Study to investigate immuno-genetics of Valley Fever

Why are some people barely affected by Valley fever while others are admitted to intensive care?

The search for answers to those questions is on, thanks to a $2.27 million grant awarded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health to the University of Arizona Valley Fever Center for Excellence.

The study will examine the immuno-genetic underpinnings of the respiratory infection caused by inhalation of fungal spores—known as Coccidioides—endemic to soils of the U.S. Southwest.

“The gist of it is that people get different kinds of severity for Valley fever. Some have no problem. Others die from it. We think it has to do with their immune response and differences in genetics behind those,” said study Principal Investigator John N. Galgiani, MD, director of the UA Valley Fever Center for Excellence and a professor of medicine in the Division of Infectious Diseases at the UA College of Medicine – Tucson.

Dr. Galgiani, with co-investigators Steve M. Holland, MD, and Yves A. Lussier, MD, will probe what makes some individuals more susceptible for the infection to spread from their lungs, causing what is called “disseminated coccidioidomycosis,” when the infection gets in the blood and moves from the lungs to skin, bones and joints, and/or to the spinal cord and brain.

Dr. Holland is NIAID’s director of the Division of Intramural Research and serves as chief of the immunopathogenesis section in its Laboratory of Clinical Infectious Diseases. He has been a co-author with Dr. Galgiani on a number of papers related to immuno-genetic studies on Valley fever.

Dr. Lussier, is director of the Center for Biomedical Informatics and Biostatistics and associate vice president for data science and chief knowledge officer at the UA Health Sciences, as well as associate director of informatics at the UA BIO5 Institute and associate director for cancer informatics and precision health at the UA Cancer Center. Also a UA professor of medicine and statistics, he is a “Big Data” expert able to decipher DNA sequencing to tease out answers others might not see.

About 60 percent of individuals who come in contact with the fungus Coccidioides that causes Valley fever—found in soils of the U.S. Southwest, parts of Mexico, and Central and South America—don’t have any symptoms, according to the U.S. Centers for Disease Control and Prevention. About 5 to 10 percent develop serious or long-term problems in their lungs. For about 1 percent, the infection spreads to other parts of the body. Of roughly 150,000 cases reported each year, Valley fever kills about 160 people.

Drs. Galgiani’s and Holland’s latest article, “Risk Factors for Disseminated Coccidioidomycosis, United States” in the February issue of the journal Emerging Infectious Diseases, notes that race/ethnicity, sex, pregnancy and immune status are critical factors to the potential severity of Valley fever infection.

In a literature review that included 370 cases of disseminated cocci over the period 1975-2014, they found an immunosuppressed person (due to age or health) was 30 to 50 percent more likely to suffer from spread of the infection. Dissemination to the central nervous system was reported in 37 percent of pregnant women infected, a third of whom died—three-quarters of those in the third trimester. At 59 percent of all such cases, whites were more likely to suffer nervous system attacks (Asians, 38 percent; blacks/Hispanics, 13 percent). Males made up 84 percent of multisite infection cases, with the number of blacks double that of any other race. Osteomyelitis, or infections reaching the bone, also was more common among minorities (blacks, 82 percent; Hispanics, 69 percent; Asians, 60 percent; whites, 29 percent).

In several patients, Drs. Galgiani and Lussier note, a gene mutation was identified by Dr. Holland that’s an indicator for susceptibility to the serious form of Valley fever. In a follow-up collaboration, Drs. Galgiani and Holland frequently identified possibly deleterious mutations in similarly affected patients. This could provide a clue as to what more subtle genetic differences might commonly be responsible for disseminated cocci.

“Taken together, these discoveries have raised the possibility that disseminated cocci is a consequence of defects or delays in early recognition and response following infection. If this hypothesis is correct, it opens up the very exciting possibility that a preventative vaccine might be effective against subsequent infection, even in some or most persons genetically susceptible to disseminated cocci,” Dr. Galgiani said.

This project permits investigators at the NIH and at the UA to work together, utilizing unique resources of each institution. Findings from these studies may provide new tests to determine which individuals are at risk of serious disease if they contract Valley fever, and also may help in the development of preventative vaccines.

Dr. Galgiani’s project, “Immuno-Genetic Basis for Human Disseminated Coccidioidomycosis” (supported by the NIAID under Award No. U01AI122275), runs through February 2021.