On July 5, 2011, an enormous wall of dust,? (“haboob,” in Arabic), blanketed Phoenix, Arizona, creating an incredible spectacle, (or stubborn nuisance, depending on your point of view). Dust storms are a common occurrence in the arid desert environments of the American Southwest.
But windborne dust could be a serious health risk, lofting spores of a sometimes-lethal fungus known as Coccidioides. The resulting ailment, referred to as coccidioidomycosis or Valley fever, has been perplexing researchers since it was initially described in 1892. These days it is with an alarming ascent in the usa.
Dr. Stephen Albert Johnston, Krupa Navalkar as well as their colleagues at Arizona State University’s Biodesign Institute happen to be investigating Valley fever. Navalkar may be the lead author of a new study describing an encouraging strategy known as immunosignaturing, which could provide clinicians with an accurate identification of Valley fever, a costly affliction that’s often misdiagnosed.
“The incidence of the disease is seemingly low due to non-sensitive diagnostic assays,” Navalkar says. As Johnston further notes, “immunosignatures could easily change those false assumptions if provided in the clinical setting.”
Navalkar is a researcher in Biodesign’s Center for Innovations in Medicine, underneath the direction of Stephen Albert Johnston, who is additionally a co-author from the new study.
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 from the soil-dwelling fungus are inhaled. Two types of the fungus exist, Coccidioides immitis and Coccidioides posadasii. They are endemic to regions of Arizona, Boise state broncos, California, Nevada, Utah, Texas and northern Mexico.
During long 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 because of farming, construction, earthquakes or dust storms.
Most individuals inhaling Coccidioides particles are assumed so that you can naturally resolve the problem, developing immunity to future spore infections. Often such non-symptomatic individuals are unaware they’ve been exposed. Others are not too fortunate, however.
In around 40 % 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 tend to be more susceptible to the severe disseminated form of the infection. The condition is also more severe in individuals with weakened immune systems in addition to pregnant women.
Infection with Coccidioides can progress through three stages of growing severity. Valley fever may be the acute form of the disease, which, if not treated, can be cultivated right into a second-stage chronic infection, lasting months or years. This form affects roughly 40 % of these exposed. The third stage of the disease, known as disseminated Coccidioides, occurs when the infection spreads through the body, affecting skin, bones and nervous system and causing skin ulcers, swollen joints and severe pain, abscesses, bone lesions, heart inflammation, uti and (potentially lethal) meningitis. Disseminated Coccidioides affects 5-10 percent of those with chronic infection.
The rapid rise in Valley fever cases within 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 annually, 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 wrongly identified as other community-acquired pneumonias.
Currently, diagnosis is completed via a technique known as immunodiffusion, which tests the blood for antibodies against Coccidioidal antigens. Because the authors note, such exams are under satisfactory, having 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 another method used to address poor people accuracy of immunodiffusion, applying an innovative new technique referred to as ‘Immunosignaturing’. The strategy can produce a detailed profile of system-wide immune activity from the small droplet of blood-typically, less than a microliter.
To produce its detailed immune portrait or immunosignature, the strategy utilizes a microarray platform. For example a glass slide imprinted with 10,000 peptides. Each peptide consists of a string of 20 amino acids, randomly arranged. The power of we’ve got the technology resides in the fact that the randomly generated peptides aren’t according to natural antigens to Coccidioides or indeed, any disease. They’re “unbiased”? towards the nature of particular disease antibodies and may therefore behave as a sort of universal diagnostic.
When a droplet of antibody-containing blood is smeared across the microarray, the random peptides become naturally occurring antigens, binding with blood antibodies in a specific pattern. Global research into the resulting immunosignature is used to establish disease-specific blueprints of immune activity.
The method potentially offers higher resolution and sensitivity to disease, in contrast to diagnostic tests measuring a single antibody-antigen binding event or a small ensemble of molecules.
In the very first round of experiments in the present study, the group used immunosignatures to find out if Valley fever infected individuals could be accurately distinguished from three other patient groups afflicted with fungal or bacterial infections.
Once an immunosignature for Valley fever was established while using 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 technique also could classify false negative Valley fever patients inside a blinded test, with 100 % accuracy, easily outpacing existing immunodiffusion methods, which could only identify 28 percent of false negatives.
The smaller, 96 peptide diagnostic array showed less specificity compared to 10K peptide array when it comes to 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 can separate Valley fever patients from those suffering from other bacterial or fungal infections. Utilizing 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 Dr. John Galgiani from the Valley Fever Center for Excellence (VFCE).
