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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]

We detected Emergomyces africanus, a thermally dimorphic fungus that causes an HIV-associated systemic mycosis, by PCR in 18 (30%) of 60 soil samples from a wide range of habitats in South Africa. Direct and indirect culture techniques were unsuccessful. Experimental intraperitoneal inoculation of conidia induced murine disease. [ABSTRACT FROM AUTHOR]

Background Skin lesions are common in advanced HIV infection and are sometimes caused by serious diseases like systemic mycoses (SM). AIDS-related SM endemic to Western Cape, South Africa, include emergomycosis (formerly disseminated emmonsiosis), histoplasmosis, and sporotrichosis. We previously reported that 95% of patients with AIDS-related emergomycosis had skin lesions, although these were frequently overlooked or misdiagnosed clinically. Prospective studies are needed to characterize skin lesions of SM in South Africa and to help distinguish these from common HIV-related dermatoses. Methods We prospectively enrolled HIV-infected adult patients living in Western Cape, South Africa, with CD4 counts ≤100 cells/μL and widespread skin lesions present ≤6 months that were deemed clinically compatible with SM. We obtained skin biopsies for histopathology and fungal culture and collected epidemiological and clinical data. Results Of 34 patients enrolled and in whom a diagnosis could be made, 25 had proven SM: 14 had emergomycosis, and 3 each had histoplasmosis and sporotrichosis; for 5 additional patients, the fungal species could not be identified. Antiretroviral therapy (ART) had been initiated in the preceding 4 weeks for 11/25 (44%) patients with SM (vs no patients without SM). Plaques and scale crust occurred more frequently in patients with SM (96% vs 25%, P =.0002; and 67% vs 13%, P =.01, respectively). Conclusions Recent ART initiation and presence of plaques or scale crust should make clinicians consider SM in patients with advanced HIV infection in this geographic area. Clinical overlap between SM and other dermatoses makes early skin biopsy critical for timely diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Summary Background The relationship between concurrent sexual partnerships and HIV risk is not fully understood. Evidence on the relationship between partner concurrency (one's sexual partner has another partner) and individual HIV risk is limited. In this study, the relationship between reported sexual partner concurrency and the risk of HIV infection was explored among South Africans. Methods Data from the third South African national HIV survey were used. In this survey, performed in 2008, questionnaires and HIV tests were administered to a nationally representative sample of 15 031 persons. Bivariate analysis and multiple logistic regression were used to evaluate the relationship between partner concurrency and HIV serostatus. Spearman's correlation was used to test the association between the prevalence of HIV and partner concurrency by race in women. Results The relationship between HIV prevalence and partner concurrency varied by race. At a cross-racial level there was a positive association between HIV prevalence and partner concurrency for women (rho = 0.95, p = 0.05). Among coloured, white, and Indian persons, HIV prevalence and partner concurrency rates were too low to allow further statistical testing. In the bivariate analysis, black African women who reported partner concurrency had a higher prevalence of HIV (36% (95% confidence interval (CI) 29.7–42.0) vs. 23% (95% CI 19.6–26.1), p < 0.001). After controlling for demographic, social, biological, and behavioural variables, the association remained statistically significant (adjusted odds ratio (aOR) 1.4, p = 0.04). The association was stronger among 15–29-year-old black African women (aOR 1.8, p = 0.03) than among women aged 30 years and older (aOR 1.3, p = 0.36). Conclusions These results suggest that partner concurrency may increase the HIV infection risk for black South African women, and in particular, for younger women. [ABSTRACT FROM AUTHOR]

Background: Blastomycosis has been reported from countries in Africa and the Middle East, but a decades-long debate has persisted regarding whether this is the same disease known in North America and caused by Blastomyces dermatitidis and Blastomyces gilchristii., Methods: We reviewed published cases of human and veterinary blastomycosis from Africa and the Middle East. We abstracted epidemiological and clinical features of cases, including sites of disease, diagnosis, management, outcomes, and, where available, genetic and antigenic typing of case isolates. In addition, we sequenced nucleic acids from 9 clinical isolates from Africa deposited in global collections as B. dermatitidis; for 5, we sequenced the internal transcribed spacer regions, and for the other 4 we sequenced the whole genomes., Results: We identified 172 unique human patients with blastomycosis, including 159 patients from 25 African countries and 12 patients from 5 Middle Eastern countries, and also identified 7 reports of veterinary blastomycosis. In humans, cutaneous disease predominated (n = 100/137, 73%), followed by pulmonary (n = 73/129, 57%) and osteoarticular involvement (n = 61/128, 48%). Unusual direct microscopy/histopathological presentations included short hyphal fragments in tissues (n = 23/129, 18%). There were 34 genotyped case isolates that comprised 4 species: Blastomyces percursus (n = 22, 65%), from 8 countries throughout all regions; Blastomyces emzantsi (n = 9, 26%), from South Africa; B. dermatitidis (n = 1, 3%), from the Democratic Republic of Congo; and B. gilchristii (n = 2, 6%), from South Africa and Zimbabwe., Conclusions: Blastomycosis occurs throughout Africa and the Middle East and is caused predominantly by B. percursus and, at least in South Africa, B. emzantsi, resulting in distinct clinical and pathological patterns of disease., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Histoplasma antigen detection in urine is a rapid diagnostic method for disseminated histoplasmosis, although cross-reactivity has been reported in specimens from patients with other thermally dimorphic fungal infections. We tested urine specimens, from persons with suspected invasive fungal infections, using a commercial monoclonal antibody Histoplasma enzyme immunoassay (EIA) at a South African national mycology reference laboratory from August 2014 through December 2018. Corresponding fungal culture and histopathology results were obtained from an electronic laboratory information system. In some cases, cultured fungal isolates were sent with the urine specimen for species-level identification by phenotypic and molecular methods. Cross-reactivity was confirmed using culture filtrates of several fungal pathogens. Of 212 referred cases, 41 (19%) were excluded since they had no recorded clinical history (n = 1), alternative diagnoses were confirmed (n = 2), or no fungal culture or histopathology results (n = 38). Eighty-seven of 212 (41%) had laboratory evidence of an invasive fungal disease, while 84 (40%) did not. Of the 87 cases, 37 (43%) were culture-confirmed mycoses: emergomycosis (n = 18), histoplasmosis (n = 8), sporotrichosis (n = 6), cryptococcosis (n = 2), talaromycosis (n = 1), and other fungi isolated (n = 2). The sensitivity and specificity of the EIA were calculated for two groups: culture-confirmed (n = 37) and histology-confirmed invasive fungal disease (n = 50). The sensitivity and specificity of the EIA for diagnosis of histoplasmosis compared to culture were 88% (7/8, 95%CI 47-100%) and 72% (21/29, 95%CI 53-87%), respectively, and for diagnosis of emergomycosis/histoplasmosis compared to histology was 83% (29/35, 95%CI 66-93%) and 93% (14/15, 95%CI 68-100%), respectively. Cross-reactions occurred in urine specimens of patients with Emergomyces africanus infection and in culture filtrates of E. africanus, T. marneffei and Blastomyces species. A commercial Histoplasma EIA had satisfactory accuracy for diagnosis of culture-confirmed histoplasmosis, but cross-reacted in urine specimens from patients with invasive disease caused by the closely-related pathogen, E. africanus and in culture filtrates of E. africanus and other related fungi., Lay Summary: Emergomyces africanus and Histoplasma capsulatum are fungi that cause a multi-system disease among HIV-seropositive persons with a low CD4 cell count. Handling live cultures of these fungi to confirm a diagnosis requires specialized laboratory equipment and infrastructure which is infrequently accessible in low-resource settings. The features of the two diseases (i.e., disseminated histoplasmosis and emergomycosis) may be indistinguishable when infected tissue is prepared, stained, and examined under a microscope. Enzyme immunoassays (EIA) have been developed as rapid diagnostic tools for the detection of a cell wall component of H. capsulatum in urine specimens, although cross-reactions have been reported in specimens from patients with other fungal infections. We evaluated the accuracy of a commercial Histoplasma EIA to diagnose histoplasmosis and to assess cross-reactions in urine specimens from persons with emergomycosis and in cultures of E. africanus and related fungi. We report a sensitivity and specificity of 88% (95%CI 47-100%) and 72% (95%CI 53-87%) for diagnosis of histoplasmosis compared to culture and 83% (95%CI 66-93%) and 93% (95%CI 68-100%) for diagnosis of either histoplasmosis/emergomycosis compared to a diagnosis made by microscopic examination of infected tissue. The assay cross-reacted in urine specimens from patients with emergomycosis and in culture filtrates of related fungi. Although the EIA cross-reacted with other related fungi, this test can decrease the time to diagnosis and facilitate early treatment of emergomycosis and histoplasmosis in South Africa., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

We reevaluated 20 cases of blastomycosis diagnosed in South Africa between 1967 and 2014, with Blastomyces dermatitidis considered to be the etiological agent, in light of newly described species and the use of more advanced technologies. In addition to histopathological and/or culture-based methods, all 20 isolates were phenotypically and genotypically characterized, including multilocus typing of five genes and whole-genome sequencing. Antifungal susceptibility testing was performed as outlined by Clinical and Laboratory Standards Institute documents M27-A3 and M38-A2. We merged laboratory and corresponding clinical case data, where available. Morphological characteristics and phylogenetic analyses of five-gene and whole-genome sequences revealed two groups, both of which were closely related to but distinct from B. dermatitidis , Blastomyces gilchristii , and Blastomyces parvus The first group ( n  = 12) corresponded to the recently described species Blastomyces percursus , and the other ( n  = 8) is described here as Blastomyces emzantsi sp. nov. Both species exhibited incomplete conversion to the yeast phase at 37°C and were heterothallic for mating types. All eight B. emzantsi isolates belonged to the α mating type. Whole-genome sequencing confirmed distinct species identities as well as the absence of a full orthologue of the BAD-1 gene. Extrapulmonary (skin or bone) disease, probably resulting from hematogenous spread from a primary lung infection, was more common than pulmonary disease alone. Voriconazole, posaconazole, itraconazole, amphotericin B, and micafungin had the most potent in vitro activity. Over the 5 decades, South African cases of blastomycosis were caused by species that are distinct from B. dermatitidis Increasing clinical awareness and access to simple rapid diagnostics may improve the diagnosis of blastomycosis in resource-limited countries., (Copyright © 2020 American Society for Microbiology.)

The ecological niche of Emergomyces africanus (formerly Emmonsia species), a dimorphic fungus that causes an AIDS-related mycosis in South Africa, is unknown. We hypothesized that natural infection with E. africanus occurs in wild small mammals. Using molecular detection with primers specific for E. africanus, we examined 1402 DNA samples from 26 species of mole-rats, rodents, and insectivores trapped in South Africa that included 1324 lung, 37 kidney, and 41 liver specimens. DNA of E. africanus was not detected in any animals. We conclude that natural infection of wild small mammals in South Africa with E. africanus has not been proven.

Recent discoveries of novel systemic fungal pathogens with thermally dimorphic yeast-like phases have challenged the current taxonomy of the Ajellomycetaceae, a family currently comprising the genera Blastomyces, Emmonsia, Emmonsiellopsis, Helicocarpus, Histoplasma, Lacazia and Paracoccidioides. Our morphological, phylogenetic and phylogenomic analyses demonstrated species relationships and their specific phenotypes, clarified generic boundaries and provided the first annotated genome assemblies to support the description of two new species. A new genus, Emergomyces, accommodates Emmonsia pasteuriana as type species, and the new species Emergomyces africanus, the aetiological agent of case series of disseminated infections in South Africa. Both species produce small yeast cells that bud at a narrow base at 37°C and lack adiaspores, classically associated with the genus Emmonsia. Another novel dimorphic pathogen, producing broad-based budding cells at 37°C and occurring outside North America, proved to belong to the genus Blastomyces, and is described as Blastomyces percursus., (© 2017 Blackwell Verlag GmbH.)

Background: We describe the geographic distribution, clinical characteristics, and management of patients with disease caused by Emmonsia sp., a novel dimorphic fungal pathogen recently described in South Africa., Methods: We performed a multicenter, retrospective chart review of laboratory-confirmed cases of emmonsiosis diagnosed across South Africa from January 2008 through February 2015., Results: Fifty-four patients were diagnosed in 5/9 provinces. Fifty-one patients (94%) were human immunodeficiency virus coinfected (median CD4 count 16 cells/µL [interquartile range, 6-40]). In 12 (24%) of these, antiretroviral therapy had been initiated in the preceding 2 months. All patients had disseminated disease, most commonly involving skin (n = 50/52, 96%) and lung (n = 42/48, 88%). Yeasts were visualized on histopathologic examination of skin (n = 34/37), respiratory tissue (n = 2/4), brain (n = 1/1), liver (n = 1/2), and bone marrow (n = 1/15). Emmonsia sp. was cultured from skin biopsy (n = 20/28), mycobacterial/fungal and aerobic blood culture (n = 15/25 and n = 9/37, respectively), bone marrow (n = 12/14), lung (n = 1/1), lymph node (n = 1/1), and brain (n = 1/1). Twenty-four of 34 patients (71%) treated with amphotericin B deoxycholate, 4/12 (33%) treated with a triazole alone, and none of 8 (0%) who received no antifungals survived. Twenty-six patients (48%) died, half undiagnosed., Conclusions: Disseminated emmonsiosis is more widespread in South Africa and carries a higher case fatality rate than previously appreciated. Cutaneous involvement is near universal, and skin biopsy can be used to diagnose the majority of patients., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)