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Emergomyces africanus is a recently identified thermally-dimorphic fungal pathogen that causes disseminated infection in people living with advanced HIV disease. Known as emergomycosis, this disseminated disease is associated with very high case fatality rates. Over the last decade, improved diagnostics and fungal identification in South Africa resulted in a dramatic increase in the number of reported cases. Although the true burden of disease is still unknown, emergomycosis is among the most frequently diagnosed dimorphic fungal infections in Southern Africa; and additional species in the genus have been identified on four continents. Little is known about the pathogenesis and the host's immune response to this emerging pathogen. Therefore, we established a murine model of pulmonary infection using a clinical isolate, E. africanus (CBS 136260). Both conidia and yeast forms caused pulmonary and disseminated infection in mice with organisms isolated in culture from lung, spleen, liver, and kidney. Wild-type C57BL/6 mice demonstrated a drop in body weight at two weeks post-infection, corresponding to a peak in fungal burden in the lung, spleen, liver, and kidney. An increase in pro-inflammatory cytokine production was detected in homogenized lung supernatants including IFN-γ, IL-1β, IL-6, IL12-p40 and IL-17 at three- and four-weeks post-infection. No significant differences in TNF, IL-12p70 and IL-10 were observed in wild-type mice between one and four-weeks post-infection. Rag-1-deficient mice, lacking mature T-and B-cells, had an increased fungal burden associated with reduced IFN-γ production. Together our data support a protective T-helper type-1 immune response to E. africanus infection. This may provide a possible explanation for the susceptibility of only a subset of people living with advanced HIV disease despite hypothesized widespread environmental exposure. In summary, we have established a novel murine model of E. africanus disease providing critical insights into the host immune components required for eliminating the infection. Author summary: Emergomyces africanus is a thermally-dimorphic fungus that was recently described as the cause of disseminated infections in persons living with advanced HIV disease in South Africa, where emergomycosis is among the most frequently diagnosed dimorphic fungal diseases. Four additional Emergomyces species have been described causing serious infections around the world, and the infection has a high case fatality rate. Despite the seriousness of this infection, the pathophysiology, immunology, diagnosis, and optimal management of emergomycosis remain largely unknown, hampered by the absence of an animal model. Here, we established a mouse model of pulmonary and disseminated emergomycosis using a clinical isolate of E. africanus with the aim of investigating the host immune response. We found that infection spread from the lungs to other organs within two weeks. We describe the effector immune responses in immune-competent mice aiding in controlled infection. We also highlight the immune-modulating components lacking in immunocompromised mice that promote susceptibilty to infection. Our study provides new insights into the components of the host immune response required for controlling Emergomyces spp. infection. [ABSTRACT FROM AUTHOR]

Herein, we review the history of these fungi, clinical features and pathogenesis of disease, what is known of their biology, and future research directions. As with other systemic dimorphic fungi, infection is presumed to occur from inhalation of conidia, followed by a temperature-dependent transformation to a yeast-like phase that is capable of causing disease and of extrapulmonary dissemination (Fig 2). Limited pulmonary disease has rarely been described, observed in the sole reported case of disease caused by I Es i . 17 Schwartz IS, Sanche S, Wiederhold NP, Patterson TF, Sigler L. Emergomyces canadensis, a dimorphic fungus causing fatal systemic human disease in North America. [Extracted from the article]

The article presents report on worsening of Emergomyces africanus infection in a HIV-infected 42 year old male on itraconazole and antiretroviral therapy. He was initially admitted for continously enlarging lesions on his nose and has a history of anorexia, weight loss, nonproductive cough, and nasal congestion.

Emergomyces africanus is a thermally dimorphic fungus that causes a systemic mycosis in immunocompromised persons in South Africa. Infection is presumed to follow inhalation of airborne propagules. We developed a quantitative PCR protocol able to detect as few as 5 Es. africanus propagules per day. Samples were collected in Cape Town, South Africa over 50 weeks by a Burkard spore trap with an alternate orifice. We detected Es. africanus in air samples from 34 days (10%) distributed over 11 weeks. These results suggest environmental exposure to airborne Es. africanus propagules occurs more commonly in endemic areas than previously appreciated. [ABSTRACT FROM AUTHOR]

The article discusses the emergence of a cluster of novel Emmonsia-like fungi as causes of systemic human mycoses worldwide. Topics covered include the difference of these novel fungi from classical Emmonsia species, the rare and unusual pulmonary disease called adiaspiromycosis, and cases of blastomycosis and histoplasmosis. Also discussed are the key emergent traits of disseminated Emmonsia disease, and the relationship between the genus Ajellomyces and Emmonsia species.