Dimorphic Pathogens

• True Pathogenic Fungi:

  • Dimorphic, endemic isolates
  • Infection of both immunocompetent and immunocompromised hosts
  • Restricted geographical distribution
  • Infections most commonly originate in lung resulting from inhalation of conidia
  • Infection can be asymptomatic, mild to disseminated and life threatening
  • Some most commonly associated with immunocompromised hosts
  • More opportunistic than true pathogen
• Histoplasma capsulatum:

  • Histoplasmosis
  • Culture Phase: Mold form-25°C, Tissue Phase: Yeast form-37°C
  • Tuberculate macroconidia, chlamydoconidia
  • Small, single budding yeast
  • Most exposure never identifiable
  • Symptoms dependent upon inhalation dose & host immune response
  • Disease Types: Acute Pulmonary Histoplasmosis, Chronic Pulmonary Histoplasmosis, Disseminated Histoplasmosis
  • Treatment: Susceptible to Itraconazole and Amphotericin B (lipid formulation)
• Coccidioides immitis:

  • Coccidioidomycosis
  • Common cause of Valley Fever in US
  • 60% of all patients asymptomatic
  • Disease Types: Primary Pulmonary Infection, Pulmonary Sequelae of Primary Coccidioidal Pneumonia, Disseminated Coccidioidomycosis
  • Treatment: 3 month to 6-month course of fluconazole
• Blastomyces dermatitidis:

  • Blastomycosis
  • Endemic in Midwestern, South-Central and Southeastern U.S.
  • Virulence & Progression of infection: 3 weeks to 3 months incubation after inhalation of conidia
  • Risk factors: Construction, excavation, recreational activity associated with woods and water ways
  • Treatment: Most no treatment necessary, fluconazole and itraconazole 1st line effective treatment
• Diagnosis of dimorphic infections:

  • Culture: Definitive “Gold-Standard”, Fungal antigen detection - ELISA, Histology, Molecular – NAAT
  • Direct Exam of Tissue Sections: PAS, GMS, hematoxylin-eosin (HE)
  • Other options of questionable utility: Serology, Skin test, Extract fungal antigens from cultured organism
• Laboratory procedures:

  • Inoculate test mold onto slant of BHI agar with 10% blood
  • Incubate fungus at 37°C for 3-5 days
  • Subculture the most yeast-like colony to a fresh slant of BHI with blood
  • Reincubate at 37°C for 3-5 days
  • Continue to make serial transfers until colony grows as yeast
  • If the fungus does not form yeast in 14 days, send to reference laboratory for animal inoculation
• Distribution of Dimorphic Fungal Infections:

  • Histoplasma capsulatum: Most common endemic mycosis in US, located from soil associated with bird and/or bat droppings
  • Coccidioides sp.: Common cause of Valley Fever in US, located from soil associated with hot, dry climates
  • Blastomyces dermatitidis: Common endemic mycosis in US, located in soil, decomposing leaves and organic matter, wooded areas associated with water
• • Bone and Joint Blastomycosis:
  • Bone: common involvement of pelvis, skull, vertebrae with necrosis, requiring surgical debridement
  • Joint: monoarthritis of the knee is most common, usually with other identified infection sites
  • Disseminated Blastomycosis:
  • CNS: 5 to 10% of cases, difficult to identify, biopsy required, often meningitis
  • Other organ involvement: abscesses common, possible involvement in ocular infections, brain, skeletal system, prostate, sinuses, pericardium
• Blastomyces dermatitidis:

  • Disease Types:
  • Pulmonary Blastomycosis:
  • Acute: can be misdiagnosed as bacterial pneumonia with symptoms like fever, chills, productive cough
  • Chronic: associated with weight loss, night sweats, fever, productive cough, chest pain resembling TB or lung cancer
  • ARDS: Adult respiratory distress syndrome found in both immunocompromised and competent individuals, associated with corticosteroid use and severe T cell dysfunction
  • Cutaneous Blastomycosis: most common extrapulmonary disease presenting as verrucous or ulcerative lesions
• Blastomyces dermatitidis:

  • Growth approximately 14 days
  • Mold: delicate, ropelike, septate hyphae with single, pyriform conidia produced on conidiophores resembling lollipops
  • Yeast: large, thick-walled yeast with a single broad-based bud attached
• Blastomyces dermatitidis Treatment:

  • Patients with mild and undiagnosed disease may recover without antifungal treatment
  • Reactivation can occur after 40 years of latency
  • Amphotericin B is the treatment choice for patients over 50 years
  • Itraconazole is now the first-line treatment for mild/moderate pulmonary and non-CNS disseminated infection
  • Treatment duration ranges from 6 to 12 months depending on infection severity and immune status
  • Echinocandins have variable results and are not recommended
• Paracoccidioides brasiliensis:

  • Endemic in Latin America, with Brazil accounting for 80% of cases
  • Associated with humid regions near rivers, forests, and agriculture crops, and with animals like armadillos, dogs, horses, cattle, monkeys, sloths, porcupines
  • Infrequent infection in children, adolescents, and young adults, with no gender bias
  • Most cases occur in individuals aged 30 to 50 years, with over 70% having an agriculture-associated occupation
• Paracoccidioides brasiliensis:

  • Virulence & Progression of infection:
  • Only 2% of individuals progress to symptomatic infection after inhalation of conidia
  • Childhood exposure may not result in symptomatic infection for over 40 years
  • T cell dysfunction, smoking, and alcoholism play a role in infection progression
  • Conidia bind macrophages using glycoprotein 43, facilitating uptake
  • Melanin production by the organism provides protection
  • Cell-mediated immunity is essential for organism control and elimination
• Paracoccidioides brasiliensis Treatment:

  • Based on severity, fungistatic treatment requiring host immune response for complete elimination
  • Amphotericin B is used for severe disseminated disease only
  • Mild disease is treated with itraconazole, voriconazole, or trimethoprim/sulfamethoxazole
  • Treatment duration is typically 1 year, with relapse occurring in 15-25% of patients even with appropriate treatment
• Sporothrix schenckii:

  • Most common subcutaneous fungal disease in the U.S., causing sporotrichosis or "Rose Gardener's Disease"
  • Endemic nationwide, commonly found in Central and South America in soil, plant matter, rose bushes, and hay
  • Most cases occur after direct inoculation through the skin, with subcutaneous involvement being most common
• Sporothrix schenckii:

  • Growth matures within 7 days
  • Mold: small, cream-colored, wrinkled hyphae with numerous conidia forming a "rosette" at conidiophore ends
  • Yeast: soft, white to tan, singly or multiply budding elliptical cells
• Sporothrix schenckii Treatment:

  • Itraconazole is the most common choice, typically administered after all lesions have resolved for 2 to 4 weeks and continued for 3 to 6 months
  • Supersaturated potassium iodide (SSKI) is another treatment option for skin sporotrichosis
  • Severe infections may require IV amphotericin B followed by oral itraconazole for a total of 12 months of treatment
• Emergomyces:

  • A new dimorphic fungal pathogen with 4 known species causing infection in different regions
  • Inhalation of conidia from contaminated soil is the mode of transmission
  • Early data suggests humoral immunity is more important, with a risk factor being immunocompromised or T cell deficiencies
• Emergomyces canadensis:

  • Mold phase after 28 days at 30°C, yeast phase after 9 days at 35°C
  • Mycelial phase showing conidia borne at the ends of conidiophores, yeast cells with narrow-based budding
  • Treatment for immunocompromised patients includes liposomal amphotericin B for 2 weeks followed by itraconazole for 12 months