SYSTEMIC MYCOSES Flashcards
1
Q
Inhalation of air borne spores
produced by molds (soil)
A
SYSTEMIC MYCOSES
2
Q
Present as saprophytes in soil and on
plant material
A
SYSTEMIC MYCOSES
3
Q
They are caused by dimorphic fungi
A
SYSTEMIC MYCOSES
4
Q
Infected persons do not communicate these diseases to others
A
SYSTEMIC MYCOSES
5
Q
TYPES OF SYSTEMIC MYCOSES
A
-BLASTOMYCES
-COCCIDIODES
-HISTOPLASMA
-PARACOCCIDIODES
6
Q
Gilchrist’s disease / blastomycosis
A
Blastomycosis
7
Q
North American Blastomycosis
A
Blastomycosis
8
Q
Blastomycosis
a chronic granulomatous and
suppurative disease that may affect
the following:
A
Skin and mucous membrane
Bones
Lungs
GUT
9
Q
Blastomycosis
Ecological
Niche:
A
• Wet acid soil
• Moist environments in wood, tree bark, rotting vegetation
10
Q
Blastomycosis
Endemic in:
A
North America in areas surrounding
the Mississippi Missouri and Ohio
rivers and their tributaries
Kentucky & Carolinas and the
Appalachian regions
Canada
Wisconsin
11
Q
- elevated, macerated, ill-defined,
scaly borders, central ulcer
A
A. (skin) Blastomycosis
12
Q
(lungs)
Blastomycosis
Inhalation —
lungs —
disseminated
A
Pulmonary
Blastomycosis
13
Q
- Affects the spine, ribs, long
bones
A
Osteoarticular
Blastomycosis
14
Q
- painful debilitating arthritis
or osteomyelitis
A
Osteoarticular
Blastomycosis
15
Q
- Affects the prostate and
epididymis in males
A
Genitourinary Blastomycosis
16
Q
Tissue specimens:
A
fixed and
stained with
H & E
GMS stain
Giemsa stain
17
Q
two antigens:
A
A and B
18
Q
(?) is reported to be the more useful of the two
A
A
19
Q
(?): extract of the yeast
form; used for skin testing
A
Blastomycin
20
Q
-
specificity of 84% to 100%, sensitivity of 57% to 62%
A
Immunodiffusion (ID) tests
21
Q
-sensitivity of 80%, specificity of 98%
A
Enzyme Immunoassay (EIA)
22
Q
Methods
A
Immunodiffusion (ID) tests
Enzyme Immunoassay (EIA)
Complement Fixation (CF) method
Chemiluminescent DNA probe
method
23
Q
Laboratory personnel who are working with any fluffy white colony should take (?) and adhere stringently to laboratory procedures.
A
special precautions
24
Q
Optimal temperature for growth is 25° to 30°C on routine media
A
Mould form
25
37°C is needed to induce the yeast phase
Yeast form
26
Primary cultures for B. dermatitidis
should be held for (?) weeks before being discarded as “no growth”
4 to 8
27
white or beige to brown at first
Blastomyces dermatitidis Mould form
28
with a waxy or glabrous texture
Blastomyces dermatitidis Mould form
29
some isolates may be fluffy
Blastomyces dermatitidis Mould form
30
are prickly in the center
Blastomyces dermatitidis Mould form
31
(?) of the colonies is tan to brown
Reverse pigment
32
Later, colonies tend to become (?), and some develop concentric rings.
fluffy or woolly
33
• ropelike strands
Mould form
34
• fine (1 to 2 um) hyaline and septated hyphae
Mould form
35
• hyaline, pyriform or globose
• average diameter of 6 um.
• Borne directly or
llaterally (“lollipop”)
Blastomyces dermatitidis Conidia
36
The thick, smooth walls of the conidia are doubly refractile (double image)
Blastomyces dermatitidis
37
Hyaline
Blastomyces dermatitidis Yeast Form
38
large (up to 20 um)
Blastomyces dermatitidis Yeast Form
39
spherical to pyriform
Blastomyces dermatitidis Yeast Form
40
with thick walls
Blastomyces dermatitidis Yeast Form
41
broad based budding yeast
Blastomyces dermatitidis Yeast Form
42
"figure eight," or hourglass, configuration of the parent-daughter combination
Blastomyces dermatitidis Yeast Form
43
reproduce by forming buds that are typically attached to the mother cell by broad (4 to 5 um) necks.
Blastomyces dermatitidis Yeast Form
44
In GMS stain the wall of the organisms stains black.
Blastomyces dermatitidis Stains
45
In PAS stain the internal structure of the organism is
red.
Blastomyces dermatitidis Stains
46
H & E
Blastomyces dermatitidis Stains
47
It can be converted from the mold form to the yeast form (using enriched media at 37°C) to confirm identification
Blastomyces dermatitidis Laboratory
Identification
48
is a thermally dimorphic organism.
Blastomyces dermatitidis Laboratory
Identification
49
• Mold form: white or beige to brown, waxy or glabrous texture to fluffy colonies
Blastomyces dermatitidis:
Culture
50
• Yeast form: waxy, wrinkled, light brown colonies
Blastomyces dermatitidis:
Culture
51
• RT: lollipop-like mycelial forms
Blastomyces dermatitidis: Morphology
52
• 37C: thick-walled broad based budding yeast (“figure of 8”or “hour glass”)
Blastomyces dermatitidis: Morphology
53
first recognized in
1892 & as a fungal
infection in 1900
Coccidioides immitis
Coccidioides posadasii
54
endemic in:
Southwestern
United States
Mexico
Pacific coast of
the United
States
Central and
South America
Coccidioides immitis
Coccidioides posadasii
55
Reservoir:
Alkaline desert soil
Dust storms
Semiarid, very hot
summers, little
rain, few freezes
Desert rodents
(vectors)
Coccidioides immitis
Coccidioides posadasii
56
Outbreaks are
associated
dust storms
archeological digs
climatic conditions
earthquakes
Coccidioides immitis
Coccidioides posadasii
57
Competent immune system:
Relatively small threat
Coccidioides immitis
Coccidioides posadasii
58
More severe in:
Dark skinned people
Pregnancy
High levels of ESTRADIOL and
PROGESTERONE
Coccidioides immitis
Coccidioides posadasii
59
Occupational hazard:
Construction workers
Farmers
Coccidioides immitis
Coccidioides posadasii
60
Coccidioides immitis
Coccidioides posadasii
Highest Risk Factor Age
Infants and elderly
61
Coccidioides immitis
Coccidioides posadasii
Highest Risk Factor Sex
Male
62
Coccidioides immitis
Coccidioides posadasii
Highest Risk Factor Genetics
Filipino, African American, Native American, Hispanic, Asian
63
Coccidioides immitis
Coccidioides posadasii
Highest Risk Factor Serum CF antibody titer
1:32
64
Coccidioides immitis
Coccidioides posadasii
Highest Risk Factor Pregnancy
Late pregnancy amd postpartum
65
Coccidioides immitis
Coccidioides posadasii
Highest Risk Factor skin test
negative
66
Coccidioides immitis
Coccidioides posadasii
Highest Risk Factor depressed cell-mediated immunity
malignancy, chemotherapy, steriod treatment, hiv infection
67
Coccidioides immitis
Coccidioides posadasii
Causes:
Coccidioidomycosis
aka: “San Joaquin fever”; “Desert
fever”, “Posada's disease”, “Desert
rheumatism”, Valley fever
68
Coccidioides immitis
Coccidioides posadasii
Causes:
erythema nodosum, or erythema
multiforme
69
(?) is probably the most virulent
of all agents of human mycoses
C. immitis
70
Very contagious
C. immitis
71
requires biosafety level 3 cabinet
C. immitis
72
Forms of
Coccidioidomycosis:
Cutaneous
Coccidioidomycosis
Primary Pulmonary
Coccidioidomycosis
Chronic Pulmonary
Coccidioidomycosis
4. Disseminated Coccidioidomycosis
5. Coccidioidomycosis in AIDS patients
73
• CXR: “egg-shaped
deformity”
Primary Pulmonary
Coccidioidomycosis
74
• Hemoptysis due to
cavitations
• fatal
Chronic Pulmonary
Coccidioidomycosis
75
showing granulomatous lesions of the face, neck
and chin (Courtesy of John Rippon, USA)
Chronic Cutaneous
Coccidioidomycosis
76
“egg-shaped deformity”
Pulmonary Coccidioidomycosis
77
Extension of pulmonary coccidioidomycosis showing a
large superficial, ulcerated plaque (Courtesy of John
Rippon, USA)
Pulmonary Coccidioidomycosis
78
- Fatal
-Meningitis & hydrocephalus
Disseminated Coccidioidomycosis
79
- most common complication
- Common cause of mortality
Meningitis & hydrocephalus
80
- pulmonary in form
Coccidioidomycosis in AIDS patients
81
2 substances used as antigen
Coccidioidin
Spherulin
82
: Is a filtrate prepared from mould cultures
Coccidioidin
83
: Extract from a tissue
culture of the yeast form
Spherulin
84
• conversion from a negative to
a positive skin test is
diagnostic of infection
Skin test
85
• quite specific, but a few cross-
reactions with other mycotic
infections
Complement Fixation (CF)
86
• Highly specific with very few
cross-reactions
Tube Precipitin (TP) Test
87
Coccidioides immitis
Coccidioides posadasii
colonies:
are white and floccose at first
Mature colonies
white to gray, but strains with lavender, buff,
cinnamon, yellow or brown pigment
Reverse: tan to dark brown or orange
Texture: Powdery
membranous or glabrous with hyphae that are
adherent to the agar
Surface = Partially or completely covered with a
cottony aerial mycelium that resembles
COBWEB
88
Culture of (?) showing a suede-like to
downy, greyish white colony with a tan to brown reverse
Coccidioides immitis
89
Coccidioides immitis
Coccidioides posadasii
Hyphae:
septate and hyaline
RACQUET hyphae may also be observed in culture
90
Coccidioides immitis
Coccidioides posadasii
Disjunctors (disjuncture cells):
contains the arthroconidia
they fragment when mature, freeing the
arthroconidia to disperse
91
Coccidioides immitis
Coccidioides posadasii
Arthroconidia:
single celled, barrel-shaped or rectangular
May round up in tissues --- spherules
Mature: contains endospores or asteroid bodies
92
“barrel-shaped arthroconidia”
Coccidioides immitis
93
(?)
spherule filled with endospores
Coccidioides immitis
94
Coccidioides immitis
Coccidioides posadasii
Direct Examination
In host tissues:
Spherules are round and refractive
and usually have thick walls.
Endospores are freed when the
mature spherule ruptures
Can be seen in intact or rupturing
spherules in tissue sections and
other specimens
95
Hyphae and developing
spherules (?)
in lung tissue
96
arthroconidium; ruptured spherule
Coccidioides immitis
97
HISTOPLASMA capsulatum
Teleomorph:
Ajellomyces capsulatus
98
Most common cause of fungal respiratory
infection
H. capsulatum var. capsulatum
99
Causes African Histoplasmosis which involves
the bones and skin
H. capsulatum var. duboisii
100
Has larger thick walled yeast cells
H. capsulatum var. duboisii
101
Causes epizootic lymphangitis and infectious
keratitis in horses
H.capsulatum var. farciminosum
102
HISTOPLASMA CAPSULATUM diseases
Darling’s disease
Spelunker’s disease
Caver’s disease
Ohio valley disease
Reticuloendotheliosis
Reticuloendothelial cytomycosis
Tingo
Maria fever
103
HISTOPLASMA CAPSULATUM
RESERVOIR:
Found in soil with high nitrogen content
Droppings of starlings, chickens and bats
Poultry house litter
104
HISTOPLASMA CAPSULATUM
UNIQUE RISK FACTORS:
Airborne transmission
Highly contagious
Epidemics occur in group activities via inhalation of a
large number of conidia
Poses no threat to people who are not immune
compromised.
105
Endemic in:
Central North America in areas surrounding the
Mississippi, Missouri, and Ohio rivers
HISTOPLASMA CAPSULATUM
106
Chronic granulomatous and suppurative
disease that involves the lungs and the RE system.
HISTOPLASMOSIS
107
5% of which progress to chronic disease or acute fulminating disease which is fatal.
Primary pulmonary histoplasmosis
108
Common in children
Primary pulmonary histoplasmosis
109
Untreated infections causes the macrophage
to spread the disease to other organs
Primary pulmonary histoplasmosis
110
Scattered erythematous
papules and pustules in an HIV-
infected individual with
disseminated (?).
histoplasmosis
111
Periodontal recession
and deep ulceration
with exposed necrotic
alveolar bone. Deep
ulceration of the
gingivae also associated
with necrotic bone
Histoplasmosis.
112
HISTOPLASMOSIS
SPECIMEN SOURCES:
Sputum and oropharyngeal scrapings
Pulmonary aspirates
Biopsied lung lesions
Aspirated pus, subcutaneous abscesses and skin
scrapings
Blood, bone marrow
and CSF
113
Histoplasma capsulatum yeasts in
the cytoplasm of (?)
neutrophils
two of three
114
HISTOPLASMA capsulatum
DIRECT EXAMINATION:
Found within cells (histiocytes)
115
- Wright’s and Giemsa stains
BM
116
- Wet preparation
Pus
117
– fixed and stained
Tissue
118
– treated with N-acetyl-L-cysteine
Mucus
119
Specimens are cultured in rich media,
such as glucosecysteine blood agar at 37°C and on Sabouraud's agar or inhibitory mold agar at 25–30°C
HISTOPLASMA capsulatum
120
HISTOPLASMA capsulatum
Mold form:
Produced in 15-25 days
Color - white, beige, brown
Texture - fluffy or glabrous, woolly
Pigment – tan
121
HISTOPLASMA capsulatum
Yeast form
Produced in 10-15 days
on BHIA with blood
Color – white, light tan
Texture – mucoid, rough
membranous
122
HISTOPLASMA capsulatum
Mold form:
(?) – very fine, septate, ropelike strands
Hyphae
123
HISTOPLASMA capsulatum
Mold form:
(?) – borne directly on hyphae
Microconidia
124
HISTOPLASMA capsulatum
Mold form:
(?) – unicellular, hyaline, smooth,
echinolate
Conidiophore
125
HISTOPLASMA capsulatum
Mold form:
(?) – develop directly on hyphae, hyaline, unicellular, large, spherical to
pyriform in shape.
Macroconidia
126
As they age, they become tuberculate
forming finger-like extensions resembling
sunflower in bloom
HISTOPLASMA capsulatum
127
At 25°C tuberculate
macroconidia are formed on a
hypha-like conidiophores
HISTOPLASMA capsulatum
128
HISTOPLASMA capsulatum
Yeast Form
(?) – small and ovoid
Blastoconidia
129
When the daughter cell is produced, they form at
the smaller end of the mother cell with narrow
neck of attachment
Blastoconidia
130
: mixture of H and M antigens
Histoplasmin
131
: extracted from yeast cultures
of H. capsulatum (more sensitive)
Yeast antigen
132
Of little diagnostic value
Skin test
133
: more widely used for diagnosis of
histoplasmosis
CF test
134
Titer between (?) is considered
presumptive evidence of histoplasmosis
8 to 32
135
: using histoplasmin as the antigen
ID Test and CIE
136
Useful screening procedures
ID Test and CIE
137
Formation of 2 precipitating bands representing
specific reactions to the H and M antigens are
diagnostic
ID Test and CIE
138
: present in active infection
H band
139
: present in early and persists even after
recovery
M band
140
Assess patient’s progress after treatment
ID Test and CIE
141
: with false positives
Latex agglutination
142
: can use serum, urine, and CSF
RIA
143
Cross-reactions with C. immitis and B. dermatitidis
RIA
144
HISTOPLASMA CAPSULATUM
Immunology
Urine antigen test (HPA) Test
Histoplasma polysaccharide antigen (HPA)
145
Antigenuria precedes development of
antibodies
Histoplasma polysaccharide antigen (HPA)
146
Histoplasma polysaccharide antigen (HPA)
Most useful in:
disseminated histoplasmosis
Persons living with AIDS
Early in acute pulmonary histoplasmosis
Predicting relapse patients receiving chronic
suppressive therapy
147
HISTOPLASMA CAPSULATUM
THERAPY:
Therapy of choice:amphotericin B followed
by fluconazole for 9 to 12 months
Patients with severe obstructive
mediastinal histoplasmosis require
amphotericin B therapy
Itraconazole may be used for outpatient
therapy
148
– acid soil in humid
areas (endemic)
Saprobic mould form
149
Plants
Saprobic mould form
150
Paracoccidioides
brasiliensis
(?) - carrier
Armadillos
151
MOT: Airborne (i.e., plants)
Paracoccidioides
brasiliensis
152
Paracoccidioides
brasiliensis
Risk factors:
(?) – combined effect of hormonal
makeup and occupations
Adult males
153
Malnutrition and in immunocompromised
patients
Paracoccidioides
brasiliensis
154
Endemic in:
Holdridge life zones
(on both sides of the
equator and the
Tropic of Capricorn)
Northwestern,
Central, and
southeastern South
America
Central America
Southern Mexico
Paracoccidioides
brasiliensis
155
Paracoccidioides
brasiliensis
Pathogenesis:
• Primarily an oral lesion (mouth, palate, nasal) ---
BV & lymphatics --- disseminated to the lungs
156
Paracoccidioides
brasiliensis Clinical Manifestations
1. Primary Pulmonary
Paracoccidioidomycosis
2. Mucocutaneous
Paracoccidioidomycosis
3. Lymphonodular
Paracoccidioidomycosis
4. Disseminated Paracoccidioidomycosis
157
• asymptomatic or subclinical
• self-limiting
• most common
Primary Pulmonary
Paracoccidioidomycosis
158
Lymphadenitis is common in younger
patients.
Cervical and submandibular chains are the most obvious manifestation and lymph nodes may progress to form
abscesses with draining sinuses.
Lymphonodular
Paracoccidioidomycosis
159
including lesions of the small or large
intestine
hepatic lesions
adrenal gland destruction
osteomyelitis
arthritis
Endophthalmitis
meningoencephalitis or focal cerebral
lesions
Disseminated Paracoccidioidomycosis
160
→ an E2 antigen extract from yeast
Paracoccidioidin
161
“band 1” (apparently identical to the E2 antigen extracted from yeast
Precipitin Test
162
– intradermal injection
Skin Tests
163
epidemiological tool
Skin Tests
164
first serologic test to be positive
Skin Tests
165
do not differentiate between past exposure and current condition
Skin Tests
166
- Sensitivity, 94% and highly specific
ID Test
167
- (+) one to three precipitin
continuous bands or identical with
the reference sera.
ID Test
168
useful for speeding the identification of cultures
Exoantigen Methods
169
Detects cell-free antigens of fungus
Exoantigen Methods
170
Used for the ID of cultures of
Blastomyces, Coccidioides, Histoplasma
& Paracoccidioides
Exoantigen Methods
171
detects P. brasiliensis cells in smears of clinical materials
Direct FA Tests
172
Faster, more sensitive, and more
specific than exoantigen tests
DNA probes
173
Too expensive
DNA probes
174
DNA probes use single strands of DNA
isolated from a known organism to
“probe” for the complementary DNA sequence in a culture or specimen
DNA probes
175
Detected with a dye, a radioisotope or an enzymatic reaction
DNA probes
176
Paracoccidioides
brasiliensis
Mould Form
✓ Slow maturation –
2 cm after 2 to 3 wks.
177
Paracoccidioides
brasiliensis
Young:
White to cream, with short, downy aerial
mycelia and elevated centers.
178
Paracoccidioides
brasiliensis
Mature:
Flat, with a membranous or velvety
texture and cerebriform or folded topography.
179
Paracoccidioides
brasiliensis
Pigment:
Beige or brown, with a yellow-brown
reverse in mature colonies.
180
Paracoccidioides
brasiliensis
Hyphae:
Very fine, hyaline and septate
181
Paracoccidioides
brasiliensis
Conidia:
Few small oval to pyriform truncate on
short conidiophores or sessile hyphae
182
Paracoccidioides
brasiliensis
Chlamydoconidia:
Terminal and intercalary, w/
racquet and coiled hyphae
183
Paracoccidioides
brasiliensis
Yeast Form:
✓ Large spherical to pyriform cells with thick
walls
✓ Reproduce by multiple budding with buds
that cover the entire surface of the parent
cell... “MARINER’s WHEEL” appearance
✓ BUDS: Attached by thin necks and easily
dislodged.
184
Paracoccidioides
brasiliensis
Microscopic:
septated hyphae and chlamydospore formation
(cotton-blue preparation) (40 X)
185
Yeast culture at (?) in trypticase soy agar.
Observe multiple budding yeast cells
characteristic of Paracoccidioides
brasiliensis (40 X).
36°C
186
Paracoccidioides
brasiliensis
(?) →treatment of choice for
most forms of the disease
Itraconazole
187
must be given for at least 6 months
Itraconazole
188
Paracoccidioides
brasiliensis
(?) → more severe
forms
Amphotericin B therapy
189
followed by either itraconazole or
sulfonamide therapy.
Amphotericin B therapy
190
(?) has some activity against
this organism, although frequent
relapses have limited its use for the
treatment of this disease
Fluconazole
