustainable design of products and system. The framework forms the underpinning philosophy of the circular economy and the new council.

“Bill’s expertise clearly lends itself to an appointment of this stature,” said Gary Dirks, director of the ASU Wrigley Institute. “It is always exciting to see members of the board of directors for Sustainability at ASU contributing to sustainability innovation at the global level.”

“Bill is a world-class innovator in his many roles as designer of the built environment, creator of new business models and communicator of what ‘sustainability’ must become in the 21st century,” said Rob Melnick, executive dean and chief operating officer of the ASU Wrigley Institute. “I can think of no one more able to accelerate and scale the circular economy from the World Economic Forum platform than Bill McDonough.”

As chair, McDonough will oversee the forum’s effort to establish proof of real-world application of the economic, social and environmental benefits of a circular economy through targeted programs that aim to elevate the discussion and actions to a global audience. Under the guidance of McDonough’s vision and strategic insights, the Meta-Council on the Circular Economy will convene top-tier international companies, stakeholders, policymakers and other business influencers to identify systemic changes needed to facilitate the shift to a sustainable global economy.

“We are delighted that Bill has agreed to chair this council,” says Dominic Waughray, head of environmental initiatives at the World Economic Forum. “He brings not only invaluable experience and knowledge in the circular economy space, but also the creative intelligence of a designer – a role which is as central to designing objects and buildings as it is to designing collaborations and encouraging systems thinking.”

McDonough calls the appointment a deep and abiding privilege. “I am honored to take on this very important role –as a designer,” he said. “Design is the first signal of human intention. A beautiful way to wage peace is by design, through commerce. The forum, which engages major influencers in the global economy, is a wonderful platform for this dialogue.”

Former special adviser on sustainable development to President Bill Clinton and author of several seminal books that focus on sustainable design of building, products, texts and enterprises, McDonough served as dean of the School of Architecture at the University of Virginia from 1994-1999 and is currently a consulting professor of civil and environmental engineering at Stanford University, where his archives will be housed.

Media projects manager, Office of Knowledge Enterprise Development