Unit 4 - Pulmonary Fungal Infections; Systemic Mycoses Flashcards
what are major themes of systemic mycoses?
- environmental: in spores/fungi in soil
- -not likely to be drug resistant, but likely unable to eradicate
- inhaled into lungs
- thermal dimorphism
- range of severity: asymptomatic clearance to death
- not person-person transmissible (not contagious)
- differential will include TB, but source is American dirt, not foreign crowds
explain what the coccidioides organism is
- how it is transmitted
- which seasons
Coccidioides immitis and posadasii
- dimorphic: mold in soil, spherule in tissue
- -grow in rainy season as noninfectious mycelia mold
- endemic in SW US and Latin America
- -dry areas; in travel and shipped material
- in dry summer soil, forms hyphae with alternating arthrospores and empty cells
- arthrospores are carried on wind
explain the pathogenesis of coccidioides
arthrospores are inhaled; infectious dose as low as 1 IU, but if higher have more symptoms
- within terminal bronchiole, changes form:
- -30 um spherules highly resistant to eradication by immune system
- -thick, doubly-refractive wall willed with endospores
- -wall ruptures to releases endospores w/in lung that develop into new spherules
which form of coccidioides is infectious? how does it spread?
arthrospores only, not spherules or endospores (which disseminate in lung)
-spreads by direct extension
what does coccidioides endospore/spherule growth lead to?
granulomatous lesions
- CMI delayed hypersensitivity response
- if CMI is healthy, infection is contained in granulomas in lungs (like TB, except it resolves)
- if immunosuppressed, disseminated infectious by hematogenous spread via MP seen in bones and meninges
- -induces immune anergy and may be fatal
what are risk factors of coccidioides?
- age
- immunocompromised
- late-stage pregnancy
- occupational
- Black/Filipino (rare fact of exception)
what is the difference between acute and chronic coccidioides?
acute: innate immunity (MP) may spread it
chronnic: lymphocytes and histiocytes initiate granuloma and giant cell formation (containment)
what does the PPD exam show for coccidioides?
PPD with coccidioidin or spherulin
+ if exposed w/ cleared or contained infection
- if unexposed or immunosuppressed (disseminated infection)
what does physical exam of contained coccidioides show?
often asymptomatic, but +PPD; if symptoms, called “valley fever” or “desert rheumatism” and subsides spontaneously
- may have influenza-like illness (fever, cough)
- 50% have lung changes on X-ray
- 10% may develop erythema nodosum (adults) or multiforme (peds), or arthralgias
- -this ironically means that the risk of dissemination is low (due to positive immune response)
what does X-ray show in coccidioides?
- infiltrates
- adenopathy
- effusions
- nodules resembling malignancy (biopsy)
- bronchoscopy is useful
what does erythema nodosum in coccidioides look like?
“desert bumps”
- red, tender nodules on exterior surfaces like lower legs
- delayed cell-mediated hypersensitivity to fungal Ag
- immunogenic complication of granulomatous diseases
what does disseminated coccoidioides look like?
may affect any organ (mostly meningitis, osteomyelitis, and skin or lymph nodes –> soft tissue abscess, hematogenously seeded)
- disseminates in 1% of general population, 10% of Africans, Filipino, or late-pregnancy, DM, cardiopulmonary
- associated with sweat, dyspnea, fever, wt loss; may reactivate after treatment
what is a good sign of coccidioides immunity?
erythema nodosum (adults) or multiforme (peds)
what do labs say about coccidioides?
- tissue specimens are spherules microscopically
- Sabouraud’s agar at 25 C shows cottony white mold; hyphae with arthrospores –> thus they are infectious
- serology for exposure and titers; they spike if disseminating
- -very specific, not sensitive
what is treatment for coccidioides?
- none for mild disease (high morbidity, low mortality)
- persisting lung lesions or disseminated: amphotericin B or itraconazole (need years of therapy)
- meningitis: fluconazole, continue as long-term suppressive, may add intrathecal amphotericin B
how to prevent coccidioides?
immunosuppressed people should avoid travel to endemic areas
explain the organism that causes Histoplasma
Histoplasma capsulatum (most common systemic mycoses)
- thermally dimorphic (mold in soil, yeast in tissue)
- two types of asexual spores; tuberculate macroconida and microconida
- endemic in patches of acidic, damp soil (Ohio and Mississippi river valley), or bird droppings (esp. starlings or bat guano)
- excavation of contaminated soil for construction can set off an outbreak
how is histoplasma different from African histoplasmosis?
Histoplasma = Histoplasma capsulatum (most common systemic mycosis)
African histoplasmosis = Histoplasma duboisii (different disease)
what are the differences between tuberculate macroconida and microconida of histoplasma?
both are forms of asexual spores
- macro: grows in culture, with thick walls and finger-like projections
- micro: infectious form from environment, with smaller, thin, smooth walls
explain the pathogenesis of histoplasma
- spores are inhaled, then engulfed by alveolar MP
- can survive endocytosis and lysosomal fusion by producing bicarbonate and ammonia (raise pH to inactivate hydrolytic enzymes)
- replicate as yeasts in MP (convert), then spread throughout body
- healthy CMI will be asymptomatic and clear at low dose (form granulomas that calcify and contain infection)
- -may see erythema nodosum during initial inflammatory response
- high dose exposure may cause pneumonia with cavitary lung lesions on primary infection
- immunosuppression (or very young/old) leads to more sever dissemination
what is clinically seen in immunosuppressed histoplasma patients?
- pancytopenia
2. ulcerated lesions on tongue
how do you diagnose histoplasma?
- PPD not useful; too many false +/-
- mild cases are nonspecific-flulike; self-limited, minimal findings, EN/EM
- cough, chest pain, hemoptysis if spreading in lungs
- -cavitary lung lesions
- granulomas in the liver and spleen
- may see weight loss in geriatric
what do labs look like in histoplasma
- tissue biopsy or bone marrow aspirate for oval yeast cells within MP
- bloodwork shows pancytopenia if disseminated
- Sabouraud’s agar shows tuberculate macroconida at 25 C, yeasts at 37 C
- ELISA for histoplasma polysaccharide Ag
- DNA probes for histoplasma RNA
- urine Ag test
- serologic tests can be useful, but may X-react w/ other fungal infectious, or turn negative in immunosuppressed
what is treatment for histoplasma?
- no treatment for mild cases
- if spreading in lung, oral itraconazole (6-12 weeks)
- if disseminated, amphotericin B; must use liposomal if kidney problems
- if meningitis, fluconazole (penetrates spinal fluid well)
explain the organism of blastomyces?
Blastomyces dermatitidis (NA blastomycosis)
- dimorphic fungus
- -mold form is hyphae w/ small, pear-shaped conidia is diagnostic
- -yeast form is round w/ doubly refractive wall and single broad-based bud
- endemic in eastern NA and Great lakes
- grows in wet, rich soil
explain the pathogenesis of blastomyces
infection by inhalation of conidia
- 50% asymptomatic infection (once yeast conversion b/c has immune-modulation BAD1)
- immunosuppression or preexisting pulmonary disease predisopose to dissemination
- -hematogenous seeding of many sites
explain the diagnostic exam of blastomyces?
- mild form: nonspecific flulike illness, resolves spontaneously
- pneumonia: high fever, chills, cough w/ mucopurulent sputum, pleuritic chest pain; rarely get EN
- chronic illness: looks like TB (pulmonary symptoms w/ weight loss, night sweats, hemoptysis
- fast, severe form: ARDS w/ fever
- all may include skin lesions, slow development (if mo-yrs old), bone/joint pain
- CXR is variable, nonspecific
what does blastomyces show on lab?
- tissue biopsy - thick-walled yeast cells with single, broad-based buds (non-caseating)
- culture - hyphae w/ small pear-shaped conidia
- PPD and serology are inadequately specific
- sputum microscopy (KOH mount) is 75% diagnostic
what is treatment for blastomyces?
- most people: itraconazole
- severe: amphotericin B
- surgical excision of loci
- meningitis: fluconazole
what does disseminated histoplasma look like?
- cardiac or CNS symptoms in addition to tongue lesions
- granulomas in liver/spleen (sonogram)
- mass lesions, meningismus, cranial nerve deficits
- GI lesions or masses
- ocular scars in the back
what are other names for paracoccidioides?
S. American blastomycosis (PCM, Lutz-Splendore-Almedia disease)
what is the organism involved in paracoccidioides?
Paracoccidioides brasiliensis
- dimorphic fungus
- -mold form has thin, septate hyphae
- -yeast form is thick-walled with multiple buds (diagnostic)
- endemic to rural Latin America (travelers or immigrants)
explain the pathogenesis for paracoccidioides?
- spores are inhaled
- early lesions occur in lungs
- asymptomatic infectiou common
- more severe infection includes oral mucous membrane lesions and LN enlargement (immunosuppressed = malnourished)
- dissemination is possible if immunosuppressed or treated for years
- cutaneous infection if minor injuries w/ spore-coated wood
what is the diagnostic exam for juvenile type paracoccidioides?
acute form (rare, but much more severe)
- in pediatrics or immunosuppressed
- skin lesions, fever, malaise, weight loss
- lymphadenopathy and hepatosplenomegaly
- history of agricultural work, malnutrition, smoking, alcoholism
- lung imaging more abnormal than breath sounds
- R-sided heart failure
- X-ray shows interstitial infiltrates or mixed lesions, usually bilateral and symmetric, in central and basal parts of lung
what is the diagnostic exam for adult type paracoccidioides?
chronic and much more common (less severe)
- very long latency period (up to 30 yrs)
- pulmonary symptoms
- oral and skin lesions
- nonspecific immunogenic symptoms
what do labs look like for paracoccidioides?
- pus or tissue samples: yeast cells with multiple buds (diagnostic; stain siler)
- culture takes 2-4 weeks
- serologic testing: significant Ab titers correlate with active disease
- skin test not helpful, non-CSF
what is treatment for paracoccidioides?
- oral itraconazole for 6 mo and IV amphotericin B if severe, then switch
- improvements in general health, as PC is more opportunistic than other systemic mycoses (correct diet, rest, smoke alcohol)
