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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:
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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
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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
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Acute invasive aspergillosis happens in
- Prolonged neutropenia: (e.g. chemotherapy for acute leukemia)
- Stem cell transplantation:
- Solid organ transplantation:
- Advanced AIDS:
- Chronic granulomatous disease
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Subacute Invasive Aspergillosis
- CNPA
- People who aren’t very immune deficient
- Pre-exising COPD
- Emphysema
- Malnutrition (several months disease)
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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
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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
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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)
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Zygomycosis: risk factors
- Neutropenia (leukemia):
- Transplant recipients:
- Diabetic ketoacidosis:
- Iron overload:
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Zygomycosis: types
- Rhinocerebral
- Pulmonary
- Disseminated (CNS, renal)
- Rx: Emergency surgical debridement, amphotericin B
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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.:
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Histoplasma capsulatum – where found?
– central U.S.:
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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
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Coccidiodes immitis: risk factors
- T-cell immunodeficiency:
- AIDS
- Steroids
- BMT
- Elderly:
- Pregnancy:
- Genetic (Asian, African American):
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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:
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Coccidiodes immitis: Dx
- “spherules” pathognomonic:
- serology
- culture
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Coccidiodes immitis: Rx
- Fluconazole
- Itraconazole
- Amphotericin B
- No therapy for asymptomatic infection
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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
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Histoplasmosis Dx
- Serology, urine and blood antigen detection, culture
- Giemsa staining of peripheral blood or marrow
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Histoplasmosis: Rx
- Itraconazole :
- Amphotericin B:
- No therapy for asymptomatic or self-limited infection
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Histoplasmosis: host defense
- Intracellular pathogen
- Can cause asymptomatic life-long infection
- Host-defense dependent on cellular immunity: tissue granulomata; Th-1 type cytokines
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Cryptococcus neoformans: risk factors
- Severe T-cell deficiency,
- AIDS:
- Smoking, outdoor occupations increase risk
- Fluconazole prophylaxis decreases risk
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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:
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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:
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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
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