2. MYCOSES
â—Ź Mycoses are classified clinically as follows:
â—Ź 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).
â—Ź 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).
3. â—Ź Fungi that are able to cause systemic illness in healthy
people are rare and confined to specific geographic
locations across the world.
â—Ź Fungal infection of internal organs.
â—Ź Primarily involve the respiratory system.
â—Ź Infection occurs by inhalation of air- borne conidia.
â—Ź By Dimorphic fungi.
â—Ź More than 95% are self limiting & asymptomatic.
â—Ź Rest are symptomatic & disseminate by hematogenous
route.
SYSTEMIC MYCOSIS
4. â—Ź These infections are caused by inhalation of the fungus, which
exhibits dimorphism. (i.e. can exist as a yeast or a mold).
â—Ź The organisms are acquired by
– Inhalation of the conidia from soil, and
– Develop in the lungs as yeasts.
â—Ź 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).
â—Ź 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)
â—Ź Therapeutics :
– Amphotericin B and
– Azoles
5.
6. 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
7. 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
10. 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
11. 1.BLASTOMYCOSIS
â—Ź Caused by : Blastomyces dermatitidis
â—Ź Inhalation of conidial spores.
â—Ź Causes a chronic granulomatous infection.
â—Ź Primary infection : Pulmonary blastomycosis.
â—Ź Secondary infection : May spread to other organs including
skin (Cutaneous mycosis).
â—Ź Osteoarticular blastomycosis : Occurs in about 30% of patients
with the spine, pelvis, cranial bones, ribs and long bones most
commonly involved.
13. DIAGNOSIS
â—Ź SPECIMENS :
– Bronchial secretion, Urine,
– Scrapings from infection foci, Sputum,
– Skin scrapings, Bone marrow,
– Pleural fluid and blood and Cerebrospinal fluid.
â—Ź 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
14. â—Ź CULTURE :
– On blood or Sabouraud agar must be incubated for several
weeks or
– Brain heart infusion agar supplemented with 5% sheep
blood.
â—Ź ANTIBODIES DETECTION :
– Using the complement fixation test and
– Agar gel precipitation.
15. 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
16. THERAPY
â—Ź Amphotericin B is the therapeutic agent of choice.
â—Ź Untreated blastomycoses : Lethal always.
17. 2.COCCIDIOIDOMYCOSIS
â—Ź Caused by : C. immitis (Dimorphic)
â—Ź Inhalation of arthrospores.
â—Ź Primary infection : Lungs.
â—Ź 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.
19. MORPHOLGY
â—Ź In cultures : Grows as mycelial form;
â—Ź In body tissues : neither buds nor produces mycelia.
â—Ź Spherical structures (spherules) with thick walls and a
diameter of 15–60 micro meter, each filled with up to 100
spherical-to-oval endospores.
20. DIAGNOSIS
â—Ź SPECIMENS :
– Bronchial secretion, Urine,
– Scrapings from infection foci, Sputum,
– Skin scrapings, Bone marrow,
– Pleural fluid, blood and Cerebrospinal fluid.
â—Ź 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).
– A positive direct microscopy demonstrating spherules (10-
80um) with endospores (2-5um).
21. â—Ź CULTURES :
– On blood or Sabouraud agar must be incubated for several
weeks or
– Brain heart infusion agar supplemented with 5% sheep
blood.
â—Ź ANTIBODIES DETECTION :
– Using the complement fixation test and
– Agar gel precipitation.
22. Culture of Coccidioides immitis showing a suede-like to downy,
greyish white colony with a tan to brown reverse.
23. 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
25. 3.HISTOPLASMOSIS
â—Ź Caused by : Histoplasma capsulatum (dimorphic fungus)
â—Ź Natural habitat (as Spore) : Soil.
â—Ź In human tissues it forms : Yeast cells.
â—Ź The sexual stage or form of this fungus is called Emmonsiella
capsulata
â—Ź Inhalation of Spores (conidia) into the respiratory tract,
â—Ź Taken up by alveolar macrophages, and become yeast cells
that reproduce by budding.
â—Ź It affects the reticulo-endothelial system (RES).
â—Ź Observed in AIDS patients.
27. DIAGNOSIS
â—Ź SPECIMENS :
– Bronchial secretion, Urine,
– Scrapings from infection foci, Sputum,
– Skin scrapings, Bone marrow,
– Pleural fluid, blood and Cerebrospinal fluid.
â—Ź 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).
– A positive direct microscopy demonstrating characteristic
yeast-like cells from any specimen should be considered
significant.
28. â—Ź CULTURE :
– On blood or Sabouraud agar must be incubated for several
weeks or
– Brain heart infusion agar supplemented with 5% sheep
blood.
â—Ź ANTIBODIES DETECTION :
– Using the complement fixation test and
– Agar gel precipitation.
30. 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).
34. â—Ź Caused by Paracoccidioidies brasiliensis (dimorphic fungus)
[Produces thick-walled yeast cells (10–30 micro meter in
Diameter), most of which have several buds].
â—Ź Inhalation of spore-laden dust.
â—Ź Natural habitat is : soil.
â—Ź Primary : chronic granulomatous infection foci are found in
the lung, occasionally Gastro intestinal mucosa.
â—Ź Starting from these foci, the fungus can disseminate
hematogenously or lymphogenously into the skin, mucosa, or
lymphoid organs.
â—Ź The disease in its inception and development is similar to
blastomycosis and coccidioidomycosis.
â—Ź The only etiological agent, Paracoccidioides brasiliensis is
geographically restricted to areas.
35. DIAGNOSIS
â—Ź SPECIMENS :
– Bronchial secretion, Urine,
– Scrapings from infection foci, Sputum,
– Skin scrapings, Bone marrow,
– Pleural fluid, blood and Cerebrospinal fluid.
â—Ź 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).
– A positive : 20-60 um, round, narrow base budding yeast
cells with multiple budding "steering wheels" from any
specimens.
36. â—Ź CULTURE :
– On blood or Sabouraud agar must be incubated for
several weeks or
– Brain heart infusion agar supplemented with 5% sheep
blood.
â—Ź ANTIBODIES DETECTION :
– Nil.
37. 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).
38. THERAPY
â—Ź The therapeutic agents of choice
– Areazol derivatives(e.g.,itraconazole),
– Amphotericin-B, and
– Sulfonamides.
Ends lethally unless treated.
41. OPPORTUNISTIC MYCOSES
â—Ź ANY fungus found in nature may give rise to
opportunistic mycoses.
– Candidiasis
– Cryptococcosis
– Aspergillosis
– Zygomycosis
â—Ź Other:
– Trichosporonosis,
– Fusariosis,
– Penicillosis.
42. 1.CANDIDIASIS
â—Ź 70% of all human Candida infections are caused by
C.albicans.
â—Ź The rest by
– C. parapsilosis,
– C. tropicalis,
– C. guillermondii,
– C. kruzei,
â—Ź and a few other rare Candida species.
43. MORPHOLOGY & CULTURE
â—Ź Pseudohyphae are observed frequently and septate mycelia
occasionally.
â—Ź C. albicans can be grown on the usual culture mediums.
â—Ź After 48 hours of incubation on agar mediums, round, whitish,
somewhat rough-surfaced colonies form.
â—Ź They are differentiated from other yeasts based on
morphological and biochemical characteristics.
44. PATHOGENESIS
â—Ź Candida is a normal inhabitant of human and animal mucosa
(commensal).
â—Ź Candiasis usually develop in persons whose immunity is
compromised, most frequently in the presence of disturbed
cellular immunity.
â—Ź The mucosa are affected most often, less frequently the outer
skin and inner organs (deep candidiasis).
â—Ź Skin is mainly infected on the moist, warm parts of the body.
â—Ź Candida can spread to cause secondary infections of the lungs,
kidneys, and other organs.
â—Ź Candidial endocarditis and endo phthalmitis are observed in
drug addicts.
49. DIAGNOSIS
â—Ź SPECIMENS :
– Bronchial secretion, Urine,
– Scrapings from infection foci, Sputum,
– Skin scrapings, Bone marrow,
– Pleural fluid, blood and Cerebrospinal fluid.
â—Ź 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).
– Native staining.
50. â—Ź CULTURES :
– On blood or Sabouraud agar must be incubated for
several weeks or
– Brain heart infusion agar supplemented with 5% sheep
blood.
â—Ź ANTIBODIES DETECTION :
– Agglutination, - Gel precipitation,
– Enzymatic immunoassays,
– Immunoelectrophoresis.
53. THERAPY
â—Ź Nystatin and azoles can be used in topical therapy.
â—Ź In cases of deep candidiasis,
– Amphotericin B is still the agent of choice, often
administered together with 5-fluorocytosine.
â—Ź Echinocandins (e.g., caspofungin) can be used in severe
oropharyngeal and esophageal candidiasis.
54. 2.ASPERGILLOSIS
â—Ź Aspergilloses are most frequently caused by Aspergillus
fumigatus, A. flavus, A. niger, A. nidulans, and A. terreus are
found less often
â—Ź Aspergilli are ubiquitous in nature.
â—Ź By inhalation of spores.
â—Ź Ingestion of products contaminated with Aspergillus
55. PATHOLOGY
â—Ź Portal of entry : Bronchial system, but the organism can also
invade the body through injuries in the skin or mucosa.
â—Ź 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.
56. FORMS OF ASPERGILLOSIS
â—Ź 1. Pulmonary Aspergillosis: including allergic, aspergilloma
and invasive aspergillosis.
â—Ź 2. Disseminated Aspergillosis
â—Ź 3. Aspergillosis of the paranasal sinuses
â—Ź 4. Cutaneous Aspergillosis.
57. DIAGNOSIS
â—Ź SAMPLES COLLECTION : Sputum, Bronchial washings and
Tracheal aspirates
â—Ź 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.
â—Ź CULTURE : SDA
â—Ź ANTI BODY DETECTION :
– Agglutination, Immunodiffusion and ELISA.
â—Ź MOLECULAR BASED DETECTION :
– PCR Detection of Aspergillus sp.
58. Aspergillosis of the lung. Methenamine silver stained tissue
section showing dichotomously branched, septate
hyphae (left) and a conidial head of A. fumigatus (right)
59.
60. THERAPY
â—Ź High-dose amphotericin B is the agent of choice.
â—Ź Azoles can also be used.
â—Ź The echinocandin (caspo fungin) has been approved in the
treatment of refractory aspergillosis as salvage therapy.
â—Ź Surgical removal of local infection foci (e.g., aspergilloma) is
appropriate.
61. 3.CRYPTOCOCCOSIS
â—Ź 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
62. PATHOLOGY
â—Ź Normal habitat of the pathogen : Soil, Frequently found in bird
drop pings.
â—Ź The portal of entry : Respiratory tract.
â—Ź The organisms are inhaled and enter the lungs, resulting in a
pulmonary cryptococcosis that usually runs an in apparent
clinical course.
â—Ź 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.
â—Ź A dangerous meningoencephalitis is the result.
63. Nodular skin lesion caused by
C. neoformans.
Ulcerated skin lesion in an
HIV+ patient
66. Bird seed agar plate showing the typical brown colour
effect seen with C. neoformans.
67. THERAPY
â—Ź Amphotericin B is the agent of choice in CNS cryptococcosis,
â—Ź Often used in combination with 5-fluorocytosine.
68. 4.ZYGOMYCOSIS
â—Ź Mucormycoses are caused mainly by various species in the
genera Mucor, Absidia, and Rhizopus.
â—Ź More rarely, this type of opportunistic mycosis is caused by
species in the genera Cunninghamella, Rhizomucor, and
others.
â—Ź All of these fungal genera are in the order Mucorales and
occur ubiquitously.
â—Ź They are found especially often on disintegrating organic plant
materials.
69. MORPHOLOGY
â—Ź Mucorales are molds that produce broad, nonseptate hyphae
with thick walls that branch off nearly at right angles
â—Ź They grow on all standard mediums.
● High, Whitish-gray to Brown, “fuzzy” Aerial mycelium.
â—Ź Culturing is best done on Sabouraud agar.
70. PATHOGENESIS
â—Ź Patients with immune deficiencies or metabolic disorders
(diabetes).
â—Ź The pathogens penetrate into the target organic system with
dust.
â—Ź 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
76. MY REFERENCES
â—Ź Medical Microbiology (2005) by Keyeser .
â—Ź Medical Microbiology (2007) by Jawetz.
â—Ź Human Microbiology (2002) by S.Hardy.
â—Ź Microbiology (2002) by Prescot
â—Ź www.mycology.adelaide.edu.au
● Pictures are adopted from “The University of Adelaide”
website.