The Known and Unknown "Knowns" of Human Susceptibility to Coccidioidomycosis

Area of Science:

• Medical Mycology
• Infectious Diseases
• Immunology

Background:

• Coccidioidomycosis results from inhaling Coccidioides fungal spores.
• While often self-limiting, it's a significant cause of community-acquired pneumonia and can lead to chronic, disseminated disease.
• Understanding susceptibility factors is crucial for managing this endemic fungal infection.

Purpose of the Study:

• To review and critically evaluate literature on human susceptibility to coccidioidomycosis.
• To examine factors influencing chronic pulmonary and extrapulmonary dissemination.
• To assess the evidence supporting commonly cited risk factors for severe coccidioidomycosis.

Main Methods:

• Literature review of historical and contemporary studies on coccidioidomycosis.
• Analysis of observational, cohort, and epidemiological data.
• Examination of evidence for genetic, immune, and demographic risk factors.

Main Results:

• Immune suppression (especially by TNF inhibitors), genetic variants, sex, and pregnancy are validated factors influencing susceptibility.
• Some commonly cited risk factors, like ABO blood group or Filipino ancestry, lack robust supporting evidence.
• Historical hypotheses regarding susceptibility have been confirmed by recent cohort studies.

Conclusions:

• Human susceptibility to coccidioidomycosis is multifactorial, with validated roles for immune status and genetics.
• Critical evaluation of the literature is needed to distinguish evidence-based risk factors from those lacking scientific support.
• Further research is warranted to elucidate the complex interplay of factors determining disease severity and dissemination.