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
What are characteristic features of blastomycosis on exam?
Mild form: nonspecific flulike illness, resolves spontaneously
Pneumonia: high fever, chills, cough w/ mucopurulent sputum, pleuritic chest pain, occasionally EN
Chronic illness: looks like TB: pulmonary symptoms w/ weight loss, night sweats, hemoptysis
Fast, severe form: ARDS w/ fever
Any may also include skin lesions, bone/joint pain
Chest Xray is abnormal but variable
Bronchoscopy with needle biopsy may be useful
T/F Skin lesions are more common with blastomyces than coccidioides or histoplasma
true
T/F blastomyces can be cultured from skin lesion
true
How do you diagnose blasomycosis?
Sputum microscopy is 75% diagnostic IF pt have pneumonia
Tissue biopsy is other method -
What would you expect to find from microscopy of sputum or culture?
hyphae w/ small pear-shaped conidia
T/F PPD and serology are specific for blastomycosis
False! NOT specific - prone to false positive
Classic culture presentation of histoplasmosis
ovoid yeast form inside macrophages - larger than bacteria
Expected blood findings from histoplasmosis in disseminated dissease?
pancytopenia
How would you culture histoplasma capitum?
Sabouraud’s agar - 2 cultures necessary unlike coccidiomycoces
25C for tuberculate macroconidia
37C for yeast
T/F ELISA for histoplasmosis can be performed from serum or urine
true for histoplasma polysaccharide antigen
T/F serologic tests are useful for diagnosis of histoplasmosis
False - Not specific - antibody titers can be useful, but may cross-react w/ other fungal infections, or turn negative in immunosuppressed
What is causes South American blastomycosis, Lutz-Splendore-Almedia disease?
Paracoccidioides brasiliensis
AKA Paracoccidioidomycosis
T/F Paracoccidioides are dimorphic with yeast and mold form
true
What defines mold form of Paracoccidioides?
thin, septate hyphae
What defines yeast form of Paracoccidioides?
thick-walled w/ multiple buds
Where is Paracoccidioides endemic to?
rural Latin America
Diagnose by sputum microscopy for yeast, culture for hyphae w/ pear-shaped conidia, biopsy for yeast w/ supperating (not caseating) granulomas.
Blastomyces (North American blastomycoses)
endemic to US Southwest, mold grows in wet weather, releases infectious arthrospores in dry, spores inhaled, change form.
Coccidioides (coccidioidomycosis)
Treat if predisposed to complications (oral azoles), meningitis (fluconazole), pregnant or disseminated (Amphotericin B).
Coccidioides (coccidioidomycosis)
Which fungus?
culture for hyphae w/ pear-shaped conidia
Blastomyces (North American blastomycoses)
This pathogenesis describes what type of infection?
Spores are inhaled
Early lesions occur in lungs
Asymptomatic infection common
More severe infection includes oral mucous membrane lesions, lymph node enlargement
Dissemination is possible if immunosuppressed (CMI) or untreated for years
Total untreated mortality 16-25%
Paracoccidioides (Paracoccidioidomycosis/South American blastomycosis/Lutz-Splendore-Almedia disease)
Which fungus?
60% Mild: asymptomatic or flulike clearance by innate or containment by CMI
Coccidioides (coccidioidomycosis)
thermally dimorphic (mold/yeast), endemic to Ohio, Missouri, and Mississippi river valleys, soil-based, infectious microconidia can be kicked up by construction projects, causes pulmonary symptoms, previously-healthy usually clear or contain in granulomas, higher-dose infection produces TB mimic, CMI-deficient host disseminates in macrophages (yeast survive lysosomal fusion), look for pancytopenia and ulcerations on tongue. Also for diagnosis: history (birds, bats, endemic area, immunocompromised, occupation), biopsy for yeast in macrophages, cultures for dimorphism, ELISA for antigen. Treat serious lung w/ itraconazole, meningitis w/ fluconazole, disseminated w/ Amphotericin B.
Histoplasma capsulatum
histoplasmosis
Which fungus? Dimorphic fungus Mold form has thin, septate hyphae Yeast form is thick-walled w/ multiple buds Endemic to rural Latin America
Paracoccidioides (Paracoccidioidomycosis/South American blastomycosis/Lutz-Splendore-Almedia disease)
This pathogenesis describes what type of infection?
Infection by inhalation of conidia
Monocytes, macrophages, neutrophils readily kill conidia but once yeast conversion takes place begin to slow down.
slowed killing due to BAD1 immune modulator on yeast
~50% Asymptomatic infection : successful clearance
Most of remainder contain infection with granulomatous response, may develop pulmonary symptoms in process (~45 days post exposure)
Immunosuppression or preexisting pulmonary disease predispose to dissemination, hematogenous seeding of many possible sites
Untreated symptomatic cases have significantmortality (~~40%)
Blastomyces (North American blastomycoses)
Which fungus?
KOH mount for yeast cells w/ multiple buds
Stain biopsies with silver for yeast cells, adult form also granulomas
Culture on Sabouraud takes 2-4 weeks
Serologic testing not available outside endemic area
Skin test not helpful
CSF smear is seldom helpful
Paracoccidioides (Paracoccidioidomycosis/South American blastomycosis/Lutz-Splendore-Almedia disease)
Which fungus?
Acute febrile respiratory illness 3-14 days after exposure
Histoplasma capsulatum
histoplasmosis
biopsy for spherules
Coccidioides (coccidioidomycosis)
This pathogenesis describes what type of infection?
infectious microconidia can be kicked up by construction projects, causes pulmonary symptoms, previously-healthy usually clear or contain in granulomas, higher-dose infection produces TB mimic, CMI-deficient host disseminates in macrophages (yeast survive lysosomal fusion
Histoplasma capsulatum
histoplasmosis
Which fungus?
History: residence in or travel to an endemic river valley, occupational exposure from soil, birds, bats, immune predisposition
Histoplasma capsulatum
histoplasmosis
Which fungus?
Fever Arthralgias Erythema nodosum Erythema multiforme Chest pain High morbidity, low mortality
Coccidioides (coccidioidomycosis)
Which fungus?
Pancytopenia
Ulcerated lesions on tongue
Histoplasma capsulatum
histoplasmosis
Which fungus?
Risk factors: age, race, pregnancy, immunocompromise, occupational high exposure
Coccidioides (coccidioidomycosis)
Which fungus?
Endemic in southwest US and Latin America
Coccidioides (coccidioidomycosis)
Which fungus? thermally dimorphic (mold/multibud yeast)
Paracoccidioides (Paracoccidioidomycosis/South American blastomycosis/Lutz-Splendore-Almedia disease)
Which fungus?
serology for dissemination
Coccidioides (coccidioidomycosis)
Which fungus? thermally dimorphic (mold/yeast),
Either Histoplasma or Blastomyces
Which fungus?
Diagnose by sputum microscopy for yeast
Blastomyces (North American blastomycoses)
Which fungus?
Diagnose by pus or tissue KOH mount for yeast with multiple buds
Paracoccidioides (Paracoccidioidomycosis/South American blastomycosis/Lutz-Splendore-Almedia disease)
Which fungus?
treatment involves healthier lifestyle (semi-opportunistic).
Paracoccidioides (Paracoccidioidomycosis/South American blastomycosis/Lutz-Splendore-Almedia disease)
Which fungus?
biopsy for yeast w/ supperating (not caseating) granulomas
Blastomyces (North American blastomycoses)
Moderate acute: pneumonia w/ purulent sputum, Moderate chronic: mimics TB, Severe acute: ARDS. May include EN or ulcerating skin lesions.
Blastomyces (North American blastomycoses)
endemic to rural Latin America, severe in children/immunocompromised, moderate in adults, usually men in agriculture or construction.
Paracoccidioides (Paracoccidioidomycosis/South American blastomycosis/Lutz-Splendore-Almedia disease)
Adult form has very long latency, skin&mucous lesions. Diagnose by pus or tissue KOH mount for yeast with multiple buds, culture.
Paracoccidioides (Paracoccidioidomycosis/South American blastomycosis/Lutz-Splendore-Almedia disease)
Innate immunity clears most cases, destroys conidia easily, yeasts are harder to kill (BAD1), graulomatous response contains most, immunosuppression predisposes to hematogenous spread
Blastomyces (North American blastomycoses)
thermally dimorphic (mold/spherule), endemic to US Southwest, mold grows in wet weather, releases infectious arthrospores in dry, spores inhaled, change form. 60% Mild: asymptomatic or flulike clearance by innate or containment by CMI, moderate: valley fever/ desert rheumatism: pulmonary+EN, severe: major pneumonia or dissemination (either bare or in macrophages). Risk factors: age, race, pregnancy, immunocompromise, occupational high exposure. Diagnose by exam, history, PPD, biopsy for spherules, culture for dimorphism, serology for dissemination. Treat if predisposed to complications (oral azoles), meningitis (fluconazole), pregnant or disseminated (Amphotericin B).
Coccidioides (coccidioidomycosis)
thermally dimorphic (mold/multibud yeast), endemic to rural Latin America, severe in children/immunocompromised, moderate in adults, usually men in agriculture or construction. Adult form has very long latency, skin&mucous lesions. Diagnose by pus or tissue KOH mount for yeast with multiple buds, culture. Treat w/ itraconazole, Amphotericin B if severe, combine with healthier lifestyle (semi-opportunistic).
Paracoccidioides (Paracoccidioidomycosis/South American blastomycosis/Lutz-Splendore-Almedia disease)
thermally dimorphic (mold/yeast), endemic to Eastern US. Innate immunity clears most cases, destroys conidia easily, yeasts are harder to kill (BAD1), graulomatous response contains most, immunosuppression predisposes to hematogenous spread. Moderate acute: pneumonia w/ purulent sputum, Moderate chronic: mimics TB, Severe acute: ARDS. May include EN or ulcerating skin lesions. Diagnose by sputum microscopy for yeast, culture for hyphae w/ pear-shaped conidia, biopsy for yeast w/ supperating (not caseating) granulomas. Treat w/ itraconazole, fluconazole if meningitis, Amphotericin B if severe.
Blastomyces (North American blastomycoses)
is widespread environmental, enabled by reduced CMI, suppresses host inflammatory response. Infection originates in lung but usually either clears or progresses to meningitis. Patient presents late in disease with meningitis and skin nodules or pulmonary symptoms. Diagnose by biopsy, CSF, crag. Treat with combinations of azoles and Amphotericin B.
Cryptococcosis
hypersensitivity rxn to infection complicating asthma or CF, diagnose on exam, treat w/ itraconazole, sinus surgery, Xolair
Aspergillosis - ABPA (Allergic bronchopulmonary aspergillosis)
Which infection is more likely to actually require treatment (greater virulance) vs require treatment once acquired?
blastomycoses
Paracoccidioidomycosis
coccidioidomycosis
histoplasmosis
blastomycoses
fungus ball complicating cavitary lung disease, diagnose by air crescent on scan, treat w/ itraconazole and/or surgery
Aspergilloma (colonizing aspergillosis)
Opportunistic fungal pathogens cause dangerous infection when paired with what risk factors?
prolonged neutropenia,
uncontrolled HIV or diabetes,
profound T-cell suppression
Effective treatment of serious disease from opportunistic fungal pathogens must: (2 things)
addresses both the current infection and the underlying problem
is a ubiquitous environmental mold, infection is rare overall but frequently fatal in predisposed population. May cause mycotoxicosis (contaminated grain), local infection (burns, prosthetic implants, contaminated contact lens solution), or deadly disseminated infection (prolonged neutropenia, HSCT recipients). Enters from sinus or wound site, circulates in blood, symptoms in skin, eye, lung. Diagnose by blood culture, histo, treat aggressively with surgery, amphotericin B, voriconazole, prognosis poor.
Fusarium
very rare deadly invasive vasculitis by environmental mold, causes infarction, invades brain from sinuses. Predisposition by uncontrolled diabetes, iron overload, immunosuppression. Diagnose by biopsy for histo, treat with amphotericin B and aggressive surgical removal of diseased tissue, prognosis poor.
Mucormycosis caused by Mucor or Rhizopus
mimics TB; try to diagnose by air crescent on scan, needle-aspirate lung fluid for microscopy
Aspergillosis CNPA (Chronic necrotizing pulmonary aspergillosis)
respiratory distress with history of profound immunosuppression, diagnose by halo sign on scan, needle or tissue biopsy for histo
Invasive aspergillosis
Treat with voriconazole+AmphotericinB, but prognosis is poor
CNPA and invasive Aspergillosis
banana-shaped macroconidia
Fusarium
Fusarium species that is the most common cause serious infection (50%)
Fusarium solani
What are the 3 presentations of Fusarium pathogenesis?
Mycotoxicosis
Immunocompetent local infection
Immunosuppressed opportunistic infection
virulence factors for Fusarium include:
immunosuppressive mycotoxins
collagenases
proteases
ability to adhere to prosthetic material
What causes Immunosuppressed opportunistic fusarium infection?
Prolonged Neutropenia
Long-term use of steroids
Profound T-cell deficiency (as in pts receiving Hematopoietic stem cell transplantation)
What causes mycotoxicosis?
trichothecene mycotoxins
Where would you find immunocompetent local fusarium infection?
Skin (burns)
Cornea (contaminated contact lens solution)
Allergic sinusitis (like ABPA)
Colonization of prosthetics & catheters
Primary species causing cryptoccocis
Cryptococcus neoformans and C. gattii
5 seriotypes
A, D, AD = ?
B,C = ?
A, D, AD = Cryptococcus neoformans
B,C = Cryptococcus gattii
**grow at 37C
What fungal species is environmental, found worldwide in soil contaminated w/ bird droppings, esp pigeon?
Cryptococcus neoformans
What features describe criptococci (under microscopy)?
Oval yeasts w/ narrow-based buds
wide polysaccharide capsule
What fungal species found in litter under eucalyptus trees?
Cryptococcus gattii
Which Cryptococcus species causes less severe disease but prefers immunocompetent hosts (more common on West coast)?
Cryptococcus gattii
T/F Cryptococci can be transmitted from human to human but only with direct blood transmission (e.g. organ transplants or needs sticks)
true - causes localized cutaneous disease
Otherwise non-human-human transmission
What factors have increased incidence of cryptococcal meningitis?
Use of steroids, survival w/ malignancy, and AIDS
T/F lung infection with cryptococci can be asymptomatic
true, or lead to pneumonia or dissemination
Pathogenesis of cryptococci involves primary inhillation of spores into lungs. From there what typically happens in the immunocompetant host?
▪ Lung infection may be asymptomatic or lead to pneumonia
▪ Can can survive as simple yeast cell (capsule protects from phagocytosis), or if phagocytosed can cause intracellular infection in alveolar macrophages
▪ Can also be expelled from macrophage and dissemenate as simple yeast through blood or stay in macrophage as trojan horse
▪ Immunocompetent hosts restrict infection to lungs
▪ Successful host raises Helper Ts, skin test conversion, antibodies to capsule
What is cause of tissue damage from c. neoformans?
very little inflammatory response or granuloma formation – organ damage is by tissue distortion from growing yeast
What are virulance factors for criptococci?
capsule,
melanin in cell wall (antiphagocytic),
Phospholipase B for invading tissue
What is a characteristic feature of C. neoformans dissemination?
meningitis w/ skin nodules
T/F C. neoformans raises very little inflammatory response or granuloma formation
true!
What is atypical about cryptococcal meningitis?
neck stiffness and fever are less common because can present and low level meningitis
most common symptoms: Headache, altered mental status, nausea and vomiting
Cryptococcomas - masses in CNS can cause focal neurologic damage
What is “crag”? what is it used for?
serology test (short for cryptococcal antigen) involves latex agglutination for cryptococcal antigen in blood and CSF
What is found on culture media (Sabouraud agar) with Cryptococcosis?
melanin
37C
In Cryptococcosis, CSF stained with india ink will demonstrate what?
yeast w/ wide capsule (halo ring) – much larger than bacteria that cause meningitis
T/F ruitine blood work may be normal in pt with Cryptococcosis
True - blunted immune response so no inflammation
Altered mental status in HIV positive pt should be tested for what?
Cryptococcosis encephalitis/meningitis
What is most useful test early on in Cryptococcosis?
crag from blood or CSF
What is treatment for cryptococcal meningitis or cryptococcoma?
Amphotericin B (liposomal if kidney issues) plus flucytosine for 2 weeks followed by 10 more weeks of fluconazole
T/F criptococcus can infect the prostate
true
what is treatment for Prostate Cryptococcosis
Fluconazole
Treatment for pulminary criptococcosis?
In immunocompetent patients may not need treatment; can use 6-12mo fluconazole or itraconazole
Treatment criptococcosis of Skin, bones, other:
Amphotericin B
What features define Aspergillus?
Septate (divided) hyphae w/ V-shaped branches
What are the 4 diseases caused by Aspergillus
1) Allergic bronchopulmonary aspergillosis (ABPA)
2) Aspergilloma or Colonizing Aspergilliosis: “Fungus ball” in lung
3) Chronic necrotizing pulmonary aspergillosis (CNPA)
4) Invasive aspergillosis
Source and pathogenesis of asperigillus?
Widespread on decaying vegetation worldwide
Infectious conidia are airborne
Conidia colonize abraded skin, burns, cornea, ear, sinuses, lung
Healthy macrophage and neutrophil response eradicates fungus, but some Aspergillus produce toxic metabolites that inhibit it, so do corticosteroids
What diseases are associated with asperigilloma?
TB, cystic fibrosis (colonizes cavitary lesions forming mass)
What cause can cause pneumonia w/ hemoptysis and granulomas in immunocompromised patients?
chronic necrotizing pulmonary aspergillosis
difficult to diagnose, high mortality
What are the virulence factors for aspergillus?
Gliotoxin: immunosuppressive
Toxic metabolites interfere with phagocytosis and opsonization
Proteases may be involved in tissue invasion
What is this seen in?
Xray or CT may show “grape cluster” or “hand in mitten” clusters of mucus-clogged bronchi
Allergic bronchopulmonary aspergillosis
What are the features/symptoms of Allergic bronchopulmonary aspergillosis
▪ Positive skin test for Aspergillus allergy with asthma or CF
▪ Coughing up brownish bronchial plugs containing hyphae
▪ Fever, wheezing & pulmonary infiltrates unresponsive to antibiotics
▪ Hemoptysis
▪ Uncontrolled asthma
▪ Purulent sinus drainage
Mass in lung with “air crescent sign” that does not invade tissue and moves around when sitting up/laying down. associated with hemoptysis, cough, fever
a) cryptococcoma
b) coccidiomycoma
c) blastomycoma
d) aspergilloma
d) Aspergilloma
B + C are made up
a = CNS mass of C. neoformans that causes focal neuro deficits
Clinical features of chronic necrotizing pulmonary aspergillosis
Subacute pneumonia unresponsive to antibiotics
Fever, cough, night sweats, weight loss
History of ineffective empiric treatment for TB
Underlying diseases that predispose chronic necrotizing pulmonary aspergillosis
Underlying disease of alcoholism, collagen-vascular disease, chronic granulomatous disease or COPD, long term corticosteroid therapy
Predisposing factors for invasive asperigillosis
History of profound immunosuppression or COPD with long-term corticosteroid therapy
Clinical features of invasive asperigillosis
Fever, cough, dyspnea, pleuritic chest pain, neutropenia, sometimes hemoptysis, worsening hypoxemia
CT scan for invasive asperigillosis shows:
characteristic halo sign: ground-glass infiltrate surrounding a nodular density. Represents a hemorrhage; invasive aspergilliosis is most common cause
Diagnosis and pathologic features of invasive Aspergillosis
Septate hyphae branching at acute angles invading tissue
• Acute inflammatory infiltrate
• Tissue necrosis
• Blood vessel invasion
• High serum levels of glactomannan antigen (ELISA)
Diagnosis and pathologic features Allergic bronchopulmonary aspergillosis
- High levels of aspergillus-specific IgE, eosinophilia
* Mucus with degenerating eosinophils and hyphae
Mucormycosis is caused by what fungi?
Mucor, Rhizopus, Absidia, several others
Rhizopus - is big one and most common on STEP 1
What is characteristic about prevalence and pathologic course of Mucormycosis
Very rare (~500/yr in US) life-threatening (50-85% mortality) sinus infections; invade brain
“death by sinus infection”
What are risk factors for mucormycosis?
uncontrolled diabetes (MAJOR CORRELATION), neutropenia, burns, leukemia, IV steroids or TNF alpha blockers, iron overload
What is route of transmission for mucormycosis?
airborne asexual spores - Usually inhaled, can also be ingested or introduced by trauma
T/F mucromycosis is highly associated with AIDS
false
What is the main host defense against mucormycosis infection?
neutrophils (innate immuninty - cell mediated may not play large role)
Where do mucormycoses proliferate?
walls of blood vessels - Cause infarction and necrosis of tissue downstream from blocked vessel
very high mortality if dissociated (~100%)
Common sites of infection for mucormycoses?
Paranasal sinuses, invading brain - leaves disfigurement if treated successfully (huge necrotic lesion) 50-70% mortality
Blood findings in mucormycosis?
neutropenia, diabetic acidosis, iron overload
T/F antigen testing and CSF findings are helpful for diagnosis
False! No useful antigen tests or CSF findings
Biopsy of tissue infected with mucormycoses demonstrate:
NONSEPTATE HYPHAE w/ broad irregular walls and BRANCHES AT RIGHT ANGLES, vascular invasion and necrosis, neutrophil infiltration.
What are 3 factors that complicate the diagnosis of mucormycosis?
It is rare
Diagnosic window is short
Initial symptoms may be nonspecific
is a ubiquitous environmental mold, infection is rare overall but frequently fatal in predisposed population. May cause mycotoxicosis (contaminated grain), local infection (burns, prosthetic implants, contaminated contact lens solution), or deadly disseminated infection (prolonged neutropenia, HSCT recipients). Enters from sinus or wound site, circulates in blood, symptoms in skin, eye, lung. Diagnose by blood culture, histo, treat aggressively with surgery, amphotericin B, voriconazole, prognosis poor.
Fusarium
is widespread environmental, enabled by reduced CMI, suppresses host inflammatory response. Infection originates in lung but usually either clears or progresses to meningitis. Patient presents late in disease with meningitis and skin nodules or pulmonary symptoms. Diagnose by biopsy, CSF, crag. Treat with combinations of azoles and Amphotericin B.
Cryptococcosis
What differentiates aspergillus and fusarium in histology?
only possible if both yeast form and mold form of fusarium are present (both have acute branching hyphae)
