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Disseminated Coccidioidomycosis. Stafford et. al., Infect Med 24 ( Suppl 8): 23-25, 2007. 31-year-old, African-American US Army Soldier Presents with fever, chills, night sweats, non-productive cough of 4 weeks Past medical history unremarkable Recently detected a painless right breast mass

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disseminated coccidioidomycosis
Disseminated Coccidioidomycosis

Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

  • 31-year-old, African-American US Army Soldier
    • Presents with fever, chills, night sweats, non-productive cough of 4 weeks
    • Past medical history unremarkable
    • Recently detected a painless right breast mass
    • Stationed at Fort Irwin, CA
disseminated coccidioidomycosis1
Disseminated Coccidioidomycosis

Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

  • Physical exam:
    • Unremarkable
    • Firm, nontender, 3-cm subcutaneous mass over right breast
    • Multiple small nontender lymph nodes were palpable in the axillae and groin
  • Lab results:
    • WBC = 11.9/µl, 30% eosinophils
    • Elevated alkaline phosphatase
disseminated coccidioidomycosis2
Disseminated Coccidioidomycosis

Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

Blood cultures = negative

Cryptococcus antigen = negative

Histoplasma urine antigen = negative

HIV antibody = negative

Tuberculin test = negative

CT scan of chest revealed diffuse, 1-2 mm micronodules in all lobes and right chest wall mass.

disseminated coccidioidomycosis3
Disseminated Coccidioidomycosis

Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

Fine needle aspirate of the mass revealed spherules filled with endospores

disseminated coccidioidomycosis4
Disseminated Coccidioidomycosis

Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

Culture grew Coccidioides immitis

Serology panel for C. immitis was positive

CSF = normal

Bone scan revealed multiple region of increased osteoblastic activity

coccidioidomycosis
Coccidioidomycosis
  • Epidemiology:
    • Endemic in arid, temperate, desert climate
      • especially Southwest United States
    • Travel history - Central-Southern CA; south NV, AZ,NM,TX
    • Fungus grows in soil and matures to form arthroconidia
    • Infection is initiated by inhalation of infectious arthroconidia
    • Filipinos, African/Native Americans & Hispanics - greatest risk of dissemination
  • Virulence factors and pathogenesis:
    • Highly infectious
    • Not highly virulent, ~99.5% of infected individuals resolve
    • Defects in CMI predispose to systemic disease
coccidioides spp lifecycle
Coccidioides spp. Lifecycle
  • Hyphae differentiate into arthroconidia, which break loose and may be suspended in the air
  • Soil disruptions and wind facilitate spread and the probability of inhalation into lungs
  • In the human host environment, in vivo differentiation produces cleavage planes and eventually huge spherules containing endospores
  • Spherules rupture releasing endospores, which can then repeat the in vivo cycle
coccidioidomycosis1
Coccidioidomycosis
  • Clinical Manifestations:
    • Not contagious
    • Route of infection: inhalation
    • Incubation: 10-21 days
    • Respiratory infection - 60% asymptomatic, all convert to skin test +
    • < 1% dissemination – soon after primary infection or years later
    • Often produces:
      • Meningitis
      • Lesions in viscera or cutaneousgranulomatous lesions which may form draining ulcers
    • Incidence in HIV-infected persons has increased
coccidioidomycosis laboratory diagnosis
Coccidioidomycosis – Laboratory diagnosis
  • Coccidioides immitis:
    • Thermally dimorphic fungus
    • In tissue: Huge (20-60 μm) thick-walled, round “spherules” filled with small (2-5 μm) endospores
    • Spherules rupture
    • In 25°C culture:
      • SDA and SDA-CC positive, 2-4 weeks; SABHI positive, 1-2 weeks
      • Hyaline septate hyphae forming barrel-shaped arthroconidia
    • At 37°C: Thermal conversion requires animals, but is not done
coccidioidomycosis laboratory diagnosis1
Coccidioidomycosis – Laboratory diagnosis
  • Coccidioidin skin test:
    • Not available in US
  • Serologic tests:
    • Combination of latex agglutination and immunodiffusion tests detects >90% early in symptomatic illness
    • Complement fixation (CF) tests for Dx
    • Serial CF titers are useful for prognosis
      • Rising titer = poor prognosis
slide12

Coccidioidomycosis

Lung tissue with a large thick-walled spherule containing multiple endospores. The smaller spherule to its left has ruptured releasing endospores.

sda sda cc
SDA + & SDA-CC +

Coccidioidomycosis

- May take ~ 2 weeks

slide16

Coccidioidomycosis

Arthroconidia

Disjuncture

coccidioidomycosis treatment
Coccidioidomycosis - Treatment
  • Treatment:
    • Most do not require anti-fungals
    • Azoles – pneumonia & nonmeningeal dissemination
    • Amphotericin B – meningeal infection and previous treatment failures
coccidioidomycosis2
Coccidioidomycosis

Stafford et. al., Infect Med 24 (Suppl 8): 23-25, 2007.

  • For our patient:
    • In spite of Amphotericin B treatment, neck pain increased and progressive enlargement of the mass was noted
    • Surgical debridement
    • Long-term antifungal therapy
  • Clues to the diagnosis of disseminated coccidioidomycosis included an infectious prodrome, peripheral eosinophilia, hilarlymphadenopathy, characteristic pattern of organ involvement (lungs, bones, soft tissues), residence in an endemic area, and African-American ethnicity.
other endemic dimorphic mycoses
Other Endemic Dimorphic Mycoses

Histopathology:

-Yeast with multiple buds

-”Mariner’s Wheel”

  • Paracoccidioidomycosis
    • Paracoccidioidesbrasiliensis
    • Endemic to Latin American countries
    • Pulmonary infection – asymptomatic, self-limiting
    • Dissemination to mucous membranes and skin
other endemic dimorphic mycoses1
Other Endemic Dimorphic Mycoses
  • PenicilliosisMarneffei
    • Penicilliummarneffei
    • HIV-infected individuals in Thailand and Southern China
    • Only species of Penicillium that is dimorphic
      • Intracellular yeast, with single septum
    • Infection mimics tuberculosis or histoplasmosis
    • Patient presentation:
      • Fever, cough, pulmonary infiltrates, organomegaly, anemia, leukopenia, thrombocytopenia
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