Dimorphic fungi: Difference between revisions

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{| class="wikitable"
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== Species ==
  
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!Organism
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* ''[[Blastomyces dermatitidis]]''
  
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!Distribution
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* ''[[Histoplasma capsulatum]]''
  
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!Diseases
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* ''[[Coccidioides immitis]]'' and ''[[Coccidioides posadasii]]''
  
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!Treatment
−
* ''[[Cryptococcus neoformans]]'' and ''[[Cryptococcus gattii]]''
  
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|-
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* ''[[Sporothrix schenckii]]''
  
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|[[Blastomyces]]
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|eastern US and Canada, with some reported in Africa
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|pulmonary infection, verrucous skin lesions, osteomyelitis, CNS infection
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|[[itraconazole]] (with [[amphotericin B]] induction if severe)
  +
|-
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|[[Coccidioides]]
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|southwestern US and parts of South and Central America
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|pulmonary infection, verrucous skin lesions, osteomyelitis, CNS infection
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|[[fluconazole]] (with [[amphotericin B]] and [[flucytosine]] induction if severe)
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|-
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|[[Histoplasma capsulatum]]
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|worldwide, including eastern North America, Central and South America, sub-Saharan Africa, and parts of Southeast Asia
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|pulmonary infection, CNS infection
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|[[itraconazole]] (with [[amphotericin B]] induction if severe)
  +
|-
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|[[Paracoccidioides brasiliensis]]
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|South America
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|pulmonary infection
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|[[itraconazole]] (with [[amphotericin B]] induction if severe)
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|-
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|[[Sporothrix schenckii]]
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|essentially worldwide
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|[[nodular lymphangitis]]
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|[[itraconazole]]
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|-
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|[[Talaromyces marneffei]]
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|Southeast Asia
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|disseminated (common in advanced [[HIV]]), pulmonary infection, abdominal abscess, skin lesions, osteomyelitis
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|[[amphotericin B]] induction followed by [[itraconazole]]
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|}
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==Background==
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===Microbiology===
   
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*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
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== Distribution ==
  
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*[[Cryptococcus]] does exhibit dimorphism, though it is predominately yeast and its dimorphism is not likely related to disease
−
* Endemic dimorphic fungi are widely distributed[[CiteRef::PMID32040709]]
  
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*Often referred to as endemic fungi based on their geographic niches
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*Includes the following genera and species:
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**[[Blastomyces]], including Blastomyces dermatitidis complex ([[Blastomyces dermatitidis]] and [[Blastomyces gilchristii]]), helices, silverae, parvus
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**[[Histoplasma capsulatum]] (var. ''capsulatum'' and var. ''duboisii'')
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**[[Coccidiodes]], including [[Coccidioides immitis]] and [[Coccidioides posadasii]]
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**[[Paracoccidioides]], including [[Paracoccidioides brasiliensis]] and [[Paracoccidioides lutzii]]
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**[[Talaromyces marneffei]]
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**[[Emergomyces]], including [[Emergomyces pasteurianus]], [[Emergomyces africanus]], [[Emergomyces orientalis]], [[Emergomyces canadensis]], [[Emergomyces europaeus]]
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**[[Sporothrix]] complex (Sporothrix brasiliensis, Sporothrix schenckii, Sporothrix globose, Sporothrix luriei)
   
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===Epidemiology===
−
[[File:Histoplasmosis_map.png|frame|Histoplasmosis]]
  
   
  +
*Endemic dimorphic fungi are widely distributed[[CiteRef::PMID32040709]]
−
[[File:Coccidiomycosis_map.png|frame|Coccidiomycosis]]
  
   
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====Histoplasmosis====
−
[[File:Blastomycosis_map.png|frame|Blastomycosis]]
  
  +
  +
[[File:Histoplasmosis_map.png|Histoplasmosis|alt=|thumb|300x300px]]
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  +
*High-endemic areas include Ohio and Mississippi river valley systems, but also in Central and South America
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**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
  +
  +
====Coccidiomycosis====
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[[File:Coccidiomycosis_map.png|Coccidiomycosis|alt=|thumb|300x300px]]
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*More common in southwestern US, especially California and Arizona (but up to Washington state), as well as parts of South and Central America
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**Concentrated heavily in San Joaquin Valley in California
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*Present in soil
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*High-risk activities: construction, military maneuvers, earthquakes/landslides, armadillo hunting, prisoners from other parts of the US that are incarcerated in California
  +
  +
====Blastomycosis====
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  +
[[File:Blastomycosis_map.png|Blastomycosis|alt=|thumb|300x300px]]
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*Found mostly in eastern North America
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**In Canada, found in northwestern Ontario, Quebec, Manitoba, and Saskatchewan
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***Kenora is the hotspot in Canada
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*More common in wooded areas, damp soil, and near waterways
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*High-risk activities include excavation and construction
  +
  +
====Emergomycosis====
  +
  +
*Different species found worldwide, including [[Emergomyces canadensis]] in Saskatchewan, Colorado, and New Mexico
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*More common in HIV patients or other immunocompromised
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==Clinical Manifestations==
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  +
===Histoplasmosis===
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{| class="wikitable"
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!
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!Acute Pulmonary
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!Cavitary and Chronic Pulmonary
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!Progressive Disseminated
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|-
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|Clinical
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|usually asymptomatic or mild; can have non-pleuritic chest pain from mediastinal or hilar lymphadenopathy; can have rheumatic features or pericarditis
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|8% develop fibrocavitary disease, associated with underlying [[COPD]]
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|
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|-
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|Immunology
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|>90% positive skin test, 20% urine antigen
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|75-95% antibodyes, 40% urine antigen
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|60-90% urine antigen
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|-
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|Culture
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|<25% positive
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|5-70% positive (more likely if cavitary)
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|50-70% positive
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|}
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===Blastomycosis===
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  +
*Inhalation is main portal of entry
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*Incubation 3 weeks to 3 months
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*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
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*CNS infection is rare
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  +
===Coccidiomycosis===
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*Asymptaomtic common in 60%
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*Early pulmonary infection
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**Mild
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**Valley fever, including arthralgias and erythema nodosum
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*Extrapulmonary dissemination
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**More common in African Americans
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===Emergomycosis===
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  +
*Cutaneous disease in immunocompromised patients, especially advanced HIV
  +
*Can also cause pulmonary disease, extrapulmonary disease, or disseminated
  +
  +
==Diagnosis==
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  +
*Notify laboratory if a [[Biosafety risk groups|risk group 3]] organism is suspected
  +
*For blood cultures, the isolator system is preferred to BacTAlert
  +
*Media
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**Brain-heart infusion with sheep blood plus antibacterials is preferred
  +
**Cycloheximide can be used to prevent growth of saprophytic molds (always with one plate without)
  +
**Incubate at 30ºC to enhance growth of mold forms
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**Incubated for 3 weeks for fungi in general, but should be extended to 4 weeks for dimorphic fungi
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***[[Coccidioides]] is the fastest-growing, within 3 to 5 days on SAB, and can grow on chocolate and sheep's blood agars
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{| class="wikitable"
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!Organism
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!Findings on Microscopy
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|-
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|[[Histoplasma]]
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|intracellular 2-4 μm yeast-like cells in macrophages, may have narrow-based budding
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|-
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|[[Blastomyces]]
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|8-15 μm yeast-like cells with broad-based budding, refractile thick cell wall, but early spherules can be confused with [[Coccioides]]
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|-
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|[[Coccidioides]]
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|spherules are thick-walled, 10-80 μm with endospores; alternating barrel-shaped arthroconidia in mycelial form
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|-
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|[[Marneffei]]
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|divides by binary fission
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|-
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|[[Emergomyces]]
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|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
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|}
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===EORTC Definition[[CiteRef::donnelly2019re]]===
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*'''Proven invasive fungal disease'''
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**Histopathology or direct microscopy of sterile material of specimens obtained from an affected site showing the distinctive form of the fungus, or
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**Recovery by culture of sterile material of the fungus from specimens from an affected site, or
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**Blood culture that yields the fungus
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*'''Probable invasive fungal disease'''
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**Requires clinical features and mycologic evidence, but host does not have to be immunocompromised for dimorphic or endemic fungi
  +
**Host factors: not applicable
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**Clinical features: evidence for geographical or occupational exposure (including remote) to the fungus and compatible clinical illness
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**Mycological evidence:
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***[[Histoplasma]] or [[Blastomyces]] antigen in urine, serum, or body fluid
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***Antibody to [[Coccidioides]] in CSF or 2-fold rise in 2 consecutive serum samples
  +
  +
==Prevention==
  +
  +
===Laboratory Safety===
  +
  +
*Many are [[Biosafety risk groups|risk group 3]] and need to notify lab if suspected
  +
*Opening the plates outside of a BSC is one of the highest risk actions
  +
  +
[[Category:Fungi]]

Latest revision as of 17:09, 7 March 2024

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

Microbiology

Epidemiology

  • Endemic dimorphic fungi are widely distributed1

Histoplasmosis

Histoplasmosis
  • 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

Coccidiomycosis

Coccidiomycosis
  • 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

Blastomycosis

Blastomycosis
  • 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

Emergomycosis

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

Clinical Manifestations

Histoplasmosis

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

Blastomycosis

  • 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

Coccidiomycosis

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

Emergomycosis

  • Cutaneous disease in immunocompromised patients, especially advanced HIV
  • Can also cause pulmonary disease, extrapulmonary disease, or disseminated

Diagnosis

  • Notify laboratory if a risk group 3 organism is suspected
  • For blood cultures, the isolator system is preferred to BacTAlert
  • Media
    • Brain-heart infusion with sheep blood plus antibacterials is preferred
    • Cycloheximide can be used to prevent growth of saprophytic molds (always with one plate without)
    • Incubate at 30ºC to enhance growth of mold forms
    • Incubated for 3 weeks for fungi in general, but should be extended to 4 weeks for dimorphic fungi
      • Coccidioides is the fastest-growing, within 3 to 5 days on SAB, and can grow on chocolate and sheep's blood agars
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

EORTC Definition2

  • 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:

Prevention

Laboratory Safety

  • Many are risk group 3 and need to notify lab if suspected
  • Opening the plates outside of a BSC is one of the highest risk actions

References

  1. ^  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.

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