L8 Flashcards
1
Q
Fungi fill an important niche in nature:
A
Principle decomposers (saprophytic) - secrete digestive enzymes
2
Q
Make up their own
A
Kingdom - Fungi are Eukaryotes
3
Q
Most fungi are
A
free living in nature and are acquired from the environment - a few are part of normal human flora.
4
Q
Most fungi are
A
• Mostly strict aerobes (a few are facultative anaerobes)
5
Q
Fungi cause disease by
A
• Cause disease by inducing an inflammatory response or through direct invasion or destruction of tissues (some produce toxins)
6
Q
Fungus have
A
defined nucleus
7
Q
Fungal Cell membrane consists of
A
ergosterol
• Mammaliancellscontaincholesterol
8
Q
Fungal Cell walls are unique
A
- With chitin, mannan and glucan
* Different from cell wall of plants and bacteria
9
Q
Fungi of medical importance - 3 major categories
A
Yeast- unicellular fungi • Example: Candida albicans
• Molds- multicellular fungi • Mycelium (vegetative)
• Dimorphic fungi- exits as both mold and yeast
10
Q
Fungal – Molds (multicellular)
A
Filamentous fungi- (mycelial - vegetative form)
11
Q
molds - reproduction
A
asexuallybyconidiathatformonthetips
of growing hyphae
• Sexual reproduction through the development of spores
12
Q
Dimorphic fungi determined by
A
Thermally dimorphic- Temperature determines whether mold or yeast
13
Q
Fungi are encountered by three ways
A
Incidental contact in the environment
• Most healthy people develop no symptoms
• High inoculum exposures and/or immunosuppression can result in infection
Normal human flora (commensal organisms)
• Usually yeasts
• Disseminated infections in immunocompromised hosts
Contact with infected individual – (dermatophyte)
14
Q
Innate immunity provides
A
great protection against fungi
15
Q
• Most fungal infections are
A
mild and self-limiting
16
Q
• Intact skin and mucosal surfaces are
A
primary barriers
-Desiccation, epithelial cell turnover, fatty acids and/or low pH of skin- important in limiting fungi
17
Q
• Bacterial normal flora compete with
A
fungi and inhibit growth
18
Q
Alterations in normal flora (antibiotics) or compromised skin/mucosal surfaces (trauma, etc.) allow for
A
entry and infection
19
Q
T cell-mediated immunity is required to eliminate
A
fungal infections.
20
Q
Phagocytosis and killing by Neutrophils is primary mechanisms for containing
A
fungal infections
21
Q
Some fungi are too large to be
A
phagocytized -Phagocytic cells secrete enzymes and reactive oxygen species that can digest or kill large fungi
22
Q
Antibodies participate in
A
killing some fungi
• minor component to protection, can even be detrimental
23
Q
Fungal Diseases examples
A
thrush, Oral histoplasmosis
24
Q
Endemic mycoses-
A
infections caused by geographically restricted fungi (true pathogens)- cause serious systemic infections in healthy individuals
25
Opportunistic mycoses-
cause life-threatening systemic disease in immunosuppressed patients.
26
Subcutaneous mycoses-
fungal disease of the skin, subcutaneous tissue, and lymphatics.
27
Superficial cutaneous mycoses-
common fungal infections limited to the skin and skin structures.
28
Histoplasmosis- endemic mycoses
Histoplasma capsulatum (Mississippi and Ohio River Valleys) Bird and bat poop
29
Endemic mycoses - Blastomycosis-
Blastomyces dermatitidis (Mississippi river valley and southeastern and North Central States) Soil mold
30
Coccidioidomycosis- endemic mycoses
Coccidioides (Southwestern United States) Dessert soils
31
Endemic mycoses description
Common infections restricted to geographical areas
• Mostly asymptomatic- or mild self- limited symptoms
• Cell-mediated immunity (CD4- T- Cells) required for clearance
• Lung is primary site of entry
32
Histoplasmosis-
| Histoplasma capsulatum description
Dimorphic soil fungus- mold in environment with macroconidia (tuberculate) and microcondidia (infectious form). At 37 °C (body temp.) assumes a yeast like form
• 90% of people have been infected in USA
• Grows in soil with high nitrogen content fertilized by birds and in caves where bat guano (poop) is present
• Clusters of infection (outbreak)- demolition of old buildings that disrupts soil
33
Histoplasma capsulatum In lungs, transforms into
yeast phase
-poorly understood process but essential for disease process.
34
Histoplasma capsulatum Reticuloendothelial (macrophage) system infection
Remains viable in macrophages-
| modulates phagolysosomal pH
35
Histoplasmosis - Disease manifestation depends on
number of conidia inhaled and the host response (cell-mediated immune response)
36
Histoplasmosis - • Most infected people have no or only
mild symptoms
37
Histoplasmosis - • Ifalargeamountisinhaledevenhealthypeopleget
severe pneumonia
38
Histoplasmosis - • Somepatientsdevelop
fever,chills,anorexia,fatigueanddry cough:
| • If healthy- infection can clear on its own without antifungal treatment
39
Histoplasmosis - • PatientswithCOPDareat
higherriskofcomplications- • Chronic cavitary pulmonary histoplasmosis, which is eventually fatal
40
Disseminated Histoplasmosis - Occurs in nearly everyone infected with
H. capsulatum- usually asymptomatic
41
Disseminated Histoplasmosis - Symptomatic disease more likely in people with
AIDS (cell-mediated immune deficiencies) or with immunosuppressive therapy
42
Disseminated Histoplasmosis - Acute disseminated histoplasmosis-
fever, chills, fatigue, mucous membrane ulcers, hepatosplenomegaly, pancytopenia, sepsis syndrome.
43
Disseminated Histoplasmosis - Chronic progressive disseminated histoplasmosis-
happens in older adults- patients die if not treated
44
Diagnosis of Histoplasmosis - Growth of organism (definitive) -
from sputum, blood, tissues, or body fluids. Can take up to 6 weeks
45
Diagnosis of Histoplasmosis - Histopathological analysis (with a special stain) of
small intracellular yeasts in bone marrow, liver, lung, or lymph nodes is quicker.
46
Treatment of Histoplasmosis - In healthy patient- self limited no
treatment needed
47
Treatment of Histoplasmosis - Mild-to-moderate infections-
Itraconazole for 3 to 12 months
48
Treatment of Histoplasmosis - Severe infections-
amphotericin B to contain, then switch to itraconazole
49
Blastomycosis - Dimorphic (fungus in environment, yeast at 37∘C)
yeast have a thick cell wall and broad- based budding
50
Blastomycosis - Endemic to
Mississippi River Valley and Southeastern states
Soil and decaying wood a likely source
51
Blastomycosis - Mostly
sporadic cases- sometimes small outbreaks
52
Blastomycosis infection - Disease occurs when
inhaled into the lungs- multiplies leading to pneumonia
53
Blastomycosis- infection - Skin lesions also
commonly occur- dissemination - spread by blood
54
Blastomycosis- infection - Granulomas can develop
• Yeast remains viable and reactivate later
55
Blastomycosis- infection - Cell-mediated immunity is necessary for
clearance-yeast are phagocytosed by macrophages and neutrophils
56
Blastomycosis- infection - Diagnosis and treatment
similar to histoplasmosis
57
Coccidioidomycosis - Valley fever - Found in
dessert soil and burrows
| of desert animals
58
Coccidioidomycosis - Valley fever - Proper environmental conditions allow
“blooms” to form (perfect storm of rainfall, heat, and wind)
59
Coccidioidomycosis - Valley fever- In endemic areas-
80% of population have been infected
60
Coccidioidomycosis - Valley fever- San Jaquin Valley Fever-
real problem for prison population- efforts to keep dust levels down
61
Coccidioidomycosis - Valley fever - Dimorphic - not
temperature dependent
62
Coccidioidomycosis - Valley fever - Arthroconidia (mold form) are highly
infectious; inhaled into alveoli (lungs)
63
Coccidioidomycosis - Valley fever - In tissues- transform into large
spherules (50-
| 100 𝝻m) filled endospores (100’s)
64
Coccidioidomycosis - Valley fever - Arthroconidia are
phagocytosed and killed, but spherules (yeast) resist phagocytosis
65
Coccidiomycosis infections - Most healthy people have
no or only mild symptoms
66
Coccidiomycosis infections - When symptomatic-
Desert rheumatism or Valley Fever
67
Coccidiomycosis infections - Acute pulmonary infection-
self-limiting (no treatment required)
68
Coccidiomycosis infections - symptoms
Chest pain, cough, fever and chills
• Joint pain (arthralgias), stiff neck, muscle aches
• Erythema nodosum (rash and painful lumps-lower legs)
• Can become disseminated disease
• Chronic pulmonary infection can occur months or years later
69
Coccidiomycosis infections - Cell-mediated immunity
(CD4 T-cells) is needed to control (AIDS patients are more susceptible)
70
Disseminated Coccidiomycosis - Increased risk in:
dark-skinned individuals, pregnant women, and immunocompromised
71
Disseminated Coccidiomycosis - Can result in
cutaneous, subcutaneous, and osteoarticular infections that spread to other organs (CNS)
72
Disseminated Coccidiomycosis - Chronic meningitis can be a
```
complication
• Fatal if not treated
• Requires life-time antifungal therapy
• Antifungals have severe side effects- light sensitivity
• Skin cancers results
```
73
Coccidiomycosis- diagnosis - Can be cultured-
growth within several days
74
Coccidiomycosis- diagnosis - Mold on plates can be highly infectious-
laboratory workers should
| be warned coccidomycosis is suspected
75
Coccidiomycosis- diagnosis - Histopathological analysis possible-
presence of spherules in tissues is diagnostic.
76
Coccidiomycosis- treatment - Itraconazole or fluconazole for
12-24 months depending on extent of
| disease.
77
coccidiomycosis - treatment - Amphotericin B-
if infection is severe
78
Opportunistic fungal pathogens-Not considered true
pathogens - only cause disease when host defenses are decreased
79
• Patients at high risk for fungal infections:
Immunocompromised patients
| Otherriskfactors
80
Immunocompromised patients
Immunosuppressive therapy- organ and stem cell transplant
• Hematological malignancies
• HIV infection
• Corticosteroids and other immunosuppressive drugs (Humara)
81
Candidiasis - Reproduce by forming
buds or blastoconidia
82
Candidiasis - Some form
hyphae in vivo (non temp- dependent dimorphism)
83
Candidiasis - Dimorphism exception –
mycelial (hyphae) not yeast form found in tissues
84
Candida albicans- Most frequent
opportunistic fungal pathogen
85
Candida albicans- Most infections are
endogenous (derived from host’s normal flora)
| • Colonized: gastrointestinal tract (mouth to rectum), vagina, and skin
86
Candida albicans-Do not cause infection unless
normal flora is disrupted or
patient is immunocomprimised:
• Broad spectrum antibiotics biggest culprit, followed by skin macerations
• Decreased T-cell function increases mucosal infections (AIDS patients)
87
Candida albicans- T-Cell-mediated immunity keeps
Candida in check on mucosal surfaces (Neutrophils) main host defense against invasion through mucosa
88
Candida albicans- Neutropenia (low neutrophils) -
candida can spread to many organs (eyes, kidneys, heart, brain, liver, and spleen) - disseminated infections
89
Candidiasis- yeast infections - Mucosal (Thrush)-
Thick, white plaques on oropharyngeal and vaginal
mucosa
• Sometimes ophthalmic
90
Candidiasis- yeast infections - Cutaneous (Intertriginous candidiasis)- Proliferation of
candida in warm moist areas of skin (groin, under breasts)
| • Babies – Diaper Rash
91
Candidiasis- yeast infections - Systemic infection (Disseminated candidiasis)
* Can follow superficial infections and central intravenous catheters, renal failure requiring dialysis
* Microabscesses in multiple organs - meningitis, eyes, liver and spleen abscesses, spine, heart on prosthetic valves
* All systemic infections of candida are life-threating and require therapy
92
Candidiasis- diagnosis - Mucosal candidiasis-
thrush
• Microscopic examination of scrapping- budding yeasts and pseudohyphae • Culture on blood agar plates- growth within 24 hrs.
93
Candidiasis- diagnosis - Invasive (disseminated) candidiasis -
hard to document
• Culture from blood (not very sensitive)- may require biopsy of involved tissue • Germ-tube test- elongated buds from yeast when exposed to calf serum
94
Candidiasis- treatment - Mucosal infections-
topical antifungal creams
| • Systemic therapy for severe cases
95
Cadidiasis - treatment - Systemic infections-
always require systemic antifungal (min. of 2 wks)
• Fluconazole and Echinocandin - most common
• Amphotericin B- used for some invasive candidiasis
96
Cryptococcosis – Cryptococcus neoformans
Environmental yeast
97
Cryptococcosis – Cryptococcus neoformans - Expresses a huge
polysaccharide capsule in host
98
Cryptococcosis – Cryptococcus neoformans - Found worldwide in
soil contaminated with bird excreta
99
Cryptococcosis - cryptococcus neoformans - Approximately 20% of cases are
in seemingly immunocompetent patients.
100
Cryptococcosis - Yeast are inhaled into
alveoli- producing asymptomatic lung
| infection
101
Cryptococcosis- In lungs, yeast produce
polysaccharide capsule- major virulence factor- prevents phagocytosis by macrophages
102
Cryptococcosis - T-Cell mediated immunity is
crucial for control of infection- capsule can prevent appropriate response
103
Cryptococcosis - Most often presents as Meningitis-
resulting from hematogenous spread from asymptomatic lung infection.
104
Cryptococcosis- Meningitis is subacute to
chronic (worsening headache, fever, cranial nerve palsies, mental status changes)
105
Cryptococcosis - AIDS patients with meningitis also present with
diffuse pulmonary infiltrates, skin lesions, and widespread visceral infection (internal organs).
106
Cryptococcosis- diagnosis - • Can easily be cultured on
agar media within a few days- easily identifed
107
Cryptococcosis- diagnosis - Observation of
encapsulated budding yeast in cerebrospinal fluid (India ink
| on slide).
108
Cryptococcosis- diagnosis - • Latex agglutination test for
capsular polysaccharide- sensitive and specific
109
Cryptococcosis- treatment - Meningitis -
Amphotericin B and flucytosine (several weeks) followed by fluconazole for several months
110
Cryptococcosis- treatment - Since the advent of
antiretroviral drugs to treat HIV infections-
| cryptococcosis meningitis is rare
111
Cryptococcosis- treatment - • Pulmonary infections –
fluconazole
112
Aspergillosis- Aspergillus fumigatus or flavus - Filamentous fungi-
mycelium of septate
hyphae
• Fluffy mold
113
Aspergillosis- Aspergillus fumigatus or flavus - Reproduce by forming
conidia and aerial conidiophores (sexual reproduction)
114
Aspergillosis- Aspergillus fumigatus or flavus - • Ubiquitous in
soil, manure, decomposing vegetation
115
Aspergillosis - Entry - Conidia are inhaled into
upper and lower respiratory tracts -
| germinate into hyphae
116
Aspergillosis - Entry - • Macrophage can kill conidia that reach
aveoli- unable to kill hyphal form
117
Aspergillosis - Entry - Neutrophils line up along
hyphae and secrete reactive oxygen intermediates that kill the fungus
118
Aspergillosis - Invasive infection only occurs in
immunocompromised host
119
Aspergillosis - infection - Angioinvasive fungus-
hyphae invade through blood vessel walls
| Tissue infarction, hemorrhage, and necrosis
120
Aspergillosis - infection - Invasive pulmonary aspergillosis-
Fever, pleuritic chest pain, cough with blood, and difficulty breathing
121
Aspergillosis - infection - Sinus invasion-
acute facial pain
122
Aspergillosis - infection - Dissemination is common-
necrotic skin lesions and brain abscess (rarely found in blood)
123
Aspergillosis - diagnosis - Growth on Sabouraud agar in
a few days (issue with contamination- common in laboratory)
124
Aspergillosis - diagnosis - Tissue biopsy- to confirm
tissue invasion (identify septate hyphae in tissue)- not specific for Aspergillus
125
Aspergillosis - treatment - • Voriconazole-
drug of choice
126
Aspergillosis - treatment - • Amphotericin B or echinocandin are also
used
127
Superficial and cutaneous mycoses - limited to
```
limited to (epidermis) skin and skin structures
• Dermatophytes (tinea)
```
128
• Subcutaneous mycoses- involve the
skin, subcutaneous tissue and lymphatics
• Sporotrichosis
• Myocytomas
• Chromoblastomycosis
129
Superficial Mycoses - Colonization of
stratum corneum by Malassezia (yeast)- normal flora
130
Superficial Mycoses - • Usually
asymptomatic
131
Superficial Mycoses - Seborrheic dermatitis
• Patches with greasy scales
| in facial hair and scalp (dandruff)
132
Superficial Mycoses - Tinea versicolor (misnomer)
| •
Hypopigmented or hyperpigmented patches on chest or neck with scaling
133
Dermatophyte Skin Infections - • Most common
fungal infections in humans
134
Dermatophyte Skin Infections - • Infect
keratinized tissues (nails, hair and skin)- Keratinase enzyme • Restricted to non-viable skin- can’t grow at body temperature (37∘C)
135
Dermatophyte Skin Infections - Clinical diseases called
tineas- (ringworm, athletes foot, jock itch) • Latin for “worm”
136
Dermatophyte Skin Infections - • May be
acute or chronic
137
Dermatophyte Skin Infections - Three etiological genera- (molds)
Microsporum
• Trichophyton
• Epidermophyton
138
Dermatophytes - Encounter - Different ecological niches
Geophilic – found in soil
• Zoophilic – domestic and wild animals
• Anthropophilic – exclusively in humans and their habitat • Often cause chronic infections
• May be difficult to treat
139
Dermatophytes - Encounter - • Not members of the
normal flora
140
Dermatophytes - Encounter - • Crowding facilitates
spread- contagious
141
Dermatophytes - Encounter - • Survives on
locker room floors
142
Dermatophytes -Entry - Innate immunity to
pathogenic fungi is high for most people
143
Dermatophytes -Entry - Skin and mucosa are excellent
barriers to fungi • Dry, cell sloughing, fatty acids, low pH
| • Bacterial flora hostile to fungal colonization
144
Dermatophytes -Entry - • Skin trauma required
Continuous moist conditions important
• Infections more common when skin is occluded with nonporous materials
• Increases hydration and temperature of skin interferes with stratum corneum function
145
Dermatophytes-Damage - • Hyphae grows
outward in centrifugal pattern
146
Dermatophytes-Damage - Viable fungal elements
at inflamed margin
• Central area has few/no viable fungi
• Healing tissue refractory to infection
147
Dermatophytes-Damage - • Systemic infections extremely
rare
Inability of dermatophytes to grow at human body temperature • Presence of non-specific serum factors
• Transferrin binds iron needed for organism to grow
148
Subcutaneous Mycoses - • “Mycoses of implantation”
Organisms usually enter skin via thorns or splinters • Infections evolve over several weeks
149
Subcutaneous Mycoses - • Generally localized with
few systemic symptoms • Lesions usually heal following antifungal treatment
150
Subcutaneous Mycoses - Immunocompromised patients
| •
Widespread cutaneous and visceral infections
151
Subcutaneous Mycoses - • Thermally dimorphic
fungus (environment - mold, tissues - yeast)
152
Subcutaneous Mycoses - • Found in
soil, moss, decaying wood and vegetation
153
Subcutaneous Mycoses - Sporotrichosis-
“rose picker’s disease” • Fungus is introduced by trauma (thorn prick)
• Starts as small lesion (ulceration and/or erythema)
• Can spreads through lymphatic vessels- Lymphocutaneous sporotrichosis
154
Subcutaneous Mycoses - Disseminated disease
only in immunocompromised patients • Afflicts joints, brain, and spine (very serious)
155
Subcutaneous Mycoses - Successfully treated with
antifungals- Itraconazole for 3-6 months
156
Other Subcutaneous Mycoses - Mostly occur in
rural tropical areas of the world (Madagascar and Brazil)
157
Other Subcutaneous Mycoses - • Caused by
soil mold
158
Other Subcutaneous Mycoses - Mycetoma (Madura foot)
Chronic infection with sinus tract nodules and
discharge of visible grains (colonies of fungus)
• Can infect the bone or muscle
159
Other Subcutaneous Mycoses - Chromoblastomycosis
Caused by “dematiaceous fungi” (black fungus) • Scaly, wart-like lesions usually on feet
• Usually require surgical intervention or amputation
160
Treatment of Fungal infections - Azoles
- Itraconazole, ketoconazole, clotrimazole, miconazole
| • Interfere with ergosterol synthesis • Fungistatic
161
Treatment of Fungal infections - Polyenes-
* Lipophilic – bind to cell wall ergosterol and forms channels
* Amphotericin B • Nystatin
* Hamycin
