Micro - pulminary fungal infections Flashcards Preview

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Flashcards in Micro - pulminary fungal infections Deck (205):
1

What is the route of infection for pulmonary fungal infections?

spore inhalation

2

What activates pulmonary fungi to cause infection?

body heat - thermal dimorphism

3

What are arthroconidia?

Arthrospores; infectious form form Coccidioides that causes coccidioidomycosis

4

Where do Coccidioides reside (source of infection)?

soil - carried by wind when soil is disturbed

5

Where are Coccidioides endemic to?

southwest US and Latin America

6

What are the two most common fungi that cause coccidioidomycosis?

Coccidioides immitis and C. posadasii

7

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

8

T/F Spherules and endospores are not infectious

true

9

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)

10

Where in the pulmonary tract do Coccidioides undergo thermal dimorphism?

terminal bronchioles

11

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

12

What form does Coccidioides adopt once it undergoes undergo thermal dimorphism?

spherule

13

T/F morality is low but morbitity is high from coccidioidomycosis

true

14

T/F coccidioidomycosis will trigger a positive PPD skin test?

true - 80% of residents in endmic population centers are PPD positive

15

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

16

What makes the pherule difficult to eradicate by the immune system?

Thick, doubly-refractive wall

17

Can coccidioidomycosis be transmitted from patient to patient?

No - must have independent exposure to spores from soil

18

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

19

What immune response clears most Coccidioides when inhaled?

alveolar macrophages

20

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

21

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

22

What 2 factors are most likely to cause pneumonia or dissemination in coccidioidomycosis?

high dose exposure or if someone is immunosuppressed

23

What cell types are involved in acute phase of coccidioidomycosis? Chronic phase?

alveolar macrophages

lymphocytes and histiocytes

24

What are the roles of lymphocytes and histiocytes in the chronic phase of coccidioidomycosis?

initiate granuloma and giant cell formation (containment)

25

What other diseases resemple the clinical features of coccidioidomycosis

Valley fever or desert rheumatism

26

What are the clinical symptoms of severe symptomatic coccidioidomycosis (5)?

Fever
Arthralgias
Erythema nodosum
Erythema multiforme
Chest pain

27

How is coccidioidomycosis disseminated in immunosupressed patients?

intracellular travel in macrophages and hematogenous spread

28

What are risk factors for coccidioidomycosis?

advanced age, immunocompromise, late-stage pregnancy, occupational high-level exposure (farmers, construction workers, archaeologists), Black or Filipino race

29

What tissues are primarily affected by disseminated coccidioidomycosis?

bones, meninges, skin or lymph nodes (presents as soft tissue abscess)

30

What can coccidioidomycosis trigger causing rapidly fatal progression?

immune anergy

31

Localized extrapulmonary infection by Coccidioides is usually caused by what?

contaminated injury

usually resolves without treatment

32

contaminated Coccidioides infections can cause what symptoms?

influenzalike illness (fever, cough)

33

What lung changes can be seen on x-ray with coccidioidomycosis?

Infiltrates
Adenopathy
Effusions
Nodules resembling malignancy (biopsy)

34

T/F PPD will be negative for disseminated coccidioidomycosis infection in immunosuppressed pt?

true

35

T/F PPD will be positive if there is a cleared or contained coccidioidomycosis infection

true

36

What is the incubation period for Coccidioides?

7-30 days

37

When are people most likely to become infected with Coccidioides?

summer or autumn

38

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)

39

T/F coccidioidomycosis associated hypersensitivity rxn may manifest in eye as conjunctivitis

true

40

coccidioidomycosis disseminated to bone causes what?

osteomyelitis

41

What differentiates coccidioidomycosis disseminated meningitis from bacterial meningitis?

symptoms similar, but onset is slow (weeks) with coccidioidomycosis

42

T/F Dramatic sweats, dyspnea, fever, weight loss are symptoms of disseminated coccidioidomycosis infection

true

43

How do you culture Coccidioides from biopsy?

Sabouraud’s agar at 25C

44

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

45

T/F serology titers are usefull for monitoring progression of coccidioidomycosis infection

true - IgG from blood and/or CSF spike indicates dissemination

46

True/false a PCR test for coccidioidomycosis is available

true

47

What CSF findings would you see from coccidioidomycosis disseminated meningitis?

lymphocytic pleocytosis, elevated protein, hypoglycorrhachia ( a low glucose level), eosinophilia, CF (compliment fixing) IgG

48

T/F serology for coccidioidomycosis are specific but less sensitive (i.e. prone to false negatives)

true

49

Treatment for persistant or disseminated infections

Amphotericin B and long-term itraconazole

50

coccidioidomycosis meningitis is initially treated with what?

fluconazole, continue as a long-term suppressive

51

severe or prolonged coccidioidomycosis meningitis is treated with what?

intrathecal amphotericin B

52

What does long term amphotericin B treatment cause? How would you treat this?

immunogenic symptoms

corticosteroids

53

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)

54

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

55

What is the most common systemic mycosis

histoplasmosis

56

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

57

What are two (asexually reproducing) ENVIRONMENTAL forms of Histoplasma capsulatum?

Tuberculate macroconidia

Microconidia

58

What are the features that distinguish Tuberculate macroconidia from Microconidia?

Tuberculate macroconidia - Thick walls, Fingerlike projections

Microconidia -Smaller, thin, smooth-walled

59

Which forms of Histoplasma capsulatum are infectious?

Microconidia

60

What is the source of Histoplasma capsulatum infection?

soil,
bird droppings, esp from starlings or bat guano

61

T/F Histoplasma capsulatum must be inhaled to cause infection

true

62

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

63

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

64

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

65

What are DEFINING symptoms of severe Histoplasma capsulatum infections

Pancytopenia
Ulcerated lesions on tongue

66

What symptoms can high dose Histoplasma capsulatum exposure cause?

High-dose exposure may cause pneumonia w/ cavitary lung lesions on primary infection

67

Which patients are most suseptible to severe Histoplasma capsulatum infection?

Very young, very old, immunosuppressed

68

T/F PPD is useful for Histoplasma capsulatum

False - many false positives

69

Both Histoplasma capsulatum and Coccidioides are thermally dimorphic and transform to yeast in tissue, what differentiates them?

Formation of spherule

70

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

71

What is a difference between TB and histoplasmosis?

drugs used for treatment differentiate

72

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)

73

what fungi causes blastomycosis

Blastomyces dermatitidis

74

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

75

Yeast form of blastomyces has what features?

round w/ doubly refractive wall
single broad-based bud

76

What regions are blastomyes endemic to?

Eastern north america and great lakes region

grows in wet rich soil

77

What is the virulance factor for blastomyces?

Yeast, not mold, produce immune-modulator BAD1 on cell surface

78

What is the infection rate of blastomyces?

~50% Asymptomatic infection : successful clearance

79

How does immune system typically defeat blastomyces?

granulomatous response, may develop pulmonary symptoms in process

80

When would pulmonary symptoms present with blastomyces infection?

(~45 days post exposure)

81

Who is susceptible for dissemination, hematogenous seeding of many possible sites

Immunosuppressed or preexisting pulmonary disease

82

T/F Untreated symptomatic cases of blastomycosis have significant mortality rate (~40%)

true

83

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

84

T/F Skin lesions are more common with blastomyces than coccidioides or histoplasma

true

85

T/F blastomyces can be cultured from skin lesion

true

86

How do you diagnose blasomycosis?

Sputum microscopy is 75% diagnostic IF pt have pneumonia

Tissue biopsy is other method -

87

What would you expect to find from microscopy of sputum or culture?

hyphae w/ small pear-shaped conidia

88

T/F PPD and serology are specific for blastomycosis

False! NOT specific - prone to false positive

89

Classic culture presentation of histoplasmosis

ovoid yeast form inside macrophages - larger than bacteria

90

Expected blood findings from histoplasmosis in disseminated dissease?

pancytopenia

91

How would you culture histoplasma capitum?

Sabouraud’s agar - 2 cultures necessary unlike coccidiomycoces

25C for tuberculate macroconidia
37C for yeast

92

T/F ELISA for histoplasmosis can be performed from serum or urine

true for histoplasma polysaccharide antigen

93

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

94

What is causes South American blastomycosis, Lutz-Splendore-Almedia disease?

Paracoccidioides brasiliensis

AKA Paracoccidioidomycosis

95

T/F Paracoccidioides are dimorphic with yeast and mold form

true

96

What defines mold form of Paracoccidioides?

thin, septate hyphae

97

What defines yeast form of Paracoccidioides?

thick-walled w/ multiple buds

98

Where is Paracoccidioides endemic to?

rural Latin America

99

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)

100

endemic to US Southwest, mold grows in wet weather, releases infectious arthrospores in dry, spores inhaled, change form.

Coccidioides (coccidioidomycosis)

101

Treat if predisposed to complications (oral azoles), meningitis (fluconazole), pregnant or disseminated (Amphotericin B).

Coccidioides (coccidioidomycosis)

102

Which fungus?
culture for hyphae w/ pear-shaped conidia

Blastomyces (North American blastomycoses)

103

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)

104

Which fungus?

60% Mild: asymptomatic or flulike clearance by innate or containment by CMI

Coccidioides (coccidioidomycosis)

105

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)

106

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)

107

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)

108

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)

109

Which fungus?

Acute febrile respiratory illness 3-14 days after exposure

Histoplasma capsulatum

(histoplasmosis)

110

biopsy for spherules

Coccidioides (coccidioidomycosis)

111

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)

112

Which fungus?

History: residence in or travel to an endemic river valley, occupational exposure from soil, birds, bats, immune predisposition

Histoplasma capsulatum

(histoplasmosis)

113

Which fungus?

Fever
Arthralgias
Erythema nodosum
Erythema multiforme
Chest pain
High morbidity, low mortality

Coccidioides (coccidioidomycosis)

114

Which fungus?

Pancytopenia
Ulcerated lesions on tongue

Histoplasma capsulatum

(histoplasmosis)

115

Which fungus?
Risk factors: age, race, pregnancy, immunocompromise, occupational high exposure

Coccidioides (coccidioidomycosis)

116

Which fungus?
Endemic in southwest US and Latin America

Coccidioides (coccidioidomycosis)

117

Which fungus?
thermally dimorphic (mold/multibud yeast)

Paracoccidioides (Paracoccidioidomycosis/South American blastomycosis/Lutz-Splendore-Almedia disease)

118

Which fungus?
serology for dissemination

Coccidioides (coccidioidomycosis)

119

Which fungus?
thermally dimorphic (mold/yeast),

Either Histoplasma or Blastomyces

120

Which fungus?
Diagnose by sputum microscopy for yeast

Blastomyces (North American blastomycoses)

121

Which fungus?
Diagnose by pus or tissue KOH mount for yeast with multiple buds

Paracoccidioides (Paracoccidioidomycosis/South American blastomycosis/Lutz-Splendore-Almedia disease)

122

Which fungus?
treatment involves healthier lifestyle (semi-opportunistic).

Paracoccidioides (Paracoccidioidomycosis/South American blastomycosis/Lutz-Splendore-Almedia disease)

123

Which fungus?
biopsy for yeast w/ supperating (not caseating) granulomas

Blastomyces (North American blastomycoses)

124

Moderate acute: pneumonia w/ purulent sputum, Moderate chronic: mimics TB, Severe acute: ARDS. May include EN or ulcerating skin lesions.

Blastomyces (North American blastomycoses)

125

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)

126

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)

127

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)

128

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)

129

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)

130

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)

131

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

132

hypersensitivity rxn to infection complicating asthma or CF, diagnose on exam, treat w/ itraconazole, sinus surgery, Xolair

Aspergillosis - ABPA (Allergic bronchopulmonary aspergillosis)

133

Which infection is more likely to actually require treatment (greater virulance) vs require treatment once acquired?

blastomycoses
Paracoccidioidomycosis
coccidioidomycosis
histoplasmosis

blastomycoses

134

fungus ball complicating cavitary lung disease, diagnose by air crescent on scan, treat w/ itraconazole and/or surgery

Aspergilloma (colonizing aspergillosis)

135

Opportunistic fungal pathogens cause dangerous infection when paired with what risk factors?

prolonged neutropenia,
uncontrolled HIV or diabetes,
profound T-cell suppression

136

Effective treatment of serious disease from opportunistic fungal pathogens must: (2 things)

addresses both the current infection and the underlying problem

137

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

138

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

139

mimics TB; try to diagnose by air crescent on scan, needle-aspirate lung fluid for microscopy

Aspergillosis CNPA (Chronic necrotizing pulmonary aspergillosis)

140

respiratory distress with history of profound immunosuppression, diagnose by halo sign on scan, needle or tissue biopsy for histo

Invasive aspergillosis

141

Treat with voriconazole+AmphotericinB, but prognosis is poor

CNPA and invasive Aspergillosis

142

banana-shaped macroconidia

Fusarium

143

Fusarium species that is the most common cause serious infection (50%)

Fusarium solani

144

What are the 3 presentations of Fusarium pathogenesis?

Mycotoxicosis
Immunocompetent local infection
Immunosuppressed opportunistic infection

145

virulence factors for Fusarium include:

immunosuppressive mycotoxins
collagenases
proteases
ability to adhere to prosthetic material

146

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)

147

What causes mycotoxicosis?

trichothecene mycotoxins

148

Where would you find immunocompetent local fusarium infection?

Skin (burns)
Cornea (contaminated contact lens solution)
Allergic sinusitis (like ABPA)
Colonization of prosthetics & catheters

149

Primary species causing cryptoccocis

Cryptococcus neoformans and C. gattii

150

5 seriotypes
A, D, AD = ?
B,C = ?

A, D, AD = Cryptococcus neoformans
B,C = Cryptococcus gattii

**grow at 37C

151

What fungal species is environmental, found worldwide in soil contaminated w/ bird droppings, esp pigeon?

Cryptococcus neoformans

152

What features describe criptococci (under microscopy)?

Oval yeasts w/ narrow-based buds
wide polysaccharide capsule

153

What fungal species found in litter under eucalyptus trees?

Cryptococcus gattii

154

Which Cryptococcus species causes less severe disease but prefers immunocompetent hosts (more common on West coast)?

Cryptococcus gattii

155

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

156

What factors have increased incidence of cryptococcal meningitis?

Use of steroids, survival w/ malignancy, and AIDS

157

T/F lung infection with cryptococci can be asymptomatic

true, or lead to pneumonia or dissemination

158

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

159

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

160

What are virulance factors for criptococci?

capsule,
melanin in cell wall (antiphagocytic),
Phospholipase B for invading tissue

161

What is a characteristic feature of C. neoformans dissemination?

meningitis w/ skin nodules

162

T/F C. neoformans raises very little inflammatory response or granuloma formation

true!

163

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

164

What is "crag"? what is it used for?

serology test (short for cryptococcal antigen) involves latex agglutination for cryptococcal antigen in blood and CSF

165

What is found on culture media (Sabouraud agar) with Cryptococcosis?

melanin

37C

166

In Cryptococcosis, CSF stained with india ink will demonstrate what?

yeast w/ wide capsule (halo ring) -- much larger than bacteria that cause meningitis

167

T/F ruitine blood work may be normal in pt with Cryptococcosis

True - blunted immune response so no inflammation

168

Altered mental status in HIV positive pt should be tested for what?

Cryptococcosis encephalitis/meningitis

169

What is most useful test early on in Cryptococcosis?

crag from blood or CSF

170

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

171

T/F criptococcus can infect the prostate

true

172

what is treatment for Prostate Cryptococcosis

Fluconazole

173

Treatment for pulminary criptococcosis?

In immunocompetent patients may not need treatment; can use 6-12mo fluconazole or itraconazole

174

Treatment criptococcosis of Skin, bones, other:

Amphotericin B

175

What features define Aspergillus?

Septate (divided) hyphae w/ V-shaped branches

176

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

177

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

178

What diseases are associated with asperigilloma?

TB, cystic fibrosis (colonizes cavitary lesions forming mass)

179

What cause can cause pneumonia w/ hemoptysis and granulomas in immunocompromised patients?

chronic necrotizing pulmonary aspergillosis

difficult to diagnose, high mortality

180

What are the virulence factors for aspergillus?

Gliotoxin: immunosuppressive
Toxic metabolites interfere with phagocytosis and opsonization
Proteases may be involved in tissue invasion

181

What is this seen in?
Xray or CT may show “grape cluster” or “hand in mitten” clusters of mucus-clogged bronchi

Allergic bronchopulmonary aspergillosis

182

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

183

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

184

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

185

Underlying diseases that predispose chronic necrotizing pulmonary aspergillosis

Underlying disease of alcoholism, collagen-vascular disease, chronic granulomatous disease or COPD, long term corticosteroid therapy

186

Predisposing factors for invasive asperigillosis

History of profound immunosuppression or COPD with long-term corticosteroid therapy

187

Clinical features of invasive asperigillosis

Fever, cough, dyspnea, pleuritic chest pain, neutropenia, sometimes hemoptysis, worsening hypoxemia

188

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

189

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)

190

Diagnosis and pathologic features Allergic bronchopulmonary aspergillosis

• High levels of aspergillus-specific IgE, eosinophilia
• Mucus with degenerating eosinophils and hyphae

191

Mucormycosis is caused by what fungi?

Mucor, Rhizopus, Absidia, several others

Rhizopus - is big one and most common on STEP 1

192

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"

193

What are risk factors for mucormycosis?

uncontrolled diabetes (MAJOR CORRELATION), neutropenia, burns, leukemia, IV steroids or TNF alpha blockers, iron overload

194

What is route of transmission for mucormycosis?

airborne asexual spores - Usually inhaled, can also be ingested or introduced by trauma

195

T/F mucromycosis is highly associated with AIDS

false

196

What is the main host defense against mucormycosis infection?

neutrophils (innate immuninty - cell mediated may not play large role)

197

Where do mucormycoses proliferate?

walls of blood vessels - Cause infarction and necrosis of tissue downstream from blocked vessel

very high mortality if dissociated (~100%)

198

Common sites of infection for mucormycoses?

Paranasal sinuses, invading brain - leaves disfigurement if treated successfully (huge necrotic lesion) 50-70% mortality

199

Blood findings in mucormycosis?

neutropenia, diabetic acidosis, iron overload

200

T/F antigen testing and CSF findings are helpful for diagnosis

False! No useful antigen tests or CSF findings

201

Biopsy of tissue infected with mucormycoses demonstrate:

NONSEPTATE HYPHAE w/ broad irregular walls and BRANCHES AT RIGHT ANGLES, vascular invasion and necrosis, neutrophil infiltration.

202

What are 3 factors that complicate the diagnosis of mucormycosis?

It is rare
Diagnosic window is short
Initial symptoms may be nonspecific

203

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

204

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

205

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)