Micro - pulminary fungal infections Flashcards
What is the route of infection for pulmonary fungal infections?
spore inhalation
What activates pulmonary fungi to cause infection?
body heat - thermal dimorphism
What are arthroconidia?
Arthrospores; infectious form form Coccidioides that causes coccidioidomycosis
Where do Coccidioides reside (source of infection)?
soil - carried by wind when soil is disturbed
Where are Coccidioides endemic to?
southwest US and Latin America
What are the two most common fungi that cause coccidioidomycosis?
Coccidioides immitis and C. posadasii
What is the cause for the spike in cases this century?
endemic areas (southwest US and Latin America - Phoenix and Tucson AZ, Bakersfield and Fresno, CA, El Paso TX.) have become geriatric
T/F Spherules and endospores are not infectious
true
What is an associated clinical symptom of coccidioidomycosis?
erythema nodosum (skin inflammation that results in reddish, painful, tender lumps - most commonly located in the front of the legs)
Where in the pulmonary tract do Coccidioides undergo thermal dimorphism?
terminal bronchioles
What is different about source of infection from infectious dimophic fungi vs TB?
infectious dimophic fungi are from american soil
TB is from foreign crops
What form does Coccidioides adopt once it undergoes undergo thermal dimorphism?
spherule
T/F morality is low but morbitity is high from coccidioidomycosis
true
T/F coccidioidomycosis will trigger a positive PPD skin test?
true - 80% of residents in endmic population centers are PPD positive
What is most important determinant of morbidity coccidioidomycosis?
Dose of pathogen exposure - single IU (reproductive spore) can trigger positive PPD but high dose causes more symptoms
What makes the pherule difficult to eradicate by the immune system?
Thick, doubly-refractive wall
Can coccidioidomycosis be transmitted from patient to patient?
No - must have independent exposure to spores from soil
Coccidioides spherules fill with endospores once they undergo thermal dimohphism in terminal bronchioles. Rupture of spherules causes endospores so spread around lungs but an additional step is needed to cause infection, what is it?
macrophage engulphment and cytokine release
What immune response clears most Coccidioides when inhaled?
alveolar macrophages
What immune response clears Coccidioides when there is large dose exposure and significant infection?
Cell mediated immunity - forms small nodule in lung similar to TB that contains and slowly eradicates infection
What are most common symptoms of coccidioidomycosis (moderate dose exposure)
non-specific flue like symptoms with low-moderate dose
In adults: Erythema nodosum is most common clinical symptom if infection persists to chronic phase
In children:Erythema multiforme
Low dose is usually cleared and asymptomatic but still causes +PPD
higher dose can cause pneumonia or dissemination
What 2 factors are most likely to cause pneumonia or dissemination in coccidioidomycosis?
high dose exposure or if someone is immunosuppressed
What cell types are involved in acute phase of coccidioidomycosis? Chronic phase?
alveolar macrophages
lymphocytes and histiocytes
What are the roles of lymphocytes and histiocytes in the chronic phase of coccidioidomycosis?
initiate granuloma and giant cell formation (containment)
What other diseases resemple the clinical features of coccidioidomycosis
Valley fever or desert rheumatism
What are the clinical symptoms of severe symptomatic coccidioidomycosis (5)?
Fever Arthralgias Erythema nodosum Erythema multiforme Chest pain
How is coccidioidomycosis disseminated in immunosupressed patients?
intracellular travel in macrophages and hematogenous spread
What are risk factors for coccidioidomycosis?
advanced age, immunocompromise, late-stage pregnancy, occupational high-level exposure (farmers, construction workers, archaeologists), Black or Filipino race
What tissues are primarily affected by disseminated coccidioidomycosis?
bones, meninges, skin or lymph nodes (presents as soft tissue abscess)
What can coccidioidomycosis trigger causing rapidly fatal progression?
immune anergy
Localized extrapulmonary infection by Coccidioides is usually caused by what?
contaminated injury
usually resolves without treatment
contaminated Coccidioides infections can cause what symptoms?
influenzalike illness (fever, cough)
What lung changes can be seen on x-ray with coccidioidomycosis?
Infiltrates
Adenopathy
Effusions
Nodules resembling malignancy (biopsy)
T/F PPD will be negative for disseminated coccidioidomycosis infection in immunosuppressed pt?
true
T/F PPD will be positive if there is a cleared or contained coccidioidomycosis infection
true
What is the incubation period for Coccidioides?
7-30 days
When are people most likely to become infected with Coccidioides?
summer or autumn
T/F erythema nodosum/multiforme is caused spherule migration to shins or other areas causing painful rashes
False - spherules stay in lungs unless severe disseminated infection - nodosum symptoms are caused by overactive immune response (type 4 hypersensitivity rxn)
T/F coccidioidomycosis associated hypersensitivity rxn may manifest in eye as conjunctivitis
true
coccidioidomycosis disseminated to bone causes what?
osteomyelitis
What differentiates coccidioidomycosis disseminated meningitis from bacterial meningitis?
symptoms similar, but onset is slow (weeks) with coccidioidomycosis
T/F Dramatic sweats, dyspnea, fever, weight loss are symptoms of disseminated coccidioidomycosis infection
true
How do you culture Coccidioides from biopsy?
Sabouraud’s agar at 25C
what is appearance of positive coccidioidomycosis infection in culture?
cottony white mold composed of hyphae with arthrospores: cultures are infectious!
Handle in Biosafety Level 3
T/F serology titers are usefull for monitoring progression of coccidioidomycosis infection
true - IgG from blood and/or CSF spike indicates dissemination
True/false a PCR test for coccidioidomycosis is available
true
What CSF findings would you see from coccidioidomycosis disseminated meningitis?
lymphocytic pleocytosis, elevated protein, hypoglycorrhachia ( a low glucose level), eosinophilia, CF (compliment fixing) IgG
T/F serology for coccidioidomycosis are specific but less sensitive (i.e. prone to false negatives)
true
Treatment for persistant or disseminated infections
Amphotericin B and long-term itraconazole
coccidioidomycosis meningitis is initially treated with what?
fluconazole, continue as a long-term suppressive
severe or prolonged coccidioidomycosis meningitis is treated with what?
intrathecal amphotericin B
What does long term amphotericin B treatment cause? How would you treat this?
immunogenic symptoms
corticosteroids
What is treatment for mild coccidioidomycosis (e.g. flue like symptoms or mild pneumonia)?
No treatment or oral azoles (no data demonstrate faster or better resolution with oral azoles)
Who must be treated regardless of sevarity of coccidioidomycosis symptoms?
predisposed to complications: severe immunosuppression, diabetes, Black/Fillipino, cardiopulmonary disease, (oral azoles)
late term pregnancy (Amphotericin B) because azoles are contraindicated
What is the most common systemic mycosis
histoplasmosis
Where are histoplasmosis infections most common in US?
Ohio, Missouri, and Mississippi River valleys: acidic damp soil with high organic content; ~80% of people who live there are exposed
What are two (asexually reproducing) ENVIRONMENTAL forms of Histoplasma capsulatum?
Tuberculate macroconidia
Microconidia
What are the features that distinguish Tuberculate macroconidia from Microconidia?
Tuberculate macroconidia - Thick walls, Fingerlike projections
Microconidia -Smaller, thin, smooth-walled
Which forms of Histoplasma capsulatum are infectious?
Microconidia
What is the source of Histoplasma capsulatum infection?
soil,
bird droppings, esp from starlings or bat guano
T/F Histoplasma capsulatum must be inhaled to cause infection
true
95% of Histoplasma capsulatum infections are cleared by alveolar macrophages, but ones that aren’t evade immune system by what mechanism?
survive endocytosis & lysosomal fusion by producing bicarbonate & ammonia; raises pH and inactivates hydrolytic enzymes
How does Histoplasma capsulatum incubate and spread?
evade macrophage lysosomal fusion by producing bicarbonate and ammonia to raise pH, then convert to yeast form and replicate
spread hemotogenous via macrophages
What kills most Histoplasma capsulatum infections?
cell mediated immunity facilitates more efficient intracellular killing by macrophages
For those that escape macrophage endocytosis - cell mediated immune system forms granulomas, eventually calcify, contain infection
What are DEFINING symptoms of severe Histoplasma capsulatum infections
Pancytopenia
Ulcerated lesions on tongue
What symptoms can high dose Histoplasma capsulatum exposure cause?
High-dose exposure may cause pneumonia w/ cavitary lung lesions on primary infection
Which patients are most suseptible to severe Histoplasma capsulatum infection?
Very young, very old, immunosuppressed
T/F PPD is useful for Histoplasma capsulatum
False - many false positives
Both Histoplasma capsulatum and Coccidioides are thermally dimorphic and transform to yeast in tissue, what differentiates them?
Formation of spherule
What are similarities between histoplasmosis and TB?
Both for granulomas in the lungs
Both macrophages as Trojan Horses during dissemination
Both require months-years of drug treatment to clear
Both are airborne
Both cause weight loss
What is a difference between TB and histoplasmosis?
drugs used for treatment differentiate
Treatment for histoplasmosis (lung vs disseminated vs meningitis)?
spreading in lung, oral itraconazole 6-12 weeks
disseminated, amphotericin B: must use liposomal if any kidney problems, follow w/ itraconazole for at least 1 year
meningitis, fluconazole (penetrates spinal fluid well)
what fungi causes blastomycosis
Blastomyces dermatitidis
T/F infectious cause of blastomycosis is mold form hyphae with small pear shape called conidia
True
Hyphae = long, branching filamentous structure of a fungus
Yeast form of blastomyces has what features?
round w/ doubly refractive wall
single broad-based bud
What regions are blastomyes endemic to?
Eastern north america and great lakes region
grows in wet rich soil
What is the virulance factor for blastomyces?
Yeast, not mold, produce immune-modulator BAD1 on cell surface
What is the infection rate of blastomyces?
~50% Asymptomatic infection : successful clearance
How does immune system typically defeat blastomyces?
granulomatous response, may develop pulmonary symptoms in process
When would pulmonary symptoms present with blastomyces infection?
(~45 days post exposure)
Who is susceptible for dissemination, hematogenous seeding of many possible sites
Immunosuppressed or preexisting pulmonary disease
T/F Untreated symptomatic cases of blastomycosis have significant mortality rate (~40%)
true