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Genetic and Other Determinants for the Severity of Coccidioidomycosis: A Clinician's Perspective
John N Galgiani1,2,3,4, Amy P Hsu5, Daniel A Powell1,4
1Valley Fever Center for Excellence, College of Medicine-Tucson, University of Arizona, Tucson, AZ 85721, USA.
Abstract:
The endemic fungal infection, coccidioidomycosis, occurs after inhalation of one or very few Coccidioides spp. spores. Infections produce diverse clinical manifestations, ranging from insignificant to extremely destructive, even fatal. Approaches to understanding this range of consequences have traditionally categorized patients into a small number of groups (asymptomatic, uncomplicated self-limited, fibro-cavitary, and extra-thoracic disseminated) and then looked for immunologic differences among them. Recently, variants within genes of innate pathways have been found to account, in part, for infections that result in disseminated disease. This discovery raises the very attractive theory that, in patients without severe immunosuppression, much of the disease spectrum can be accounted for by various combinations of such deleterious variants in innate pathways. In this review, we summarize what is known about genetic determinants that are responsible for the severity of coccidioidal infections and how complex innate genetic differences among different people might account for the spectrum of disease observed clinically.
Insights
Genetic variations in innate immune pathways may explain the diverse severity of coccidioidomycosis infections. Understanding these genetic factors is key to predicting disease outcomes in patients without severe immunosuppression.
Area of Science:
- Mycology
- Immunology
- Genetics
Background:
- Coccidioidomycosis is an endemic fungal infection caused by inhaling Coccidioides spp. spores.
- Infections present a wide spectrum of clinical outcomes, from asymptomatic to fatal disseminated disease.
- Traditional approaches focused on broad patient categories and immunological differences.
Purpose of the Study:
- To review the genetic determinants influencing coccidioidomycosis severity.
- To explore the role of innate immune gene variants in the disease spectrum.
- To propose a theory linking genetic variations to clinical manifestations in non-immunosuppressed individuals.
Main Methods:
- Literature review of studies on genetic factors in coccidioidomycosis.
- Analysis of research on innate immune pathways and their variants.
- Synthesis of findings to explain disease spectrum variability.
Main Results:
- Recent discoveries link variants in innate immune genes to disseminated coccidioidomycosis.
- Deleterious variants in innate pathways are proposed to account for much of the observed disease spectrum.
- Genetic differences among individuals may underlie varying infection severity.
Conclusions:
- Genetic determinants, particularly variants in innate immune pathways, play a significant role in coccidioidomycosis severity.
- Complex genetic variations offer a compelling explanation for the diverse clinical manifestations of this fungal infection.
- Further research into these genetic factors can improve understanding and potentially predict disease outcomes.
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