Respiratory Infections 8 Flashcards
Fungal RTIs- primary pathogens
(healthy & immunocompromised) • Histoplasma capsulatum • Blastomyces dermatidis • Coccidioides immitis • Paracoccidioides brasiliensis
Fungal RTIs Opportunistic Pathogens
Immunocompromised individuals
Aspergillus spp.
Cryptococcus neoformans
Pneumocystis jirovecii
general features for primary fungal mycoses
• If symptomatic: most commonly presents like an acute, community- acquired pneumonia:
– Cough
– Fever
– Chest pain
• Consider as an option if a diagnosed CAP isn’t responding to antibiotics
Sometimes: disseminate to extrapulmonary sites:
• Granulomatous lesions on skin or mucous membranes
• Rheumatologic syndromes – arthritis/arthralgia, erythema nodosum, erythema multiforme
pathogenesis of systemic fungal mycoses
- Initial infection
• Exposure via inhalation
• Fungal attachment
• Dimorphic conversion and/or extension of hyphae - Virulence factors
• Incomplete killing of inhaled conidia —> germination
• Tissue invasion
• Enter bloodstream and disseminate - Damage results from:
• Inflammatory response
• Direct damage to tissues
• Fungal enzymes
Lab Diagnosis of fungal mycoses
Clinical samples: Sputum, Bronchoalveolar lavage (BAL), Transtracheal aspirate, Lung biopsy
• Techniques used include:
– Direct microscopy, Histopathology, Culture
• (fungalspecificstains,Sabourand’sagar)
– Serology (limited; not available for all infections)
• Enzyme Immunoassay (EIA), Immunodiffusion (ID)
– Molecular
• PCR
Histoplasmosis clinical presentation
- Chest x-ray: nodular infiltrates in all lobes
- BAL showed mycelium and oval yeasts
- mainly Asymptomatic
Extrapulmonary manifestations
Acute syndromes:
- Pneumonia
- Disseminated disease
(Immunocompromised individuals)
Chronic syndromes:
Cavitary pulmonary lung disease
Calcified lymph nodes
Mediastinal fibrosis
H. capsulatum var capsulatum
– Pulmonary & disseminated infections
– Eastern US and Latin America
– Thinner cell walls; smaller size (2-4 μm)
H. capsulatum var duboisii
– Skin and bone lesions
– Tropical Africa
(“African histoplasmosis”)
– Thicker walled; larger yeasts (8-15 μm)
Biology of histoplasmosis
- exists as mold with aerial hyphae
- hyphae produce macroconidia and microconidia spores
- microconidia inhaled
- warm temp signals transformation to an oval budding yeast
- yeast are phagocytized by immune cells and transported to lymph nodes
- blood stream
Histoplasma capsulatum epidemiology
Fungus naturally found in acidic soil with high nitrogen content.
- E.g., enriched with bird or bat droppings
Outbreaks therefore associated with:
• Areas where birds/bats roost, e.g. caves, old buildings
• Areas where buildings are undergoing demolition or reconstruction
• Rotting trees
Pathogenesis of Histoplasmosis
- Microconidia and hyphae are aerosolized and inhaled
- Phagocytized by alveolar macrophages
- Macrophages travel to local lymph nodes
- Travel through blood to other body locations
Histology of histoplasmosis
Non-encapsulated, thick walled and narrow base budding yeasts in alveolar macrophages (*Facultatively intracellular)
Clinical presentation of blastomycosis
Acute • Non-specific,self-limited • Cough • Nonproductive becomes productive • Fever • Chestpain • SOB
• Acute illness: resembles bacterial pneumonia, with mucopurulent or purulent sputum
• Chronic illness: resembles TB (low fever, cough, fatigue, chest pain, night sweats)
Cutaneous lesions : verrucous or ulcerated in appearance
Biology of blastomycosis
- exists as mold with separate aerial hyphae
- these spores are inhaled
- warm temp in host signals transformation into broad based budding yeast
- yeast colonizes the lung or disseminate into blood stream to skin, bones, joints, cns.
Blastomyces dermatitidis epidemiology
• Soil,decaying organic material
Not associated with bats or bird droppings
• Outbreaks associated with contact with disturbed soil
• Exposure risk: outdoor activities e.g., hunting, camping, forestry work
• Reportable in: Arkansas Louisiana Michigan Minnesota Wisconsin
Histopathological findings for blastomyces
Clinical presentation: Coccidioidomycosis (Valley fever)
• Primarycoccidioidal pneumonia
- Resembles a community acquired pneumonia:
• Cough• Chest pain • Fever
- Generalized systemic symptoms
• Fever• Drenching night sweats• Weight loss
Immunologic:
• Rheumatological, e.g., arthralgia
• Cutaneous, e.g., erythema nodosum
Biology of coccidioidomycosis
- exists as mold with spectate hyphae
- hyphae fragment into arthroconidia which are easily aerosolized when disturbed
- arthroconidia are inhaled and settle in lungs
- transforms to spherules
- spherules divide until they are filled with endospores (protect against phagocytosis)
- spherules ruptures—> endospores released and disseminate
Coccidioidomycosis (Valley Fever) epidemiology
- southwestern states, Mexico, Brazil
- dry season
California: C. immitis
Outside California: C. posadasii
Clinical presentation: Paracoccidioidomycosis
Paracoccidioides brasiliensis
Chronic form
• Reactivation of primary infection
• More common form
• Men 30-60 y/o/a
Lungs: pulmonary infiltrates
• dry cough
• dyspnea
Can often have extensive lung involvement without symptoms of pulmonary disease
Ulcerative and nodular mucocutaneous lesions in the nares and mouth
Clinical presentation: Cryptococcosis
• Latent Symptomatic: • Pulmonary symptoms – pneumonia like illness • Cough • Fever • Chest pain • Weight loss • CNS – Cryptococcal meningitis
Two species of pathogenic Cryptococcus:
C. gattii
C. neoformans
Histology of cryptococcus
India ink prep: Polysaccharide capsule is clear halo around yeast cells
Cryptococcus neoformans Pathogenesis
• Inhalation triggers production of capsule
- Antiphagocytic function
• Melanin production
- Protect against attack by immune effector cells and oxidative products
• Strong affinity for CNS – Neurotropic
Cryptococcus neoformans epidemiology
Grows well in decaying wood, soil; especially soil enriched by bird droppings (NB: birds are not vectors)
Common fungal infection in AIDS patients with CD4+ T cell count <100 cells/μL, Sarcoidosis, on immunosuppressive therapy
Transmission
Inhalation of spores or dessicated yeast cells
Pneumocystis jirovecii clinical presentation
progressive dyspnea, nonproductive cough, fever for days to weeks.
• Extrapulmonary lesions (<3%) - lymph nodes, spleen, liver, and bone marrow
• Hallmark of infection –
interstitial pneumonitis w/mononuclear infiltrate (predominately plasma cells)
Pneumocystis jirovecii biology and epidemiology
• Has cholesterol in place of ergosterol in cell wall
• Difficult to grow in culture
3 developmental stage in the life cycle: Trophic, Precystic, Cystic
Epidemiology:
Common fungal infection in AIDS patients with CD4+ T cell count <200 cells/μL
Pneumocystis jirovecii Pathogenesis
• Tropic form attaches to epithelium
• Interaction of P. jirovecii with alveolar epithelial cells
and macrophages triggers inflammatory response
Clinical presentation: Aspergillosis
• Allergic • Invasive aspergillosis - fever, chest pain, cough w blood • Pulmonary aspergillosis • Disseminated aspergillosis • Aspergilloma(fungalball)
Aspergillus sp.: Biology
• Conidia are being inhaled regularly! • Septate hyphae, acute-angle branching • Aspergillus species associated with infection include: A. fumigatus A. flavus A. niger
Epidemiology:
• Decaying organic matter, air and soil.
Aspergillosis Pathogenesis
- Inhaled conidia are phagocytosed
* Failure to active cellular immunity due to immuncompromise —> clinical disease
