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Micro 03 - Systemic Mycoses

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Five systemic fungi
Histoplasma Capsulatum
Blastomyces dermatidis
Paracoccidioides brasilensis
Coccidioides immitis
Cryptococcus neoformans
Systemic fungi infection begins in the ______ and disseminates from there
Lungs
Systemic fungi infections usually present initially as ________
pneumonia
4 thermally dimorphic fungi

Systemic fungis that is yeast-like
1. H. capsulatum
2. P. brasilensis
3. B. dermatidis
4. Coccidioides immitis

Yeast-like = Cryptococcus neoformans
Dimorphism:
-growth at 25'C in culture is _______
-growth at 37'C is ________
Filamentous

Yeast-like or unicellular
Histoplasmosis initial disease characteristics
-Flu-like pneumonia
-50-90% have sub-clinical course
-5% show acute pneumonia
Progression of Histoplasmosis disseminated disease is associated with ________
underlying immunosuppression
Histoplasmosis infection route is often associated with ______.

Infection by inhalation of ______

Spores are phagocytosed by _______
-bind to ______
bat or bird poop

Conidia (asexual spores)

Macrophage
-CD11/CD18 integrins
Histoplasmosis:
-__1__ reproduces within macrophage
-interacts with macrophage to suppress generation of __2__
-activively changes pH of __3__
-phagocytosis by __4__ may predispose fungi to be pathogenic on evolutionary scale
1. Yeast
2. oxygen radicals
3. phagosome
4. Amoeba
Histoplasmosis:
-__1__ may form in Spleen or Liver
Calcified granulomas
Distribution of Histoplasmosis
Midwest USA
-Ohio and Mississippi River Valleys
Histoplasma that is also present in Africa
H. duboisii
-similar to Blastomycosis
-skin, liver, lung, bone
Histoplasmosis:
-in a healthy individual, following heavy inoculum, __1__ symptoms developing following a LATENCY PERIOD of __2__.
-Host immune system begins inhibiting grown of organism in infected M0 by __3__
-CMI DTH develops within __4
1. Flu-like
2. 10-25 days
3. 7-18 days
4. 3-6 wks
5. host survival
6. clearance of organism
Histoplasmosis Pulmonary symptoms
Non-productive cough
Fever
Enlarged Lymph nodes
Histoplasmosis Disseminated symptoms
Fatigue
Weakness
Malaise
Describe the Thermo-conversion of Histoplasmosis

-25'C = rough walled macroconidia on Saouraurd Glucose agar

-37'C = yeast-like colony
Diasnosis of Disseminated Histoplasmosis requires demonstration of organism at ___________
Extrapulmonary sites
-immunologic tests are better for monitoring treatment than for primary diagnosis
Histoplasma Antigen Test:
-__1__ antigen
-titers show how __2__ or __3__ the infection is
1. Wheat antigen
2. active
3. widespread
Histoplasmosis Treatment:
-most infections are __1__
-treat acute pulmonary disease if symptoms present greater than __2__ with __3__ followed by __4__
1. self-limiting
2. 1 month
3. Amphotericin B
4. Itraconazole
Disease caused by Blastomycosis
Pneumonia/skin and/or bone lesions
Blastomycosis is asymptomatic in up to ____% of cases due to some natural resistance
50%
Describe the pneumonia associated with Blastomyces
indolent onset of pneumonia with a 30-45 day incubation!!!
Blastomycosis causes Extrapulmonary disease in what percent of patients?
25-40%
Geographic distribution of Blastomycosis
NOrth America and parts of Africa
Endemic in UPPER and CENTRAL MIDWEST
Blastomycosis exists in these animals (2)
dogs
Horses
Point source outbreaks of Blastomycosis are associated with _________
rotting vegetation along streams or rivers
Part of the body that is commonly infected with Blastomyces in HIV patients
CNS
Blastomycosis:
-sexual infection in genus __1__
-infection by inhalation of __2__
-spores are phagocytosed by __3__
-yeast reproduces within _4_
-__5__adhesion inhibits TNF-alpha.
-__6__ are not present
1. Aiellomyces
2. conidia
3. macrophages
4. macrophages
5. W1-1
6. Calcifications
Diagnosis of Blastomycosis

-Culture from tissue
-Broad-based budding yeast cells
-MiraVista Ag detection
List the differences between Histo and Blasto

*
DOC for mild Blastomycosis
Itraconazole for 2 months
Life threatening treatment for Blastomycosis
AmB then Itraconazole
Treatment for Disseminated Blasto
Amphtotericin B or Fluconazole followed by Itraconazole
Cure rate of Blastomycosis with this drug is very high
Amphotericin B
-relapse rate ~3%
nickname for Paracoccidiomycosis
South American Blastomycosis
Paracoccidiomycosis infections occur where geographically?
South and Central America
Most infections of Paracoccidiomycosis occur in this group of people
Men aged 20-50
-especially coffee growers
*9X more common in men
Paracoccidiomycosis lesions are where?

Oral and Nasal Cavity
Describe the Pulmonary infection of Paracoccidiomycosis
Asymptomatic or
Cough, purulent sputum, chest pain
Lymphadenopathy
Paracoccidioides brasiliensis exists in __1__
Infection follows inhalation of __2__.
Spores convert to yeast at _3_
Mycelia to yeast transition is inhibited by __4__
Lesions are secondary to __5__
1. soil
2. conidia
3. 37'C
4. 17-B-Estradiol
*why women not infected*
5. pulmonary infection
Diagnosis of Paracoccidiomycosis

Ships-wheel arrangement of spores
-2 to 20 microns in diameter
-doubly refractile wall
Paracoccidiomycosis treatment
-Sulfa drugs are used in S. America but require long-term administration
-Itraconazole and Voriconazole are best treatment (6 months)

**relapse if frequent**
2 causative agents of Coccidioidomycosis
Coccidioides Immitis
C. posadsii
Coccidioidomycosis is often called ______
Valley Fever
Most common disease of Coccidioidomycosis
Pneumonia
*night-sweats and joint pain*
*5-10% have nodules/cavities*
Where is Coccidioidomycosis endemic?
SW USA

also in Argentina and Paraguay
In what things is Coccidioidomycosis found?
Soil, Dust as Arthrospores (spore that results from fragmentation of hyphae)

Chimpanzee, Horses
Patients of these descents are at a higher risk of dissemination with Coccidioidomycosis
African
Philippino
Coccidioidomycosis:
-once inhaled, C. immitis dust-borne artho-conidia convert at 37'C to form large __1__ in tissue

spherules
Coccidioidomycosis:
-Spherules burst releasing __1__ which grow to form new __2__
1. Endospores
2. spherules
Diagnosis of Coccidioidomycosis
-Spherules in stained tissue
-Complement fixation for IgG anticoccidioidal Ab's
-Culture
-Antigen preps
When is treatment for Coccidioidomycosis pneumonia recommended?
-if patient loses >10% of body weight

-if night-sweats persist >3 wks.
Coccidioidomycosis treatment for non-meningeal spread
Itraconazole
Coccidioidomycosis treatment for meningitis
Fluconazole
Intrathecal AmB
*follow-up for 2 years
Coccidioidomycosis:
-mortality up to __% in AIDS in 1 month
-__ is more relevant than HIV status
70

CD4 count
Cryptococcosis commonly causes relapsing _______

It is sometimes considered ______
meningitis

Opportunistic
Difference between Cryptococcosis and other systemic mycoses
Not Thermally Dimorphic
Cryptococcosis is related to _______
common jelly fungus
Alternate names for Cryptococcosis
Torulosis or European Blastomycosis
Unique feature of Cryptococcus neoformans
acidic mucopolysaccharide capsule
Cryptococcus is associated with these two things
Pigeon poop

Eucalyptus trees
Cryptococcosis:
-infection is initiated by inhalation of organism from the __1__
-spread from lungs occurs via the __2__
-is a defining illness for __3__
-first identified as causing __4__ in 1905
-disseminates to __5__
1. soil
2. blood
3. AIDS
4. meningitis
5. prostate (skene's gland in females)
Cryptococcosis clinically most often presents as ______
Meningitis
-headache
-fever of several weeks
-sometimes solitary pulmonary nodule
Diagnosis of Cryptococcosis

-India ink prep shows acidic capsule = use for IC'ed

-Antigen test for detection of polysaccharide in CSF
Treatment for Cryptococcosis
AmB + FLUCYTOSINE then Fluconazole

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