Emergomycosis
Also known as: Emergomyces Infection, Emmonsia Infection, Disseminated Emergomycosis
Emergomycosis is a systemic infection caused by thermally dimorphic fungi of the genus Emergomyces (family Ajellomycetaceae, related to Histoplasma and Blastomyces). It was described in the last 15 years and first recognised in South Africa as the cause of a disseminated disease in people with advanced HIV.
Emergomyces africanus is the commonest species, and it is among the commonest endemic mycoses in southern Africa, where it was widely mistaken for histoplasmosis.
Disease follows inhalation of conidia, is usually disseminated with skin lesions, and occurs mainly in people with advanced HIV disease and in other immunosuppressed patients. Mortality is 30 to 50 percent.
| Species | Distribution and hosts |
|---|---|
| Emergomyces africanus | South Africa, Lesotho, and southern Africa; advanced HIV and, less often, other immunosuppression |
| Emergomyces pasteurianus | Europe, Asia, Africa, and Uganda; immunosuppressed hosts, including transplant, with skin and lung disease and in people with HIV |
| Emergomyces orientalis | China and South East Asia; HIV and other immunosuppression |
| Emergomyces canadensis | Canada and parts of Africa, with disease in HIV and in immunocompetent hosts |
| Emergomyces europaeus | Europe; rare cases in immunosuppressed hosts |
| Other emergomycetes | Genera and species related to the group are described, and the group is expanding |
| Feature | Description |
|---|---|
| Dimorphism | Mould at 25 to 30 degrees Celsius, yeast at 37 degrees Celsius |
| Mould phase | Slow growing, white to tan colonies with hyaline septate hyphae and small conidia in flower like arrangements |
| Yeast phase | Small yeasts of 2 to 4 micrometres, with narrow based budding, inside macrophages, resembling Histoplasma capsulatum; some forms are larger, with broad based budding |
| Culture | The yeast phase grows in 7 to 21 days at 37 degrees Celsius on enriched media; the mould phase is hazardous in the laboratory |
| Identification | Sequencing of the internal transcribed spacer region and other loci; mass spectrometry with an extended database; microscopy alone does not separate it from Histoplasma |
| Aspect | Details |
|---|---|
| Geography | South Africa (the best described; more than 100 cases reported, with an incidence that grows with testing), and other parts of Africa, Europe, Asia, North America, and Australia |
| Reservoir | Soil and the environment (not known precisely); outbreaks have not been reported, and hosts are infected by inhalation |
| Host | Advanced HIV disease (CD4 below 100 cells per microlitre, and a median CD4 of about 20 to 30 cells per microlitre), solid organ transplant, immunosuppressive therapy, haematological malignancy, and rarely immunocompetent hosts |
| Burden | In Cape Town and Johannesburg, it is one of the commonest causes of a systemic mycosis in people with HIV |
| Clinical context | Often diagnosed after tuberculosis and histoplasmosis are considered, and 30 to 50 percent of patients have concurrent tuberculosis |
| Feature | Details |
|---|---|
| Systemic | Fever, weight loss, fatigue, night sweats, and cough |
| Skin | Present in 70 to 80 percent: papules and plaques that are often umbilicated or necrotic, with a molluscum contagiosum like appearance; also ulcers, nodules, and acneiform, papulonecrotic, and hyperkeratotic (verrucous) lesions on the face, trunk, and limbs, which may be extensive |
| Respiratory | Dyspnoea, and chest radiograph with diffuse reticulonodular infiltrates, consolidation, and lymphadenopathy |
| Reticuloendothelial | Hepatosplenomegaly, lymphadenopathy, and pancytopenia |
| Laboratory | Raised lactate dehydrogenase, anaemia, thrombocytopenia, raised alkaline phosphatase, and hypoalbuminaemia |
| Other organs | Gastrointestinal, bone marrow, central nervous system, and eye, rarely |
| Immunosuppressed non HIV patients | Skin and lung disease, with fever |
| Immune reconstitution inflammatory syndrome | After antiretroviral therapy, with new or worsening skin lesions |
| Course | Subacute disease, with a median of 2 to 4 weeks of symptoms before diagnosis; shock and organ failure in severe cases |
| Condition | Points that separate it |
|---|---|
| Histoplasmosis (classic and African) | Yeast size and budding pattern are similar; sequencing, culture, and geography separate them; the Histoplasma antigen is positive in many cases of emergomycosis |
| Talaromycosis | Central septum (fission) and red pigment |
| Disseminated tuberculosis and non tuberculous mycobacteria | Acid fast bacilli; coinfection is frequent |
| Cryptococcosis | Capsule and antigen |
| Kaposi sarcoma and lymphoma | Histology |
| Pneumocystis pneumonia | Polymerase chain reaction and stains |
| Molluscum contagiosum, syphilis, and drug eruptions | Histology and serology |
| Blastomycosis | Broad based budding and large yeasts |
| Test | Details |
|---|---|
| Skin biopsy | The most useful test: histology with methenamine silver and periodic acid Schiff shows small yeasts in macrophages, with a granulomatous or diffuse inflammatory pattern; culture and polymerase chain reaction on a second sample |
| Bone marrow, lymph node, and blood | Microscopy and culture; blood culture is positive in a minority |
| Culture | Slow; sequencing is required to identify the species |
| Antigen | Histoplasma antigen enzyme immunoassay (urine and serum) cross reacts in many patients, with moderate sensitivity (about 70 to 85 percent), so a positive result is treated as supportive and does not separate the two diseases; no specific commercial antigen is available |
| Molecular tests | Polymerase chain reaction and sequencing of tissue |
| Biomarkers | Beta D glucan may be positive |
| Other tests | HIV test, CD4 count, full blood count, liver tests, chest radiograph, sputum for mycobacteria, and cryptococcal antigen |
| Susceptibility | Reference broth microdilution (no breakpoints); minimal inhibitory concentrations are low for amphotericin B, itraconazole, voriconazole, and posaconazole, higher for fluconazole, and the echinocandins are less active |
Evidence comes from case series, because no controlled trials exist, so management is extrapolated from histoplasmosis.
| Element | Details |
|---|---|
| Induction | Liposomal amphotericin B 3 to 5 mg per kg intravenously once daily (or deoxycholate 0.7 to 1 mg per kg once daily where liposomal is not available) for at least 2 weeks, or until clinical improvement |
| Consolidation | Itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily (400 mg per day) for 10 weeks (a total of 12 weeks of therapy), and for 12 months in severe disease |
| Mild disease | Itraconazole 200 mg twice daily for 12 weeks, and amphotericin B first if the illness is severe or in a patient with HIV |
| Secondary prophylaxis | Itraconazole 200 mg once daily in HIV, until the CD4 count is above 100 cells per microlitre for at least 6 months on antiretroviral therapy |
| Alternatives | Voriconazole 6 mg per kg every 12 hours on day 1, then 4 mg per kg every 12 hours (oral 200 mg every 12 hours), posaconazole delayed release 300 mg every 12 hours on day 1, then 300 mg daily, or isavuconazonium sulphate 372 mg every 8 hours for 6 doses, then 372 mg daily; fluconazole is inferior and is used where other drugs are not available |
| Antiretroviral therapy | Start within 2 weeks of the start of antifungal therapy, with attention to the immune reconstitution inflammatory syndrome, which is managed by continuing both treatments, with corticosteroids for severe disease |
| Tuberculosis | Treat coinfection, with attention to rifampicin interactions (rifampicin lowers itraconazole levels, so voriconazole or higher doses and levels are needed; rifabutin is an alternative) |
| Surgery | Not routine |
| Monitoring | Clinical response, skin lesions, itraconazole levels (at least 1 microgram per mL), liver tests, renal function, potassium, and magnesium in those on amphotericin B |
Mortality is 30 to 50 percent in series from southern Africa, with most deaths in the first weeks and with delays in diagnosis. Survivors respond well to amphotericin B and itraconazole. In other immunosuppressed patients, mortality varies by host and by time to treatment, and skin disease alone has a better outcome.
Antiretroviral therapy and early HIV diagnosis are the main preventive measures. No primary prophylaxis is established. Awareness among clinicians, skin biopsy in people with HIV who have skin lesions, and access to diagnostics and amphotericin B improve outcomes.
