Systemic mycoses

SYSTEMIC
MYCOSES

Wednesday, January 11, 2012

SUMMARY OF DEEP MYCOSES

DISEASES AND SAPROPHYTIC PHASE PARASITIC PHASE
ETIOLOGIC AGENT
Blastomycosis budding yeast with
septate mycelium; conidia are
Blastomyces dermatitidis broad base bud
pyriform, globose or double
colonies are white or beige,
fluffly or glaborous
Histoplasmosis septate mycelia microconidia; small single budded
Histoplasma capsulatum tuberculate macroconidia yeast
colonies are white and buff

Coccidioidomycosis septate mycelium fragment to spherule (10-20 u) with
Coccidiodes arthroconidia; colonies are endospores
immitis buff or white and moth

Paracoccidiodomycosis similar to B. dermatitidis large multiple budding
Paracoccidioides yeast


CHARACTERISTICS TO REMEMBER

Monomorphic Dimorphic

No change in form/state Change in form in
in response to stimulus response to stimulus like
like temperature. temperature. Example
Example, yeast at 25° C yeast at 37° C and
and 37° C mycelium at 25° C

Examples: Mycelium = Examples: Histoplasma capsulatum;
Blastomyces dermatitidis;
Aspergillus species; Yeast
Paracoccidiodes brasiliensis;
= Cryptococcus species Coccidiodes immitis


FACTORS AFFECTING DIMORPHISM

Temperature

Oxidation-reduction potential

Availability of sulfhydril groups

CO2 tension


Histoplasma capsulatum

Dimorphic

Mycelial phase: 25° C

Macroconidia
(8-14μm)

Microconidia
(2-4μm)

Histoplasma capsulatum

At 37°C or at body
temperature =
budding yeast 2-3 x
3-4 μm

Found predominantly
in histiocytes


LIFE CYCLE

soil with high nitrogen content, associated with the
guano of bats and starlings

rotting guano mixed with soil & feathers of the birds

open environment, soil is nitrogen rich with a rainfall
of 35-50 inches and 67-87% relative humidity

caves, the main habitat of bats, which are the
reservoir of Histoplasma capsulatum


LIFE CYCLE


CLASSIFICATION OF
HISTOPLASMOSIS

TYPE OF SPECIFIC
COMMENTS
INFECTION DISORDER
• Asymptomatic or
• Occurs with
mild like ﬂu
normal exposure
illness
• Acute pulmonary • Occurs with
Normal Hosts
histoplasmosis heavy exposure
• Pericarditis,
• Rare
mediastinal
complications
ﬁbrosis

CLASSIFICATION OF
HISTOPLASMOSIS

TYPE OF SPECIFIC
COMMENTS
INFECTION DISORDER

• Occurs in
• Disseminated individuals who
histoplasmosis have an immune
Opportunistic defect
Infection • Occurs in
• Chronic
individuals who
pulmonary
have a structural
histoplasmosis
defect


CLINICAL FORMS & SYMPTOMS

TYPE OF INFECTION SPECIFIC DISORDER
• Asymptomatic or ﬂu-like syndrome

Primary acute • Chest pain, shortness of breath and hoarseness

• Radiologically, discrete lung lesion may or may not develop

• Large pulmonary lesions develop

Chronic cavitary • lesions may exist in a relative quiescent state

• Often mistaken for tuberculosis

• Only small percentage progress into this clinical forms

• Disease of reticuloendothelial system in which organs infection may
Severe disseminated develop
• In massive dissemination, it could be fatal


HISTOPLASMOSIS


LABORATORY DIAGNOSIS

Direct Examination:
KOH; Wright/Giemsa

Culture: SDA; Smith and
Goodman (for
contaminated specimen);
Yeast Extract = place the
CM in a plastic bag


LABORATORY DIAGNOSIS

Skin test with
histoplasmin Ag

CF test

Immunodiffusion
test


TREATMENT & PREVENTION

Amphotericin B for
disseminated infection

Itraconazole for
immunocompromised
patients
Cleaning of bat
droppings

Blastomyces dermatitidis

2 phases: asexual & sexual

(asexual phase)

Ajellomyces dermatitidis
(sexual phase)

Dimorphic fungus


MYCELIAL FORM

The mycelial phase at 25° C showed typical
pyriform microconidia , which are about 2-4
microns in diameter.

YEAST FORM

At 37° C and at body temperature, this
organism is a yeast 8-15 microns in diameter.

Buds are produced singly and are attached to
parent cell by broad base.


LIFE CYCLE

The mode of transmission: inhalation of the
spores or the microconidia

Natural habitat: remains an enigma

Favors environment with high nitrogen
content, acid pH, abundant moisture, and
perhaps enriched with animal excreta


BLASTOMYCOSIS
Chicago Disease = Gilchrist’s disease = North American Blastomycosis


CLINICAL FORMS SYMPTOMS

Pulmonary • Fever, cough and hoarseness
• Productive cough, fever and weight loss
after several months
• Radiographically resembles tuberculosis

Systemic • Extension of pulmonary form
• Common sites of involvement are liver
and spleen
• Granulomatous lesions are present

Cutaneous • Indicates systemic disease
• May result from direct inoculation from
the soil

TESTS IMPORTANT FEATURES

1. Direct Microscopic 20% KOH
• specimen is sputum for pulmonary form
and skin for cutaneous form
• Biopsy material can also be used
• Look for the presence of broad based
buds

2. Culture Saborauds, Mycosel or Mycobiotic Agar
• Fluffy, whitish brown fungus with pyriform
spores
• Culture is not routinely done

3. Skin Test Blastomycin
• Has a tendency of high cross reactivity
• Little diagnostic value



Amphotericin B has been used but with erratic
results

2-hydroxystilbamidine

Ketoconazole, less nephrotoxicity

Prevent fomite inhalation in endemic
area


Coccidioides immitis

Amphotericin B has been used but with erratic results

Asexual phase: Coccidiodes immitis

Sexual phase: not known

MYCELIAL STAGE (25°C)

septate hyphae mature in a manner such that alternate cells
develop into arthroconidia being separated by vacuolized cells

 arthroconidia separate readily and have a “barrel” shape
appearance



YEAST FORM

In tissue and at body temperature:

Develops into spherules (sporangia;
10-60μm) ﬁlled with endospores (2-5μm)


COCCIDIOMYCOSIS

Posada’s Disease = San Joaquin Valley Fever = Desert Rheumatism


Generally difﬁcult to manage
regardless of drug use

Amphotericin B is the drug of choice

Itraconazole and ﬂuconazole have
been tried with little success

Prevent spores inhalation


CLINICAL FORMS SYMPTOMS

Primary Pulmonary • Occurs 7-28 days after inhalation of
single spore
• Positive skin test
• Flu-like fever, malaise and cough
• 10% develop erythrema nodosum or
erythrema multiforme
Benign Form • Precipitin and complement fixation titers
appear
• Development of well defined lung
cavitation
• Exist for years and could be unnoticed
Disseminated Form • 1 in 500 patients progressed into this
state
• Fungi spreads into various organs
• Prognosis is grave



1. Direct Microscopic 10-20% KOH
• sputum, tissue or skin are used as specimen
• look for the presence of spherules

2. Culture Saboraud’s medium with or without antibiotics
• room temperature, white fluffy fungus
• arthrospores are dangerous to work with
• Never try the organism in the petri dish but always
on the bottle or test tube
• Examine on the 3rd or 4th day, but must kill
organisms with formalin before attempting to
make an LPCB mount
• Can prepare exoantigen

3. Others Skin test
• conversion back to skin test positive (anergy) is an
indication of grave prognosis


Paracoccidioimycosis brasiliensis

Dimorphic

Mycelial stage (25°C): no
typical sporulation

Yeast stage (37°C): with
several budding cells
attached to the parent cell,
some in a “mariner’s
wheel” arrangement

about 2-30μm


LIFE CYCLE

Transmitted by inhalation of
the spores

Restricted to South and Central
America

Isolated in acidic soil and its
growth requires increased
humidity

natural habitat remains to be
elucidated


PARACOCCIDIODOMYCOSIS

South American Blastomycosis = Lutz-
Splendore-Almeida’s Disease

A chronic granulomatous disease of skin,
mucous membranes, lymph nodes and internal
organs

Central and South America more speciﬁcally in
Brazil

PARACOCCIDIODOMYCOSIS

Females are as susceptible to infections as males,
but the incidence of clinical disease in males is
nine times higher

Primary pulmonary disease is often inapparent

Disseminated disease often causes ulcerative
lesions of the buccal, nasal and occasionally
gastrointestinal mucosa.



1. Direct Microscopic 10-20% KOH
• 1-2 drops are used
• demonstration of multiple budding yeast

2. Culture Saboraud’s
• At room temperature it grows a non
spore forming septate fungus
Brain Heart Infusion at 35° C
• It produces yeast that is seen in tissue

3. Others • Paracoccidioidin skin test
• Complement fixation test
• Immunodiffusion test
Dr. Supachai Basit



Amphotericin B

Itraconazole

Long term therapy is required

Prevent inhalation of dust in endemic
area


Cryptococcus neoformans

Monomorphic:
always in yeast form
whether at 25° or at
37° C.

Unique feature: acidic
mucopolysaccharide
capsule


LIFE CYCLE

The etiologic agent of cryptococcosis has been
recovered in large numbers from the excreta

debris of pigeon roosts, thus it appears to survive
well in a dessicated, alkaline, nitrogen-rich and
hypertonic environment

There is a close relationship to the habitats of
pigeon, but the organism does not infect the bird


Dr. Supachai Basit


CRYPTOCOCCOSIS

Busse-Buschke’s Disease, Torulosis, European
Blastomycosis

The disease is worldwide in distribution.

This yeast has been repeatedly isolated from sites
inhabited by pigeons, particularly their roosts and
droppings.

Pigeons are not naturally infected.

CRYPTOCOCCOSIS

Primary pulmonary cryptococcosis is usually
inapparent but may be chronic, subacute or acute.

The clinical entity is most often seen in
cryptococcal meningitis.

Osseous and cutaneous disease can be present
without apparent neurologic involvement.


CRYPTOCOCCOSIS: CUTANEOUS FORM


CRYPTOCOCCOSIS: NEUROLOGIC FORM



1. Direct Microscopic India Ink Stain
• Cerebrospinal fluid (CSF) is used as
specimen
• The organisms appear as yeast about
8-12 microns in diameter, which are
usually surrounded by clear capsules

2. Culture Saboraud’s medium with or without
antibiotics
• either at room temperature or at 35° C,
the colonies develop after 1-3 weeks
incubation as shiny, slimy, light tan
yeast colonies
3. Others Latex Agglutination Test
Urease Test Positive
Dr. Supachai Basit


IN CULTURE



Amphotericin B in combination with
5-ﬂuorocytosine have been successful

Fluconazole is as effective too

Clean pigeon droppings

Avoid visiting caves without protective
gears

Systemic mycoses

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