Deep mycoses are;

systemis. Mycoses •Common in America Continent

1-coccidioidomycosis •Reservoir: Soil and nature
2-histoplasmosis •Route of infection: Inhalation of spores
3-blastomycosis •All are dimorphic fungi
4-paracoccidiomycosis •Generally asymptomatic

1-coccidioidomycosis :
• Geographical Prevalence: Commonly found in arid regions of North and South America,
notably in the southwestern United States (Arizona, California) and parts of Mexico, Central,
and South America. The fungus thrives in dry, dusty environments.
• Causative Organism: Coccidioides immitis is a dimorphic fungus, meaning it has two
different forms - mold (in soil) and tissue (inside the body). In soil, it exists as mold
producing infectious arthrospores.
• Route of Infection: Inhalation of fungal spores is the primary route of infection.
Disturbance of soil, construction work, or activities that stir up dust in endemic areas can
lead to the release of these infectious arthrospores into the air, which when inhaled can
cause infection.
• Tissue Form: Inside the body, the fungus transforms into a larger, round structure
called a spherule, which ranges from 30-100µm in diameter. These spherules contain
endospores and can cause tissue damage and inflammation.
• Persons at Risk: Agricultural workers, construction workers, archaeologists, and
others involved in activities that expose them to dusty environments in endemic regions are
at higher risk of contracting Coccidioidomycosis.
• Reservoir: The primary reservoir for Coccidioides immitis is the soil. The fungus lives
in the soil in the form of mold, and certain environmental conditions like dryness and
disturbance contribute to the release of infectious spores into the air.
• Clinical Presentation: Symptoms can vary widely from mild flu-like symptoms to
severe pneumonia and, in some cases, disseminated disease affecting multiple organs. Fever,
cough, chest pain, and fatigue are common symptoms.

-Skin manifestations: Verrucous lesions,

ulcerate…..Dissemination (CNS)
-Involvement of lympathics
Progressive infection:
»Pulmonary (Fever↑, dyspnea, cyanosis,
mucopurulent- bloody sputum)
» CNS (menengitis),
» Skin (abscess formation), » bone destruction
Diagnosis:
Specimen: Sputum, pus, tissue sp.(biopsy)
Microscopy: Spherules and endospores (KOH), direct fluorescein
method
Serology: Precipitation, Complement Fixation Test
Histopathology
Skin test: Coccidioidin
Treatment: Amphotericin-B

2.HISTOPLASMOSIS
•Common in USA, Africa, Pasific and Indian Ocean
•Rare in Turkey
Causative organism: Histoplasma capsulatum (dimorphic fungi)
Nature: Macroconidium, microconidium
Tissue: Yeast (2-3x3-4μm), in the macrophage
Target site: Reticuloendothelial system
(RES)
•Reservoir: Soil
•Route of infection: Inhalation of spores

Clinical appearence: Asymptomatic

Pulmonary infection →
•Flu-like infection
•Acute pulmonary histoplasmosis (rare)
•Chronic pulmonary disease,
•Disseminated disease( immunosupressed patients)
•Local infection (tongue, subcutaneous, lympathics,joint,
endocard, larenx…..)
Diagnosis:
Specimen: Blood, bone marrow, liver, spleen, lymph node,
sputum, cerebrospinal fluid, scrapings (skin, mucous
membranes),biopsy
Microscopy: KOH, Giemsa, Wright
(budding yeasts inside
the macrophage)
Culture: SDA
Room temperature:
Cottony white → yellow, brown surface
Yellow-brown, leathery back
 37°C
Serology: Latex agglutination, precipitation
test, CFT
Histopathology
Skin Test: Histoplasmin
Treatment: Amphotericin-B

3- BLASTOMYCOSIS :
•Common in North America and Africa
•Causative agent:Blastomyces dermatitidis (dimorphic fungus)
Mold:Conidium
Yeast:Broad-based yeast with a single bud
•Reservoir: Soil containing organic debris ( animal droppings, wood and plant
material)
•Route of infection: Inhalation of conidia
•Persons at risk: Persons collecting firewood or working in tearing of old
buildings.
Clinical appearance:
«Granulomatous lesions»
•Primary pulmonary disease,
•Chronic cutaneous blastomycoses,
•Disseminated disease (Urogenital system, liver, spleen, lymph nodes, heart,
CNS, thyroid, adrenal…..)
Diagnosis:
•Specimen: Scarpings, exudate, tissue sp. (biopsy)
Microscopy: KOH, Giemsa
Culture : SDA
•Serology: CFT
•Skin test:
Blastomycin
Treatment:
Amphotericin-B
 4- PARACOCCIDIOMYCOSIS

•Common in South America

•Causative organism: Paracoccidioides brasiliensis (dimorphic)
Mold: Conidium
Yeast: Oval/round , surrounded by many buds (4-40µm)
•Route of infection: Inhalation of spores
•Reservoir: Soil with high humidity
Clinical appearence:
•Asymptomatic
or
•Skin/ mucosa involvement (Papules in mouth or nasal
mucosa, LAP)
•Lymph nodes
•Gastrointestinal tract
•Mixed type ( Pulmonary, adrenal gland, liver, spleen, CNS,
bone)
Diagnosis
•Specimen: Sputum, crusts, pus, biopsy
•Microscopy: Yeast (KOH)
Culture: SDA

Skin test: Paracoccidioidin

Treatment: Amphotericin-B
Oral itraconazole

Summary
 Subcutaneous mycoses :

Sporotrichosis
Sporothrix schenckii
Chromomycosis
Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporum carrionii
Rhinosporidiosis
Rhinosporidium seeberi

1- sporotrichosis
Cause: Sporothrix schenckii (Dimorphic fungus)

-25˚C – mold, 37°C – yeast

-Saprophytic fungus – decaying vegetation, soil
-Traumatic inoculation of soil, plants, and organic matter contaminated with the fungus.
-Occupational hazard – florists, agricultural workers, miners, wood workers……….
-Common in South America, South Africa.
-Rare in Turkey.

Clinical apperence
Also known as 'Rose thorn disease‘
a) Local lymphangitis (1-2 weeks)
Formation of subcutaneous nodules (round,
hard, elastic, non-painful).
Skin lesions characteristically follow lymphatic pathways
Lymphocutaneous lesions on hand,forearm and face
Nodules ulcerate
No fever
b) Systemic: Rare-
Can disseminate (fungemia
Diagnosis :
Lymph node puncture, discharge, scarpings around the ulcer
Microscopy: Gram… cigar shaped yeasts.
Culture :

‘Flower-like- conidial
arrangement of Sporothrix
Treatment :
Local -potassium iodine, terbinafine
Disseminated (Systemic)- Amphotericin B, intraconazole

2-CHROMOMYCOSIS

Causes: Fonsecaea pedrosoi, Phialophora verrucosa, Cladosporum carrionii

Male, 30-50 years, in rural areas
Soil inhabiting fungi, enters hand or feet after trauma

Clinical appearance:
-Unilateral swelling of lower limb;
Subcutaneous nodules
Scaly lesion
Ulcerated lesion
Thickened skin.
-Secondary bacterial infection causes pus production
-Recurrent infections results in fibrosis with scar formation causing lymphatic obstruction
(Elephantiasis)

Diagnosis:
Microscopy:
Hyphea (septate)
Large spherical clumped cells attached to one another
Culture:
Colonies of fungi are dark or blackish
Treatment:
-Surgery, Heat therapy and/ or Cryotherapy
-Local antifungal agents- Usually resistant (terbinafine, itraconazole)

Rhinosporidiosis :
Cause :Rhinosporidium seeberi

Exogenious- Found in lakes and oceans (water and aquatic plants)

In endemic regions- common in India, Ceylon
Rare in Turkey.
Males, 20-30 years
 Clinical appereance:

Polypoid masses of nasal mucosa, conjunctiva, genitalia and rectum

Painless,itchy
Diagnosis:
White spots over the polypoid masses
(scarpings/ biopsy material)
Microscopy:
KOH…. Presence of spores and sporangium.
Culture:
No culture
Treatment:
Surgery

PDF3 : OPPORTUNİSTİC MYCOSES

Opportunistic mycosis; is a fungal disease occurring in human’s with a compromised immune system.
Advances in medicine have resulted in increase in fungal infections!!!
Common Opportunistic Fungi

1-Candida spp. (Candidiasis)

2-Cryptococcus neoformans (Cryptococcosis)
3-Aspergillus fumigatus (Aspergillosis)
4-Mucor, Rhizopus spp. (Zygomycosis)
5-Penicillium, Fusarium, Geotrichum spp.

1-CANDİDIASIS

-Important cause of opportunistic fungal infections (Candidiasis =Moniliasis)

Members of resident microbiota (oral, vaginal, gastrointestinal tract, skin)
-Candida, an omnipresent resident, opportunistically leads to frequent
endogenous infections in compromised hosts."
-Candida causes mycoses in vulnerable individuals, affecting skin, mucosa,
and organs."
 Predisposing factors:(causes)
-Immunosupression (Corticosteroids, HIV,…)
-Recipients with organ transplantation
-Broad spectrum antibiotics (prolonged usage)
-Diabetes mellitus
-Infancy – Old age – Pregnancy
-Malnutrition (dietary protein deficiency, zinc and iron
deficiencies)
-Obesity
-Skin humidity
***Most common patogenic species is; C. albicans.
-Others are; C.tropicalis, C.glabrata, C.krusei
Morphology :
Candida: Ovoid, Gram-positive yeast forming blastospores,
pseudomycelium, aerobic, non-capsulated."
Candida culture: Thrives on Sabouraud Dextrose agar (SDA) at 22°C-37°C,
yielding 'S'-smelling white to cream colonies, predominantly in yeast
phase, displaying a blend of yeast cells and pseudomycelium in vivo."

Differential diagnosis of C. albicans includes:

• Germ tube formation in human sera at 37°C within 2 hours
• Chlamydospore formation on Corn-meal agar
• Biochemical tests such as Fermentation and Assimilation tests."

Clinical Manifestations
1- Oral Candidiasis:
- (Moniliasis):
• Appearance: Superficial white patches or plaques on the mucosal surfaces
of the mouth or skin.
• Associated Causes: Linked to factors like poor oral hygiene, dietary protein
deficiency, ill-fitting dentures, oral burns from hot food or drinks, systemic
conditions (medications, allergies, radiation therapy), or infections.
These white patches, often resembling curdled milk or cottage cheese, are a
hallmark of oral candidiasis and can occur on the tongue, inner cheeks, gums,
palate, and throat.
-(angular stomatitis) :
Irritation and fissuring in the corners of the lips is termed ''angular stomatitis''
Infants and old persons are affected
In immunocompromised /AIDS-commonly seen
2-vulvo-vaginitis :
White patches on vaginal mucosa
Causes itching, soreness, white discharge
Common in pregnancy
 3-skin :

4. Organ candidiasis: Pulmonary (common), gastrointestinal, urinary, disseminated.

5. Chronic Mucocutaneous Candidiasis: Disseminated infection in patients with cellular immun deficiencies

Diagnosis of Candidiasis:
Specimen Collection:
• Skin scrapings, mucosal scrapings, vaginal secretions, blood, and various body fluids are collected
for testing.
Microscopy:
• Gram stain and potassium hydroxide (KOH) preparation are used to visualize Gram-positive yeast
cells, blastospores, and pseudohyphae.
Culture:
• Sabouraud Dextrose Agar (SDA) culture is employed for growth.
• Identification involves observing specific characteristics:
• Germ tube production in human sera.
• Chlamydospore formation on special media (like Corn Meal Agar).
• Biochemical tests assessing fermentation and assimilation.
Serology:
• Latex agglutination and Enzyme-Linked Immunosorbent Assay (ELISA) tests are utilized for
serological identification.
Skin Test:
• Candidin skin test may be performed for diagnosis, involving a skin reaction to assess
hypersensitivity to Candida antigens.
Treatment :
local : Nystatin
Miconazole. Systemic:
Ketaconazole
Amphotericin-B
Flucytosine

2-CRYPTOCOCCOSİS:
Cryptococcus neoformans :
Most common infection in AIDS patients.
Pigeons harbors the C.neofromans
in nature.
Inhalation (pigeon droppings)
Morphology :

Cryptococcus neoformans: A round, capsulated yeast measuring 4-10 microns, identified through
negative staining (Indian Ink, Nigrosin), observed in KOH preparations, and confirmed by PAS and
Mucicarmine staining highlighting its distinctive capsule.

Pathogenesis

Cryptococcus neoformans enters via spore inhalation, penetrating deep into the lungs, often resulting in
self-limiting infections; however, it can cause pulmonary infections, forming distinct nodules termed
Cryptococcomas.

Clinical Manifestations of Cryptococcosis:

• Pulmonary Infection: Initial site of entry
often leading to localized lung involvement.
• Meningitis: Commonly presents as chronic
meningitis or meningoencephalitis, particularly
severe in immunocompromised individuals.
• Granulomatous Lesions: Found in various
organs, contributing to systemic infection.
• Impact of T Lymphocyte Function:
Dysfunction exacerbates clinical symptoms and
severity.
• AIDS-Associated Cryptococcosis: 3-20%
of AIDS patients develop this infection, often
Diagnosis of Cryptococcosis:
leading to chronic meningitis with symptoms like
• Specimen Collection:
headache, low-grade fever, visual disturbances,
• Sputum and Cerebrospinal Fluid (CSF)
and potential fatality.
are collected for testing.
• Disseminated Form: Spreads to involve
• Microscopy:
skin, mucosa, organs, and bones.
• Indian Ink and Fluorescent Antibody
• Treatment Impact: Effective treatment
Test (FAT) are used for microscopic
reduces morbidity and can lead to cure,
examination to detect the presence of
especially in non-immunosuppressed patients.
Cryptococcus neoformans.
• Culture:
• Culturing at 37°C on appropriate
media results in creamy, white, yellow, or
brown colonies. The urease test confirms
the identity of the isolate.
 • Serology:
• Antigen Detection: Latex agglutination and Treatment
Fluorescent Antibody Test (FAT) for antigen detection. Immune competent - Fluconazole,
• Antibody Detection: Indirect Itraconazole
Immunofluorescence Assay (IFA), Complement Fixation Immune deficient – Amphotericin-B,
Test (CFT), Hemagglutination to detect antibodies. Flucytosine
• Skin Test: AIDS patients are not totally cured
• Cryptococcin skin test might be employed for Relapses are frequent with fatal
diagnosis, eliciting a delayed hypersensitivity reaction outcome.
to Cryptococcus antigens. Avoid contact with birds

3-ASPERGILLOSIS:
-In nature > 100 Aspergillus species
-Few are important as human pathogens
-Fungal spores enters through respiratory tract
An opportunistic pathogen in immunosupressed patients (AIDS
Morphology :
Mycelial fungus
Separate hyphae with distinctive sporing structures
Spore bearing hyphae – conidiophores terminates in a swollen cell vesicle surrounded by one or two
rows of cell chains ( asexual conidia)

Clinical Manifesitations :

Allergic Aspergillosis:
Seen in atopic individuals with high IgE levels. 10-20% of asthmatics react to A. fumigatus due to
repeated heavy exposure to a higher number of spores."
Aspergilloma:
Fungal ball in preexisting lung cavities (e.g., tuberculosis), mycelium surrounded by fibrous wall, causing
cough, sputum, and potentially haemoptysis."

Invasive Aspergillosis:
Affects immunocompromised patients, often with underlying diseases. Neutropenia is a common
predisposing factor, especially fatal in bone marrow recipients. A. fumigatus is the primary infecting
species. The fungus invades blood vessels, leading to thrombosis and septic emboli. It can spread to the
kidney, causing endocarditis. Rarely, paranasal granulomas occur, invading sinuses, bones, orbit, and
brain."
 Diagnosis
Culture :
SDA (Grey, green,black colonies )
Microscopy:

4-ZYGOMYCOSİS

Zygomycosis (Mucormycosis or Phycomycosis): Caused by Rhizopus, Mucor, and Absidia. Saprophytic mold
spreading from nasal mucosa to paranasal sinuses, orbit, brain, and lungs, often leading to fatal
outcomes. Treatment with antifungals can improve prognosis."

Morphology :
Majority are with broad aseptate mycelium with many number of asexual spores inside a sporangium
which develops at the end of the aerial hyphae

Mucor :
Microscopy
Non septate hyphae
Having branched sporangiophores with sporangium at terminal ends
Rhizopus :
Microscopy :
Shows non septate hyphae
Sporangiophores in groups
They are above the rhizoids

Clinical Manifestations
-Patients may manifest with «Rhinocerebral zygomycosis»
-Associated with diabetus mellitus, leukemia or lymphomas
-Spread from nasal mucosa to bone, paranasal sinuses, orbit and brain
-Causes extensive cellulitis and tissue destruction
-Rapidly fatal if untreated
-Severe immunocompromised may manifest as primary cutaneous lesions
-Rarely infects burns patients

Diagnosis
Nasal discharges, sputum, rarely contain many fungal elements
Histopathology (Biopsy)
more reliable than culturing
Histological sections: contain ‘non septate hyphae’ in thromboses vessels or sinuses
surrounded by leukocytes or giant cells

Microscopy
KOH preparation shows broad aseptate branching mycelium,
and distorted hyphae
Methenamine silver staining is more sensitive.
Culture
SDA
Treatment
Early diagnosis highly essential for effective cure
High doses of IV Amphotericin B
Surgical interventions
Control of underlying disease a basic requirement for better
clinical outcome