Introduction to medical mycology 3rd level.docx

ssuser45686d 146 views 108 slides Aug 16, 2024
Slide 1
Slide 1 of 108
Slide 1
1
Slide 2
2
Slide 3
3
Slide 4
4
Slide 5
5
Slide 6
6
Slide 7
7
Slide 8
8
Slide 9
9
Slide 10
10
Slide 11
11
Slide 12
12
Slide 13
13
Slide 14
14
Slide 15
15
Slide 16
16
Slide 17
17
Slide 18
18
Slide 19
19
Slide 20
20
Slide 21
21
Slide 22
22
Slide 23
23
Slide 24
24
Slide 25
25
Slide 26
26
Slide 27
27
Slide 28
28
Slide 29
29
Slide 30
30
Slide 31
31
Slide 32
32
Slide 33
33
Slide 34
34
Slide 35
35
Slide 36
36
Slide 37
37
Slide 38
38
Slide 39
39
Slide 40
40
Slide 41
41
Slide 42
42
Slide 43
43
Slide 44
44
Slide 45
45
Slide 46
46
Slide 47
47
Slide 48
48
Slide 49
49
Slide 50
50
Slide 51
51
Slide 52
52
Slide 53
53
Slide 54
54
Slide 55
55
Slide 56
56
Slide 57
57
Slide 58
58
Slide 59
59
Slide 60
60
Slide 61
61
Slide 62
62
Slide 63
63
Slide 64
64
Slide 65
65
Slide 66
66
Slide 67
67
Slide 68
68
Slide 69
69
Slide 70
70
Slide 71
71
Slide 72
72
Slide 73
73
Slide 74
74
Slide 75
75
Slide 76
76
Slide 77
77
Slide 78
78
Slide 79
79
Slide 80
80
Slide 81
81
Slide 82
82
Slide 83
83
Slide 84
84
Slide 85
85
Slide 86
86
Slide 87
87
Slide 88
88
Slide 89
89
Slide 90
90
Slide 91
91
Slide 92
92
Slide 93
93
Slide 94
94
Slide 95
95
Slide 96
96
Slide 97
97
Slide 98
98
Slide 99
99
Slide 100
100
Slide 101
101
Slide 102
102
Slide 103
103
Slide 104
104
Slide 105
105
Slide 106
106
Slide 107
107
Slide 108
108

About This Presentation

Medical mycology


Slide Content

Medical Mycology
By: Dr. Abeer Esmail

Lec.1: Introduction and General characteristic of Fungi
•Medical mycology is the study of mycoses of man and their etiologic agents.
Mycoses are the diseases caused by fungi. Of the several thousands of species of
fungi that are known, less than 100 are pathogenic to man.
•In addition to those species which are generally recognized as pathogenic to man
it is firmly established that under unusual circumstances of abnormal
susceptibility of patient, or the traumatic implantation of the fungus, other fungi
are capable of causing lesions. Those are called (Opportunistic Fungi.)
•These circumstances may be :
1. A debilitating condition of thehost, as Diabetes.
2.A concurrent disease such as leukemia.
3.Prolonged treatment with corticosteroids.
4.Immunosuppressive drugs or an antibiotic for long duration.

General characteristic of Fungi
Fungi are eukaryotic microorganisms that
contain a definite nucleus with a surrounding
nuclear membrane.
Their cell wall is rigid composed largely of
polysaccharides and chitin and without
chlorophyll.
They are widely distributed in the environment
and can survive in extreme conditions where
nutrients are limited.
Most fungi are saprophytes (living off dead organic matter) in soil
and water.
Fungi are infrequent causes of diseases in animals and humans.
Fungi usually are non motile and reproduce sexually and asexually.

The Role of Fungi in nature and Human life
The fungi are heterotrophic, needing organic compounds as nutrient and their
role in nature as scavengers, breaking down the complex carbohydrates and
proteins of the dead bodies of other organisms.
Only a few of them are pathogens and most those affecting man are facultative
rather than obligate parasites.
Fungi have mainly role in making of bread, fermented drinks, cheese and
antibiotics.
The mortality for some fungal disease is especially high because:-
They resemble bacterial diseases and are misdiagnosed.
Diseases are mostly occurred in compromised patient in whom the
immune response is poor.

Morphology of Fungi :
The fungi are divided into four main morphological forms.
The Molds:
( Also called filamentous or mycelial fungi).
The term mold is generally used to describe a fungus which produces hyphae.
Molds are multicellular fungi composed of branching filaments or tubules
structures called Hyphae.

In most fungi, the hyphae have regular cross walls (septa). They called septate
hyphae. The septa divide the hyphae into individual compartments, each
compartment contains cytoplasm and one or more nuclei. Thus each hypae may
contain several nuclei,
In lower fungi the septa are absent, so they are called Aseptate (coenocytic)
Hyphae. In Aseptate hyphae the cytoplasm and the nuclei circulate freely,
The hyphae grow by forming branch and interface to form a meshwork hyphae
called Mycelium of mold be divided into:

The Vegatative portion:
•The major part of the mycelium grows on the substrate and penetrate it to obtain
a nutrients or grow.
The Reproductive portion:
Hyphae constitute the aerial mycelium from the vegetative mycelium.
The aerial mycelium disseminate various kinds of spores in the air.
The aerial structure can be observed in laboratory as well as in nature as fuzz or
cottony filaments.
The Yeast:
Yeast are typically round or
oval unicellular fungi reproduce
by budding to from buds
(Blastospores),
The only pathogenic yeast is
Cryptococcus neoformans.

The Dimorphic Fungi:
Grow either as filament or as yeast, according to cultural conditions.
Growth usually take place in the mycelia form on culture media at 22°C
and in the soil (Saprophylic phase).
Yeast form appear on media at 37°C and in animal body (parasitic
phase). Histoplasma capsulatum is the most important of them.

Identification of Fungi:
•The identification of molds is based on the:
•Study of their macroscopic and microscopic morphology .
•Types of spores they produce.
•The identification of yeasts is based on their ability to ferment sugars and
to assimilate carbon and nitrogen compounds.
Laboratory Diagnosis depends on:
1)- Recognition of the pathogen in tissue by microscope.
2)- Isolation of the causal fungus in culture media.
3)- Use of serological tests.
Classification of Fungi is baised on :
1)- The method of sexual reproduction.
2)- The method of Asexual reproduction.

3)- The morphology.

The fungi can be included within four major division of Eumycetes
Eumycetes: (Truefungi):
1)- Zygomycetes 3)- Basidiomycetes
2)- Ascomycetes 4)- Deuteromycetes
GROWTH AND REPRODUCTION
[1] Yeasts:
Most yeasts reproduce by an asexual process called budding.
Budding: is a process of Blastospore formation.
During this process protuberance is form on the mother cell surface, Buds
enlarge and separate from the parent cells.
The separate cell from the mother cell called Blastospore.
Some bud is not separated from mother cell to produce chain of elongated cells
this called pseudomycelium or pseudohyphae that resemble the mycelium of
molds, although some species of yeast produce true mycelium.

Binary fission:
A few reproduce by binary fission, this is similar
to process that occur in bacteria.
Sporulation in yeast may be occur by sexual or
asexual means and is similar to that process in molds.
On solid media yeast grows and form moist,
creamy, mucoid colonies resembling those of
staphylococci.
Budding

[2 ] Molds :
Molds reproduce by forming various kind of spores often large numbers by
asexual cell division or as a result of sexual reproduction.
Many fungi can produce more than type of spores depending on the
growth condition.
In the laboratory cultures, molds mainly produce asexual spores.
On artificial medium they are seen as filamentous mold colony which may be dry
and powdery ( cottony).
Yeasts
Molds

SEXUAL REPRODUCTION OF MOLDS :
Sexual reproduction is achieved by fertilization process involving male and
female sex cells (Gametes).
Sexual reproduction is an infrequent form of reproduction for most fungi in the
laboratory or infected humans, but it frequent occurs in nature especially on
plants.

Zygomycetes have asexual and asexual life cycles. In the sexual life cycle, plus and minus
mating types conjugate to form a zygosporangium

The lifecycle of an ascomycete is characterized by the production of asci during the sexual
phase. The haploid phase is the predominant phase of the life cycle.

The lifecycle of a basidiomycete alternates generation with a prolonged stage in which two
nuclei (dikaryon) are present in the hyphae.

[3] Ascospores:
Formed within a sac called Ascus. Ascus
is usually enclosed in fruiting body called
Ascocarps which contain 4-8 Ascospores.
[1] Oospores:
Results from fusion offemalestructure
calledOogoniumandmalestructure
[2] Zygospores:
Results from fusion of two hyphae and
their nuclear contents to form a single
thick-walled spores.
There are four types of sexual
spores:
called Antheridium

Include:
TYPES OF ASEXUAL SPORES:
1. Sporangiospores 2. Conidiospores 3. Thallospores
[4]
Basidiospores:
Basidiospores are borne at the tip of basidium which is
clubbed shaped. There are four spores on surface of the
Basidium.
e.g.hyphaecalleda sporangiophore,
Mucor and Rhizopusspp.
within a swollen, spherical sac , called
sporangiumattheendofspecialized
sporesformedendogenouslyAsexual
1. Sporangiospores:

2. Conidiospores
Conidia (Singular Conidum) are asexual spores formed at the
tips of the side of the hypae. They may be direct attached to
the hyphae or may be carried on specialized hyphae called
conidiophores.
There are two types of conidia:
[A] Macroconidia:
-They are multicellular(2-8 cells).
-They are large and important in species differentiation.
[B] Microconidia:
-They are unicellular(single cells)
-They are small and may be round or in cluster shapes.
The conidum becomes detached when mature.

[A] Arthrospores:
A spore formed by septation followed by
fragmentation of hyphae when mycelia old.
These segmented mycelia are either cubic
or round and the spores in them occur
without swelling of Mycelia.
(3) Thallopsores:
Asexual spores arising from the thallus (vegatitive part of a fungus) are called
thallospores which are subdivided into:
Arthrospores.
Blastospores.
Chlamydospores.

[B] Blastospores:
Spores arising from the vegetative hyphae by a process of
budding as in budding yeasts.
They represent a simple budding from parent cells (mother
cells).
They appear as:
Single daughter or as
Cluster cell called pseudohyhae.
[C] Chlamydospores:
They are also called Resting Spores
formed when cell swells up due to
migration of protoplasm from a number of
hyphal segments into a single segment,
then becomes much enlarged and acquired
a thick cell wall.

Fungal Infections, Mycoses: diseases cause by fungi
Superficial infections: involve outermost layers of skin and its appendages
[ nails or hair] ( Dermatophytosis)
Cutaneous infections: involve deeper layers of skin causing allergic or
inflammatory response
Subcutaneous infections: fungi with low virulence, localized infection, or
spread by mycelial growth
Systemic infections: caused by true pathogenic fungi or opportunistic saprobes

Pathogenicity and virulence
Depending on the virulence and pathogenicity there are broadly two types of fungi:
true pathogenic fungi and
opportunistic fungi.
The ability of the fungi to grow at 37 °C and adapt to the environment
(dimorphism) inside the host tissues helps them to establish and cause infection.
Factors responsible for fungal pathogenicity are specific to the fungus. Enzymes,
toxins and by products of various fungi play an important role in their virulence and
pathogenicity.
Aspergillus spp. produces proteases and aspartic acid proteinase.
Gliotoxin and restrictocin are the toxins produced by Aspergillus spp.
Candida spp. is an opportunistic fungi, that being a normal flora of human can
be responsible for significant infections from superficial skin and nail infections
to urinary tract infections and candidemia.

Function Fungal pathogens
Exoenzymes
a. Alkaline
protease
Degrades collagen, elastin, enhances
invasion of lung tissue.
Aspergillus flavus, A.
fumigatus, Rhizopus
spp.
b. Elastase Degrades elastin, scleroproteins, enhances
invasion of elastin containing tissue (lung,
skin, blood vessels)
Aspergillus flavus, A.
fumigatus,
dermatophytes.
c. Keratinase ,
collagenase
Degrades scleroproteins in skin dermatophytes.
d. Acid proteaseCleavage of IgA2 Candida spp, A.
fumigatus,
Toxins
a. Aflatoxin Hepatotoxicity Aspergillus flavus
b. Endotoxin Tissue necrosis Aspergillus flavus, A.
fumigatus
Dimorphism
Evasion of host defenses
Environmental and tissue forms present different and
surface features , requiring different host response of
mechanisms to contain each form
True pathogens and
opportunistic

Virulence factors associated with cell wall components
component activity
α-(1,3)-glucan
Antigenic masking of WR-1 adhesin
Resistance to digestion by phagocytosis
Destruction of macrophages in vitro
Glucuronoxylomannan Resistance to phagocytosis
Melanin Interference with oxidative metabolism of
phagocytes.

Drug Resistance
The antifungal antibiotics target various stages of metabolic
pathways and are placed in different groups including azoles,
polyenes, fluoropyrimidine analogs, echinocandins, morpholines,
allylamines and thiocarbamates.
5- Fluorocytocine (5-FC) and 5-Fluorouracil are the two
antifungals derived synthetically from DNA nucleotide
cytosine that are used to treat human infections.
5-FC possesses a broad spectrum of activity not only against
fungi but also protozoa.
5-FC has been recommended against fungal infections always as
a combination drug with other antifungal agent as fungi have
ability to acquire resistance.
Amphotericin-B nystatin and natamycin are only the three
polyene/macrolide group of antifungal drugs used to treat
human infections which are synthesized from Streptomyces
bacteria

Are common; molds grow on any damp
organic surface, and spores are constantly in
the air.
Spores and volatile fungal toxins may play a
role in fungal allergies
Generally occur in individuals with other
allergies.
Fungal diseases
A.Fungal allergies
B.Mycotoxicosis
May result from ingestion of fungal-
contaminated foods (e.g. ergotism resulted from
ingestion of bread made with ergot-contaminated
grain or aflatoxicosis caused by ingestion of
poultry feed contaminated with aflatoxin).
Also include ingestion of a psychotropic
(e.g. Psilocybe) or toxic (e.g. Amanita)
mushroom.
These mushroom poisonings are also referred
to as Mycetismus

C.Fungal infections (mycoses)
Range from superficial to overwhelming systemic infections that are rapidly fatal
in the compromised host.
Are increasing in frequency as a result of increased use of antibiotics, corticosteroids,
and cytotoxic drugs.
Are commonly classified as superficial, cutaneous, subcutaneous, and
systemic infections.
The systemic infections are subdivided into those caused by pathogenic fungi
and those caused by opportunistic fungi (Table 1)
type of mycosis Causative fungal agents Mycosis
Superficial
Malassezia species Pityriasis versicolor
Hortaea werneckii Tinea nigra
Trichosporon species White piedra
Piedraia hortae Black piedra
Cutaneous
Microsporum species, Trichophyton
species, and Epidermophyton floccosum
Dermatophytosis
Candida albicans and other Candida
species
Candidiasis of skin,
mucosa,

Subcutaneous
Sporothrix schenckii Sporotrichosis
Phialophora verrucosa, Fonsecaea pedrosoi ,,
others
Chromoblastomycosis
Pseudallescheria boydii, Madurella mycetomatis,
others
Mycetoma
Exophiala, Bipolaris, Exserohilum, and others Phaeohyphomycosis
Endemic
(primary,
systemic)
Coccidioides immitis, C posadasii Coccidioidomycosis
Histoplasma capsulatum Histoplasmosis
Blastomyces dermatitidis Blastomycosis
Paracoccidioides brasiliensis Paracoccidioidomycosis
Opportunistic
Candida albicans and other Candida species candidiasis
Cryptococcus neoformans Cryptococcosis
Aspergillus fumigatus and other Aspergillus
species
Aspergillosis
zSystemic Species of Rhizopus, Absidia, Mucor,
and other
ZYgomycetes
Penicillium marneffei
Mucormycosis
Zygomycosis
Penicilliosis

Diagnosis of fungal infections
1.Clinical manifestations suggestive of fungal infection
Pneumonia or flu-type infection that has lasted
longer than or is more severe than a viral flu.
Pneumonia resulting from exposure to dust
with bird or bat guano (e.g. a cave explorer) or
to desert sand.
Chronic respiratory problem with weight
loss and night sweats
Fever of unknown origin that does not respond
to antibacterial agents or initially responds and
then worsens; mixed infections occur
commonly in severely compromised patients
Any infection with negative bacterial cultures
that does not respond to antibiotics and does
not appear viral
Signs of meningitis in a compromised patient

2.Microscopic examination
1.Potassium hydroxide: (KOH) in a wet mount of skin scrapings breaks down the
human cells, enhancing the visibility of the unaffected fungus.
2.A nigrosin or India ink: wet mount of cerebrospinal fluid (CSF) highlights the
capsule of Cryptococcus neoformans; however, this method is insensitive
(misses 50% of cases).
3.Giemsa or Wright's stain: of thick blood or bone marrow smear may detect
the intracellular Histoplasma capsulatum.
4.Calcofluor white stain: A special fluorescent stain that binds strongly to
structures containing cellulose and chitin. It is useful for the identification of fungi
in the tissues. It binds to the chitin in the cell walls of the fungi. It is especially
useful for the identification of Candida albicans and the causative agents of
zygomycosis

Direct examination of an agar plate under a microscope before agar block cutting

3.Histologic staining (special fungal stains for fixed tissues)
Are necessary because fungi are not
distinguished by color with hematoxylin
and eosin (H and E) stain.
Gomori methenamine-silver stain (fungi are
stained dark gray to black)
Periodic acid-Schiff reaction (fungi are stained
hot pink to red)
Gridley fungus stain (fungi are stained purplish rose with a yellow background)
Calcofluor white stain (may be used on tissue sections; fungi have a fluorescent blue-
white appearance on a dark background)
4.Laboratory cultures for fungi
Must be specially ordered.
Use special media (e.g. Sabouraud's dextrose medium), enriched
media (e.g., blood agar) with antibiotics to inhibit bacterial growth,
and enriched media with both antibiotics and cycloheximide
(which inhibits many saprophytic fungi).

a.Identification of yeast cultures
Traditionally has been based on morphologic characteristics (presence of capsule,
formation of germ tubes in serum, and morphology on corn-meal agar) and
biochemical tests (urease, nitrate reduction, and carbohydrate assimilations and
fermentations).
Can also be accomplished with DNA probes, which are available for Cryptococcus.
b.Identification of filamentous fungal cultures
It is based on morphologic criteria
Can also be accomplished with DNA probes, but only some are
available.
c.Serologic testing
It is used to identify patient antibodies specific to the fungi.
It is complicated by some cross-reactivity among pathogenic fungi.
5.Fungal antigen detection
It uses known antibodies to identify circulating fungal antigens in a patient's serum,
CSF, or urine.

Antifungal Susceptibility Testing

E. Treatment with antifungal drugs
1.Amphotericin B
2.5-Fluorocytosine (5-FC, flucytosine)
3.Miconazole
4.Ketoconazole
5.Fluconazole
6.Itraconazole
7.Potassium iodide (KI)
8.Griseofulvin
9.Nystatin
10.Tolnaftate, clotrimazole, econazole, ciclopirox, olamine, naftifine,
haloprogin, and terbinafine

Host–Fungi Interaction
The Process of Infection Like any other microbial pathogen, fungal
infection also involves some basic steps such as :
(1)entry and adherence to the host tissue,
(2)invasion of the host tissue,
(3)multiplication, colonization and dissemination in the tissues, and
(4)evasion of the host immune system and damage to the tissues.
Fungi reproduce by spreading microscopic spores. These spores are often present
in the air and soil, where they can be inhaled or come into contact with the surfaces
of the body, primarily the skin. Consequently, fungal infections usually begin in
the lungs or on the skin.
A method of transmission is the movement or the transmission of pathogens from
a reservoir to a susceptible host. Once a pathogen has exited the reservoir, it needs
amode of transmission to the host through a portal of entry. Transmission can be
by direct or indirect contact or through airborne transmission.

Relation between Fungi and Human
1.Commensalisms: it is a relation in which fungi benefit and human is not harm from this
relation.
2.Mutualism: it is a relation in which both fungi and human are benefit.
3.Parasitism: it is a relation in which fungi is benefit and human harm form this relation .
* Methods of Transmission:
1.Direct contact
2.Inhalation
3.Infection
4.Inoculation
5.Insects
6.Laboratory infection.
7.Congenital
* From different sources:
1.Man
2.Animals (dermatophytes)
3.Insects
4.Soil
5.Water
6.Food
susceptibleatoTransmission
host:

Attachment to the host tissue:
Filamentous hyphae and germ tube help fungi in attachment to host tissue (Candid
albicans).
Some natural immunity against attachment of fungi:
1.Change and replace of epithelial cells.
2.Movement of cilia cells
3.Peristaltic movement of intestinal.
4.Washing movement of Urinary tract solutions.
Invasion of Host tissue:
Penetration of host cell by fungi is difficult process, so most of infection occurs after
injury or accidents or burns.
But some fungi contain some enzymes help in penetration of host cells and tissues:
1.Hyaluronidase → split hyaluronic acid (component of connective tissue).
2.Fibrinolysin → break down the fibrin barrier in tissues.
3.Protease → break down protein
4.Lipase → break down lipids and fats.
5.DNase → break down DNA of the host cell.
6.Keratinase → break down keratin layer of skin and nails

Colonization and Multiplication of the fungi in the host tissue:
Fungi must reach certain count in order to case disease and it differ between genus
and species of fungi
In order the fungi can multiply, physical and nutritional conditions must be suitable
to the microorganism, in addition to competition with other fungi and human
secretions.
MID (Minimum Infection Dose): is the minimum number of fungi required to
cause infection or disease.
Ability to over come phagocytes (Macrophages and Neutrophils): By
Capsule : Coryptococcus neoformans.
Coagulase enzyme: by forming fibrin barrier around fungal cell so macrophage
can not move (e.g. Candida albicans).
Leukocidins toxin: which kill phagocytes.
Multiply inside Macrophage: so prevent its action and the effect of antibodies
(e.g. Histoplasma capsulatum).
Ability to produce Fungal toxins (Mycotoxins):
e.g. Aflatoxins (B1, B2 , G1, G2, M1, M2)
Exit from the host and survival outside the host long enough for step 1 to
occur and invade other host.

Metabolism is a term that is used to describe all chemical
reactions involved in maintaining the living state of the cells
and the organism.
Metabolism can be conveniently divided into two categories:
Catabolism - the breakdown of molecules to obtain
energy
Anabolism - the synthesis of all compounds needed by
the cells
Fungal Metabolism
Primary metabolites: are essential compounds for growth to
occur and include proteins, carbohydrates, nucleic acids
and lipids. these primary products must be synthesized if they
cannot be obtained from the growth medium. These primary
metabolites have essential and obvious roles to play in the
growth of the fungus.
Typically, primary metabolites are associated with the rapid
initial growth phase of the organism and maximal production
occurs near the end of this phase. Once the fungus enters the
stationary phase of growth, however, primary metabolites
may be further metabolized.
Examples of primary metabolites produced in abundance:
enzymes, fats, alcohol and organic acids as well as, low
molecular weight compounds.

Primary metabolism is used for:
1.Growth and development of hyphal structure
2.Energy metabolism
3.Regulation of metabolism
4.Intermediate in biosynthesis of compound.
Secondary metabolites; Organic compounds , with low molecular weight ,which are
not essential for fungal growth but their natural production have certain
significances.
Furthermore, secondary metabolites are derived from a few common biosynthetic pathways
which branch off the primary metabolic pathways and are often produced as families of
related compounds, often specific for a group of organisms.
Fungi are a rich source of secondary metabolites and have been of interest for humans for
thousands of years.
Secondary metabolism is used for:
1.Competition
2.Antagonism
3.self-defense mechanisms against other living organisms to allow the fungus to occupy
the niche and utilize the food.
Types of Fungal secondary metabolites

Strobilurin (antifungal)
Gibberellins (growth
Hormons)
Herbicides (control weeds)
Mycotoxins (poisneous)
Insecticides ( control insects)
Enzymes (proteins)
Pigments (dyes)
Antibiotics (drugs)
Pharmacological drugs

Differences between primary metabolism and secondary metabolism
importance or the reasons for interest in secondary metabolites
industries:
Antibiotic: Penicillin and cephalosporin
Itaconic acid: cloth industries
Gibberellin: plant growth regulator
Animal feed
Pigment

Bioluminescence

Fungi and Human Diseases
Humans have a high level of innate immunity to fungi and most of the infections they
cause are mild and self-limiting.
This resistance is due to:
1.The fatty acid content of the skin
2.The pH of the skin, mucosal surface and body fluids.
3.Epithelial cell turnover.
4.Normal flora.
5.Transferrin.
6.Cilia of the respiratory tract.
Fungi are able to cause human diseases in three generalized ways:
1.Allergies: may follow sensitization to specific fungous antigens.
2.Fungi may elaborate or indirectly generate toxic substances called Mycotoxins.
3.Some fungi are able to cause infections and grow actively on human or animal host.

Four types of mycotic diseases
1.Hypersensitivity - an allergic reaction to molds and spores.
2.Mycotoxicosis - poisoning of man and animals by feeds and food products
contaminated by fungi which produce toxins from the grain substrate.
3.Mycetism - the ingestion of toxin (mushroom poisoning).
4.Infection - pathogenic fungi which cause infections. When fungi do pass the
resistance barriers of the human body and establish infections, the infections
are classified according to the tissue levels initially colonized:
Superficial mycosis : infections limited to the outermost layers of the skin and hair.
Cutaneous mycosis : infection that is restricted to the keratinized layers of the
skin, hair and nails (Dermatophytosis).
Subcutaneous mycosis : infection involves the dermis, subcutaneous tissue,
muscle, and fascia. These infections are chronic and are initiated by trauma to the
skin.
Systemic mycosis : infection that originates primarily in the lungs and may spread
to many organ systems (Dimorphic fungi).
Opportunistic mycosis : infection of patients with immune deficiencies who
would otherwise not be infected. (Ex. AIDS, diabetes mellitus, immunosuppressive
therapy,..)

Medical Mycology
By: Dr. Abeer Esmail
Fungal Diseases
Superficial Mycoses
Dermatophytosis

Dermatophytosis
Some dermatophytes are spread directly from one person to another (anthropophilic
organisms). Others transmitted to humans from soil (Geophilic organisms), and
still others spread to humans from animal hosts (zoophilic organisms)
Generally don't induce a cellular response to the infection. Have primarily
cosmetic symptoms.
They are also identified based on their origin into:
1.Anthropophilic dermatophytes (man).
2.Zoophilic dermatophytes (animals).
3.Geophilic dermatophytes (soil).

Dermatophytosis are superficial mycoses caused by fungi called
dermatophytes that can invade stratum carenum and keratinized
tissues.
Infections by dermatophytes may be transmitted from animal to
animal, animal to human , human to human, and human to animal in
a cyclic manner.

Superficial Mycoses
Superficial mycoses are infections limited to the outermost layers of the
skin and hair.
Generally don't induce a cellular response to the infection.
Have primarily cosmetic symptoms.
Include Pityriasis (tinea) versicolor, tinea nigra, and white or black piedra
DiseaseEtiological Agent Symptoms Identification of Organism
Pityriasis
versicolor
Malassezia furfurHypopigmented
macules
"Spaghetti and meat balls"
Appearance of organisms in skin
scrapings
Tinea
nigra
Exophiala
we. rneckii
Black macules Black, 2-celled oval yeast in skin
scrapings.
Black
piedra
Piedraia hortaiBlack nodule on hair
shaft
Black nodule on hair shaft
composed of spore sacs and spores.
White
piedra
Trichosporom
beigelii
Crème-colored
nodules on hair shaft
White nodule on hair shaft
composed of mycelia that fragment

into arthrospores.

1.Pitriasis versicolor :
is a superficial fungal infection caused by Malassezia furfur.
Malassezia furfur is normally a commensal of human skin (in 90% of adults). It is
an obligate lipophilic, requiring long-chain fatty acids for growth. Three Malassezia
species have been recovered from human specimens:
1.Malassezia furfur.
2.Malassezia sympodialis.
3.Malassezia pschydermatis.
Clinical significance:
Malassezia furfur is the agent of the superficial disease Pityriasis (tinea) versicolor. It is an
infection of the stratum of the skin. Lesions appear as scaly, Hypopigmented or
hyperpigmented (yellow-brown, brown or red, white) patches mainly on the neck, torso and
limbs. The infection is largely cosmetic, becoming apparent when the skin fails to tan
normally. The disease has world-wide distribution. It is common in temperate zones and
very

prevalent in the tropics.

Elements resulting in growth of tinea
versicolor:
Hot and humid environments
Excessive perspiration
Oily and greasy skin
People who are immunosuppressed
People who utilize adrenal cortical steroids for
long durations surplus utilization of warm and
humid tanning booth
Laboratory diagnosis
Hyphae and yeast-like cells
of Malassezia furfur which
show spaghetti and meatballs
appearance under
microscope.
1.Direct examination: the fungus observed readily when skin scrapings are mounted in
KOH and ink. The presence of short, slightly curved, septate hyphal elements that form
short chains, clusters of oval to round, thick-walled yeast cells that produce buds (spaghetti
and meat balls).
2.Isolation and identification: Olive oil must be added to the medium (Sabouraud's Dextrose
agar). After incubation at 35ºC-37ºC under normal atmospheric conditions, growth appears
2-4 days.

in

Differential diagnosis
The following rashes can be confused with tinea versicolor:
Vitiligo
Pityriasis alba
Seborrheic dermatitis
Syphilis
Pityriasis rosea
Nummular eczema
Guttate psoriasis
Therapy : Personal hygiene + any antifungal drug (Ketoconazole,
clotrimazole, Itraconazole, miconazole,...)

2. Tinea nigra:
A superficial fungal infection of skin caused by Hortaea werneckii. characterized by brown to
black macules which usually occur on the palmar aspects of hands and occasionally the
plantar and other surfaces of the skin.
World-wide distribution, but more common in tropical regions of Central and South
America, Africa, South-East Asia and Australia.
The etiological agent is Hortaea (Phaeoannellomyces) werneckii a common saprophytic
fungus believed to occur in soil, compost, humus and on wood in humid tropical and sub-
tropical regions.
Clinical manifestations:
Skin lesions are characterized by brown to black macules which usually occur on the palmar
aspects of hands and occasionally the plantar and other surfaces of the skin. Lesions are non-
inflammatory and non-scaling. Familial spread of infection has also been reported.

Differential diagnosis
Tinea nigra should be
differentiated from the
following:
conidia of Hortaea werneckii from the
culture colonies
1.Malignant melanoma
2.Junctional nevus
3.Addison's disease
Treatment
Usually, topical treatment with Whitfield's ointment
(benzoic acid compound) or an
imidazole agent twice a day for 3-4 weeks is effective
conidia of Hortaea
werneckii from skin
scrapings
Laboratory diagnosis:
1.Clinical Material: Skin scrapings.
2.Direct Microscopy: Skin scrapings should be examined using 10% KOH and Parker ink or calcofluor
white mounts.
3.Culture: Clinical specimens should be inoculated onto primary isolation media, like Sabouraud's dextrose
agar Yeast-like conidia and chlamydospores are observed. These conidia are round end and have a central
septum and hence appear as bicellular
4.Serology: Not required for
diagnosis
Typical brown to
black, non-scaling
macules on the
palmar aspect of the
hands. Note there is
no inflammatory
reaction.
the mycelium of this fungus

3. White piedra:
is a superficial cosmetic fungal infection of the hair shaft caused by Trichosporon beigelii.
Infected hairs develop soft greyish-white nodules along the shaft. Essentially no
pathological changes are elicited. White piedra is found worldwide, but is most common in
tropical or subtropical regions.
Clinical manifestations:
Infections are usually localized to the axilla or scalp but may also be seen on facial hairs and
sometimes pubic hair. White piedra is common in young adults. The presence of irregular,
soft, white or light brown nodules, 1.0-1.5 mm in length, firmly adhering to the hairs is
characteristic of white piedra.
Yeast fungus (Trichosporon cutaneum)
with septate hyphae and pseudohyphae.
Trichosporon spp. is a yeast isolated
from soil, water, vegetables, mammals,
and birds. It is also a part of the normal
flora of mouth, skin and nails and is the
causative agent of white piedra,
superficial infections and invasive
trichosporonosisin humans.
Trichosporon cutaneum has been often
synonymous and classified as
Trichosporon beigelii.

Laboratory diagnosis:
1.Clinical Material: Epilated hairs with white
soft nodules present on the shaft.
2.Direct Microscopy: Hairs should be
examined using 10% KOH and Parker ink or
calcofluor white mounts. Look for irregular,
soft, white or light brown nodules, 1.0-1.5
mm in length, firmly adhering to the hairs.
3.Culture: Hair fragments should be implanted
onto primary isolation media, like
Sabouraud's dextrose agar. Colonies of
Trichosporon beigelii are white or yellowish
to deep cream colored, smooth, wrinkled,
velvety, dull colonies with a mycelia fringe.
4.Serology: Not required for diagnosis.
Management: Shaving the hairs is the simplest
method of treatment. Topical application of an
imidazole agent may be used to prevent
reinfection

4. Black piedra:
is a superficial fungal infection of the hair shaft caused
by Piedra hortae, an ascomycetes fungus forming hard
black nodules on the shafts of the scalp, beard, moustache
and pubic hair. It is common in Central and South
America and South-East Asia.
Clinical manifestations: Infections are usually localized
to the scalp but may also be seen on hairs of the beard,
moustache and pubic hair. Black piedra mostly affects
young adults and epidemics in families have been reported
following the sharing of combs and hairbrushes. Infected
hairs generally have a number of hard black nodules on
the shaft.
Black Piedra. Piedraia hortae
forms a hard superficial
pigmented nodule around the
hair shaft.

Laboratory diagnosis:
1.Clinical Material: Epilated hairs with hard black
nodules present on the shaft.
2.Direct Microscopy: Hairs should be examined using
10% KOH and Parker ink or calcofluor white. Look
for darkly pigmented nodules that may partially or
completely surround the hair shaft. Nodules are made
up of a mass of pigmented with a stroma-like centre
containing asci.
3.Culture: Hair fragments should be implanted onto
primary isolation media, like Sabouraud's dextrose
agar. Colonies of Piedra hortae are dark, brown-
black
and take about 2-3 weeks to appear.
4.Serology: Not required for diagnosis.
Management: The usual treatment is to shave or
cut the hairs short, but this is often not considered
acceptable, particularly by women. In-vitro
susceptibility tests have shown that Piedra hortae
is sensitive to terbinafine and it has been
successfully used, at a dose of 250 mg a day for 6
weeks, to treat a 23 year old Swedish Caucasian

man following a 4 month visit to India (Gip, 1994).

Dermatophytosis (Tinea infection)
Dermatophyte infections referred to as Tinea infections are limited to the
superficial layers of the epidermis particularly the stratum corneum and the
high keratin – concentration containing appendage structures, the hair and
nails.
Dermatophytes produce enzymes such as keratinase that penetrate
keratinized tissue.
Tinea infections are superficial fungal infections caused by the three genera
of dermatophytes: Trichophyton, Microsporum and Epidermophyton.
Commonly, the infections caused by these organisms are named according to
the sites involved into:
1.Tinea capitis refers to a dermatophyte infection of the head and scarp.
2.Tinea barbae affects the beard area.
3.Tinea faciei tends to occur in the non bearded area of the face
4.Tinea corporis occurs on the body surface.
5.Tinea manuum is limited to the hands.
6.Tinea pedis to the feet.
7.Tinea unguium (onychomycois) infects the toenails.
8.Tinea cruris infection of groin

1.Tinea capitis
Tinea capitis is the most common fungal infection in
school-aged children (6-18 yr.).
2. Tinea faciei is a fungal infection of the face. It
generally appears as a red rash on the face, followed by
patches of small, raised bumps. The skin may peel while
it is being treated.
Tinea faciei tends to occur in the non bearded area of the
face. The patient may complain of itching and burning,
which become worse after sunlight exposure. Some round
or annular red patches are present
3. Tinea barbae
Tinea barbae is a rare dermatophytic infection that is limited to
the bearded areas of the face and neck.
Because the usual cause is a zoophilic organism, farm workers
are most often affected. Tinea barbae may cause scaling,
follicular pustules, and erythema
The cause of tinea barbae is most often a zoophilic
(animal) fungus:
1.T. verrucosum (originating from cattle),
2.T. mentagrophytes var. equinum (originating from horses)
Tinea barbae
Tinea faciei
Tinea capitis

4. Tinea corporis
Tinea corporis or ringworm often appears initially as a red, scaly
papule spreading outward, with a coalescence of papules into
plaques that become scaly. The lesion becomes an annular,
pruritic plaque on glabrous (smooth and bare) skin, with a scaly,
slightly raised edge at the advancing border
5. Tinea cruris
Tinea cruris, frequently called “jock itch, it is a
dermatophyte infection of the groin. This
Dermatophytosis is more common in men than in women
and is frequently associated with tinea pedis . Tinea cruris
occurs when ambient temperature and humidity are
high.Tinea cruris affects the proximal medial thighs and
may extend to the buttocks and abdomen .
6. Tinea pedis
Tinea pedis, also called “athlete’s foot”, is a fungal
infection of the foot that is very common among
homeless populations.
Tinea corporis
Tinea cruris
Tinea pedis

Dermatophyte fungiNon dermatophyte
fungi
Yeast
Epidermophyton
floccosum
Trichophyton
mentagrophytes
Trichophyton rubrum
Acremonium sp
Alternariasp.
Aspergillus sp.
Fusarium species
Scytalidium dimidiatum
Scopulariopsis species
Scytalidium hyalimum
Candida
albicans
7.Tinea unguium (Onychomycosis)
Tinea unguium, a dermatophyte infection of the nail, is a
subset of onychomycosis, which also may be caused by yeast
and nondermatophyte mold. It often occurs in people who
frequently wet their hands such as domestic workers,
cleaners, kitchen and laundry staff.
Major causes of onychomycosisare:
8. Tinea manuum
Tinea manuum is a fungal infection of one or, occasionally, both
hands. It often occurs in patients with tinea pedis. The palmar surface
is diffusely dry and hyperkeratotic. When the fingernails are involved,
vesicles and scant scaling may be present, and the condition resembles
dyshidrotic eczema.

Diagnosis of Cutaneous mycosis:
1.Direct Microscopic examination: using 10-20% KOH
2.Cultivation of samples : there is many media used for fungal cultivation , “ Cyclohexamide
(Actodine) must be added to the media to suppress the growth of saprophytic fungi like
Aspergillus and Penicillium and antibacterial drug (e.g. Chloramphenicol,...) to inhabit the
growth of bacteria. The most important media used for cultivation of dermatophytes are:
Sabouraud’s dextrose agar,
Wood's lamp
Malt extract agar,
Corn meal agar,.
3.Inoculation of experimental animals.
4.Wood's lamp and U.V. Lamp
examination. (positive cases give yellow
green color).
* Treatment of Cutaneous mycosis:
Tolfanate, Clotrimazole, Miconazole, Ketoconazole, Fluconazole, Terbinafine, Griseofulvin, Ciclopirox,

terbinafine,...

•Subcutaneous Mycosis is a disease characterized by a heterogeneous group of
infection that is result from direct penetration of the fungus into the dermis and
subcutaneous tissue through traumatic injury.
•The fungus spreads by local deep tissue invasion from the inoculation site.
•The disease usually remains localized then slowly spreads to adjacent tissue and
eventually to the lymphatic.
There are four general types of subcutaneous mycosis:
Subcutaneous Mycosis

1.Chromoblastomycosis: is chronic subcutaneous
fungal infection characterized by the growth of large
wart-like thickenings that frequently referred to as
cauliflower lesions.
Distribution: World-wide distribution but more
common in bare footed populations living in tropical
regions.
Etiological agents: various dematiaceous
hyphomycetes associated with decaying vegetation or
soil into cuts or wounds:
•Cladophialophora carrionii
•Phialophora verrucosa
•Fonsecaea compacta
•Fonsecaea pedrosoi
Clinical diagnosis: The diseases begin in the legs and feet:
1.Start as small scaly papules or nodules (painless but may be
itchy).
2.Satellite lesions gradually a rise.
3.Then rash area enlarges.
4.Raised irregular plaques (Scally or verrucose)
5.Lesion becomes timorous (Cauliflower like).

Laboratory Diagnosis:
oClinical specimens: skin scrapings and biopsy.
oDirect microscopic examination: 10% KOH and parker ink. Brown pigmented
planate-dividing, rounded sclerotic bodies, dividing by binary fission and not by
budding.
oCulture: into Sabouraud's dextrose agar. Colony is typically olivaceous-black with
a suede-like surface.
Treatment:
1.Surgical excision.
2.Flucytosine.
3.Itraconazole (400mg/day) + Terbinafine (500mg/day) for 6-12 month.
•Fonsecaea pedrosoi
Cladophialophora carrionii

2. Sporotrichosis : is a chronic subcutaneous fungal infection
caused by Sporothrix schenkii. This microorganism is a mold while
grown in soils, were it is naturally found. Once it has infected a host,
it grows as yeast.
Sporothrix schenkii is a dimorphic fungus ( Ascomycetes).
In soil: Filamentous fungi (mold)
In human body: yeast form.
The infection follows an injury by rose thorn, barberry bush, ....
Clinical symptoms: locates under the skin
The patient’s history is very important when making a clinical
diagnosis. Most times, it follows a history of thorn prick on the thumb
of a gardener.
1.Start as small red painless elevation→ increase in size and become
painful.
2.Spread along the vessels of lymphatic system causing lymph
nodes.
3.Causes pulmonary and meningeal diseases in AIDs patients

SUBCUTANEOUS FORMS: A pustule usually develops at the point of
inoculation, which will ulcerate. It may remain localized or will infect the
lymphatic system and from there, the disease will progress up to the arm
with ulceration, abscess formation, break down of the abscess, discharge of pus
and healing. The progression will usually stop at the axilla.
When it is localized, the lesions take one or two forms, both of which will
wax and wane over the years.
A painless smooth or verrucosum erythematous papulonodular lesion (0.5-
4cm diameter) which often ulcerate and can be followed by secondary lesions
along the line of proximal lymphatics is seen.
A fixed (plaque) form which does not spread locally and can spontaneously
resolve has been described.

Diagnosis:
* At 25ºC: Septate hyaline hyphe, conidiophore and conidia are observed.
Conidia two types:
1.Unicellular, hyaline to brown, oval arranged in rosette like clusters at the tips
of conidiophore.
2.Brown, oval or triangular, thick-walled attached directly to the sides of
the hyphe.
*At 37ºC: produce oval to cigar-shaped (cigar bodies) yeast cells, single
or multiple buds.
*Colony: Young colonies → white colour for some time at 25C.
Older colonies → turn black due to production of dark conidia.
Treatment:
1.In subcutaneous lesions: by Potassium Iodide.
2.Pulmonary infection: Amphotericin B, Itraconazole, Ketaconazole.

3. Mycetoma (Maduromycosis &madura foot): is a
subcutaneous fungal infection caused by number of
different fungi and actinomycetes characterized by draining
sinuses, granules and tumefaction.
Distribution: World wide distribution but most common in
bare footed population living in tropical or subtropical
regions
Etiological agents:
Fungi: Bacteria:
Madurella mycetomii
Acremonium spp.
Exophiala spp.
Curvularia spp.
Fusarium spp.
Aspergillus nidulans
Actinomadura madura
Streptomycessomaliensis
Nocardia asteroids
Nocardia brasiliensis

Clinical manifestations:
The diseases results from the traumatic implantation of the etiological agents and
usually involves the cutaneous and subcutaneous tissue, fascia and bone of the foot
and hand.
1.Start as small hard painless nodule.
2.Soften the surface and ulcerate to discharge .
3.A viscous purulent fluid containing granules.
4.Spread to bone causing deformity.

Laboratory Diagnosis:
1.Clinical specimens: tissue biopsy or excised sinus and fluids with granules.
2.Direct Microscopic Examination: fluid containing granules should be
examined by 10% KOH + Parker ink or Calcofluor white mounts.
3.Culture: on Sabouroud's dextrose agar and Blood agar media.
Treatment:
1.Bacteria: Antibiotic (Streptomycin + Dapsone)
2.Fungi:
oSurgical removal of dead tissue
oAntifungal ( Ketoconazole, Itraconazole, ) 8-24 month.
Madurella mycetomatis

4.Rhinosporidiosis
Rhinosporidiosis is a rare, chronic, granulomatous
infection, caused by an organism once believed to be
a sporozoan, but now considered to be a fungus
named Rhinosporidiumseeberi.
It is a disease of the mucous membrane, frequently
involving the nasal passages and ocular tissue,
conjunctiva, lachrymal sac, canali-culus, sclera and lid.
However sporadic involvement has been observed in the
pharynx, paranasal sinus, maxillary sinus, lip, tongue,
palate, epiglottis, tonsil, trachea and bronchus, aural canal,
skin, parotid gland, urethra, penis, vagina, bone, wrist and
foot.
Clinical manifestations
In nasal rhinosporidiosis, the patient complains of
swelling and foreign body sensation in the nose
accompanied by itching, sneezing, and bleeding. Initially
the lesions are small but they progress to large and
pedunculated 'strawberrylike' polypoid mass.

In ocular rhinosporidiosis, the lesions involve
the conjunctiva.
Early lesions are asymptomatic but eventually cause
discharge, photophobia, redness, and secondary
infection.
In cutaneous rhinosporidiosis, the skin lesions
begin as papillomas which become warty and exude
myxomatous material.
Laboratory diagnosis
Clinical Material: Biopsy
Direct Microscopy: show large round or oval
sporangia up to 350 μm in diameter .
The sporangium may be filled
with endospores.
Culture: Rhinosporidium seeberi has never
been isolated in culture.
Treatment
Electrosurgery excision of the lesions
Antifungals (e.g. dapsone, amphotericin B,
griseofulvin)

Medical Mycology
By: Dr. Abeer Esmail
Fungal Diseases
Systemic mycoses

Systemic mycosis is fungal
infection that is generalized
throughout the body.
Most often, systemic
mycosis is acquired through
inhalation of air borne
spores and is started in the
lungs.
The initial pulmonary
infection is often
subclinical or mild and
resolves on its own.
The fungi that cause
primary systemic mycosis
are dimorphic:
1.Inside the human (37Cº
): Yeast
2.In the environment
(25Cº ): Filamentous

1.Coccidioidomycosis- Valley fever
It is a fungal disease caused by Coccidioides
immitis
It is normally mild or self –limited fungal
infection that begins in the lungs and
occasionally spreads to other parts of the
body.
Infection results from inhalation of C.
immitis spores that originate in soil. The
sores convert into large, round spherules
which invade the tissue of the lunge. The
spherules enlarge, and then rupture
releasing several small spores.
Pathogenicity of C. immitis:
1.Primary Coccidioidomycosis: 60% of
patients without symptoms. 40% symptoms
rang from mild respiratory symptoms to
severe pneumonia, and normally heal
spontaneously.
2.Disseminated Coccidioidomycosis : is rare
complication where the infection spreads to
bones, skin, joints, subcutaneous tissue,
invade the tissue of the lunge
Large,
whichroundspherules
Parasiticalcycle:
brain (meninges), fatal if not treated.

Laboratory Diagnosis:
1.Clinical specimens: body fluids and biopsies.
2.Direct microscopic examination: presence of C.
immitis spherules in body fluid or biopsies. The size
of spherules rang between 20-80 µm, thick walls and
endospores contained inside.
3.Culture: Sabouraud's dextrose agar or blood agar.
4.Serology: IgG anticoccidioidal antibodies.
5.Skin test.
Treatment:
Primary Coccidioidomycosis: unnecessary.
Disseminated Coccidioidomycosis: Amphotericin B,
Ketoconazole, Itraconazole.
Saprophytic cycle

2.Paracoccidioides brasiliensis:
Infection occurs by inhalationof spores of Paracoccidioides
brasiliensis from environmental source (soil)
Pathogenicity of Paracoccidioides brasiliensis:
1.Pulmonary infection
* If Spread to other part of the body via blood and lymph causing:
2.Enlargement of liver and spleen and abdominal pain
If the mucous membrane of the mouth and nose infected produce
3.Sores and leak fluid through the skin.
Laboratory Diagnosis:
1.Culture of pus and sores
2.Serological test.
Treatment:
1.Oral antifungal drug (Ketoconazole or Itraconazole), In severe cases: Intravenous Amphotericin B +
Itaconazole
In the environment: Filamentous inside the human: yeast forms

Blasomycosis skin lesions
3.Blastomycosis
then the spore convert into large
yeasts in the lungs
wood,rotting
decomposedsoil,
and
from
vegetation
Inhalation of spores of fungus
Blastomyces dermatitidis .
The infection begins in the lungs
and occasionally spreads
through the blood to skin, bones
and other tissue.
More in males 20-69 years old.
bycausedinfectionFungal

The spore convert into large yeasts in the lungs.
Clinical symptoms of Blastomycosis:
Begins in the lung (no symptoms), some may have cough and
muscle aches.
Then the infection becomes chronic causing fever, chest pain,
weigh
loss and skin wounds.
If spread to skin, bone, prostate, mucous membrane of the
mouth, nose, or larynx the lesions become swollen, warm and tender.
Laboratory Diagnosis:
1.Clinical specimen: sputum, pus and urine samples.
2.Culture: on Sabouraud's dextrose agar.
Treatment:
Amphotericin B

4.Histoplasmosis
It is a fungal disease caused by
Histoplasma capsulatum
which infect the
reticuloendothelial system,
bone marrow, liver, lung and
spleen.
The ecological niche of H.
capsulatum is black bird
roosts, chicken houses and bat
caves.
Clinical symptoms: 3 forms
1.Acute pulmonary (shortness
of breath and cough which
become productive).
2.Chronic pulmonary.
3.Disseminated (fatal if not
treated) cough, bloody sputum,
lose of weigh and anorexic,
night sweats like tuberculosis.

Laboratory Diagnosis:
1.Clinical specimens: sputum, biopsy from diseased organ and bone marrow
(excellent source of the fungus which tend to grow in the reticulo- endothelial
system).
2.Yeasts usually found in monocytes or in PMN's. (Small yeast 5-6 µ in diameter).
3.Culture on Sabouraud's dextrose agar at 25 ºC → White cottony mycelium after
2- 3 weeks. When colony ages it tern to tan color.
4.Serology: Latex agglutination, Complement fixation, Immunodiffusion and EIA.
Treatment:
Amphotericin B
Itraconazole

Opportunistic Mycosis
•Opportunistic Mycosis: are infection caused by fungi that are inherently of limited
virulence but can cause either local or disseminated diseases in persons who are
immunocompromised.
•In recent years, the incidence of opportunistic mycosis has continued to increase.
•Avoiding exposure to opportunistic mycosis is impossible because they are either ubiquitous
in the environment or are part of the normal microbial flora.
1.Penicilliosis
•Belongs to Class: Deutromycetes
•Its filamentous saprophyticus fungi.
•Most common of all laboratories contaminates and can easily
isolate from body surfaces and respiratory specimens.
•Theonlypathogenicspeciesis:Penicilliummarneffei:
dimorphic
At 37C inside the human: Yeast form
At 25 C outside the human: filamentous form
Some species of Penicillium produce Mycotoxins:
•P. chrysogenium
•P. citrinum
•P. commune

Pathogenicity:Casesdiseasescalled
(Penicilliosis)
1.Abscess, arthritis, lymphadenitis.
2.Enlarged spleen (AIDS)
3.Enlarged liver (AIDS)
4.Mycotic keratitis
5.Pulmonary
infection Urinary tract
infection
Laboratory Diagnosis:
1.Directmicroscopicexamination:septate
hyphal elements 1.5-5µm diameter.
Yeast like cells of Penicillium marneffei.
2.Isolation and Identification:
Sabouraud's dextrose agar without
Cyclohexamide.
Growth rate: rapid mature within 4 days.
P. marneffei: rapid mature within 4 days at 25-
30C, slow at 37C, colony: raddish, green centre,
yellow or white edge.
Red pigment diffuses into the media, reverse is
red.

Yeast like take up to 14 days on 5-10% sheep
blood agar.

byfungal
2.Aspergillosis
•Filamentous-saprophytic moulds.
•Class: Deutromycetes
•Some species have teleomorphic (sexual stage): Ascomycetes.
•Most important medical species:
Aspergillus fumigatus.
Aspergillus niger.
Aspergillus flavus.
 Pathogenicity:Humanbecomeusually
infectedby inhalingthere spores.
1.Invasive lung infection
2.Pulmonary fungus ball: fungus colony grows within a congenital or
inflammatory lung cyst.).
3.Allergic bronchopulmonary aspergillosis.
4.Externalotomycoses:inflammationoftheexternalear
infection.
5.Mycotic keratitis: fungal infection of the cornea of the eye.
6.Sinusitis.,Endocarditis.
7.Central Nervous system infection.
8.Onychomycosis.
9.Some produce mycotoxin (aflatoxin)
11. Invasion of tissue
External otomycoses
Onychomycosis

Infectious life cycle of A. fumigatus. Aspergillus is ubiquitous in the environment, and asexual
reproduction leads to the production of airborne conidia. Inhalation by specific
immunosuppressed patient groups results in conidium establishment in the lung, germination, and
either PMN-mediated fungal control with significant inflammation (corticosteroid therapy) or
uncontrolled hyphal growth with a lack of PMN infiltrates and, in severe cases, dissemination
(neutropenia).

Laboratory diagnosis:
Specimen: Biopsy, sputum, skin scrapings, infected nails,....
Direct microscopic examination: Hyphal elements may
be observed and vary with type of infection:
a.In acute invasive infection: hyaline (colorless), closely septate
hyphae 3-6 µm diameter, branch dichotomously.
b.In chronic infection: short, distorted hyphae, wide 12µm.
Culture: Sabourauds dextrose agar (without cyclohexamide) rapid
growth 3 days at 25-28ºC.
Serological test: to detect circulating antibodies.
1.Agar gel immunodiffusion (ID).
2.Enzyme Linked Immunosorbent Assay (ELISA).
3.Radioimmunoassay (RIA).
4.Indirect immunofluorescence.
- A varity of testes have been developed to detect soluble antigens of
Aspergillus spp. in serum , urine, or other body fluids (e.g. RIA,
ELISA, Immunoblotting).
Skin test: to detect allergic bronchopulmonary Aspergillosis.
Therapy:
1.Allergic from Aspergillosis: by corticosteroids + antifungal +
surgical resection.
2.Amphotericin B + Flucytosine.

3.Mucoromycosis
Ubiquitous, monomorphic saprophytes.
•Class: Zygomycetes.
•Zygomycosis (Phycomycosis): It is uncommon disease frequently fatal fungal
infection arises rarely in healthy people (Diabetes mellitus, malignant haemologic
disorders, burns,…..).
•Most common genus:
Rhizopus spp.,
Absidia spp.,
Mucor spp.,
Rhizomucor spp.
Pathogenicity: Zygomycosis (Phycomycosis, Mycoromycosis):
•First the diseases develop in nosal mucosa or the sinuses then spread to soft part of
the orbit and the brain.
1.Paranasal infection
2.Rhinoorbital infection
3.Rhinocerebral infection
4.Pulmonary infection
5.Gastrointestinal infection

Laboratory Diagnosis:
Specimen: Biopsies of pulmonary, rhinocerebral, cutaneous lesions.
Direct microscopic examination: wide, non septate hyphae with
right angled branching may be seen.
Culture: On Sabouraud's dextrose agar without
Cyclohexamide Rapid growth 3-4 days at 25-27ºC
Immunodiagnosis: no serological test available at present.
Therapy: Amphotericin B + Surgical debridement
Yeast of Medical Important
Yeast of Medical Importance are a species of unicellular fungi capable of producing diseases
of human and animals.
They are ubiquitous in environment, found on fruits, vegetables, animals bodies, normal
flora in and on human bodies (endogenous).
General Characteristics: unicellular, eukaryotic, budding cells generally round or oval
called blastoconidia. If not separated a pseudohyphae is fomed.
Some yeast produce true septate hyphae in host tissues.
Culture: Colonies of yeast cells usually moist, creamy or glabrous.
Some yeast are capsulated → mucoid colony.
Some produce hyaline colony → due to cartenoid pigments.
Others produce dark pigmented colony → due to presence of melanins pigments.

The important of direct microscopic examination:
To identify wither:
1.Presence or absence of encapsulated yeasts.
2.Presence or absence of pseudohyphae.
3.Presence or absence of true hyphae or arthroconidia.
4.Size and shape of the yeast cell.
5.Numbers of buds and nature of their attachments to the mother cell.
1.Candidasis
Classification: Class: Deutromycetes
•Teleomorphic genera: Clavispora, Debarymyces, Pichia, Issatchenkia, ......
Several species arenormal flora ofskin , mucousmembrane, gastrointestinal tractand arepotential
pathogens.
Candida albicans:
•is the species of yeast most frequently isolated from clinical specimens.
•Two serotypes of C. albicans: A & B
•They are able to attach epithelial cell membranes.
•Germ tubes are more adhesive than yeast cells.
•Most strainsof C.albicanssecrete proteasecapable ofdigestinghost immunoglobulinsandother
substrates.
•Candida albicans produce budding yeast when grow normal flora and hyphal form during tissue invasion
(Dimorphism).
•Normal serum at 37ºC for 90 min., C. albicans and some of C. stellatoidea begin to form true hyphae.

,
PredisposingfactorsofopportunisticCandidainfection
are:
•Physiologic (pregnancy, old age, infancy).
•Traumatic (burns, maceration,...)
•Haematological (anaemia, leukaemia, lymphoma,..)
•Endocrine(Diabetesmellitus,ironmetabolic
disorders,..)
•Antibacterial antibiotics, steroid treatment, surgery
cytotoxic drugs,..)
•Others (AIDS, malnutrition, malignancey,.....)
Pathogenicity:Candidiasis
1.Cutaneous and mucosal: oral thrush, stomatitis,
onychomycosis, vaginal thrush, balanitis).
2.Systemic: follow the introduction of Candida sp.
into the blood stream (meningitis,
endophthalmitis, endocarditis, bronchpulmonary,
infant diarrhoea, cystitis, arthritis, )
3.Chronic mucocutaneous candidosis: its
infection of any or all of the epithelial surfaces of
the body (skin, oral mucosa, upper respiratory
tract, gastrointestinal, urinary, genital
epithelium, )
4.Allergic reactions to Candida antigen.

IDS patient.
yndrome
Laboratory Diagnosis:
1.DirectExamination:appearanceofbranching,septate
hyphae, pseudohyphae, oval cell, budding cells.
2.Isolation and Identification: on Corneal agar or Sabouraud's
dextrose agar. Growth rate rapid, mature in 2-3 days.
3.Germ tube test: for rapid identification of C. albicanis. This
test allows the detection of the Germ Tubes which are the
initial stage of hyphae formation. These are the short, non-
septate germinating hyphae which are one half the width
and three to four times the legnrh of the yeast from which
they originate. Approximately 95-97% of Candida albicans
isolate develop germ tube when incubated in a
proteinaceous media at 35C for 2.5-3 hours.
4.Utilization of Carbohydrates: on yeast nitrogen base agar
containing bromocreasol purple indicator, or by API-20C
yeast system (BioMerieux-Vitek).
Treatment:
1.Cutaneous and mucosal: Nystatin, Clotrimazole, Ketoconazole,...
2.Systemic: Amphotericin B, Flucytosine.
Chronic mucocutaneous: Amphotericin B, Flucytosine, Miconazole
Oral soor; surface infection of cheek mucosa and tongue by Candida albicans in an A
.b. Chronic mucocutaneous candidiasis in a child with a cellular immunodeficiency s
Germ Tubes

2.Cryptococcosis
Classification: Class: Deutromycetes
•Cryptococcus neoformans is considered the only human
pathogen(notapartofnormalfloraofhumanor
animals).
•Cryptococcus:unicellularfungiwithsinglebudding
characterize by large mucopolysaccharide capsule.
•Most important human pathogen: Cryptococcus
neoformans (not a part of normal flora of humans and
animals)
•Cryptococcus neoformans: is round to oval yeast like
fungi with single budding and narrow neck between
parent and daughter cell.
•Cells are characterized by presence of a
mucopolysaccharide capsule.
•Colonies are mycoid, exhibit a wide range of colours.
•Produce urease and utilize various carbohyderates.
•Cryptococcus neoformans: 4 serotypes A,B,C, D.
•Serotype A, D: teleomorphic state: C. neoformans var.
neoformans (is the most common associated with
pegeon, bird droppings, soil.
•Serotype B,C: teleomorphic state: C. neoformans var.
gattii (with the distribution of Eucalyptus tree).

Laboratory Diagnosis:
Clinical specimens: spiral fluid, aspirates from skin lesions, sputum, biopsy, ….
•Microscopic examination: directly in an India –ink preparation for presence of
budding yeast cells with capsule
•Isolation and identification: on most laboratory media
without cyclohexamide (e.g. Sabouroud's Dextrose
Agar, Malt extract agar, Corn meal extract agar, Potato
extract agar,…
•Growth rate: rapid , mature in 2-3 days (25-37 ºC).
•Colony: flat or slightly elevated, shiny, moist, mucoid,
colour creamy to tan colour.
On corn meal –Tween 80 agar: round, dark walled,
budding cells.
•Immunodiagnosis: specific rabbit anticryptococcus
neoformans antiserum for detection the capsular antigen.
•Latex agglutination test: Latex coated with specific
rabbit immunoglobulin and mixed with dilution of
patient serum or spinal fluid → agglutination (positive
Cryptococcus infection).

Therapy: Amphotericin B + Flucytosine.

Treatment
Because they are eukaryotic, fungi are biochemically similar to the human host.
Therefore it is difficult to develop chemotherapeutic agents that will destroy the
invading fungus without harming the patient.
Finding an agent that will selectively injure fungal cell walls without damaging
the host cell.
The cell membranes of all eukaryotic cells contain sterols; ergosterol in the fungal
and cholesterol in the mammalian cell membrane.
Most drugs will usually have serious side effects on the host!
Antifungal agents (some!)
•Amphotericin B – a polyene antimycotic. It has a greater affinity for ergosterol in
the cell membranes of fungi than for the cholesterol in the host's cells, causes
disruption of the cell membrane. Rather toxic.
•Azoles - ketoconazole, fluconazole, and itraconozole, are being used for muco-
cutaneous candidiasis, dermatophytosis, and for some systemic fungal infections.
The mechanism of action of the azoles is the inhibition of ergosterol synthesis.
•Griseofulvin - very slow-acting drug which is used for severe skin and nail
infections.
•5-fluorocytosine - inhibits RNA synthesis and has found its main application in
cryptococcosis.