Fungal Respiratory infections Flashcards
What are some opprotunistic molds by their category?
- Hyaline Molds – Aspergillus Sp. – Fusarium – Zygomycetes
- Dermatiaceous Molds – Pseudoallescheria boydii – Scedosporium inflatum – Bipolaris spicifera
- Yeasts – Cryptococcus neoformans – Candida Spp. – Trichosporon beigelii
What are some pathogenic dimorphic fungi?
• Histoplasma capsulatum • Coccidioides immitis • Blastomyces dermatitidis • Penicillum marneffei • Sporothrix schencki
What are the classes of aspergillosus disease in the lungs?
- Allergic – Extrinsic allergic alveolitis – Extrinsic asthma – Allergic bronchopulmonary aspergillosis – Allergic aspergillus sinusitis
- Saprophytic – Pulmonary aspergilloma
- Invasive – Bronchopneumonia – Necrotizing tracheobronchitis – Invasive sinusitis – Chronic necrotizing aspergillosis – Disseminated aspergillosis
Who is at higher risk and lower risk of getting Aspergillosis?
– Highest Risk • Allogeneic HSCT • Hematologic malignancies and neutropenia
– Lower risk • Autologous HSCT • Solid organ transplant • HIV • Prolonged steroids
What are the clinical manifestations of invasive sinopulmonary aspergillosis?
Clinical Manifestation – Invasive sinus disease • Headache, stuffiness, fever, epistaxis • Proptosis, cranial nerve palsies – Invasive pulmonary disease • Fever, cough, pleuritic pain, hemoptysis
Diagnosis of aspergillosis?
- Radiology – CT scan (ground-glass attenuation surrounding a pulmonary nodule “Halo sign”) – Other features (multiple nodules, lobar infiltrates to pleura)
- Cultures – Positive culture interpreted with risk factors – Significant in hematologic malignancies, neutropenia, HSCT
- Histology – Dichotomous acute-angle branching hyphae
- Serology – Galactomannan assay
Therapy for Aspergillosis?
Therapy
– Amphotericin B
– Azoles • Itraconazole • Voriconazole • Posaconazole
– Echinocandins • Caspofungin • Anidulofungin
– Combination Therapy
– Immunomodulating agents • G-CSF
General features of Cryptococcus? Immunity?
General – World wide – usually in excreta of birds (pigeons) – Species • Cryptococcus neoformans var. grubii (immunosuppressed) • Cryptococcus var. gatti (immunocompetent)
– Immunity • Cell mediated • Th1 response – Production of TNF, IFN, IL2
Predisposing factors to a Cryptococcus infection?
– HIV infection
– Corticosteroids
– Solid organ transplant
– Hematologic malignancies
– CD4 T-cell lymphopenia
– Connective tissue diseases • Sarcoid, SLE, RA – Monoclonal antibodies • Etanercept, infliximab, alemtuzumab
– Cirrhosis
– Pregnancy
Clinical manifestations of Cryptococcus?
Most often • CNS • Respiratory
– Less often • Prostate • Skin • Bone • Urinary tract • Blood
What is most important about Cryptococcus? Clinical manifestations?
- Most important portal of entry
- Clinical manifestations – Asymptomatic – Fever, nonproductive cough, chest pain, weight loss – Acute respiratory failure – Immunocompromised have associated CNS involvement
Radiology of Cryptococcus?
- Radiology – Most often – Well defined single nodules – Multiple pulmonary nodules • Cavitation in compromised
- Less often – Pleural effusion – Hilar adenopathy – Diffuse reticulonodular infiltrates
Serology of Cryptococcus?
Serology – Cryptococcal antigen is negative in immunocompetent
Lab diagnosis of Cryptococcus?
– Direct exam of specimens • Round encapsulated yeast cells (5 – 20 mm)
– Histopathology • Pulmonary nodules, BAL, lung tissue • Gomoris methenamine silver stain, PAS stain, FontanaMasson silver stain
– Serology • Cryptococcal antigen – Not helpful in diagnosing and deciding therapy – Usually negative in competent patients with localized respiratory infection
• Cryptococcal antibody – False positive with blastomycosis, histoplasmosis
– Culture • Nohyphae or pseudohyphae • Urease positive
Management of Cryptococcus?
– Asymptomatic with positive respiratory secretions • Observe vs. therapy
– Immunocompromised or symptomatic • Fluconazole • Itraconazole • Amphotericin B
– Severe immunocompromised with symptoms • Amphotericin B plus flucytosine for 2 weeks, then fluconazole for 10 weeks
Epidimiology of Histoplasmosis?
– Endemic in Mississippi and Ohio River Valley • Very high in Indianapolis
– Large flocks of birds • Landscaping, cleaning in attics, and barns • Tearing down structures where birds nest
– Cave explorers (spelunking) • Bats
Pathogenesis of Histoplasmosis?
– Microcondia is infectious form • To alveoli and engulfed by neutrophils and macrophages
– Yeast phase • Exists intracellular in macrophages • Spreads to hilar and mediastinal nodes and hematogenous to RES
– Cell mediated immunity • Internally controls the disease • Severe disease in CMI deficient
– Exists in latent infection • Reactivates in immunocompromised
Explain the clinical manifestations of histoplasmosis pulmonary infection?
Pulmonary Infection
– Acute pulmonary histoplasmosis • Fever, chills, fatigue, myalgia, dyspnea, non-productive cough • Chest x-ray – Patchy infiltrates – Multilobar, nodular infiltrates with hilar and mediastinal nodes
– Granulomatous mediastinitus • Large mediastinal, hilar nodes, necrotic • Impinge on adjacent structures • Dysphagia, chest pain, cough • Tracheoesophageal fistula
– Chronic cavitary pulmonary histoplasmosis • Fever, fatigue, anorexia, weight loss, productive cough, hemoptysis • Chest x-ray • Mimmics tuberculosis • Cavitary upper lobe infiltrate
– Fibrosing mediastinitus • Young women • Excessive fibrotic response in mediastinum • Entrapment of great vessels and bronchus • Dyspnea, cough, wheezing, hemoptysis • Superior vena cava syndrome, heart failure, pulmonary emboli
Diagnosis of Histoplasmosis?
– Growth on tissue or fluid samples definitive for diagnosis • Uniform appearing 2 – 4 mm oval budding yeast
– Stains • Methenamine silver or Periodic Acid-Schiff (PAS) • Bone marrow, liver, lymph nodes, ulcers
– Urine antigen • Useful for disseminated infection
– Antibody tests • Immunodiffusion (H or M antibodies) • Complement fixation • Useful for chronic disseminated or chronic pulmonary histoplasmosis
Explain a disseminated infection in histoplasmosis? Seen in? Symptoms? Labs?
– Seen mostly in immunocompromised patients • AIDS, transplants, TNF inhibitor, steroids
– Symptoms • Chills, fever, malaise, anorexia, weight loss, dyspnea • Hypotension, ARDS, sepsis syndrome, DIC
– Lab • Pancytopenia, elevated alkaline phosphatase
Treatment of histoplasmosis?
– Severe • Amphotericin B
– Mild to Moderate • Azoles (Itraconazole, Fluconazole, Voriconazole)
– Echinocardins • Inactive
Blastomycosis epidimiology?
– Endemic in South Central and North Central USA • Wisconsin, Minnesota, Southern Ontario, Manitoba, Alberta
– Natural habitat • Soil, decaying wood • Large outbreak in beaver pond
– Seen in outdoorsmen • African Americans • Aboriginal population of Manitoba
Pathogenesis of blastomycosis?
– Acquired through inhalation of mold form into alveoli
– Change to yeast form in lungs and multiply • Dissemination hematogenously before immunity develops
– Immunity • Neutrophils • CMI with T cells, macrophages • More severe disease in immunocompromised
Pulmonary manifestations of Blastomycosis? Chest x-ray?
– Asymptomatic
– Overwhelming severe infection • ARDS
– Acute pneumonia • Atypical presentation without response to antibiotics
– Sub acute, chronic pneumonia • Fever, night sweats, fatigue, productive cough, dyspnea
– Chest x-ray • Often mass-like lesions • Multiple nodular lesions • Lobar infiltrates • Cavitary lesions • Hilar, mediastinal nodes rarely seen
Cutaneous lesions of Blastomycosis?
Cutaneous lesions • Well circumscribed, nonpainful papules, nodules, plaques • May be verrucous with microabscess • May ulcerate • May be confused with squamous cell cancer, atypical pyoderma gangrenosum or nontuberculous mycobacterial lesions
Commonly seen other clinical manifestations of Blastomycosis without skin or pulmonary?
– Genitourinary • Prostate
– Septic arthritis
– Osteomyelitis
Diagnosis of Blastomycosis? Serology?
– Growth of organism from tissue biopsy, sputum, or body fluid is definitive – Histopathology from tissue biopsy • Early diagnosis • Yeasts are large, thick-walled, and buds single and broad based • Stain with methenamine silver or PAS
– Serology • Antibody tests not sensitive nor specific • Urine antigen is available
Therapy for Blastomycosis?
– Severe disseminated disease • Amphotericin B
– Mild to moderate disease • Azoles – Itraconazole preferred – Fluconazole higher dose 800 mg q.d. – Voriconazole – no data – Posaconazole – no data
Describe the epidiomolgy of coccidiomycosis?
- Dimorphic Fungus – Arthroconidia (spores) – Spherule with endospores (tissue)
- Region – Southwestern USA – San Joaquin Valley – Arizona – Mexico
- Ecology – Soil organism (arthroconidia) – Dispersed in air
- Persons at risk – Occupation with soil exposure – Immunocompromised patients • AIDS • Transplants • TNF antagonists • Pregnancy – Persons of Filipino or African-American descent
Pathogenesis of coccidiomycosis?
– Arthroconidia are inhaled – Ingested by pulmonary macrophages • Convert to spherule with hundreds of asexual endospores
– Spherule ruptures • Endospores disseminate hematogenously to other organs
– Host control is through cell-mediated immunity
Clinical presentation of Coccidiomycosis?
– Primary pulmonary infection • Asymptomatic • Resembles CAP or influenza
– Fever, cough, pulmonary infiltrates • Most resolve spontaneously • Special conditions
– Rheumatologic syndromes » Erythema nodosum, erythema multiforme
– Pleural effusion
– Immunosuppression » Develops into progressive disease and dissemination – Pregnancy »3 rd trimester with complications – Race » Filipinos, African-Americans with progression
Outcomes of the primary coccidiomycosis infection?
– Uneventful healing
– Coccidioidoma • Benign mass-like lesion
– Progressive or persistent pneumonia • In immunocompromised • Usually infiltrates are present over 2 months and progress with cavitation
– Chronic pulmonary coccidiomycosis • 5% of patients • Smoldering over years • Nodules may cavitate and fibrose • Destroy lungs progressively • May need resection
– Disseminated disease • All regions of body except GI • Mortality high – CNS • Life long therapy
Diagnosis of Coccidiomycosis?
– Culture • Most definitive for diagnosis
– Histopathologic findings • Methenamine silver, PAS • Spherules with endospores
– Immunologic • Complement fixation – 1:16 or > worsening disease • Immunodiffusion • ELISA, IgG, IgM (sensitive and specific)
Therapy for Coccidiomycosis?
– Amphotericin B • Primary disease • CNS
– Azoles • Ketoconazole (not used) • Itraconazole • Fluconazole
– Primary disease • Voriconazole • Posaconazole
– Echinocandins • New agents
