Coccidioidomycosis

(coccidioidal Granuloma, Valley Fever, San Joaquin Fever)

Definition

  • Caused by
  • Coccidioides
  • Thermally dimorphic fungi
  • C. immitis
  • Mostly in San Joaquin in California
  • C. posadasii
  • found
  • Easily confused with other fungal infections due to similar histopathology

Case Report 1

Nakamura, Hitomi, Tetsuya Nakamura, Masato Suzuki, Fujihiko Minamoto, Naoki Oyaizu, Toshio Shiba, Makoto Miyaji, and Aikichi Iwamoto. Disseminated coccidioidomycosis with intravertebral and paravertebral abscesses. Journal of Infection and Chemotherapy. 2002. 8: 0178 - 0181

-October of 1997, a 28-year old Japanese man returned to Japan after living in Arizona for 5 years.

-3 months later he developed a fever.

-MRI revealed multiple abscesses surrounding the vertebral bodies from Th7 to Th12.

-A drainage tube was inserted temporarily for diagnostic and therapeutic purposes.

-The drained pus was cultured on brain heart infusion agar with 1% dextrose (BHIDA). Also, cultured on Bact Yeast Nitrogen agar.

-Fungus was identified as Coccidioides immitis.

-After drainage, fever subsided, but new abscesses formed along the inserted drainage tube.

-Sept. 3, 1998: Patient was transferred to the ResearchHospital, Institute of Medical Science. When admitted, he had no fever, but complained of mild back pain.

-Tests revealed that C-reactive protein was elevated to 1.97mg/dl (normal range, <0.25).

-Coccidioidin skin test and HIV1 test were negative. Chest X-ray and chest CT were normal.

-IV of amphotericin B was administered, but was stopped after one week due to the patient’s nausea and renal dysfunction.

-Sept. 14, 1998: oral fluconazole at 600mg/day. Back pain subsided in a few weeks.

-December, 1998: Patient was discharged.

-After two years of oral fluconazole treatment, all abscesses disappeared; except for a small high signal intensity lesion on a T2-weighted image.

-As of August, 2001, the patient was well and was still receiving fluconazole treatment.

Case Report 2

  • Crum, Nancy F. , Ballon-Landa, Gonzalo. 2006. Coccidioidomycosis in Pregnancy : Case Report and Review of the Literature. 119: 993e11-993e17
  • 21 yr old, Hispanic female, at 32 weeks pregnant.

-Admitted to the hospital with lower back pain, chills, fever and elbow pain

  • Medical history

-Gestational diabetes mellitus

-Drug Abuse

-Negative for HIV.

  • Magnetic Resonance performed

-Lumbar vertebral lesion was present.

-Biopsy was planned for after the pregnancy.

  • Initial Testing

-Blood culture was negative

-Purified protein skin test was also negative.

-One week later the patient’s blood became positive for a mold and patient was recalled.

  • Examination upon re-admittance

-Had a fever of 103o F

-Respiratory distress

-Labor was induced and the baby was born.

  • Secondary Testing

-Blood cultures grew Coccidioides immitis.

  • Initial Treatment

-Treated with amphotericin B

  • Patient developed respiratory failure despite treatment

-Computed tomography showed worsening military infiltrates, mediastinal adenopathy, and a destructive sternal bone lesion

  • Biopsy

-Biopsy of the lumbar and sternal bone lesions grew C. immitis.

  • Secondary Treatment

-Discharged after 30 days and given oral fluconazole 800 mg daily.

  • Symptoms worsened

-Re-admitted 2 weeks later with a seizure

-Lesion were found in here brain common with coccidioidomas.

-Lumbar puncture was negative.

-Repeated magnetic resonance imaging showed new abscesses growing on areas of the lumbar.

  • Treatment

-Lipid formation of amphotericin B, at 5mg per day

-Fluconazole , at 1600mg daily

  • Three months after diagnosis

-Patient continued to improve and the newborn showed no sign of coccidioidomycosis.

Case Report 3

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Presentation of Diseases

  • Acute self limiting respiratory infection
  • Occurs 7 to 21 days after exposure
  • Acquired through inhalation of spores
  • Chronic infection
  • Called progressive coccidioidomycosis
  • Pulmonary condition or systemic conditionwhich may be fatal
  • Involves subcutaneous tissue, cutaneous tissue, pulmonary, visceral organs, bony tissue, and meninges
  • Once in the lungs these turn into spherules
  • Forms of disease
  • Asymptomatic
  • ~50% of patients
  • Acute
  • Pulmonary syndrome
  • Cough, chest pain, shortness of breath, fever, and fatigue
  • Pneumonia occurs in immunocompromised people
  • On skin
  • Popular rash, erythema nodosum and erythema multiforme
  • Chronic
  • Between 5 – 10% of individuals
  • Presents as pulmonary nodules or peripheral thin walled cavities
  • Chronic skin disease
  • Keratotic and verrucose ulcers
  • Subcutaneous flucuant abscesses
  • Joints/bones
  • Synovitis and effusion
  • Affects knees, wrists, feet, ankles, or pelvis
  • Meningeal diseases
  • Very dangerous
  • Classis meningeal symptoms
  • Hydrocephalus

Histopathology

  • Stains
  • H & E stain
  • PAS stain
  • GMS stain
  • Gridley Stain
  • Cells apparent in slides
  • Giant cells
  • Granulomatous inflammation
  • Granulomatous inflammation around developing spherules
  • Hyphae
  • Present in pulmonary cavitiesand without arthroconidia
  • This can be confused with aspergillus
  • Observed in necrotic nodules
  • Found also in brain tissue, cerebrospinal fluid

Laboratory Aspects

  • Culture
  • On Sabouraud glucose agar
  • Round, double refractile thick walled spherules
  • 20 - 80 in diameter
  • Endospores
  • 2-5μm in diameter
  • Released when spherule ruptures
  • Once out of spherule remain close to eachother
  • Appear moist, membranous gray to steel gray culture
  • Later develop aerial mycelium that are white and cottony
  • Older cultures of mycelium are gray
  • Flattened surface areas in mycelium
  • Globular structure
  • Colonies
  • Develops in 3-5 days
  • Slide mounts
  • 25 degrees
  • Shows branched hyaline septate hyphae
  • Racquet hyphae in young cultures
  • Chains of thick walled barrel shaped arthroconidia
  • Separated by clear spaces
  • These are empty cell remnants
  • Walls of the empty cells break and are present on either end of the fused conidia
  • 37 degrees
  • Large, round thick walled spherules filled with endospores
  • Grows as mold and doesn’t produce spherules unless put in special medium

Epidemiology and Ecology

  • Isolated in soil and air in endemic areas
  • Southwestern United States
  • Also Northern Mexico, Honduras, Guatemala, Venezuela, Bolivia, Colombia, Paraguay, and Argentina.
  • Outbreaks occur usually after dust storms, earthquakes, and excavation
  • Stirring of arthrocondia

Treatment and Prevention

  • Amphotericin B
  • Less active
  • Ketoconazole
  • Flucoconazole
  • Preferred in those with meningitis
  • itraconazole

References

  • Medical Mycology and Human Mycoses. Beneke, Everett S., Alvin L. Rogers. Belmont, Calfifornia (1996):136 – 141
  • Medically Important Fungi: A Guide to Identification 3rd edition 1995 American Society for Microbiology Washington D.C. (186 – 187).