Lec39 Fungi Flashcards
What are the medical classifications of fungi?
- systemic dimorphic endemic fungi
- opportunistic fungi
- superficial dermatophytes
- subcutaneous mycoses
What are examples of systemic dimorphic endemic fungi?
- histoplasma
- coccidioides
- blastomyces
- paracoccidioides
- penicillium
What are examples of opportunistic fungi?
- candida
- cryptococcus
- aspergillus
- mucorales
What are examples of superficial dermatophytes?
- trichophyton
- malassezia
What are examples of subcutaneous mycoses?
- sporothrix
- madurella
What are general properties of systemic dimorphic endemic fungi
- can disseminate throughout blood stream, can exist as yeast and mold, often associated with certain geographic areas
What is the structure of fungi?
- type of eukaryote
- has true nucleus and organelles [dif from bacteria]
- has cell wall made of primarily chitin
- cell membrane is made of ergosterol instead of cholesterol
What should you think when you see cryptococcus neoformans?
meningitis in HIV pt
What is mech of action echinocandins?
inhibit synthesis of fungal cell wall
What is mech of action azoles/allylamines?
inhibit ergosterol syntehsis of cell membrane of fungi
What is mech of action flucytosine?
inhibits nucleic acid synthesis
What fungus is associated with pts receiving total parenteral nutrtition [TPN] through some sort of central line?
candida albicans
What are properties of candida albincans
- unicellular yeast –> replicates by budding + mitotis
- form pseudohyphae
- can be used to form germ tube
- can also form true hyphae
- sometimes form chlamydospores
What are pseudohyphae?
chains of individual budding cells with constrictions = similar to hyphae but never completely separated
What is a germ tube?
elongated hyphal appendage from yeast cell to first constriction
sign of candida albicans
What are hyphae?
continuous tubes with septae separating each nuclei, no indentation at site of constriction
What is a chlamydospore?
- the life stage that survives in nutrient deficient media or in poor conditions
- terminal doublewalled cell arising from hyphae
What is immune rxn to mucosal candida?
- cell mediated immunity predominates for mucosal, chronic muco-cutaneous or GI candidiasis
- thus if you have lack of cell mediated immune [HIV] get mucosal candida [oral/esophageal]
What are common sites of candida in pt with normal immune?
- vulvovaginal candidiasis [especially after antibiotics eradicate normal flora]
What disease associated with vulvovaginal candidiasis?
yeast infection! especially after antibiotics eradicate normal flora
What disease associated with cutaneous candidiasis?
- diaper rash in infants
- rash in warm/moist areas [like under breast] especially in diabetic or person just recently had antibiotics
- fungal infection in nail plate [rarely]
Which species of candida most common in blood stream infection?
C. albicans = 46% MAJOR ONE
C. glabrata = 20%
C. parapsilosis = 14%
C. tropicalis = 12%
What is pathogenesis of candida bloodstream infection? What are some endpoint diseases?
pt recently on antibiotics, currently has catheter
- can cause: yeast form on heart valve, miliary abscesses in kidney, disseminated skin lesion, splenic candidiasis, endophtalmitis
37 yo F with severe aplastic anemia, neutropenic, thrombocytopenic, received anti-thymocyte globulin and cyclosporine, find multiple hepatosplenic abcesses and white lesions on liver
candida albicans
Who generally gets systemic candidiasis?
pts with - prolonged neutropenia, catheters, parenteral nutrition, broad spectrum antibiotics
Who gets mucutaneous disease?
can happen in immunocompetent hosts but way more frequent in pts with AIDS
How do you treat candida?
fluconazole when possible
amphotericin or echinocandins for non-albicans
How do you diagnose candida?
blood culture or direct visualization on biopsy, KOH test [germ tube]
What are properties of cryptococcus neoformans?
- encapsulated fungus
- found in environment [in pigeon droppings]
What are clinical signs of cryptoccus neoformans?
- wide range -> mainly asymptomatic colonization of respiratory airway –> can also get dissemination with fatal infections [nodular pulm infiltrates, non-blanching rash, skin lesion with umbilication]
- likes to invade CNS –> fungal meningitis
How does cryptococus neoformans enter body?
- enters primarily via lungs from aerosolization of pigeon droppings
What are the virulence factors of cryptococcus?
- capsule [main one]
- phenotypic switching
- melanin
What is role of capsule in cryptococcus infection?
- prevent phagocytosis
- reduces production of inflammatory cytokines
- depletes complement components
What is role of phenotypic switching in cryptococcus?
- changes in polysaccharide capsule and cell wall after yeasts resistance to phagocytosis and immune responses
What is role of melanin in cryptococcus?
- pigment with antioxidant activity
- moderates cell wall integrity and charge, interferes with antifungal susceptibility
- inhibits antibody-mediated phagocytosis
- protects from extrem temp
What stains do you use to culture cryptococcus?
- PAS
- silver stain
How do you treat cryptococcus?
amphotericin [with 5FC for serious illness] then as get better transition to oral fluconazole
How do you diagnose cryptococcus?
- serum test for cryptococcal capsular antigen of blood or CSF [rapid test]
- visualization of organism on biopsy or CSF [india ink see capsule]
- blood or CSF cultures
Who gets serious cryptococcus infection?
most serious infections = pts with AIDS
What are properties of histoplasma capsulatum?
- dimorphic fungus
- primarily
How is histoplasma capsulatum tranmitted / who gets it?
- primary infection from inhalation of microconidia
- high concentration of it found in bat poop
- associated with severe disease in immunocompetent with heavy exposure [spelunking, construction work]
What happens to those with defects in cellular immunity and histoplasmosis?
- defect in cellular immunity can result in reactivation/dissemination
- have 80% mortality in untreated disseminated histoplasmosis
What are sigs of acute histoplasmosis?
- acute pulm illness
- may see disseminated pulm scarring on CT, looks like miliary TB
- pericarditis
- spreads to liver/spleen/bone marrow in disseminated –> get pancytopenia
How is histoplasmosis diagnosed?
- urine histoplasma antigen [more sensitive for AIDS than non-AIDS pts] = major way
- bone marrow biopsy [tendency to infect liver, spleen, and bone marrow]
- blood cultures [silver stain]
- CSF antigen
- liver or lymph node biopsy
Where is highest prevalence of histoplasma in US?
along ohio river vallery
How do you treat histoplasma?
- treat with amphotericin then transition to
- itraconazole or voriconazole
Where is blastomycosis endemic?
south america, middle US
- has geo overlap with histoplasmosis
How is blastomyces dermatidis acquired?
- natural habitat is soil, decaying wood, river banks
- saprophytic mold in soil at 25C
- acquire through inhalation mold-form conidia [spores] into alveoli [rarely by direct cutaneous inoculation]
What are properties of blastomyces?
- dimorphic fungus in moist soil
- yeast phase divides with broad based budding = cells are still attached have broad wall between them
What are the pulm manifestations of blastomycosis
- wide spectrum
- can have asymptomatic self limiting pulm infection
- focal pulm infection resembling bacterial pneumonia
- subacute to chronic pneumonia with mass-like lesions, multiple nodular lesions, lobar infiltrates, cavitary lesions in immunocompetent
What are cutaneous manifestations of blastomyces dermatidis?
- cutaneous lesions generally result from hematogenous spread
- pathology = mix of granulomatous and neutrophilic response [microabcesses]
- get lesions wingle or multiple papules, nodules, microabcesses
What are clinical manifestations of blastomycosis generally?
- most disease is pulm, can have some cutaneous disease
How do you diagnose blastomyces?
- by culture or visualization of yeast phase with broad based budding
how do you treat blastomyces?
- amphotericin B
- traconazole, flluconazole
Where is coccidioides immitis infection found? what are two diseases of its infection?
- in southwest US desert [texas, NM], mexico, central and south america
- called: coccidioidomycosis and san joaquin valley fever
Where does coccidioides live? How is it transmitted?
- propagates in soil in desert
- grows as mold at 25C and produces mycelia that give rise to barrel-shaped arthroconidia = infectious unit
- arthroconidia become aerosolized and inhaled by humans
- within human arthroconidia differentiates into large endosporulating spherule
What is the coccidioides spherule?
- the form of the fungus that exists in humans
- composed of large sphere containing many endospores
- releases endospores which disseminate infection
What are clinical manifestations of coccidioidomycosis?
- primary pulm infection [some asymptomatic]
- mild flu-like symptoms 10-16 days post exposure = cough, fever, chest pain, headache, chills, anorexia
- in 5% have san joaquin valley fever
What are symptoms of san joaquin valley fever?
- erythema nodosum
- erythema multiforme
- arthralgias “desert rheumatism”
- conjunctivitis
- hypersentitivity rxn to fungal proteins
What are some examples of activities that give pts higher inoculum and thus more likely to get symptomatic disease?
- archaeological excavation
- construction project
- military exercise
Who gets disseminated coccidioides infection?
- immunocompromised
- genetically high risk groups [filipino, African american, native american]
How do you diagnose coccidioides infetion?
culture of pulmonary specimens –> spherule is diagnostic
how do you treat coccidioides?
- amphotericin B
- then fluconazole in immunocompromised
What is mariner’s wheel morphology?
- characteristic finding of paracoccidioides fungus
What are properties of paracoccidioides brasiliensis?
- characterstic mariners wheel appearance representing multiple budding in mold phase
- often oval to round cell
- buds have narrow stalks compared to blastomycosis
- dimorphic fungus
Where is paracoccidioides brasiliensis endemic?
- south america from mexico to argentina, highest rates in brazil
Who gets paracoccidioides primarily?
- much higher prevalence in males [estrogen may inhibit]
What are clinical manifestations of paracoccidiodes brasiliensis?
- primary lung infection
- can have long latency with reactivation > 10 yrs
- patchy nodular densities/consolidations in lung
- lymphadenopathy
- cutaneous fistule
How is paracoccidiodes transmitted?
- primary infection via lung then dissemination
How do you diagnose paracoccidioides?
- culture of biopsied material or BAL specimens
What is treatment for paracoccidioides?
- itraconazole [main] or trimpethoprim-sulfamethoxazole
- amphotericin B if severe
Where is peniillium marneffei endemic?
- tropical asia –> thialand, north india, china, hong kong, vietnam, taiwan
What is penicillium marneffei infection associated wtih?
- opportunistic infection with AIDS
Whare are properties of P. marneffei?
- thermal dimorphism
- mycelium with septate hyphae at 25C
- yeast with binary fission replication at 37C
- saprophytic
What is reservoir for penicillium marneffei?
- zoonotic [bamboo rat]
What are clinical features of peniccilium marneffei?
- primary pulm pathogen
- produces chronic pulm infection
- in immunosuppressed disseminates hematogenously –> hepatomegaly, skin lesions [umbilicated appearance] , generalized lymphadenopathy, fever, weight loss
How do you diagnose peniillium marneffei?
- visualization of yeast phase –> characterized by binary fission
How do you treat penicillium marneffei?
amphotericin and 5-FC
