Dimorphic fungi

Organism	Distribution	Diseases	Treatment
Blastomyces	eastern US and Canada, with some reported in Africa	pulmonary infection, verrucous skin lesions, osteomyelitis, CNS infection	itraconazole (with amphotericin B induction if severe)
Coccidioides	southwestern US and parts of South and Central America	pulmonary infection, verrucous skin lesions, osteomyelitis, CNS infection	fluconazole (with amphotericin B and flucytosine induction if severe)
Histoplasma capsulatum	worldwide, including eastern North America, Central and South America, sub-Saharan Africa, and parts of Southeast Asia	pulmonary infection, CNS infection	itraconazole (with amphotericin B induction if severe)
Paracoccidioides brasiliensis	South America	pulmonary infection	itraconazole (with amphotericin B induction if severe)
Sporothrix schenckii	essentially worldwide	nodular lymphangitis	itraconazole
Talaromyces marneffei	Southeast Asia	disseminated (common in advanced HIV), pulmonary infection, abdominal abscess, skin lesions, osteomyelitis	amphotericin B induction followed by itraconazole

Background

Broad category of fungi that exist in a mold form at lower temperatures in the environment, and a yeast form at higher temperatures in the host body
Cryptococcus does exhibit dimorphism, though it is predominately yeast and its dimorphism is not likely related to disease
Often referred to as endemic fungi based on their geographic niches
Includes the following genera and species:
- Blastomyces, including Blastomyces dermatitidis complex (Blastomyces dermatitidis and Blastomyces gilchristii), helices, silverae, parvus
- Histoplasma capsulatum (var. capsulatum and var. duboisii)
- Coccidiodes, including Coccidioides immitis and Coccidioides posadasii
- Paracoccidioides, including Paracoccidioides brasiliensis and Paracoccidioides lutzii
- Talaromyces marneffei
- Emergomyces, including Emergomyces pasteurianus, Emergomyces africanus, Emergomyces orientalis, Emergomyces canadensis, Emergomyces europaeus
- Sporothrix complex (Sporothrix brasiliensis, Sporothrix schenckii, Sporothrix globose, Sporothrix luriei)

High-endemic areas include Ohio and Mississippi river valley systems, but also in Central and South America
- However, 12-20% of cases in US occur outside of endemic areas
- In Canada, mostly along St. Lawrence seaway and Great Lakes drainage
More recently, cases have been diagnosed in Alberta and Saskatchewan
Also found in Asia and Africa, throughout, with var. duboisii in West Africa (mostly skin and soft tissue disease)
Associated with soil contaminated by bird or bat guano

More common in southwestern US, especially California and Arizona (but up to Washington state), as well as parts of South and Central America
- Concentrated heavily in San Joaquin Valley in California
Present in soil
High-risk activities: construction, military maneuvers, earthquakes/landslides, armadillo hunting, prisoners from other parts of the US that are incarcerated in California

Found mostly in eastern North America
- In Canada, found in northwestern Ontario, Quebec, Manitoba, and Saskatchewan
  - Kenora is the hotspot in Canada
More common in wooded areas, damp soil, and near waterways
High-risk activities include excavation and construction

Different species found worldwide, including Emergomyces canadensis in Saskatchewan, Colorado, and New Mexico
More common in HIV patients or other immunocompromised

	Acute Pulmonary	Cavitary and Chronic Pulmonary	Progressive Disseminated
Clinical	usually asymptomatic or mild; can have non-pleuritic chest pain from mediastinal or hilar lymphadenopathy; can have rheumatic features or pericarditis	8% develop fibrocavitary disease, associated with underlying COPD
Immunology	>90% positive skin test, 20% urine antigen	75-95% antibodyes, 40% urine antigen	60-90% urine antigen
Culture	<25% positive	5-70% positive (more likely if cavitary)	50-70% positive

Inhalation is main portal of entry
Incubation 3 weeks to 3 months
In outbreaks, 50% of exposed developed symptoms
Primarily presents with pulmonary blastomycosis with influenza-like illness, acute pneumonia, ARDS, or chronic pneumonia
Skin is most common extrapulmonary site, but can also infect bone and prostate
CNS infection is rare

Asymptaomtic common in 60%
Early pulmonary infection
- Mild
- Valley fever, including arthralgias and erythema nodosum
Extrapulmonary dissemination
- More common in African Americans

Organism	Findings on Microscopy
Histoplasma	intracellular 2-4 μm yeast-like cells in macrophages, may have narrow-based budding
Blastomyces	8-15 μm yeast-like cells with broad-based budding, refractile thick cell wall, but early spherules can be confused with Coccioides
Coccidioides	spherules are thick-walled, 10-80 μm with endospores; alternating barrel-shaped arthroconidia in mycelial form
Marneffei	divides by binary fission
Emergomyces	2.5-5 μm small yeast form with narrow-based budding; septate hyphae with conidiophores at right answers, with conidia clustered in florettes of 2 to 3 conidia

Proven invasive fungal disease
- Histopathology or direct microscopy of sterile material of specimens obtained from an affected site showing the distinctive form of the fungus, or
- Recovery by culture of sterile material of the fungus from specimens from an affected site, or
- Blood culture that yields the fungus
Probable invasive fungal disease
- Requires clinical features and mycologic evidence, but host does not have to be immunocompromised for dimorphic or endemic fungi
- Host factors: not applicable
- Clinical features: evidence for geographical or occupational exposure (including remote) to the fungus and compatible clinical illness
- Mycological evidence:
  - Histoplasma or Blastomyces antigen in urine, serum, or body fluid
  - Antibody to Coccidioides in CSF or 2-fold rise in 2 consecutive serum samples

^ Ashraf N, Kubat RC, Poplin V, Adenis AA, Denning DW, Wright L, McCotter O, Schwartz IS, Jackson BR, Chiller T, Bahr NC. Re-drawing the Maps for Endemic Mycoses.. Mycopathologia. 2020. doi:10.1007/s11046-020-00431-2. PMID 32040709.