Coccidioidomycosis (CM) is an endemic disease in the western United States, northern Mexico, and Central and South America. The severity of coccidioidal infection is highly variable, with potential factors including comorbidities and the patient’s innate and adaptive immune response. Based on data from a predominantly healthy and mainly Caucasian male survey conducted nearly a century ago, approximately 60% of infections are asymptomatic, with an estimated 40% of people experiencing some respiratory symptoms; with 10% of those diagnosed with CM. Disseminated disease occurs in approximately 1% of cases and can involve the meninges and, potentially, any place in the body. It is not yet fully understood why some people experience severe disease while many people do not; it is understood that the immune response has a major role. Immunomodulators, including dupilumab and interferon-gamma (IFN-γ), have shown promise in treating patients with disseminated infection. This article summarizes the latest genetic and immunologic evidence demonstrating immune dysfunction. Immunomodulators and potential therapeutic strategies based on the above are reviewed.

As Valley fever (coccidioidomycosis) vaccine candidates progress towards human trials, a challenge to their eventual introduction is understanding vaccine demand and addressing vaccine hesitancy. We assessed intent to accept a Valley fever vaccine for humans and dogs in two populations living in highly endemic regions: employees at Kern Medical (KM) in Bakersfield, California (N = 103) and members of the public in West Texas (N = 230). We compared the weighted proportions of each population willing to vaccinate themselves and their dogs by demographic and coccidioidomycosis risk factors and assessed the importance of vaccine-related factors on vaccine uptake in each population. We found that 42% (95% confidence interval (CI): 34–49%) of West Texas residents and 76% (95% CI: 63–85%) of KM employees were willing to accept a coccidioidal vaccine, while 49% (95% CI: 41–58%) of West Texas residents and 74% (95% CI: 58–86%) of KM employees were willing to vaccinate their dogs. Among West Texas residents, vaccination willingness was significantly higher among those with prior awareness of Valley fever (adjusted odds ratio (aOR): 3.83, 95% CI: 1.73, 8.49). Across both study populations, absence of side effects was the most important condition that would increase vaccination willingness. Our results indicate substantial interest in a Valley fever vaccine while suggesting that increased Valley fever awareness and minimal vaccine side effects may be important for increased uptake.