Valley fever is an invasive fungal infection caused when immunologically naïve individuals are exposed to arthroconidia of Coccidioides spp. from an environmental source. Coccidioides are thermally dimorphic human fungal pathogens; the genus is comprised of two species: C. immitis and C. posadasii. Coccidioides spp. have two life cycles: the saprobic life cycle, where the cells grow as mycelia and develop arthroconidia in the environment, and the parasitic life cycle as a spherule within the host [1]. The dimorphic transition from arthroconidia to spherule within the host is regulated by temperature, presence of host cells, and other host-specific factors 2•, 3••.

Coccidioides spp. are found in semiarid to arid soils across the southwestern United States, Mexico, and parts of Central and South America [4]. In the United States, C. posadasii is predominantly found in Arizona and Texas, whereas C. immitis inhabits regions of California through Washington state [5]. It is estimated that the endemic range will expand due to increasing drought and temperature across the western US [6]. According to the United States Centers for Disease Control, Valley fever cases have increased in the last 20 years, especially in Arizona and California [7]. Approximately 20,000 cases are reported annually, but Valley fever is not reportable in all states and often only severe infections are registered; the estimated actual annual case load is 206,000–360,000 6, 8.

Coccidioides spp. are primary pathogens and can infect immunocompetent patients; the disease is typically more severe in immunocompromised individuals [9]. About 60% of cases are asymptomatic or subclinical, 30% of individuals exhibit symptoms of community-acquired pneumonia, and 10% are complicated cases of Valley fever, with potential for dissemination to surrounding tissues 10•, 11. Within 1–3 weeks after exposure, patients who develop pulmonary symptoms may experience flu-like symptoms, including cough, chest pain, night sweats, fatigue, and weight loss [10]. Variations in disease progression coupled with delayed diagnosis have contributed to challenges in understanding early innate immune responses to infection. Genetic variation within strains, virulence factors, and host susceptibility genes could all play a critical role in disease manifestation.