Brian Locke

Fungal Infections

Dimorphic Fungal Infections

Mold form and yeast form

mold = cold (nature, 25-30c)

Yeast in the beast (in organism, 37c)

Endemic fungi = natural habitat is limited to a given region

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Coccidiodes Imitis / Posadacii

Desert regions - classically in Arizona and San Joaquin valley, but does have outbreaks into southern utah

60% of infections asymptomatictic

  • Pneumonia is predominant (may have joint- 'desert rheumatism' and rash: erythema nodosum or multiform)

Transmission: inhale the spores -> 1-4 week incubation time. Can reactivate after transplant - so give post-transplant prophylaxis.

Radiographically - lobar/interstial infiltrate, nodule, or mass-like (occasionally cavitary)

Diagnose with:

  • eosinophilia.
  • some day EIA for antigens may be more widely use
  • serology - cocci antibody panel (has all 3 of: ELISA, immunofixation/immunodiffusion, complement fixation which gives you a way to monitor response. ELISA has lots of false positivities, particularly with IgM - which is cross reactive)
  • culture (grows within 1 week) - reverts back to yeast form so can be infectious. very specific (no 'contaminants')

Treatment:

  • can observe mild symptoms in immunocompetent
  • treat all patients with immunocompromised or soft tissue infection. Fluconazole, Posaconazole, or (if disseminated) Amphotericin

Treatment guideline - https://www.idsociety.org/practice-guideline/coccidioidomycosis/

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Histoplasma Capsulatum

Smallest yeast in tissue. Has hyphae. Can be intracellular

Inhale spores from soil (esp excavated - construction, agriculture. Also caves - grows well in guano). No human-human transmission. 7-21 d incubation.

Mimics Tb. Goes along with HIV.

  • 50-60% asymptomatic.
  • Can cause pneumonitis or sarcoidosis/malignancy mimic acutely.
  • Generally doesn't disseminate unless very immunosuppressed.
  • Chronic complications include fibrosing mediastinitis / pericarditis, or lymphadenopathy. Often causes liver/spleen calcification.

Diagnosis:

  • urine and serum antigen tests (order both, together). Not great sensitivity in immunocompetent. Some cross reactivity with blast > cocci. Can cause false positive galactomannon.
  • gold standard: culture takes up to 4 weeks. Only grows 10% of time (higher if cavitary or disseminated), so prefer multiple samples.

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Blastomyces Dermitidis

Yeast looks like a snow man (broad based budding)

Decaying organic matter, inhalation exposure.

Longer incubation: 30-45 days

Presentation:

  • Classic: more cutaneous manifestations (chronic, verrucous).
  • Pneumonia can be subclinical (50%) and chronic. If acute, flu-like.
  • chronic: mimics Tb/malignancy often with mass-like infiltrate or fibronodular infiltrates.

Diagnosis:

  • blastomyces antigen - very cross reactive (79% specific). BDG will be negative.
  • histopathology
  • culture 1-3 weeks

Treatment:

  • can forego treatment if mild

Similar distribution to history - though more in the northeast.

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Paracoccidiodes Brasilensis

"Captains Wheel" in yeast form.

Chronic, progressive, systemic illness. Mostly reticuloendothelial involvement (e.g spleen) in acute form, then lung in the chronic form. In addition to infiltrates, cause pHTN and fibrosis.

Inhaled spores, very long incubation.

Concentrated in Brazil / south america. Diagnose with culture (other diagnostics not available).

Taloromyces (Penicillium)

HIV infected individuals from SE Asia. Skin lesions that mimic molluscum. Diagnosed by culture.

Aspergillus

ABPA

Almost exclusively in Asthma, Bronchiectasis, CF. Some HLA / Familial predilection. Lower prevalence in dry climates (e.g. utah)

Th2 response - abnormal airways allows the normal inhalation of aspergillus to build up and cause higher burden colonization (e.g. failure to clear spores -> persistent inflammatory response)

Dx criteria: [ ]

Steroids is treatment (e.g. 0.5 mg/kg for 2 weeks, then alternating days). Itra/Vori (itra has interactions with inhaled corticosteroid so drop dose). Maybe omalizumab but data sparse.

Chronic Aspergillosis

Treat if symptomatic, progressive with 4-6 month of Oral triazole (itra, vori, posa). Extend to 9 months if not better, then resect.

Aspergilloma

Fungal ball. Hyphae + extra cellular matrix. Minimal or no symptoms - lack of progression over 3 months. Serologic or micro evidence of Aspergillus.

CCPA

Chronic Cavitary Pulm Asp - aspergilloma in cavity. +Inflammatory symptoms and markers. Need evidence of aspergillus. Will progress over 3 months on imaging. So needs treatment

CFPA

Chronic fibrotic pulmonary aspergillosis - end stage of CCPA. Loss of lung function associated with the above.

Aspergillus Nodule

<3cm, can have cavitary component. Similar to malignancy, crypto, cocci

Subacute invasive aspergillosis

Mildly immunocompromised host (old, DM, etOH, immunomodulators) - similar to CCPA but progresses quickly and histo shows invasion.

Acute Aspergillosis

####Invasive Pulmonary Aspergillosis usually from fumigatus (though dissemination is usually from other types). Prolonged, severe neutropenia or t-cell disregulation are predisposing.

Imaging: variable - solid micro nodular opacity progressing to consolidation, cavitation, effusion. "Halo sign" is hemoptysis/invasion, "air crescent sign" = later in course.

In immunocompromised host:

  • Serum GM Se/sp: 80%/80%
  • BAL GM: 85/90
  • BDG: 80/80
  • Both+ 95/95+

Treat with Voriconazole (though doesn't cover Mucor, so may need to exclude) - causes visual SE. Iso, Posa. Caspo+Vori has synergy if the patient is in trouble.