Fungi Flashcards
Which primary Fungal infections from inhalation
Cryptococcus
Histoplasmosis - dimorphic
Paracoccidioidomycosis - dimorphic
Talaromyces - dimorphic
Coccidioides - dimorphic
Blastomyces - dimorphic
[no human-human]
Which fungal infection has a tendency to migrate from lungs -> target Joints/bones/skin/CNS?
What is the skin disease?
Geography?
Found where?
Rx mild?CNS? Disseminated?
coccidioides immitis - califonia ‘Valley fever’
C. Posadasii - everywhere else
Skin rash, either diffuse pruritic erythematous rash or erythema multiforme or erythema nodosum
Western US central/south America
Itraconazole for mild
Amphotericin B for severe / disseminated
dimorphic fungus
[coccyx is a bone]
Generally when would you use fluconazole vs itraconazole for fungal infetions
Fluconazole -> CNS / joints
-Azole of choice for candida, crypto, and CNS cocci
Itra -> skin / abdo
-blasto , histo , sporo , and non CNS cocci.
Which primary fungal infection Lung - > (lymph nodes) skin and mucus eg oral nasal
Geography?
Found where?
Rx if mild?
paracoccidioides brasiliensis (lutzii)
Jungle soil brazil/peru/columbia
itraconazole
Which fungal infection if infection in HIV starts in lung -> CNS?
Found where?
2 strains - which one causes meningitis in immunocompetent?
Cryptococcus. neoformans - Bird poo [new poo to fall on the mans]
Cryptococcus. Gatti - Eucalyptus trees
-Can cause cryptococcus meningitis even in immunocompetent [Gatt out of my head]
Any extrapulm/CNS manifestations are always in immunocompromised
Which primary fungal infection Lung - > liver/spleen + nodes + (skin/adrenal)
Found where?
Geography?
Rx if mild?
Which -azole is the only one that doesn’t really work?
histoplasma capsulatum
bird poo and soil
Worldwide - mostly in the Americas
Particularly cavitating in lungs
[-capsule in the lungs
-spleen protects from capsulated bacteria. liver capsule pain]
Itraconazole - mild/mod disease
Liposomal Amphotericin B if severe /disseminated disease
[Fluconazole sucks for histo]
Which fungal infection mostly lungs -> Skin pustules, papules, warts or ulcers. They are usually painless?
Found where
Rx if mild?
blastomyces dermatitidis
North America
-(little bit in Africa / middle east)
Itraconazole
Ampho if disseminated / CNS
Histoplasmosis bug
Histoplasma capsulatum - dimorphic fungus
Histoplasmosis infection from? clincial features acute vs chronic pulm sx?
Bat / bird poo
-Get from inhalation eg from caves
May be asymptomatic
Acute pulm histoplasmosis
-acute broncopulm illness with generalised shadowing on CXR
Chronic pulm histoplasmosis
-Causes pulm nodules which can be seen on CXR. may cause focal consolidation / cavitation
Who gets acute disseminated histoplasmosis? Differentiate from cryptococcus?
Immunocompromised - often AIDS
Much more oral ulceration in histoplasmosis
Histoplasmosis dx? rx?
Blood / sputum culture
intradermal histoplasmin skin test
From any other biopsy / sample
Often self limiting
Best is 200mg daily itraconazole [can use fluconazole]
-may require either term secondary prophylaxis
Cause of African histoplasmosis? often called? how is it different?
Histoplasma capsulatum duboisii
‘Progressive disseminated histoplasmosis’
Usually presents with skin nodules / ulcers
2 key stains for fungi
Periodic acid-schiff (PAS)
methenanine silver
KOH
Pustule / nodule usually on hand followed by spread along lymphatics causing nodular ulcerating lesions most commonly? rx?
Sporothrix schenckii
itraconazole for 3 months
sporotrichosis diangnosis
smear microscopy and culture in Sabouraud’s medium
Common age and gender paracocci? Geography
Males aged 30-50
-Oestrogen prevents transformation of mould to yeast
Humid rain forest around 1000-1500m
South America only
Acute vs chronic paracocci
Usual age
Skin test
Which organ common
Acute
- young ~20s
- Skin test negative (Don’t mount a TH1 response)
- Fever + lymph nodes + liver/spleen + skin
Chronic
- Older ~45
- skin test positive
- Lung + oral mucosa (some lymph nodes)
Which paracocci - Lymphadenopathy, oral ulcers and bilat pulm infiltrates
Chronic adult (multifocal)
Which paracocci with hepatosplenomegally and these facial lesions
Acute-juvenile
Pulm paracocci differentiate from TB
Apex of lung look normal
-cavitary lesions and pleural effusions are
less common
[Similar to histoplasmosis]
Paracocci vs mucosal leish oral lesions
Para - haemorrhagic dots, gum/teeth/lips involvement common
Painful
Leish - nasal collapse, granuloma
Paracocci chronic vs acute biopsy
Acute - more extensive necrosis, more yeast
Chronic - granulomas, and fibrosis
2 main culture mediums for fungi
Sabouraud Dextrose Agar (SDA)
Mycosel Agar (Chloramphenicol + Cycloheximide)
Name 3 fungi that can cause primary subcut disease
Sporothrix schenckii/ brasiliensis
Fonsecaea pedrosoi
Lacazia loboi
Madurella mycetomatis
Most likely Dx?
Sporotricosis
Most likely?
Sporotrichosis
Most likely
Sporotricosis
What temp do I grow best at?
sporotrichosis 25-30 degrees
Sporothrix . schenckii diagnosis
Culture -> microscopy
Chromoblastomycosis
Chromoblastomycosis
Chromoblastomycosis diagnosis
Sclerotic bodies on KOH stain
[culture several forms - Phialophora verrucosa, Fonsecaea pedrosoi, Fonsecaea compact, Cladophialophora carrionii]
Mycetoma
Mycetoma with these grains?
Fungal - eumycetoma
KOH stain - can see hyphae on grain
Swelling of foot - which stain best to see hyphae on grain?
PAS - eumycetoma
Dx eumycetoma?
Direct examination: Hyphae within the grains
Black grains
Culture: Madurella mycetomatis
[Madurella grisea, Pseudoallesheria boydii]
Spot dx?
Lobomycosis
Lacazia loboi blastospores, KOH (x400)
Lacazia loboi blastospores, Histopatology, Grocott x 400
Lobomycosis dx?
Direct examination: Round to lemon shaped-cells
- either singly or in short chains.
[Culture: Never isolated]
Paracocci
Gums affected
Paracoccidiodes brasiliensis blastospores, KOH (x 400)
Paracoccidiodes brasiliensis blastospores, Grocott (x 400)
Paracoccidiodes brasiliensis dx?
Direct examination: Characteristic budding yeasts. (85%)
Culture: Paracoccidioides brasiliensis and Paracoccidioides lutzii.
Histopathology: Characteristic budding cells
Serology: Immunodiffusion test* easy
Histoplasmosis
Histoplasma capsulatum blastospores (Giemsa stain, 1000x)
Histoplasma capsulatum, Culture and KOH preparation (x400)
Histomplasmosis Dx?
Lots of options …
Urine Antigen
Culture - Histoplasma capsulatum complex (Sepedonium chrysospermum)
Serology - immunodiffusion
Histopathology - Giemsa stain: *very small Small yeast cells
C. neoformans blastospore (India ink)
Yeast cells of C.neoformans, Mayer’s mucicarmine stain ( X1000 )
Mayers - stains cryptococcus capsule red
Cryptococcus diagnosis
India Ink: Encapsulated yeasts
Culture: Cryptococcus neoformans, Cryptococcus
gattii
Histopathology: Encapsulated yeasts
Serology: Latex agglutination test,
Crypto Antigen LFA test (CRAG)
Aspergillus hyphae (KOH)
Aspergillus hyphae (KOH)
Dichotomous branching hyphae of Aspergillus, PAS (X1000)
Aspergillus fumigatus (KOH X400)
Aspergillus flavus (KOH X400)
Aspergillus niger (KOH X400)
Aspergillous diagnosis
Direct examination: Branching hyphae
Culture: Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus oryzae, etc.
Histopathology: Branching hyphae
Serology:
-Antibodies: Immunodiffusion
-Antigen: Platelia, Aspergillus Antigen Immunoassay.
What is this?
Immunodiffusion - negative sample is one at the bottom
Histoplasma
NOT amatigotes
Histoplasma
Histoplasma
Morphology of macro-colony of:
(A) Aspergillus flavus;
(B) Aspergillus fumigatus;
(C) Aspergillus niger
on Sabouraud Dextrose agar (top images),
micro-colonies on slide agar (bottom images).
Aspergillus fumigatus (culture)
Aspergillus niger (Culture)
What carries the virulence for cryptococcus
Capsule - acapsular forms cause almost no disease
[Capsule is:
-Antiphagocytic
-Depletes complement
-Produces antibody unresponsiveness
-Dysregulates cytokine secretion
-Produces brain oedema]
Common finding in phenotypically normal patients who get cryptococcal CNS? usually how long to diagnosis from start of symptoms?
antibodies to IFN γ receptors
Diagnosis takes:
-3 months for normal people
-1 month for immunocompromised
Who gets cryptococcus cellulitis
Mostly organ transplant
[HIV + other immunocompromised]
Note capsule on biopsy
Along with drug rx what is the key aspect of cryptococcal meningitis Rx
Therapeutic LP
Why is this not a bacterial pneumonia? 3 key DDx
Nodular - especially if multinodular
Bilateral
[fungal / TB / nocardia]
Cause of central African histoplasmosis
Histoplasma duboisii
35 yo man with advanced HIV; CD4=13
He presents with 2 week h/o progressive diffuse papular rash, fever (40C), hypotension (90/50) and dyspnea (RR= 36).
Alveolar biopsy show image + bone marrow all demonstrate
Histoplasma capsulatum
blood with intracellular
H. capsulatum
KOH prep from sputum with narrow
based budding yeasts
H capsulatum
KOH prep from sputum with narrow
based budding yeasts
H capsulatum
41 YOM with rheumatoid arthritis related interstitial lung
disease on immunosuppressive medications who presented with syncope and acute gastrointestinal bleeding. Duodenal perf
Had incidentally discovered cavitary nodules on CT chest
lesion on tongue
Histoplasma capsulatum
Silver stain (GMS)
lymphadenopathy, hepatosplenomegaly, and skin and mucous membrane lesions (papules, pustules, ulcers, and nodules).
Adrenal insufficiency and hypercalcemia should raise suspicion of?
Disseminated histoplasmosis
Histoplasmosis Ix?
Urine / serum antigen
Culture
Serology - immunodiffusion
Histopathology
Histoplasma capsulatum
Visited desert in califonia 4 weeks ago. Now arthralgia and erythema nodosum
Coccidioides immitis
18yo male college student from south Alabama with a 6 months h/o scant sputum production with streaky hemoptysis. Aching in joints.
Insulin dependent DM (age 3),
SH: He visited Laredo, TX, and Northern Mexico on a
hunting trip approx 2 years ago (2 weeks prior to initial
episode of CAP). No tobacco or drugs. He drinks alcohol
Coccidiodes spp .
Most common site affected in Disseminate Coccidioidomycosis
skin
[bones and joints especially knee / vertebrae]
bar causes of immunosuppression, name 2 at-risk groups for disseminated Coccidioidomycosis?
, African American and Filipino men >60 years.
Pregnant women 2-3rd trimester
Coccidioidomycosis ix?
Lateral flow device best
Culture - grows in 3-7 days
histopathology. Identification of spherules
Coccidioidomycosis CNS infection and cant toleerate fluconazole / AmphoB
Voriconazole for those who cannot tolerate fluconazole
Name 2 causes of sporotrichosis? which in China&India?
Sporothrix schenckii
(S. mexicana, S. globosa, S. brasiliensis, S. luriei)
Sporotrichosis Rx
Itraconazole
-Treatment of choice in most settings
Fluconazole
-Not as effective as itra , but available and well tolerated
Terbinafine 500 mg bid
-Effective but expensive
Sporotrichosis local therapy
Heat - thermotherapy
Saturated solution of Potassium Iodide (SSKI)
Which inhaled fungi is most commonly dissemninated at presentsiton?
Blastomycosis
-pulmonary (60-80%),
-skin (40-60%),
-osseous (20-30%),
-genitourinary (10%)
-CNS (<5%)
Classic broad based budding yeast with doubly refractile cell wall of B. dermatitidis
Broad based budding yeast =
PAS stain of B. dermatitidis
Diagnosis blastomycosis
-characteristic broad based budding yeasts in clinical specimens.
-Culture hard
-Serologic test (urine assay, MiraVista Diagnostics) is sensitive but non specific, cross reacts with Histo/Cocci antigens
Main difference with fungal and mammal cells?
Fungal has a rigid cell wall
- we just have a cell membrane
Flucytosine mechanism
DNA synthesis
[only antifungal with this mechanism]
Azoles work on cell membrane
Toxicity with amphotericin 2 parts?
During infusion -> fever / rigors / hypotension
Renal toxicity + HypoK/Mg
Amphotericin mechanism
Binds to cell membrane (not wall) to ergosterol and makes a pore
-> leaks K/Mg = fungicidal
2 Key fungi resistant to ampho B
Aspergillus terreus
Candida auris
How do the -azoles work?
Azoles inhibit the synthesis of ergosterol by blocking demethylation of lanosterol
Why ketoconazole rarely used
Very hepatotoxic
Oral only
Which has more interactions intra or fluconazole
Itra
Key side issue with itraconazole bar drug interactions
Fluid retention + increased BP
->heart failure in susceptible people
[liver disease too]
Which candida does fluconazole not work on
Candida krusei
[Kruseis past]
Which of the -azoles does not work on aspergillus?
fluconazole
Which -azoles work against the zygomycetes - eg mucormycosis
Posaconazole
Isavuconazole
voriconazole side effects
Temporary visual disturbance
Rash and link to skin Ca
Mild hepatotoxicity
[v - visual]
Which of the -azoles has the broadest spectrum? Key issue?
Posaconazole (analogue of itraconazole)
-Has same issue with fluid retention/cardiac as itra too
Which 2 azoles get into the CNS best
Fluconazole
Voriconazole
Aspergillosis first choice azole
Voriconazole
What class is Caspofungin? Mechanism? Admisinisteration? side effects?
Echinocandins
-Inhibit B-D glucan synthase
only IV
Very few side effects and interactions
What are the only organisms sensitive to Echinocandins (-fungins)?
Candida
Aspergillus
[PCP]
1st line Rx invasive candida? When would they not be?
-Fungins Eg Caspofungin
CNS
[also low data for opthal/urine candida]
Flucytosine (5-FC) key side effects
Pancytopenia (think its almost 5-FU chemo)
-Mild hepatic/GI
5-FC works on which 2 bugs? which sneaky resistant one?
Cryptococcus
Candida - but NOT C. krusei
(it kreuseis past)
SSKI
supersaturated potassium iodide only real use
Sporotrichosis
Coccidioides immitis spherules
Name the dimorphic fungi
Body Heat Temperature Probably Changes Shape
Blastomyces dermatitidis.
Histoplasma capsulatum
Talaromyces marneffei
Paracoccidioides brasiliensis.
Coccidioides immitis.
Sporothrix schenckii.
Nasal stuffiness, facial pain and oedema with necrotic black nasal turbinates. Dx? Looks like on microscopy? Rx?
Mucor ssp
Amphotericin B and Posiconazole
wide ribbon-like, non-septated hyphae that are right angle branching.
