SYSTEMIC MYCOSES `

SYSTEMIC MYCOSES
M.THILAKAR
LS1154
THIRD YEAR.,
M.SC. LIFE SCIENCES,
BDU.

MYCOSES
● Mycoses are classified clinically as follows:
● SYSTEMIC : (Infections of internal organs of the body)
– Primary mycoses (coccidioidomycosis, histoplasmosis,
blastomycoses, histoplasmosis).
– Opportunistic mycoses (surface and deep yeast mycoses,
aspergillosis, mucormycoses, phaeohyphomycoses,
hyalohyphomycoses, cryptococcoses, penicilliosis,
pneumocystosis).
● SUPERFICIAL : (Infections confined to the skin or mucous
membranes that do not invade into deeper tissues or organs)
– Subcutaneous mycoses (sporotrichosis,
chromoblastomycosis, Madura foot (mycetoma).
– Cutaneous mycoses (pityriasis versicolor,
dermatomycoses).

● Fungi that are able to cause systemic illness in healthy
people are rare and confined to specific geographic
locations across the world.
● Fungal infection of internal organs.
● Primarily involve the respiratory system.
● Infection occurs by inhalation of air- borne conidia.
● By Dimorphic fungi.
● More than 95% are self limiting & asymptomatic.
● Rest are symptomatic & disseminate by hematogenous
route.
SYSTEMIC MYCOSIS

● These infections are caused by inhalation of the fungus, which
exhibits dimorphism. (i.e. can exist as a yeast or a mold).
● The organisms are acquired by
– Inhalation of the conidia from soil, and
– Develop in the lungs as yeasts.
● Change in temperature determines the form. That fungus is a
mold when grown at 25°C but grows as yeast at body
temperature. (Thermal dimorphism).
● Starting from foci in the lungs,
– The organisms can then be transported, hematogenously or
lymphogenously, to other organs (including the skin, where
they cause granulomatous, purulent infection foci)
● Therapeutics :
– Amphotericin B and
– Azoles

Agent infection Dissemination Drug of choice
Blastomyces
dermatitidis
Blastomycosis
(southern states of
America)
Skin and bone
Later nervous system and
visceral organs
Amphotericin
B
itraconazole
Coccidioides
immitis
Coccidioidomycosis
(southern states of
America, Mexico
and the northern-
most countries of
South America)
Skin, bones, joints,
subcutaneous tissues, and
visceral organs
Amphotericin
B
Paracoccidioid
oes brasiliensis
Paracoccidioidomyc
osis
Oro-nasal mucosa
latter spleen, liver, intestine
and skin
Amphotericin
B + sulfas or
azoles
Histoplasma
capsulatum
Histoplasmosis Acute pneumonia (cave
disease)
Chronic pneumonia (smoker)
Disseminated
(immunocompromised)
Primary cutaneous
(lab accidents)
Amphotericin
B
PRIMARY SYSTEMIC MYCOSIS

SPECIE MOLD FORM YEAST FORM
OPPORTUNISTIC
Cryptococcus
neoformans
- No pseudohyphae;
encapsulated
Candida albicans - Blastoconidia,
chlamydoconidia,
pseudohyphae + germ tube
Aspergillus Uniseriate/biseriate -
SYSTEMIC (Dimorphic)
Histoplasma
capsulatum
Tuberculate macroconidia Small intracellular yeast
Blastomyces
dermititidis
Lollipop forms Large yeast cells w/ broad
based buds; double contoured
wall
Coccidiodes immitis Thick walled;
arthroconidia
Round walled spherules; Barrel
shape
Paracoccidiodes
brasiliensis
Similar to lollipop forms Mariner’s wheel-multiple
blastoconidia budding from
sides of large blastospore
Micky mouse cap
IDENTICAL FEATURES

PRIMARY SYSTEMIC MYCOSES
(DIMORPHIC)

PRIMARY SYSTEMIC MYCOSES
• Infections of internal organs of the body.
• Caused by dimorphic fungi.
• The following are the Systemic mycoses :
1. Blastomycosis,
2. Coccidioidomycosis
3. Histoplasmolysis
4. Paracoccidioidomycosis

1.BLASTOMYCOSIS
● Caused by : Blastomyces dermatitidis
● Inhalation of conidial spores.
● Causes a chronic granulomatous infection.
● Primary infection : Pulmonary blastomycosis.
● Secondary infection : May spread to other organs including
skin (Cutaneous mycosis).
● Osteoarticular blastomycosis : Occurs in about 30% of patients
with the spine, pelvis, cranial bones, ribs and long bones most
commonly involved.

DIAGNOSIS
● SPECIMENS :
– Bronchial secretion, Urine,
– Scrapings from infection foci, Sputum,
– Skin scrapings, Bone marrow,
– Pleural fluid and blood and Cerebrospinal fluid.
● MICROSCOPIC EXAMINATION :
– 10% KOH and Parker ink or calcofluor white mounts.
(Skin, Body fluids).
– PAS digest, Grocott's methenamine silver (GMS) or Gram
stain (Tissue sections)
– Positive direct microscopy demonstrating characteristic
yeast-like cells from any specimen

● CULTURE :
– On blood or Sabouraud agar must be incubated for several
weeks or
– Brain heart infusion agar supplemented with 5% sheep
blood.
● ANTIBODIES DETECTION :
– Using the complement fixation test and
– Agar gel precipitation.

Broad based budding and thickened cell
walls and globose shape are
characteristic of the yeast form of
Blastomyces dermatitidis
One-celled conidia formed on
short conidiophores.
Blastomyces dermatitidis

THERAPY
● Amphotericin B is the therapeutic agent of choice.
● Untreated blastomycoses : Lethal always.

2.COCCIDIOIDOMYCOSIS
● Caused by : C. immitis (Dimorphic)
● Inhalation of arthrospores.
● Primary infection : Lungs.
● Secondary infection :
– May spread to other organs including skin.
– Other silent infections (60% of infected persons) to severe
pneumonia.
– May produces granulomatous lesions in skin, bones, joints,
and meninges.

COCCIDIOIDOMYCOSIS
Extension of pulmonary
coccidioidomycosis
showing a large superficial ulcerated
lesion
Chronic cutaneous
granulomatous lesions of the face,
neck and chin

MORPHOLGY
● In cultures : Grows as mycelial form;
● In body tissues : neither buds nor produces mycelia.
● Spherical structures (spherules) with thick walls and a
diameter of 15–60 micro meter, each filled with up to 100
spherical-to-oval endospores.

DIAGNOSIS
● SPECIMENS :
– Pleural fluid, blood and Cerebrospinal fluid.
stain (Tissue sections).
– A positive direct microscopy demonstrating spherules (10-
80um) with endospores (2-5um).

● CULTURES :
– On blood or Sabouraud agar must be incubated for several
weeks or
blood.
– Using the complement fixation test and
– Agar gel precipitation.

Culture of Coccidioides immitis showing a suede-like to downy,
greyish white colony with a tan to brown reverse.

Tissue section showing
typical endo sporulating
spherules of
C. immitis
Coccidioides immitis
Coccidioides immitis
showing typical single-
celled, hyaline, rectangular
to barrel-shaped, alternate
arthroconidia

THERAPY
● Amphotericin-B
● Anoralazole derivative may be used.

3.HISTOPLASMOSIS
● Caused by : Histoplasma capsulatum (dimorphic fungus)
● Natural habitat (as Spore) : Soil.
● In human tissues it forms : Yeast cells.
● The sexual stage or form of this fungus is called Emmonsiella
capsulata
● Inhalation of Spores (conidia) into the respiratory tract,
● Taken up by alveolar macrophages, and become yeast cells
that reproduce by budding.
● It affects the reticulo-endothelial system (RES).
● Observed in AIDS patients.

DIAGNOSIS
● SPECIMENS :
– A positive direct microscopy demonstrating characteristic
yeast-like cells from any specimen should be considered
significant.

Culture of Histoplasma capsulatum

Tissue morphology of H. capsulatum var. capsulatum (left)
showing numerous small narrow base budding yeast
cells (1-5um diam) inside macrophages and H. capsulatum var.
duboisii (right) showing larger sized budding yeast
cells (5-12 um in diam).

THERAPY
● Amphotericin B
is only indicated in severe infections, especially the disseminated
form.

4.PARACOCCIDIOIDOMYCOSIS
Ulcerated lesion on the
pharyngeal mucosaExtensive destruction
of facial features
Ulcerated lesion on the
nasal mucosa

● Caused by Paracoccidioidies brasiliensis (dimorphic fungus)
[Produces thick-walled yeast cells (10–30 micro meter in
Diameter), most of which have several buds].
● Inhalation of spore-laden dust.
● Natural habitat is : soil.
● Primary : chronic granulomatous infection foci are found in
the lung, occasionally Gastro intestinal mucosa.
● Starting from these foci, the fungus can disseminate
hematogenously or lymphogenously into the skin, mucosa, or
lymphoid organs.
● The disease in its inception and development is similar to
blastomycosis and coccidioidomycosis.
● The only etiological agent, Paracoccidioides brasiliensis is
geographically restricted to areas.

DIAGNOSIS
● SPECIMENS :
– A positive : 20-60 um, round, narrow base budding yeast
cells with multiple budding "steering wheels" from any
specimens.

● CULTURE :
– On blood or Sabouraud agar must be incubated for
several weeks or
blood.
– Nil.

Multiple, narrow base, budding yeast cells "steering wheels" of
P. brasiliensis. GMS stained lung section (left) and phase
contrast of cells from a culture (right).

THERAPY
● The therapeutic agents of choice
– Areazol derivatives(e.g.,itraconazole),
– Amphotericin-B, and
– Sulfonamides.
Ends lethally unless treated.

OPPORTUNISTIC MYCOSES
● ANY fungus found in nature may give rise to
opportunistic mycoses.
– Candidiasis
– Cryptococcosis
– Aspergillosis
– Zygomycosis
● Other:
– Trichosporonosis,
– Fusariosis,
– Penicillosis.

1.CANDIDIASIS
● 70% of all human Candida infections are caused by
C.albicans.
● The rest by
– C. parapsilosis,
– C. tropicalis,
– C. guillermondii,
– C. kruzei,
● and a few other rare Candida species.

MORPHOLOGY & CULTURE
● Pseudohyphae are observed frequently and septate mycelia
occasionally.
● C. albicans can be grown on the usual culture mediums.
● After 48 hours of incubation on agar mediums, round, whitish,
somewhat rough-surfaced colonies form.
● They are differentiated from other yeasts based on
morphological and biochemical characteristics.

PATHOGENESIS
● Candida is a normal inhabitant of human and animal mucosa
(commensal).
● Candiasis usually develop in persons whose immunity is
compromised, most frequently in the presence of disturbed
cellular immunity.
● The mucosa are affected most often, less frequently the outer
skin and inner organs (deep candidiasis).
● Skin is mainly infected on the moist, warm parts of the body.
● Candida can spread to cause secondary infections of the lungs,
kidneys, and other organs.
● Candidial endocarditis and endo phthalmitis are observed in
drug addicts.

Forms of candidiasis
● 1. Oropharyngeal candidiasis
● 2. Cutaneous candidiasis
● 3. Vulvovaginal candidiasis and balanitis
● 4. Chronic mucocutaneous candidiasis
● 5. Neonatal and congenital candidiasis
● 6. Oesophageal candidiasis
● 7. Gastrointestinal candidiasis
● 8. Urinary tract candidiasis
● 9. Meningitis
● 10. Ocular candidiasis

Oropharyngeal candidiasis: including thrush, glossitis,
stomatitis and angular cheilitis (perleche)

Cutaneous candidiasis: including intertrigo, diaper
candidiasis, paronychia and onychomycosis

DIAGNOSIS
● SPECIMENS :
– Native staining.

● CULTURES :
– On blood or Sabouraud agar must be incubated for
several weeks or
blood.
– Agglutination, - Gel precipitation,
– Enzymatic immunoassays,
– Immunoelectrophoresis.

Typical moist colonies of Candida

THERAPY
● Nystatin and azoles can be used in topical therapy.
● In cases of deep candidiasis,
– Amphotericin B is still the agent of choice, often
administered together with 5-fluorocytosine.
● Echinocandins (e.g., caspofungin) can be used in severe
oropharyngeal and esophageal candidiasis.

2.ASPERGILLOSIS
● Aspergilloses are most frequently caused by Aspergillus
fumigatus, A. flavus, A. niger, A. nidulans, and A. terreus are
found less often
● Aspergilli are ubiquitous in nature.
● By inhalation of spores.
● Ingestion of products contaminated with Aspergillus

PATHOLOGY
● Portal of entry : Bronchial system, but the organism can also
invade the body through injuries in the skin or mucosa.
● The following localizations are known for aspergilloses:
– Aspergillosis of the respiratory tract,
– Endophthalmitis develops two to three weeks after surgery,
– An eye injury,
– Cerebral aspergillosis develops after hematogenous
dissemination,
– Less in : Endocarditis, Myocarditis, and Osteomyelitis.

FORMS OF ASPERGILLOSIS
● 1. Pulmonary Aspergillosis: including allergic, aspergilloma
and invasive aspergillosis.
● 2. Disseminated Aspergillosis
● 3. Aspergillosis of the paranasal sinuses
● 4. Cutaneous Aspergillosis.

DIAGNOSIS
● SAMPLES COLLECTION : Sputum, Bronchial washings and
Tracheal aspirates
● MICROSCOPICAL EXAMINATION :
– Sputum, washings and aspirates make wet mounts in either
10% KOH & Parker ink or Calcofluor and/or Gram stained
smears;
– Tissue sections should be stained with H&E, GMS and
PAS digest.
– Methenamine silver stain.
● CULTURE : SDA
● ANTI BODY DETECTION :
– Agglutination, Immunodiffusion and ELISA.
● MOLECULAR BASED DETECTION :
– PCR Detection of Aspergillus sp.

Aspergillosis of the lung. Methenamine silver stained tissue
section showing dichotomously branched, septate
hyphae (left) and a conidial head of A. fumigatus (right)

THERAPY
● High-dose amphotericin B is the agent of choice.
● Azoles can also be used.
● The echinocandin (caspo fungin) has been approved in the
treatment of refractory aspergillosis as salvage therapy.
● Surgical removal of local infection foci (e.g., aspergilloma) is
appropriate.

3.CRYPTOCOCCOSIS
● C. neoformans is an encapsulated yeast.
● The individual cell has a diameter of 3–5 micro meter and is
surrounded by a polysaccharide capsule several micrometers
wide.
● C. neoformans can be cultured on Sabouraud agar at 30–35 C
with an incubation period of three to four days

PATHOLOGY
● Normal habitat of the pathogen : Soil, Frequently found in bird
drop pings.
● The portal of entry : Respiratory tract.
● The organisms are inhaled and enter the lungs, resulting in a
pulmonary cryptococcosis that usually runs an in apparent
clinical course.
● From the primary pulmonary foci, the pathogens spread
hematogenously to other organs, above all in to the central
nervous system (CNS), for which compartment C. neoformans
shows a pronounced affinity.
● A dangerous meningoencephalitis is the result.

Nodular skin lesion caused by
C. neoformans.
Ulcerated skin lesion in an
HIV+ patient

DIAGNOSIS
● SAMPLE COLLECTION :
– Cerebrospinal fluid (CSF), biopsy tissue, sputum,
bronchial washings, pus, blood and urine..
– India ink (Encapsulated Yeast), PAS digest, GMS and
H&E, mucicarmine stain
● CULTURE :
– SDA (Creamy mucoid colony), Bird seed agar.
● ANTIBODY DETECTION :
– Latex agglutination test.

Bird seed agar plate showing the typical brown colour
effect seen with C. neoformans.

THERAPY
● Amphotericin B is the agent of choice in CNS cryptococcosis,
● Often used in combination with 5-fluorocytosine.

4.ZYGOMYCOSIS
● Mucormycoses are caused mainly by various species in the
genera Mucor, Absidia, and Rhizopus.
● More rarely, this type of opportunistic mycosis is caused by
species in the genera Cunninghamella, Rhizomucor, and
others.
● All of these fungal genera are in the order Mucorales and
occur ubiquitously.
● They are found especially often on disintegrating organic plant
materials.

MORPHOLOGY
● Mucorales are molds that produce broad, nonseptate hyphae
with thick walls that branch off nearly at right angles
● They grow on all standard mediums.
● High, Whitish-gray to Brown, “fuzzy” Aerial mycelium.
● Culturing is best done on Sabouraud agar.

PATHOGENESIS
● Patients with immune deficiencies or metabolic disorders
(diabetes).
● The pathogens penetrate into the target organic system with
dust.
● The infections are classified as follows according to their
manifestations :
– Rhino-cerebral mucor mycosis
– Pulmonary mucor mycosis
– Disseminated mucor mycosis
– Gastrointestinal mucor mycosis,
– Cutaneous mucor mycosis

Zygomycosis caused by
Basidiobolus ranarum
Ulcerated cutaneous
zygomycosis

DIAGNOSIS
● SAMPLE COLLECTION :
● Skin scrapings, Sputum and
● Needle biopsies from pulmonary lesions;
● Nasal discharges, scrapings, and Biopsy tissue
– Nonseptate, ribbon-like hyphae which branch at right
angles, sporangium
● CULTURE :
– SDA (cotton candy appearence).
● There is no method of antibody-based diagnosis.

THERAPY
● Amphotericin B is the antimycotic agent of choice.
● Surgical measures as required.

MY REFERENCES
● Medical Microbiology (2005) by Keyeser .
● Medical Microbiology (2007) by Jawetz.
● Human Microbiology (2002) by S.Hardy.
● Microbiology (2002) by Prescot
● www.mycology.adelaide.edu.au
● Pictures are adopted from “The University of Adelaide”
website.

SYSTEMIC MYCOSES `

Recommandé

Recommandé

Contenu connexe

Tendances

Tendances (20)

En vedette

En vedette (20)

Similaire à SYSTEMIC MYCOSES `

Similaire à SYSTEMIC MYCOSES ` (20)

Plus de THILAKAR MANI

Plus de THILAKAR MANI (14)

Dernier

Dernier (20)

SYSTEMIC MYCOSES `