Coccidioidomycosis: Epidemiology, Fungal Pathogenesis, and Therapeutic Development

Abstract

Purpose of Review Coccidioidomycosis can result from the inhalation of infectious spores of Coccidioides species (spp.) immitis or posadasii. Clinical manifestations range from mild flu-like disease to severe disseminated infection that can require life-long therapy. Burden of this mycosis is high in the southwest region of the USA where it is well characterized, and in many areas of Mexico and Latin America where it is inadequately characterized. Here, we provide historical data and current knowledge on Coccidioides spp. pathogenesis as well as recent progress in therapeutic and vaccine development against coccidioidomycosis. Recent Findings The virulence mechanisms of Coccidioides spp. are largely unknown; however, production and regulation of a spherule glycoprotein, ammonium production, and melanization have all been proposed as integral factors in Coccidioides spp.' pathogenesis. Therapeutic options are limited and not 100% effective, but individualized treatment with triazoles or amphotericin B over the course of pulmonary or disseminated infection can be effective in resolution of coccidioidomycosis. Human immunization has not been achieved but efforts are ongoing. Summary Advances in therapeutic and vaccine development are imperative for the prevention and treatment of coccidioidomycosis, especially for those individuals at risk either living or traveling to or from endemic areas.

Important Mycosis of Wildlife: Emphasis on Etiology, Epidemiology, Diagnosis, and Pathology—A Review: PART 2

“…Infection by Coccidioides occurs following the inhalation of arthroconidia from both Coccidioides species , which are endemic to arid and semi-arid regions of North America [ 46 , 47 ]. Coccidioides species infect reptiles, birds, humans, and other mammals, including wild mammals [ 42 , 44 ].…”

“…It is speculated that ammonia release is involved in the virulence of Coccidioides [ 52 ]. This fungus is sensitive to environmental pH changes [ 47 , 52 ]. For example, when either the saprophytic or parasitic phase is in acidic cultures, the fungus releases NH 3 /NH 4 + and urease enzyme, which catalyzes the hydrolysis of urea into two ammonia molecules that neutralize the acid [ 47 , 52 , 53 ].…”

“…This fungus is sensitive to environmental pH changes [ 47 , 52 ]. For example, when either the saprophytic or parasitic phase is in acidic cultures, the fungus releases NH 3 /NH 4 + and urease enzyme, which catalyzes the hydrolysis of urea into two ammonia molecules that neutralize the acid [ 47 , 52 , 53 ]. Ureases are well-characterized virulence factors in other microorganisms [ 47 ].…”

Modern aspects of coccidioidomycosis laboratory diagnosis

“…Это связано с минимальной инфицирующей дозой, необхо-димой для заражения макроорганизма, которая составляет от 10 до 50 артроконидий [9,10]. После инкубационного периода, составляющего от 7 до 21 суток, грибы рода Coccidioides вызывают широкий спектр симптомов, начиная от субклинических респираторных проявлений до тяжелых диссеминированных форм [11]. Прогрессирование заболевания чаще всего регистрируют у лиц с ослабленным иммунитетом.…”

Coccidioidomycosis in 26 horses in California, USA: case series and review of the literature

“…The endospores eventually develop into other endospore-filled spherules completing the life cycle and, frequently, disseminating to other organs. 8,11 Direct inoculation of arthroconidia through the skin can also occur, but is uncommon, 1,10,15 and this inoculation typically does not result in systemic disease.…”