In this part 1 of a 2-part continuing medical education series, the epidemiology, clinical features, and diagnostic methods for fungal skin neglected tropical diseases (NTDs), which include eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis, are reviewed. These infections, several of which are officially designated as NTDs by the World Health Organization (WHO), cause substantial morbidity and stigma worldwide and are receiving increased attention due to the potential for climate change-related geographic expansion. Domestic incidence may be increasing in the setting of global travel and immunosuppression. United States dermatologists may play a central role in early detection and initiation of appropriate treatment, leading to decreased morbidity and mortality.

In this part 2 of a 2-part continuing medical education series, the management, outcomes, and morbidities for fungal skin neglected tropical diseases (NTDs), including eumycetoma, chromoblastomycosis, paracoccidioidomycosis, sporotrichosis, emergomycosis, talaromycosis, and lobomycosis are reviewed. While fungal skin NTDs are associated with poverty in resource-limited settings, they are more often associated with immunosuppression and global migration in the United States. These infections have a high morbidity burden, including disfigurement, physical disability, coinfection, malignant transformation, mental health issues, and financial impact. For most fungal skin NTDs, management is difficult and associated with low cure rates. Dermatologists play a central role in initiating appropriate treatment early in disease course in order to improve patient outcomes.

We performed in vitro antifungal susceptibility testing of manogepix against the yeast phase of 78 Emergomyces africanus, 2 Emergomyces pasteurianus, and 5 Blastomyces emzantsi isolates using a reference broth microdilution method following Clinical and Laboratory Standards Institute recommendations. All three pathogens had low minimum inhibitory concentrations ranging from <0.0005 to 0.008 mg/L. Manogepix should be investigated in animal models and potentially in future human clinical trials for endemic mycoses.

Emergomycosis is an endemic mycosis caused by the Emergomyces species. Infections due to this agent have been reported globally. Hence, the present systematic review on Emergomyces infections was conducted to study the disease epidemiology, underlying diseases and risk factors, causative agents, and treatment and outcome. The MEDLINE, Scopus, Embase, and Web of Science databases were searched systematically with appropriate keywords from January 1990 to October 2022. A total of 77 cases of emergomycosis were included in the analysis. Emergomycosis was most commonly seen in patients with human immunodeficiency virus (HIV) infection (n = 61, 79.2%) and HIV-uninfected patients with or without other comorbidities (n = 16, 20.8%). The underlying disease and risk factors significantly associated with emergomycosis in the HIV-infected patients were CD4+ T-cell counts less than 100 cells/mm3 (n = 55, 90.2%), anaemia (n = 30, 49.2%), and thrombocytopenia (n = 17, 27.9%), whereas in the HIV-uninfected patients, treatment with immunosuppressive drugs (n = 10, 62.5%), renal disease (n = 8, 50%), transplant recipients (n = 6, 37.5%), and diabetes mellitus (n = 4, 25%) were the significant risk factors associated with emergomycosis. Emergomyces africanus (n = 55, 71.4%) is the most common causative agent, followed by E. pasteurianus (n = 9, 11.7%) and E. canadensis (n = 5, 6.5%). E. africanus was most often isolated from HIV-infected patients (n = 54, 98.2%), whereas E. pasteurianus was most common in HIV-uninfected patients (n = 5, 55.6%). The all-cause mortality rate of the total cohort is 42.9%. No significant variation in the mortality rate is observed between the HIV-infected patients (n = 28, 36.4%) and the HIV-uninfected patients (n = 5, 6.5%). In conclusion, with an increase in the immunosuppressed population across the globe in addition to HIV infection, the case burden of emergomycosis may increase in the future. Hence, clinicians and mycologists should be vigilant and clinically suspicious of emergomycosis, which helps in early diagnosis and initiation of antifungal treatment to prevent disease mortality.

Emergomycosis is an emerging deadly infectious disease caused primarily by a little-known airborne pathogen Emergomyces africanus, which can cause clinical management challenge especially in patients with advanced HIV disease. This minireview describes Es. africanus as the main cause of emergomycosis in Africa as well as considers contributing factors to the difficulties encountered in managing this infection. Emergomycosis is common in HIV-positive persons with low CD4 lymphocyte count and has an estimated fatality of 50%. The infection exhibits airborne transmission with pulmonary and extrapulmonary manifestations leading to skin lesions. However, the pathogenesis of Es. africanus is still poorly understood. The management of the infection is complicated due to lack of defined diagnostic and therapeutic guidelines. Limited expertise, poor research funding, and lack of awareness and national surveillance are thought to impact the recognition and prioritisation of the infection. These factors may ultimately assign emergomycosis a \'neglected infection status\' even as it is suspected to be prevalent in more African countries than previously recognised. Increased awareness and integrated and targeted strategies such as mobilising manpower in clinical mycology are of paramount importance in managing emergomycosis in Africa and beyond.

Invasive fungal diseases (IFDs) are of huge concern in resource-limited settings, particularly in Africa, due to the unavailability of diagnostic armamentarium for IFDs, thus making definitive diagnosis challenging. IFDs have non-specific systemic manifestations overlapping with more frequent illnesses, such as tuberculosis, HIV, and HIV-related opportunistic infections and malignancies. Consequently, IFDs are often undiagnosed or misdiagnosed. We critically reviewed the available literature on IFDs in Africa to provide a better understanding of their epidemiology, disease burden to guide future research and interventions. Cryptococcosis is the most encountered IFD in Africa, accounting for most of the HIV-related deaths in sub-Saharan Africa. Invasive aspergillosis, though somewhat underdiagnosed and/or misdiagnosed as tuberculosis, is increasingly being reported with a similar predilection towards people living with HIV. More cases of histoplasmosis are also being reported with recent epidemiological studies, particularly from Western Africa, showing high prevalence rates amongst presumptive tuberculosis patients and patients living with HIV. The burden of pneumocystis pneumonia has reduced significantly probably due to increased uptake of anti-retroviral therapy among people living with HIV both in Africa, and globally. Mucormycosis, talaromycosis, emergomycosis, blastomycosis, and coccidiomycosis have also been reported but with very few studies from the literature. The emergence of resistance to most of the available antifungal drugs in Africa is yet of huge concern as reported in other regions. IFDs in Africa is much more common than it appears and contributes significantly to morbidity and mortality. Huge investment is needed to drive awareness and fungi related research especially in diagnostics and antifungal therapy.

Emergomycosis is a recently described emerging opportunistic fungal infection among individuals living with HIV, in whom it is a cause of significant mortality and morbidity. This article retrospectively reports on a presumptive case of extensive cutaneous emergomycosis in a young immunocompromised patient from Lesotho. The histopathological features on skin biopsy were in keeping with emergomyces infection. The lesions responded to treatment with amphotericin B and oral fluconazole.
UNASSIGNED: This case contributes to the existing evidence that as an emergent opportunistic infection, emergomycosis is possibly widespread in Africa but the true extend of the disease is not fully defined. This is further aggravated by the diagnostic difficulty as a result of limited resources in some areas in the region.

The endemic mycoses blastomycosis, coccidioidomycosis, histoplasmosis, paracoccidioidomycosis, cryptococcosis, sporotrichosis, talaromycosis, adiaspiromycosis, and emergomycosis are mostly caused by geographically limited thermally dimorphic fungi (except for cryptococcosis), and their diagnoses can be challenging. Usual laboratory methods involved in endemic mycoses diagnosis include microscopic examination and culture of biological samples; however, serologic, histopathologic, and molecular techniques have been implemented in the last few years for the diagnosis of these mycoses since the recovery and identification of their etiologic agents is time-consuming and lacks in sensitivity. In this review, we focus on the immunologic diagnostic methods related to antibody and antigen detection since their evidence is presumptive diagnosis, and in some mycoses, such as cryptococcosis, it is definitive diagnosis.

Purpose of Review In this review, we provide an overview of emergomycosis from a clinical perspective and discuss the taxonomy and classification of the pathogens, epidemiology, pathophysiology of infection and mechanisms of pathogenesis, immunology, clinical manifestations, laboratory culture and diagnosis, molecular characterisation, therapy and prognosis. Recent Findings While Emergomyces pasteurianus is the most geographically-widespread species, Emergomyces africanus is endemic to Southern Africa and causes disseminated disease with cutaneous involvement primarily among patients with advanced human immunodeficiency virus (HIV) disease. Summary Emergomycosis, a disseminated clinical disease resulting from infection with dimorphic fungi in the genus Emergomyces, occurs primarily among immunocompromised patients. Further knowledge is needed on the pathophysiology, diagnosis and management of emergomycosis.

Recently, the global emergence of emergomycosis, a systemic fungal infection caused by a novel dimorphic fungus Emergomyces species has been observed among immunocompromised individuals. Though initially classified under the genus Emmonsia, a taxonomic revision in 2017 based on DNA sequence analyses placed five Emmonsia-like fungi under a separate genus Emergomyces. These include Emergomyces pasteurianus, Emergomyces africanus, Emergomyces canadensis, Emergomyces orientalis, and Emergomyces europaeus. Emmonsia parva was renamed as Blastomyces parvus, while Emmonsia crescens and Emmonsia sola remained within the genus Emmonsia until a taxonomic revision in 2020 placed both the species under the genus Emergomyces. However, unlike other members of the genus, Emergomyces crescens and Emergomyces sola do not cause disseminated disease. The former causes adiaspiromycosis, a granulomatous pulmonary disease, while the latter has not been associated with human disease. So far, emergomycosis has been mapped across four continents: Asia, Europe, Africa and North America. However, considering the increasing prevalence of HIV/AIDS, it is presumed that the disease must have a worldwide distribution with many cases going undetected. Diagnosis of emergomycosis remains challenging. It should be considered in the differential diagnosis of histoplasmosis as there is considerable clinical and histopathological overlap between the two entities. Sequencing the internal transcribed spacer region of ribosomal DNA is considered as the gold standard for identification, but its application is compromised in resource limited settings. Serological tests are non-specific and demonstrate cross-reactivity with Histoplasma galactomannan antigen. Therefore, an affordable, accessible, and reliable diagnostic test is the need of the hour to enable its diagnosis in endemic regions and also for epidemiological surveillance. Currently, there are no consensus guidelines for the treatment of emergomycosis. The recommended regimen consists of amphotericin B (deoxycholate or liposomal formulation) for 1-2 weeks, followed by oral itraconazole for at least 12 months. This review elaborates the taxonomic, clinical, diagnostic, and therapeutic aspects of emergomycosis. It also enumerates several novel antifungal drugs which might hold promise in the treatment of this condition and therefore, can be potential areas of future studies.