Micro - pulminary fungal infections Flashcards
1
Q
What is the route of infection for pulmonary fungal infections?
A
spore inhalation
2
Q
What activates pulmonary fungi to cause infection?
A
body heat - thermal dimorphism
3
Q
What are arthroconidia?
A
Arthrospores; infectious form form Coccidioides that causes coccidioidomycosis
4
Q
Where do Coccidioides reside (source of infection)?
A
soil - carried by wind when soil is disturbed
5
Q
Where are Coccidioides endemic to?
A
southwest US and Latin America
6
Q
What are the two most common fungi that cause coccidioidomycosis?
A
Coccidioides immitis and C. posadasii
7
Q
What is the cause for the spike in cases this century?
A
endemic areas (southwest US and Latin America - Phoenix and Tucson AZ, Bakersfield and Fresno, CA, El Paso TX.) have become geriatric
8
Q
T/F Spherules and endospores are not infectious
A
true
9
Q
What is an associated clinical symptom of coccidioidomycosis?
A
erythema nodosum (skin inflammation that results in reddish, painful, tender lumps - most commonly located in the front of the legs)
10
Q
Where in the pulmonary tract do Coccidioides undergo thermal dimorphism?
A
terminal bronchioles
11
Q
What is different about source of infection from infectious dimophic fungi vs TB?
A
infectious dimophic fungi are from american soil
TB is from foreign crops
12
Q
What form does Coccidioides adopt once it undergoes undergo thermal dimorphism?
A
spherule
13
Q
T/F morality is low but morbitity is high from coccidioidomycosis
A
true
14
Q
T/F coccidioidomycosis will trigger a positive PPD skin test?
A
true - 80% of residents in endmic population centers are PPD positive
15
Q
What is most important determinant of morbidity coccidioidomycosis?
A
Dose of pathogen exposure - single IU (reproductive spore) can trigger positive PPD but high dose causes more symptoms
16
Q
What makes the pherule difficult to eradicate by the immune system?
A
Thick, doubly-refractive wall
17
Q
Can coccidioidomycosis be transmitted from patient to patient?
A
No - must have independent exposure to spores from soil
18
Q
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?
A
macrophage engulphment and cytokine release
19
Q
What immune response clears most Coccidioides when inhaled?
A
alveolar macrophages
20
Q
What immune response clears Coccidioides when there is large dose exposure and significant infection?
A
Cell mediated immunity - forms small nodule in lung similar to TB that contains and slowly eradicates infection
21
Q
What are most common symptoms of coccidioidomycosis (moderate dose exposure)
A
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
Q
What 2 factors are most likely to cause pneumonia or dissemination in coccidioidomycosis?
A
high dose exposure or if someone is immunosuppressed
23
Q
What cell types are involved in acute phase of coccidioidomycosis? Chronic phase?
A
alveolar macrophages
lymphocytes and histiocytes
24
Q
What are the roles of lymphocytes and histiocytes in the chronic phase of coccidioidomycosis?
A
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
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What diseases are associated with asperigilloma?
TB, cystic fibrosis (colonizes cavitary lesions forming mass)
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What cause can cause pneumonia w/ hemoptysis and granulomas in immunocompromised patients?
chronic necrotizing pulmonary aspergillosis
difficult to diagnose, high mortality
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What are the virulence factors for aspergillus?
Gliotoxin: immunosuppressive
Toxic metabolites interfere with phagocytosis and opsonization
Proteases may be involved in tissue invasion
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What is this seen in?
| Xray or CT may show “grape cluster” or “hand in mitten” clusters of mucus-clogged bronchi
Allergic bronchopulmonary aspergillosis
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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
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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
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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
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Underlying diseases that predispose chronic necrotizing pulmonary aspergillosis
Underlying disease of alcoholism, collagen-vascular disease, chronic granulomatous disease or COPD, long term corticosteroid therapy
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Predisposing factors for invasive asperigillosis
History of profound immunosuppression or COPD with long-term corticosteroid therapy
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Clinical features of invasive asperigillosis
Fever, cough, dyspnea, pleuritic chest pain, neutropenia, sometimes hemoptysis, worsening hypoxemia
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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
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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)
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Diagnosis and pathologic features Allergic bronchopulmonary aspergillosis
* High levels of aspergillus-specific IgE, eosinophilia
| * Mucus with degenerating eosinophils and hyphae
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Mucormycosis is caused by what fungi?
Mucor, Rhizopus, Absidia, several others
Rhizopus - is big one and most common on STEP 1
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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"
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What are risk factors for mucormycosis?
uncontrolled diabetes (MAJOR CORRELATION), neutropenia, burns, leukemia, IV steroids or TNF alpha blockers, iron overload
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What is route of transmission for mucormycosis?
airborne asexual spores - Usually inhaled, can also be ingested or introduced by trauma
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T/F mucromycosis is highly associated with AIDS
false
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What is the main host defense against mucormycosis infection?
neutrophils (innate immuninty - cell mediated may not play large role)
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Where do mucormycoses proliferate?
walls of blood vessels - Cause infarction and necrosis of tissue downstream from blocked vessel
very high mortality if dissociated (~100%)
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Common sites of infection for mucormycoses?
Paranasal sinuses, invading brain - leaves disfigurement if treated successfully (huge necrotic lesion) 50-70% mortality
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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
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Biopsy of tissue infected with mucormycoses demonstrate:
NONSEPTATE HYPHAE w/ broad irregular walls and BRANCHES AT RIGHT ANGLES, vascular invasion and necrosis, neutrophil infiltration.
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What are 3 factors that complicate the diagnosis of mucormycosis?
It is rare
Diagnosic window is short
Initial symptoms may be nonspecific
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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
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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)
