Opportunistic mycoses 2 + Deep Mycoses

Question 1

___ is a heavily encapsulated, neutrotrophic yeast that primarily causes meningoencephalitis

Answer 1

Cryptococcus neoformans

(C in cryptococcus - for capsule; neo - neutrophils (sorta))

Question 2

Describe the transmission/pathogenesis of Cryptococcus

Answer 2

Tx: spore inhalation

Pathogenesis: Inhalation of yeast >> replication in lung >> fungus crosses blood brain barrier via capsule expansion or zona occludans (tight junctions) or enters epithelial cells/macrophages which send it into the brain parenchyma

Question 3

Describe the 2 main virulence factors of Cryptococcus neoformans

Answer 3

Heteropolysaccharide (glucuronoxylomannan) capsule - inhibits phagocytosis

Phenoloxidase - production of melanin; the bug’s cell wall has melanin that serves as an oxidative sink (visualized by the white dude Fontana Masson)

Question 4

At what CD4 count are HIV+ patients at risk for Cryptococcus infections?

Name 2 other risk factors for Cryptococcus infection

Answer 4

100ul or less

High dose corticosteroids

Solid organ transplant recipients receiving immunosuppressive agents

Question 5

Which organism is indicated below?

Answer 5

Cryptococcus neoformans (note that the clear space around the red yeast shows where the capsule is - it breaks down in this fixation which is why it doesn’t stain)

Question 6

How does a patient with Cryptococcal meningoencephalitis present?

What happens in the brain that can lead to cortical blindness and herniation?

Answer 6

Headache, impaired concentration, memory loss, confusion, lethargy

Increased intracranial pressure due to capsule expansion >> cortical blindness, herniation

Question 7

Why are inflammatory markers muted in Cryptococcus meningoencephalitis?

Answer 7

Capsule inhibits host immune response + this is likely happening in an immunocompromised host anyway

Question 8

How do you Dx Cryptococcus infection?

Answer 8

Direct exam (easy to see in HIV+ pts)

Culture (also do wet mount with India ink - see clear halos around bug and aggregations of yeast forms)

Cryptococcal Ag test

PCR (some false negatives)

Question 9

Rx for Cryptococcal infection

Answer 9

Ampho B + 5FC (just think of how the 2 rhyme) + fluconazole maintenance

**adjunctive Rx: relief of increased intracranial pressure**

(you treat Crypto C with amphoB and 5FC)

Question 10

___ opportunistic pneumonia caused by an obligate parasite-fungus

Answer 10

Pneumocystic pneumonia

Question 11

___ is the causative agent of Pneumocystic pneumonia

Answer 11

Pneumocystis jirovecii

Question 12

An HIV infected patient presenting with tachypnea, dyspnea, alveolar interstitial pulmonary infiltrates + hypoxia has ___ until proven otherwise

Answer 12

An HIV infected patient presenting with tachypnea, dyspnea, alveolar interstitial pulmonary infiltrates + hypoxia has Pneumocystis until proven otherwise (pt also has non-productive cough)

Question 13

Which organism causes the pathology below?

Answer 13

Pneumocystis jirovecii

**advanced stage diffuse alveolar-interstitial pneumonia (bat-wing appearance)

(most of the diffuse-ness is host protein)**

Question 14

How do you Dx Pneumocystis infection?

Answer 14

Dx: bronchoalveolar lavage >> staining >> cysts with endospores and once released, become trophozoites

Trophs are obligate parasites and like to infect alveolar macrophages

(can visualize both cysts - GMS or calcoflour stain and trophs - Wright-Giemsa or immunoflourescence)

Also do PCR

Question 15

What is the 1st line Rx for Pneumocystis pneumonia?

Answer 15

TMP-SMX (also used as Prx in high risk pts) - think Pneumocystis is almost a protozoan but not really so that’s why you ca treat it w/ antibiotics

Others:

Pentamidine

Primaquine/Clindamycin

Dapsone-trimethoprim

Atovaquone

Question 16

The host defense hallmark of Histoplasmosis is ___

Which fungus is the causative agent of histoplasmosis?

Answer 16

Granuloma formation (non caseating or caseating)

Histoplasma capsulatum

Question 17

In an immunocompetent host, what kind of granuloma is formed in response to Histoplasmosis infection?

Answer 17

Granuloma with NO necrosis (this is an immunocompetent host)

Question 18

What kind of granuloma in response to Histoplasma infection forms in an immunocompromised host?

Answer 18

Poorly formed granulomas with histiocytosis and caseation occurs with many intracellular yeasts

Question 19

Which set of lung xrays belongs to an immunocompetent vs immunocompromised host with Histoplasma infection? (what are the features of each)

Answer 19

Top panel: immunocompetent host - Solitary or scattered asymptomatic pulmonary nodules

Bottom panel: immunocompromised host - disseminated, multiple pulmonary nodular interstitial infiltrates

Question 20

How do you Dx Histoplasma infection?

Answer 20

Direct exam and cultures of sputum, BAL fluid

Blood cultures

Histoplasma urinary Ag

Tissue Biopsy

Question 21

Which organism is this and what infection does it cause?

Answer 21

Histoplasma capsulatum

Question 22

What is the treatment of Histoplasmosis?

Answer 22

Itraconazole for mild to moderate infection

Liposomal amphotericin B for severe disseminated infection

Question 23

Which fungus is this and what infection does it cause?

Answer 23

Blastomyces dermatitidis yeast: broad based budding and double refractile wall

Causes blastomycosis

Question 24

What infection/organism is characterized by pyogranulomatous inflammatory response in bone, skin and lungs (seen on biopsy) and grows hyphae with slender clavate to pyriform conidia?

Answer 24

Blastomycosis (caused by Blastomyces)

Question 25

Blastomycosis typically affects 3 body systems/ organs. Name them.

Answer 25

Lung, skin and bone | (B - bone, L for lung and S for skin)

Question 26

How do Dx blastomycosis infection?

Answer 26

Direct exam of induced sputum and BAL fluid Culture DNA probe Tissue Biopsy

Question 27

Rx for Blastomycoses

Answer 27

Itraconazole for mild to moderate infection Liposomal amphotericin B for severe disseminated infection

Question 28

\_\_\_ is a pyogranulomatous infection of the **lungs, brain, skin, bones**, and other tissues caused by **Coccidioides spp**

Answer 28

Coccidiodomycosis

Question 29

Which fungus is this and what infection does it cause?

Answer 29

Coccidiodes (causes coccidiodomycosis) \*\*the fungi live as arthroconidia in the environment tend to be joined together (easily wafted into the air and enter the body via inhalation) \*\*note that they exist as spherules in tissue. Spherules are loaded with endospores and those are responsible for causing disease (not eradicated by macrophages)

Question 30

Describe how Coccidiodomycosis is transmitted

Answer 30

Organism grows in soil \>\> forms hyphae following rainfall (which makes the environment moist) \>\> hyphae become arthroconidia which are easily wafted into the air \>\> inhalation \>\> conversion to spherules in human host \>\> release of endospores that chew up lung tissue and further propagate infection

Question 31

What is the difference between Histo and Coccidiodomycosis infection in the lungs (i.e. which one has lung cavities that calcify vs ones that don't)?

Answer 31

Histo cavities calcify whereas Cocc won't

Question 32

Coccidiodes causes what specific type of meingoencephalitis?

Answer 32

Basilar meningoencephalitis

Question 33

2 groups at risk for disseminated Coccidiomycosis

Answer 33

Individuals of American and Filipino descent \*also immunecompromised hosts\*

Question 34

How do you Dx coccidiodomycoses?

Answer 34

Serology Direct examination – looking for spherule Culture Biopsy

Question 35

What is the Rx of Coccidiodomycosis?

Answer 35

**Basically fluconasole for life** **\*\*** * Itraconazole or fluconazole for mild to moderate infection * Fluconazole for chronic treatment of coccidioidal meningitis * Liposomal amphotericin B for severe disseminated infection