1. Major Fungal Pathogens
    • Yeasts: Candida species; Cryptococcus neoformans
    • Filamentous fungi (molds): Aspergillus species; zygomycetes; rarer molds
    • Dimorphic fungi: Histoplasma capsulatum; Coccidioides immitis; Blastomyces dermatiditis; Penicillium marnefeii
    • Pneumocystis carinii – now called Pneumocystis jiroveci:
  2. Candidiasis
    • Candida species are endogenous flora
    • Naturally colonize the mouth, bowel and vaginal mucosa and skin surfaces
    • Common cause of vaginitis
    • Thrush (oral mucosal candidiasis) usually indicates profound T-cell depression
  3. Candida isolated from respiratory secretions
    • Almost always represents upper airway colonization and not true infection, therefore rarely requires therapy
    • Candida pneumonia sometimes documented in highly immunocompromised cancer patients:
    • Aspiration of oral secretions
    • Hematogenous pulmonary candidiasis is a rare, but well-descriped entity
    • Dx: Definitive diagnosis requires biopsy showing yeast within tissue
    • They are very often inhaled, but need to be in a particular stage of replication- hyphae- to be detected by the immune system
  4. Acute invasive aspergillosis happens in
    • Prolonged neutropenia: (e.g. chemotherapy for acute leukemia)
    • Stem cell transplantation:
    • Solid organ transplantation:
    • Advanced AIDS:
    • Chronic granulomatous disease
  5. Subacute Invasive Aspergillosis
    • CNPA
    • People who aren’t very immune deficient
    • Pre-exising COPD
    • Emphysema
    • Malnutrition (several months disease)
  6. Aspergillosis: spectrum of diseases governed by host factors
    • Invasive aspergillosis isn’t one disease, spectrum related to host
    • Acute invasisve aspergillosis is a rapidly progressive, frequently fatal disease that occurs in the highly immunocompromised
    • Chronic forms of invasive pulmonary aspergillosis (e.g. chronic necrotizing pulmonary aspergillosis)
    • Typically occur in patients without severe immune impairment, progress over months to years, and require prolonged therapy
  7. Allergic bronchopulmonary aspergillosis
    • This is NOT invasisive disease
    • Occurs in pts with NORMAL immunity; Th2 disease
    • Inflammatory disorder resulting from airway colonization with Aspergillus hyphae
    • Asthma; elevated total serum IgE
    • Rx: steroids – but if really needed, antifungals
  8. Invasive aspergillosis: prevention and early Dx
    • Prevention: protected hospital environment; antifungal prophylaxis in highest risk cancer and transplant recepients
    • Dx: Chest CT scan, Galactomannan antigen assay, B-glucan assay, PCR (experimental)
  9. Zygomycosis: risk factors
    • Neutropenia (leukemia):
    • Transplant recipients:
    • Diabetic ketoacidosis:
    • Iron overload:
  10. Zygomycosis: types
    • Rhinocerebral
    • Pulmonary
    • Disseminated (CNS, renal)
    • Rx: Emergency surgical debridement, amphotericin B
  11. Dimorphic Fungi – get the travel history!
    • Coccidiodes immitus – Southwest U.S.:
    • Histoplasma capsulatum – central U.S.:
    • Blasomyces dematitid – central U.S.
    • Penicillium marneffei – SE Asia

    • Coccidiodes immitus – where found?
    • – Southwest U.S.:
  12. Histoplasma capsulatum – where found?
    – central U.S.:
  13. Dimorphic fungi – pathogenesis
    • Yeast form at body temperature
    • Hyphal form in nature
    • Acute infection by inhalation of spores
    • Usually asymptomatic
    • Symptoms: Fever, pulmonary infiltrates, hypoxia
    • Immunocompromised – higher likelihood of dissemination
    • Reactivated disease can occur
  14. Coccidiodes immitis: risk factors
    • T-cell immunodeficiency:
    • AIDS
    • Steroids
    • BMT
    • Elderly:
    • Pregnancy:
    • Genetic (Asian, African American):
  15. Coccidiodes immitis: manifestations
    • Immunocompromised:
    • Fulminant disseminated disease is common and has high mortality rate
    • Disseminated disease may precede pulmonary findings
    • Erythema nodosum – immunologic response to pathogen
    • Tropism for CNS:
  16. Coccidiodes immitis: Dx
    • “spherules” pathognomonic:
    • serology
    • culture
  17. Coccidiodes immitis: Rx
    • Fluconazole
    • Itraconazole
    • Amphotericin B
    • No therapy for asymptomatic infection
  18. Histoplasmosis
    • Inhalation of spores
    • Usually asymptomatic:
    • Symptoms when present: Fever, pulmonary infiltrates (acute infection)
    • Acute sepsis syndrome
    • Disseminated: military pattern on CXR, RES, marrow, adrenals, CNS, eye, cutaneous
  19. Histoplasmosis Dx
    • Serology, urine and blood antigen detection, culture
    • Giemsa staining of peripheral blood or marrow
  20. Histoplasmosis: Rx
    • Itraconazole :
    • Amphotericin B:
    • No therapy for asymptomatic or self-limited infection
  21. Histoplasmosis: host defense
    • Intracellular pathogen
    • Can cause asymptomatic life-long infection
    • Host-defense dependent on cellular immunity: tissue granulomata; Th-1 type cytokines
  22. Cryptococcus neoformans: risk factors
    • Severe T-cell deficiency,
    • AIDS:
    • Smoking, outdoor occupations increase risk
    • Fluconazole prophylaxis decreases risk
  23. Cryptococcus neoformans: how acquired and manifestations
    • Acquired by inhalation:
    • MENINGITIS: most common manifestation!
    • Pneumonia
    • Ocular endopthalmitis: increased intracranial pressure; direct optic nerve involvement
    • Hematogenous:
    • Skin:
  24. Patients at risk for Pneumocystis jiroveci (formerly carinii – PCP)
    • Severe compromise of T-cell immunity
    • AIDS (CD4<200)
    • Vasculitis: related to use of steroids; high-dose steroids + myelotoxic agent > steroids alone
    • Malignancies: ALL, Lymphoma, T-cell depleting agents, high-dose steroids
    • Congenital or acquired T-cell deficiencies:
  25. Pneumocystis jiroveci: Dx
    • Generally requires bronchoalveolar lavage (BAL): sensitivity >90%
    • Spontaneously expectorated sputum not helpful: sputum induction with ypertonic nebulizer useful if positive, but not very specific
    • Dx established by visualization (not culture):
    • Cell wall stains (e.g. silver stain)
    • Fluorescent antibody
Card Set