‫الحقيبة التعليمية لمادة الفايروسات والفطريات‬

Professor Dr. Ali Abdulhusain Mahdi ‫االستاذ الدكتور علي عبدالحسين مهدي‬
Assist.Prof. Dr. Abdulameer J. Mohammed ‫االستاذ المساعد الدكتور عبداالمير جاسم محمد‬
Dr. Omar Sadik Shalal ‫المدرس الدكتور عمر صادق شالل‬
Lecturer

Myucology
Lecture 1 : Introduction
MYCOLOGY: Is the study of fungi and their multiple functions in nature.
Introduction:-
• Mykes(Greek word) : Mushroom
• Fungi are eukaryotic protista; differ from bacteria and other prokaryotes.
1. Cell walls containing chitin (rigidity & support), mannan& other
polysaccharides .
2. Cytoplasmic membrane contains ergosterols .
3. Possess true nuclei with nuclear membrane & paired chromosomes.
4. Divide asexually, sexually or by both.
5. Unicellular or multicellular.
Taxonomy:
Kingdom Characteristic Examples
Monera Prokaryocyte Bacteria E. coli
Protista Eukaryocyte Protozoa E.histolytica
Fungi Eukaryocyte Fungi Mushroom , Candida sp.
Plants Eukaryocyte Plants Moss
Animals Eukaryocyte Arthropods Arthropods,Mammals,Man

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WHAT ARE FUNGI?

Fungi are not plants. Fungi form a separate group of higher organisms, distinct
from both plants and animals, which differ from other groups of organisms in several
major respects :-
First: fungal cells are encased within a rigid cell wall, mostly composed of chitin and
glucan. These features contrast with animals, which have no cell walls, and plants,
which have cellulose as the major cell wall component.
Chitin :Is a long-chain polymer of a N- acetyl glucosamine, a derivative of glucose,
and is found in many places throughout the natural world.
glucan molecule:-Is a polysaccharide of D-glucose monomers, linked by glycosidic
bonds. Many beta-glucans are medically important. They represent a drug target for
antifungal medications .

Second: fungi are heterotrophic. This means that they are lacking in chlorophyll and
cannot make their organic food as plants can, through photosynthesis. Fungi live
embedded in a food source or medium, and obtain their nourishment by secreting
enzymes for external digestion and by absorbing the nutrients that are released from
the medium.

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Third: fungi are simpler in structure than plants or animals. There is no division of
cells into organs or tissues. The basic structural unit of fungi is either a chain of
tubular, filament-like cells, termed a hypha or hyphae (plural) or an independent single
cell.
Fourth: fungi reproduce by means of microscopic propagules called spores. Many
fungi produce spores that result from an asexual process .Many fungi are also capable
of sexual reproduction. Some species are homothallic and able to form sexual
structures within individual colonies.

• Simplest fungus :- Unicellular budding yeast

• Hypha :- Elongation of apical cell produces a tubular, thread like structure

called hypha , Hyphae may be septate or non-septate

• Mycelium :- Tangled mass of hyphae is called mycelium. Fungi producing

mycelia are called molds or filamentous fungi.

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General properties of fungi:

1. They are eukaryotic; cells contain membrane bound cell organelles including
nuclei, mitochondria, golgi apparatus, endoplasmic reticulum, lysosomes etc. They
also exhibit mitosis.
2. Have ergosterols in their membranes and possesses 80S ribosomes.
3. Have a rigid cell wall and are therefore non-motile, a feature that separates them
from animals. All fungi possess cell wall made of chitin.
4. Are chemoheterotrophs (require organic compounds for both carbon and energy
sources) and fungi lack chlorophyll and are therefore not autotrophic.
5. Fungi are osmiotrophic; they obtain their nutrients by absorption.
6. They obtain nutrients as saprophytes (live off of decaying matter) or as parasites
(live off of living matter).
7. All fungi require water and oxygen and there are no obligate anaerobes.
8. Typically reproduce asexually and/or sexually by producing spores.
9. They grow either reproductively by budding or non-reproductively by hyphal tip
elongation.
10. Food storage is generally in the form of lipids and glycogen.

Many fungal pathogens of humans and animals change their growth form
during the process of tissue invasion. These dimorphic pathogens usually change
from a multicellular hyphal form in the natural environment to a budding, single-
celled form in tissue. In most multicellular fungi the vegetative stage consists of a
mass of branching hyphae, termed a mycelium. Each individual hypha has a rigid
cell wall and increases in length as a result of apical growth. In the more primitive
fungi, the hyphae remain aseptate (without cross-walls). In the more advanced
groups,however, the hyphae are septate

Beneficial Effects of Fungi:

1. Decomposition‫ ))تحلل‬- nutrient and carbon recycling.
2. Biosynthetic factories. The fermentation property is used for the industrial
production of alcohols, fats, citric, oxalic and gluconic acids.

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3. Important sources of antibiotics, such as Penicillin.

4. Model organisms for biochemical and genetic studies. Eg: Neurosporacrassa
5. Saccharomyces cerviciaeis extensively used in recombinant DNA technology,
which includes the Hepatitis B Vaccine.
6. Some fungi are edible‫( )(صالح لالكل‬mushrooms).
7. Yeasts provide nutritional supplements such as vitamins and cofactors.
8. Penicillium is used to flavor Roquefort(‫ )نوع من االجبان‬and Camembert cheeses.
9. Ergot( ‫ )مرض يصيب الحبوب‬produced by Clavicepspurpurea contains medically
important alkaloids that help in inducing uterine contractions, controlling bleeding
and treating migraine.
10. Fungi (Leptolegnia caudate and Aphanomyceslaevis) are used to trap mosquito
larvae in paddy( ‫ )الشلب‬fields and thus help in malaria control.
Harmful Effects of Fungi:
1. Destruction of food, lumber(‫)االخشاب‬, paper, and cloth.
2. Animal and human diseases, including allergies.
3. Toxins produced by poisonous mushrooms and within food (Mycetism and
Mycotoxicosis).
4. Plant diseases.
5. Spoilage( ‫ )تلف‬of agriculture produce such as vegetables and cereals( ‫ )حبوب‬in
the godown(‫) مخازن الحبوب‬.
6. Damage the products such as magnetic tapes and disks, glass lenses, marble
statues(‫)تماثيل المرمر‬, bones and wax.
The differences between bacteria and fungi:
1. Fungi are eukaryotes while bacteria are prokaryotes.
2. Bacteria are single celled whereas most fungi are multicellular except for
yeast.
3. The compositions within their cell walls are different.
4. Fungi are heterotrophs while Bacteria can be autotrophs or heterotrophs.
5. Bacteria have 3 distinct shapes while fungi have various shapes.
6. Bacteria reproduce asexually via binary fision whereas fungi are capable of
reproducing both sexually or asexually.

Lecture 2 : Morphology ,Classification and Reproduction of fungi

Morphology of fungi:

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Fungi exist in two fundamental forms; the filamentous (hyphal) and single
celled budding forms (yeast). But, for the classification sake they are studied as
moulds, yeasts, yeast like and dimorphic fungi.

Moulds:
The thallus of mould is made of hyphae, which are cylindrical tube like
structures that elongates by growth at tips. A mass of hyphae is known as mycelium. It
is the hypha that is responsible for the filamentous nature of mould. The hyphae may
be branched or unbranched. They may be septate or aseptate. Hyphae usually have
cross walls that divide them into numerous cells. These cross walls, called septa have
small pores through which cytoplasm is continuous throughout the hyphae. Therefore
all hyphal fungi tend to be coenocytic (multinucleate). With exception of zygomycetes
(Rhizopus, Mucor), all moulds are septate. Non-septate hyphae are considered to be
more primitive because if a hyphal strand is damaged the entire strand dies. When a
septate hyphal strand is damaged, the pores between adjacent compartments can be
plugged, thus preventing death of the whole hyphal strand.

Mycelium are of three kinds:

1. Vegetative mycelium are those that penetrates the surface of the medium and
absorbs nutrients.
2. Aerial mycelium are those that grow above the agar surface
3. Fertile mycelium are aerial hyphae that bear reproductive structures such as conidia
or sporangia.
Since hypha is the structural unit of mould, the mycelium imparts colour, texture and
topography to the colony. Those fungi that possess melanin pigments in their cell wall
are called phaeoid or dematiaceous and their colonies are coloured grey, black or
olive. Examples are species of Bipolaris, Cladosporium, Exophiala, Fonsecaea,
Phialophora and Wangiella Those hyphae that don't possess any pigment in their cell
wall are called hyaline. Hyphae may have some specialized structure or appearance
that aid in identification. Some of these are:

a) Spiral hyphae: These are spirally coiled hyphae commonly seen in Trichophyton
mentagrophytes.
b) Pectinate body: These are short, unilateral projections from the hyphae that
resemble a broken comb. Commonly seen in Microsporum audouinii.

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c) Favic chandelier: These are the group of hyphal tips that collectively resemble a
chandelier or the antlers( ‫ )قرن الوعل‬of the deer (antler hyphae). They occur in
Trichophyton schoenleinii and Trichophyton violaceum.
d) Nodular organ: This is an enlargement in the mycelium that consists of closely
twisted(‫ ) مجدول‬hyphae. Often seen in Trichophyton mentagrophytes and Microsporum
canis.
e) Racquet hyphae: There is regular enlargement of one end of each segment with the
opposing end remaining thin. Seen in Epidermophyton floccosum, Trichophyton
mentagrophytes.
f) Rhizoides: These are the root like structures seen in portions of vegetative hyphae in
some members of zygomycetes.

Yeasts:
Yeasts are unicellular spherical to ellipsoid cells. They reproduce by budding,
which result in blastospore (blastoconidia) formation. In some cases, as the cells buds
the buds fail to detach and elongate thus forming a chain of elongated hyphae like
filament called pseudohyphae. This property is seen in Candida albicans. The same
species also have the ability to produce true hypha, which is seen as germ tube. The
difference between the two is that there is a constriction in psueudohyphae at the point
of budding, while the germ tube has no constriction. Some yeast such as Cryptococcus
and the yeast form of Blastomyces dermatatidis produce polysaccharide capsule.
Capsules can be demonstrated by negative staining methods using India ink or
Nigrosin. The capsule itself can be stained by Meyer Mucicarmine stain.
Some yeasts are pigmented. Rhodotorula sps produces pink colonies due to carotenoid
pigments while some yeasts such as Phaeoannellomyces werneckii and Piedraia hortae
are dematiaceous, producing brown to olivaceous colonies. True yeasts such as
Saccharomyces cerviciae don't produce pseudohyphae. Yeast-like fungi may be
basidiomycetes, such as Cryptococcus neoformans or ascomycetes such as Candida
albicans.

Classification of fungi:
Fungi were initially classified with plants and were a subject of interest for
botanists; hence the influence of botany can be seen on their classification. In 1969
R.H Whittaker classified all living organisms into five kingdoms namely Monera,
Protista, Fungi, Plantae and Animalia. Traditionally the classification proceeds in this
fashion:

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Kingdom - Subkingdom - Phyla/phylum - Subphyla - Class - Order - Family - Genus-

Species .This classification is too complicated to be dealt here.
There are alternate and more practical approaches, one based on sexual reproduction
and the other based on morphology of the thallus (vegetative structure).
Based on Sexual reproduction:
1. Zygomycetes: which produce through production of zygospores.

2. Ascomycetes: which produce endogenous spores called ascospores in cells called

asci.

3. Basidiomycetes: which produce exogenous spores called basidiospores in cells

called basidia.

4. Deuteromycetes (Fungi imperfecti): fungi that are not known to produce any sexual
spores (ascospores or basidiospores).

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Based on Morphology:
1. Moulds (Molds): Filamentous fungi Eg: Aspergillus sps, Trichophyton rubrum

2. Yeasts: Single celled cells that buds Eg: Cryptococcus neoformans, Saccharomyces
cerviciae

3. Yeast like: Similar to yeasts but produce pseudohyphae Eg: Candida albicans

4. Dimorphic: Fungi existing in two different morphological forms at two different

environmental conditions.
They exist as yeasts in tissue and in vitro at 37C ° and as moulds in their natural habitat
and in vitro at room temperature. Eg: Histoplasma capsulatum, Blastomyces
dermatidis, Paracoccidiodes brasiliensis, Coccidioides immitis Some 200 "human
pathogens" have been recognized from among an estimated 1.5 million species of
fungi.

Biased on the site of infection ( Clinical Classification ):-

1- Superficial infection.
2- Cutaneous infection .
3- Subcutaneous infection.
4- Systemic infection .
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5- Opportunistic infection .

Reproduction in fungi:
Fungi reproduce by asexual, sexual and parasexual means. Fungi can reproduce
asexually by fragmentation, budding, or producing spores, or sexually with
homothallic or heterothallic mycelia.
Asexual reproduction is the commonest mode in most fungi with fungi
participating in sexual mode only under certain circumstances. The form of
fungus undergoing asexual reproduction is known as anamorph (or imperfect
stage) and when the same fungus is undergoing sexual reproduction, the form is
said to be teleomorph (or perfect stage). The whole fungus, including both the
forms is referred as holomorph.

mportance of Spores:
A. Biological
1) Allows for dissemination
2) Allows for reproduction
3) Allows the fungus to move to new food source.
4) Allows fungus to survive periods of adversity.
5) Means of introducing new genetic combinations into a population
B. Practical
1) Rapid identification (also helps with classification)
2) Source of inocula for human infection
3) Source of inocula for contamination

Lecture 3 : Superficial mycosis, tinea types and dematiaceuos (black

fungi)
DEFINITION AND GENERAL CHARACTERISTICS OF CUTANEOUS
MYCOSES

Fungal diseases that affects the skin, hair and nails. They are generally restricted the
keratinized tissue.They cause inflammatory response.

DERMATOPHYTOSES

Etiological fungi are called “dermatophytes” (They are keratinophilic fungi)

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• There are 3 genera:-

Microsporum

Trichophyton

Epidermophyton

• Dermatophyte infections are called Tinea (= Ringworm)

Ring worm:

DERMATOPHYTES ARE CATEGORIZED INTO 3 TYPES ACCORDING TO

SOURCES OF INFECTION

1. Geophilic dermatophytes

2. Zoophilic dermatophytes

3. Anthropophilic dermatophytes

GEOPHILIC DERMATOPHYTES

Inhabit soil where they decompose keratinaceous debris of dead animals

1-Microsporum gypseum :-

Microsporum nanum:-

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ZOOPHILIC DERMATOPHYTES:- Parasitic on animals:-

1-Trichophyton equinum

2-Microsporum canis

3-M. mentagrophytes var Mentagrophytes

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ANTHROPOPHILIC DERMATOPHYTES:-

Primarily parasitic to man. Man as exclusive host for maintenance and dissemination
of species

1- Trichophyton rubrum

2- Trichophyton schoenleinii

3- Trichophyton tonsurans

4- Trichophyton mentagrophytes var interdigitale

5-Microsporum audounii

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6- Epidermophyton floccosum:-

Clinical manifestations of dermatophytoses:

A. Skin invasion = ringworm

B. Hair invasion

Favic type (inside, with oil deposits and air)

Ectothrix type (outside; the hyphae are accumulated around the hair shaft)
Endothrix type (inside)
Tinea capitis Scalp, eyebrow, eyelashes
Tinea favosa Cup shaped crusts
Tinea corporis Rings with scaly centers
Tinea imbricata Concentric rings caused by T. concentricum
Tinea barbae Bearded area of face and neck
Tinea cruris Jock itch, moist groin area
Tinea pedis Athlete’s foot Toe webs, soles and nails
Tinea manuum Interdigitate areas and palmar surfaces
Tinea ungium (Onychomycosis)Invasion of nail plate Thickened, discolored and
brittle nails

Laboratory diagnosis of dermatophytoses

A-Skin scraping, + infected hair

KOH preparation
B- Potassium hydroxide (KOH): dissolves keratin and free hyphae from the cell

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C- Calcofluor white (CFW) stains chitin at the cell wall

Need fluorescent microscopy. Improve the sensitivity and specificity of diagnosis

Culture: SDA or SDA with chloramphenicol and cycloheximide (mycosel agar) at

room temperature at least 2 weeks Identification:

Microscopic characteristics:- Gross colors and textures

Trichophyton rubrum:-
White, cottony colony. Wine red pigment on reverse side.
• Pencil-shaped macroconidia

• Microconidia (club-shaped, tear drops)

Trichophyton mentagrophytes:-

Flat, white to cream color, powdery to granular surface

• Cigar-shaped macroconidia

• Microconidia present

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• Coiled or spiral hyphae

Microsporum gypseum:-

Light brown, powdery colony:

Spindled-shaped macroconidia, Microconidia present

Epidermophyton floccosum:-

Fluffy colony

• Club-shaped macroconidia

• Microconidia ABSENT

Dermatophytes:-

1-Microsporum:- Infect skin, hair and nails

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Microscopic appearance : Macroconidia: Rough walled

Microconidia: Present : Macroconidia more than microconidia

2-Trichophyton:- Infect skin and hair

Microscopic appearance : Microconidia: Present:- Microconidia more than macroconidia

Macroconidia: Smooth walled

3- Epidermophyton:- Infect skin and nails

Microscopic appearance

Macroconidia: Smooth walled:- Microconidia: ABSENT: Chlamydoconidia

Black fungi:

Black Fungus or mucormycosis is a rare but dangerous invasive fungal infection

caused by a group of molds called mucormycetes. Black fungus commonly affects the
sinuses and lungs but can affect skin and brain. People can get infected when they
inhale the mold spores or touch the mold spore. A skin infection can occur after the
fungus enters the skin through a scrape, burn, or other type of skin injury.
Mucormycosis is not contagious from person to person. You cannot get it from an
infected person.

Most cases of mucormycosis are sporadic (meaning they occur infrequently) but
outbreaks do occasionally occur. Most outbreaks are associated with water leaks, poor
air filtration, building construction, and natural disasters. Healthcare providers who are
concerned about an unusual number of cases should contact their state or local public
health department

Symptoms depend on where in the body the fungus is growing and can include facial
swelling, fever, skin ulcers, and black lesions in the mouth.

Lecture 4 : Subcutaneous mycosis :

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These are infections confined to the dermis, subcutaneous tissue or adjacent

structures. infection may arise following the wounding of the skin and the introduction
of vegetable matter. these mycoses are rare and confined mainly to tropical regions.
they tend to be slow in onset and chronic in duration. an example is sporotrichosis
caused by sporothrix schenckii. the fungus is dimorphic, being a mould that can
convert to a yeast form at 37°c on rich laboratory media or in infection.
Sporotrichosis:-
Is a disease caused by the infection of the fungus Sporothrix schenckii. This
fungal disease usually affects the skin, although other rare forms can affect
the lungs, joints, bones, and even the brain. Because roses can spread the disease, it is
one of a few diseases referred to as rose-thorn or rose-gardeners' disease.
Because S. schenckii is naturally found in soil, hay, sphagnum moss, and plants,
it usually affects farmers, gardeners, and agricultural workers. It enters through small
cuts and abrasions in the skin to cause the infection. In case of sporotrichosis affecting
the lungs, the fungal spores enter through the respiratory pathways. Sporotrichosis can
also be acquired from handling cats with the disease; it is an occupational hazard for
veterinarians.
Pathophysiology
Infection with the dimorphic soil fungus S schenckii is usually acquired from
organic matter through cutaneous inoculation. The mycosis has also been transmitted
from animals through bites or scratches. Cats have been responsible for cases among
veterinarians and for a large outbreak in Rio de Janeiro, Brazil. See the image below.

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Types of sporotrichosis
 Cutaneous (skin) sporotrichosis is the most common form of the infection. It
usually occurs on a person’s hand or the arm after they have been handling
contaminated plant matter.
 Pulmonary (lung) sporotrichosis is very rare but can happen after someone
breathes in fungal spores from the environment.
 Disseminated sporotrichosis occurs when the infection spreads to another part of
the body, such as the bones, joints, or the central nervous system. This form of
sporotrichosis usually affects people who have weakened immune systems, such as
people with HIV infection (see Risk & Prevention).

Mycetoma: is a suppurative and granulomatous subcutaneous mycosis, which is

destructive of contiguous bone, tendon, and skeletal muscle. Mycetoma is
characterized by the presence of draining sinus tracts from which small but grossly
visible pigmented grains or granules are extruded. These grains are microcolonies of
fungi causing the infection.

Diagnosis of Mycetoma
Specimen collection: Aspiration (best),drainage, tissue biopsy /section • Examination
of grains

• Examination of grains:-

• Record size, color, shape and consistency of grains

• Direct microscopic examination: KOH/LPC preparations (LPC = lactophenol cotton

blue)

• Culture Standard mycological media or aerobic/anaerobic bacterial culture condition

Treatment

Treatment is difficult due to inability of drugs to infiltrate lesions, combination of

medicine and surgery is the best Eumycotic mycetoma: Amphotericin B

Actinomycotic mycetoma: Antibiotics

Lecture 5 : infection due to filamentous fungi ( Aspergillosis ):

Aspergillosis :-

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Aspergillus spp. are widely distributed fungal moulds found in soil and other
organic matter. They have also been isolated in air-conditioning systems. There are
more than a hundred different species but most human disease is caused
by Aspergillus fumigatus or Aspergillus niger. Occasionally, Aspergillus
clavatus and Aspergillus flavus cause human illness.

What Is Aspergillosis?
Aspergillosis is an infection, allergic reaction, or fungal growth caused by
the Aspergillus fungus. The fungus usually grows on decaying vegetation and dead
leaves. Exposure to the fungus doesn’t necessarily guarantee to get aspergillosis.
Almost everyone encounters the fungus on a daily basis and never contracts the
illness. It’s more likely to infect people with a weak immune system or a lung disease.

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Aspergillus flavus

Aspergillus niger

Aspergillus fumigatus
What Are the Types of Aspergillosis and Their Symptoms?
Different types of aspergillosis affect the body in different ways. Certain
conditions and medications increase the risk for developing each type. Different types
of aspergillosis have different symptoms.

Allergic Bronchopulmonary Aspergillosis (ABPA):-

In allergic bronchopulmonary aspergillosis (ABPA), the fungus causes allergic
reactions such as coughing and wheezing. The patient`s more susceptible to this type
of aspergillosis if he have lung problems such as cystic fibrosis or asthma. ABPA also
causes shortness of breath, and general feelings of being unwell.

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Investigation:-
Diagnosis is made on the basis of a deterioration in the patient's clinical condition (the
underlying asthma or CF symptoms worsen), being a susceptible patient and the
presence of the following:

 Eosinophilia.
 Positive skin test to Aspergillus spp.
 Elevated serum immunoglobulin E (IgE).
 Positive serology for Aspergillus spp.
 New infiltrates on CXR or CT scan.
 Sputum microscopy and culture may also reveal the presence of Aspergillus spp.

Invasive Aspergillosis:-
The more likely to have an invasive type of aspergillosis if the immune system
is weakened by chemotherapy and conditions such as leukemia, cancer, and AIDS.

A weakened immune system makes it more difficult to fight off infections. This
type of aspergillosis invades the lung tissues and can spread to the kidneys or brain. If
invasive aspergillosis goes untreated, it can cause infectious pneumonia. Infectious
pneumonia can be life-threatening in people with compromised immune systems.
Invasive aspergillosis often occurs in people who already have other medical
conditions, so it can be hard to separate the symptoms of invasive aspergillosis from
those of the other conditions. Known symptoms of invasive aspergillosis include:
 a cough (sometimes with blood)
 pain in the chest
 shortness of breath
 fever
Also, an infection of the lungs can spread throughout the body, causing new
symptoms.

Investigations:-
 Invasive aspergillosis is a difficult condition to diagnose and must be specifically
sought in symptomatic patients who are severely immunocompromised.
 CXR may show nodules, cavitary lesions or pulmonary infiltrates.
 CT scanning may show characteristic changes in the lungs, including the 'halo sign' (a
haziness surrounding a nodule or infiltrate).

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 The sputum, lung tissue from biopsy, or bronchoalveolar lavage (BAL) fluid may
show the characteristic hyphae, using appropriate special stains. Aspergillus spp. may
also be cultured from these sources.
 There is an assay to detect a component of the cell wall of Aspergillus spp., called
galactomannan. This has the potential to be used as screening in those at high risk of
invasive aspergillosis. Serum levels can be monitored on a regular basis.
Galactomannan can also be detected in BAL fluid. Serum galactomannan can be
detected several days before the presence of clinical signs, an abnormal chest
radiograph, or positive culture.
 Another fungal cell wall constituent, B-glucan, can also be detected in the serum and
has a potential role in diagnosis.
 Polymerase chain reaction (PCR) techniques are also being studied to
detect Aspergillus spp. in blood and BAL fluid.
 Results may be negative and empirical therapy is often started on clinical grounds in
deteriorating patients.

Aspergilloma:-
The tuberculosis patient`s or another lung disease, exposure to the fungus can
cause to develop a fungus growth. Also called a fungus ball, this type of growth
usually consists of fungus, clots, and white blood cells. The growth doesn’t typically
spread to other areas of the body. However, the ball can become larger and damage the
lung tissues.
With an aspergilloma, the patient`s may have a cough, with or without blood, and
shortness of breath.
Other symptoms of different types of aspergillosis can include:
 pain in the chest and bones
 vision difficulties
 blood in urine
 less urine
 headaches
 chills
 difficulty breathing
 skin sores
 bloody phlegm
Investigations
 CXR shows a mass within a pulmonary cavity, often in the upper lobe. A crescentic
outline of air may be seen to surround a solid mass.

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 CT scanning can reveal the structure of the mycetoma in more detail. Supine and
prone CT scans should be performed to demonstrate the mobility of the mass, which is
a highly suggestive sign.
 Most show elevated serum precipitin levels to Aspergillus spp.

Lecture 6: Infection caused by yeasts :

Candidiasis:- is a fungal infection caused by yeasts that belong to the genus Candida.
Species:-
There are over 20 species of Candida yeasts that can cause infection in humans, the
most common of which is Candida albicans. Candida yeasts normally live on the skin
and mucous membranes without causing infection; however, overgrowth of these
organisms can cause symptoms to develop. Symptoms of candidiasis vary depending
on the area of the body that is infected.
There is an increasing incidence of infections caused by C. glabrata and C.
rugosa, which could be because they are frequently less susceptible to the currently
used azole antifungals. Other medically important Candida species include C.
parapsilosis, C. tropicalis, and C. dubliniensis.

Photomicrograph of the fungus Candida albicans

Candida species : general feature:

- Normal flora
- Yeast like fungi
- Reproduction by budding
- Culture morphology : white to opaque on SDA
- Only candida albican has germ tube feature

Type candidiasis:
1- Oropharyngeal / Esophageal Candidiasis ("Thrush"):-
Candidiasis that develops in the mouth or throat is called "thrush" or
oropharyngeal candidiasis. The most common symptom of oral thrush is white

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patches or plaques on the tongue and other oral mucous membranes. This infection is
uncommon among healthy adults.
Risk of oral Candidiasis:-
Candida infections of the mouth and throat are uncommon among adults who
are otherwise healthy. Oral thrush occurs most frequently among babies less than one
month old, the elderly, and groups of people with weakened immune systems. Other
factors associated with oral and esophageal candidiasis include:
 HIV/AIDS
 Cancer treatments
 Organ transplantation
 Diabetes
 Corticosteroid use
 Dentures
 Broad-spectrum antibiotic use
Lab. Diagnosis of Oral Candidiasis:-
By taking a scraping of the affected areas to examine under a microscope. A
culture may also be performed; however, because Candida organisms are normal
inhabitants of the human mouth, a positive culture by itself does not make the
diagnosis.
2- Genital / vulvovaginal candidiasis (VVC):-
Genital / vulvovaginal candidiasis (VVC) is also sometimes called a "yeast
infection," and it occurs when there is overgrowth of the normal yeast in the vagina.
Candida is always present in and on the body in small amounts. However, when an
imbalance occurs, such as when the normal acidity of the vagina changes or when
hormonal balance changes, Candida can multiply. When that happens, symptoms of
candidiasis may appear.
Symptoms of Genital / Vulvovaginal Candidiasis:-
Women with VVC usually experience genital itching, burning, and sometimes
a "cottage cheese-like" vaginal discharge. Men with genital candidiasis may
experience an itchy rash on the penis.
Risk of Genital / Vulvovaginal Candidiasis:-
Nearly 75% of all adult women have had at least one "yeast infection" in their
lifetime. On rare occasions, men can also get genital candidiasis. VVC occurs more
frequently and more severely in people with weakened immune systems. Other
conditions that may put a woman at risk for genital candidiasis include:
 Pregnancy
 Diabetes

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 Long-term use of broad-spectrum antibiotics

 Use of corticosteroid medications
Lab.Diagnosis of Genital / Vulvovaginal Candidiasis:-
Usually the diagnosis is made by taking a sample of the vaginal secretions
and looking at the sample under a microscope to see if an abnormal number
of Candida organisms are present. A fungal culture may not always be useful
because Candida species are normal inhabitants of the body.
3- Invasive Candidiasis:-
Invasive candidiasis is a fungal infection that can occur when Candida yeasts
enter the bloodstream. Candidemia (a bloodstream infection with Candida), is
extremely rare in people without risk factors.
Symptoms of Invasive Candidiasis:-
The symptoms of invasive candidiasis are not specific. Fever and chills that do
not improve after antibiotic therapy are the most common symptoms. If the infection
spreads to other organs or parts of the body such as kidneys, liver, bones, muscles,
joints, spleen, or eyes, additional symptoms may develop, which vary depending on
the site of infection. If the infection does not respond to treatment, the patient’s
organs may stop working.
Risk of Invasive Candidiasis:-
Candidemia (a bloodstream infection with Candida), is the fourth most
common bloodstream infection among hospitalized patients in the United States.
People at high risk for developing candidemia include:
 Intensive care unit (ICU) patients
 Surgical patients
 Patients with a central venous catheter
 People whose immune systems are weakened (such as people with HIV/AIDS)
 Very low-birth-weight infants
Lab.Diagnosis of Invasive Candidiasis:-
Invasive candidiasis is primarily diagnosed through blood culture.

Cryptococcus:-
Cryptococcus (Greek for "hidden sphere") is a genus of fungus. These fungi
grow in culture as yeasts. The sexual forms or teleomorphs of Cryptococcus species
are filamentous fungi in the genus Filobasidiella. The name Cryptococcus is used
when referring to the yeast states of the fungi.

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General characteristics
The cells of these species are covered in a thin layer of glycoprotein capsular
material that has a gelatin-like consistency and that, among other functions, serves to
help extract nutrients from the soil. However, the C. neoformans capsule is different,
in being richer in glucuronic acid and mannose, having O-acetyl groups, and
functioning as the major virulence factor in cryptococcal infection and disease.

Infectious species
There are about 37 recognized species of Cryptococcus, but the taxonomy of the
group is currently being re-evaluated with up-to-date methods. The majority of species
live in the soil and are not harmful to humans. Very common species
include Cryptococcus laurentii andCryptococcus albidus. Of all species, Cryptococcus

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neoformans is the major human and animal pathogen. However, Cryptococcus

laurentii and Cryptococcus albidus have been known to occasionally cause moderate-
to-severe disease, to be specific meningitis, in human patients with compromised
immunity (owing to HIV infection, cancer chemotherapy, metabolic
immunosuppression, et cetera).

C. neoformans
Cryptococcus neoformans is the most prominent medically important species.
It is best known for causing a severe form of meningitis and meningo-encephalitis in
people with HIV/AIDS. It may also infect organ transplant recipients and people
receiving certain cancer treatments. C. neoformans is found in the droppings of wild
birds, often pigeons; when dust of the droppings is stirred up it can infect humans or
pets that inhale the dust. Infected humans and animals do not transmit their infection
to others; they are not infectious. When plated on Niger or birdseed agar, C.
neoformans produces melanin, which causes the colonies to have a brown color, and it
is believed that this melanin production may be an important virulence factor.

Field stain showing Cryptococcus

species in lung tissue

Other species of Cryptococcus which cause moderate infections :-

C. gattii
C. albidus
C. uniguttulatus:

Antigenic Structure:-

The capsular polysaccharides, regardless of serotype, have a similar structure:

They are long, unbranched polymers consisting of an -1,3-linked polymannose

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backbone with -linked monomeric branches of xylose and glucuronic acid. During
infection, the capsular polysaccharide is solubilized in spinal fluid, serum, or urine and
can be detected by agglutination of latex particles coated with antibody to the
polysaccharide. With proper controls, this test is diagnostic of cryptococcosis. Patient
antibodies to the capsule can also be measured, but they are not used in diagnosis.

Pathogenesis:-

Infection follows inhalation of the yeast cells, which in nature are dry,
minimally encapsulated, and easily aerosolized. The primary pulmonary infection may
be asymptomatic or may mimic an influenza-like respiratory infection, often resolving
spontaneously. In patients who are compromised, the yeasts may multiply and
disseminate to other parts of the body but preferentially to the central nervous system,
causing cryptococcal meningoencephalitis. Other common sites of dissemination
include the skin, eye, and prostate gland. The inflammatory reaction is usually
minimal or granulomatous.

Clinical Findings:-

The major clinical manifestation is chronic meningitis with spontaneous

remissions and exacerbations. The meningitis may resemble a brain tumor, brain
abscess, degenerative central nervous system disease, or any mycobacterial or fungal
meningitis. Cerebrospinal fluid pressure and protein may be increased and the cell
count elevated, whereas the glucose is normal or low. Patients may complain of
headache, neck stiffness, and disorientation. In addition, there may be lesions in skin,
lungs, or other organs.

The course of cryptococcal meningitis may fluctuate over long periods, but all
untreated cases are ultimately fatal. About 5–8% of patients with AIDS develop
cryptococcal meningitis. The infection is not transmitted from person to person.

Diagnostic Laboratory Tests

Specimens:-

Specimens include spinal fluid, tissue, exudates, sputum, blood, and urine.
Spinal fluid is centrifuged before microscopic examination and culture.

Microscopic Examination:-

Specimens are examined in wet mounts, both directly and after mixing with India ink,
which delineates the capsule.

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Cryptococcus spp. can be distinguished under Gram staining - the India Ink method is
just a confirmatory test.

Culture:-

Colonies develop within a few days on most media at room temperature or 37

°C. Media with cycloheximide inhibit C neoformans and should be avoided. Cultures
can be identified by growth at 37 °C and detection of urease . Alternatively, on an
appropriate diphenolic substrate, the phenol oxidase (or laccase) of C neoformans
produces melanin in the cell walls and colonies develop a brown pigment.

Serology:-

Tests for capsular antigen can be performed on cerebrospinal fluid and serum.
The latex slide agglutination test for cryptococcal antigen is positive in 90% of
patients with cryptococcal meningitis. With effective treatment, the antigen titer
drops—except in AIDS patients, who often maintain high antigen titers for long
periods.

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Treatment:-

Combination therapy of amphotericin B and flucytosine has been considered the

standard treatment for cryptococcal meningitis, though the benefit from adding
flucytosine remains controversial. Amphotericin B (with or without flucytosine) is
curative in most patients. Since AIDS patients with cryptococcosis will almost always
relapse when amphotericin B is withdrawn, they require perpetual suppressive therapy
with fluconazole. Fluconazole offers excellent penetration of the central nervous
system.

Epidemiology & Control:-

Bird droppings (particularly pigeon droppings) enrich for the growth of C

neoformans and serve as a reservoir of infection. The organism grows luxuriantly in
pigeon excreta, but the birds are not infected. In addition to patients with AIDS or
hematologic malignancies, patients being maintained on corticosteroids are highly
susceptible to cryptococcosis.

Lecture 7: Opportunistic mycosis : Penicillosis

Penicillium :-
is a genus of ascomycetous fungi of major importance in the natural
environment as well as food and drug production.
Some members of the genus produce penicillin, a molecule that is used as
an antibiotic, which kills or stops the growth of certain kinds of bacteria inside the
body. Other species are used in cheesemaking. According to the Dictionary of the
Fungi (10th edition, 2008), the widespread genus contains over 300 species.
Species:-

 Penicillium marneffei, a thermally dimorphic species endemic in Southeast Asia,

which presents a threat of systemic infection to AIDS patients
 Penicillium camemberti, which is used in the production
of Camembert and Brie cheeses
 Penicillium candidum, which is used in making Brie and Camembert. It has been
reduced to synonymy with Penicillium camemberti
 Penicillium chrysogenum , which produces the antibiotic penicillin
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 Penicillium roqueforti, which is used in making Roquefort, Danish Blue cheese,

and also recently Gorgonzola
 Penicillium verrucosum produces ochratoxin A
 Penicillium viridicatum produces ochratoxin
Characteristics:-
The thallus (mycelium) typically consists of a highly branched network of
multinucleate, septate, usually colorless hyphae. Many-branched conidiophores sprout
on the mycelia, bearing individually constricted conidiospores. The conidiospores are
the main dispersal route of the fungi, and often are green in color.
Sexual reproduction involves the production of ascospores, commencing with the
fusion of an archegonium and an antheridium, with sharing of nuclei. The irregularly
distributed asci contain eight unicellular ascospores each.
Economic value:-
Several species of the genus Penicillium play a central role in the production of cheese
and of various meat products. To be specific,Penicillium molds are found in Blue
cheese. Penicillium camemberti and Penicillium roqueforti are the molds
on Camembert, Brie, Roquefort, and many other cheeses. Penicillium nalgiovense is
used to improve the taste of sausages and hams, and to prevent colonization by other
molds and bacteria.
In addition to their importance in the food industry, species
of Penicillium and Aspergillus serve in the production of a number of
biotechnologically produced enzymes and other macromolecules, such as gluconic,
citric, and tartaric acids, as well as several pectinases, lipase, amylases, cellulases, and
proteases. Some Penicillium species have shown potential for use
in bioremediation because of their ability to break down a variety of xenobiotic
compounds.
The genus includes a wide variety of species molds that are the source molds of
major antibiotics. Penicillin, a drug produced by P. chrysogenum (formerly

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P. notatum), was accidentally discovered by Alexander Fleming in 1929, and found to

inhibit the growth of Gram-positive bacteria

Culture of Penicillium sp.

Penicillium marneffei:-
Penicillium species are usually regarded as unimportant in terms of causing human
disease. Penicillium marneffei, discovered in 1956, is different. This is the only
known thermally dimorphic species of Penicillium, and it can cause a lethal systemic
infection (penicilliosis)with feverand anaemia similar to disseminated cryptococcosis.

Epidemiology:-
There is a high incidence of penicilliosis in AIDS patients in SE Asia; 10% of patients
in Hong Kong get penicillosis as an AIDS-related illness. Cases of P. marneffei human
infections (penicillosis) have also been reported in HIV-positive patients
in Australia, Europe, Japan, the UK and the U.S.. All the patients, except one, had
visited Southeast Asia previously.
Discovered in bamboo rats (Rhizomys) in Vietnam,it is associated with these rats and
the tropical Southeast Asia area. Penicillium marneffei is endemic
in Burma (Myanmar), Cambodia,Southern China, Indonesia, Laos, Malaysia, Thailad
and Vietnam.
Although both the immunocompetent and the immunocompromised can be infected, it
is extremely rare to find systemic infections in HIV-negative patients.
The incidence of P. marneffei is increasing as HIV spreads throughout Asia. An
increase in global travel and migration means it will be of increased importance as an
infection in AIDS sufferers.
Penicillium marneffei has been found in bamboo rat faeces, liver, lungs and spleen. It
has been suggested that these animals are a reservoir for the fungus. It is not clear

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whether the rats are affected by P. marneffei or are merely asymptomatic carriers of
the disease.

Clinical Presentation:-
Patients commonly present with symptoms and signs of infection of the
reticuloendothelial system, including generalized lymphadenopathy, hepatomegaly,
and splenomegaly. The respiratory system is commonly involved as well; cough,
fever, dyspnea, and chest pain may be present, reflecting the probable inhalational
route of acquisition. Approximately one-third of patients may also exhibit
gastrointestinal symptoms, such as diarrhea.

Laboratory diagnosis:-
The fact that Penicillium marneffei is thermally dimorphic is a relevant clue when
trying to identify it. However, it should be kept in mind that other human-pathogenic
fungi are thermally dimorphic as well. Cultures should be done from bone marrow,
skin, blood and sputum samples.
Plating samples out onto two Sabouraud agar plates, then incubating one at 30 °C and
the other at 37 °C, should result in two different morphologies. A mold-form will
grow at 30 °C, and a yeast-form at 37 °C.
Mycelial colonies will be visible on the 30 °C plate after two days. Growth is initially
fluffy and white and eventually turns green and granular after sporulation has
occurred. A soluble red pigment is produced, which diffuses into the agar, causing the
reverse side of the plate to appear red or pink. The periphery of the mold may appear
orange-coloured, and radial sulcate folds will develop.
Under the microscope, the mold phase will look like a typical Penicillium, with
hyaline, septate and branched hyphae; the conidiophores are located both laterally and
terminally. Each conidiophore gives rise to three to five phialides, where chains of
lemon-shaped conidia are formed.
On the 37 °C plate, the colonies grow as yeasts. These colonies can be cerebriform,
convoluted, or smooth. There is a decreased production in pigment, the colonies
appearing cream/light-tan/light-pink in colour. Microscopically, sausage-shaped cells
are mixed with hyphae-like structures. As the culture ages, segments begin to form.
The cells divide by binary fission, rather than budding. The cells are not yeast cells,
but rather arthroconidia. Culturing isn't the only method of diagnosis. A skin scraping
can be prepared, and stained with Wright's stain. Many intracellular and extracellular
yeast cells with crosswalls are suggestive of P. marneffei infection. Smears from bone
marrow aspirates may also be taken; this is regarded as the most sensitive method.
These samples can be stained with the Giemsa stain. Histological examination can also
be done on skin, bone marrow or lymph nodes.

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The patient's history also is a diagnostic help. If they have traveled to Southeast Asia
and are HIV-positive, then there is an increased risk of them having penicilliosis.
Antigen testing of urine and serum, and PCR amplification of
specific nucleotide sequences have been tried, with high sensitivity and specificity.
Rapid identification of penicilliosis is sought, as prompt treatment is critical.
Treatment should be provided as soon as penicilliosis is suspected.

Treatment:-
2 weeks of amphotericin B, then 10 weeks of oral itraconazole.

Genomics Sexual reproduction

P. marneffei had been assumed to reproduce exclusively by asexual means based on
the highly clonal population structure of this species. However, studies by Henk et
al.[6](2012) revealed that the genes required for meiosis are present in P. marneffei. In
addition, they obtained evidence for mating and genetic recombination in this species.
Henk et al.[6] concluded that P. marneffei is sexually reproducing, but recombination
in natural populations is most likely to occur across spatially and genetically limited
distances resulting in a highly clonal population structure. It appears that sex can be
maintained in this species even though very little genetic variability is produced.

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Lecture 8: Systemic mycosis :

Coccidioides immitis (causing coccidioidomycosis):-

C. immitis is a dimorphic saprophytic fungus that grows as a mycelium in the
soil and produces a spherule form in the host organism. It resides in the soil in certain
parts of the southwestern United States, most notably in California and Arizona. It is also
commonly found in northern Mexico, and parts of Central and South America. C.
immitis is dormant during long dry spells, then develops as a mold with long filaments
that break off into airborne spores when it rains. The spores, known as arthroconidia, are
swept into the air by disruption of the soil, such as during construction, farming, or an
earthquake. Windstorms may also cause epidemics far from endemic areas. In December
1977 a windstorm in an endemic area around Arvin, CA led to several hundred cases,
including deaths, in non-endemic areas hundreds of miles away.

A Coccidioides immitis spherule containing endospores.

Blastomyces dermatitidis (causing blastomycosis):-

Blastomyces dermatitidis is the causal agent of blastomycosis, an invasive and
often serious fungal infection found occasionally in humans and other animals in regions
where the fungus is endemic. The causal organism is a fungus living in soil and wet,
decaying wood, often in an area close to a waterway such as a lake, river or
stream. Indoor growth may also occur, for example, in accumulated debris in damp sheds
or shacks. The fungus is endemic to parts of eastern North America, particularly boreal
northern Ontario, southeastern Manitoba, Quebec south of the St. Lawrence River, parts
of the U.S. Appalachian mountains and interconnected eastern mountain chains, the west
bank of Lake Michigan, the state of Wisconsin, and the entire Mississippi
Valley including the valleys of some major tributaries such as the Ohio River. In
addition, it occurs rarely in Africa both north and south of the Sahara Desert, as well as
in the Arabian Peninsula and the Indian subcontinent. Though it has never been directly
observed growing in nature, it is thought to grow there as a cottony white mold, similar
to the growth seen in artificial culture at 25 °C (77 °F). In an infected human or animal,

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however, it converts in growth form and becomes a large-celled budding

yeast. Blastomycosis is generally readily treatable with systemic antifungal drugs once it
is correctly diagnosed; however, delayed diagnosis is very common except in highly
endemic areas.

Paracoccidioides brasiliensis (causing paracoccidiodomycosis):-

P. brasiliensis is a thermally dimorphic fungus distributed in Brazil and South
America. The habitat of the infectious agent is not known, but appears to be aquatic.
In biopsies, the fungus appears as a polygemulating yeast with a pilot's wheel-like
appearance.
Paracoccidioidomycosis is a systemic mycosis caused by the dimorphic
fungus Paracoccidioides brasiliensis. Strong evidence indicates this fungus infects the
host through the respiratory tract. It frequently involves mucous membranes, lymph
nodes, bone, and lungs. Unlike other systemic mycoses, it can cause disease in
immunocompetent hosts, although immunosuppression increases the aggressiveness of
the fungus. Also uniquely, it rarely causes disease in fertile-age women, probably due
to a protective effect of estradiol.

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Lecture 9: Histoplasmosis:
Histoplasmosis:-
is an infection caused by breathing in spores of a fungus often found in bird and
bat droppings. Histoplasmosis is most commonly transmitted when these spores
become airborne, often during cleanup or demolition projects.
Soil contaminated by bird or bat droppings also can transmit histoplasmosis, so
farmers and landscapers are at a higher risk of contracting the disease.
People can get histoplasmosis after breathing in the microscopic fungal spores from
the air. Although most people who breathe in the spores don’t get sick, those who do
may have a fever, cough, and fatigue. Many people who get histoplasmosis will get
better on their own without medication, but in some people, such as those who have
weakened immune systems, the infection can become severe.

Symptoms of histoplasmosis include:

 Fever
 Cough
 Fatigue (extreme tiredness)
 Chills
 Headache
 Chest pain
 Body aches
Symptoms of histoplasmosis may appear between 3 and 17 days after a person
breathes in the fungal spores. Histoplasmosis is diagnosed by:
 Biopsy of the lung, skin, liver, or bone marrow
 Blood or urine tests to detect histoplasmosis proteins or antibodies
 Cultures of the blood, urine, or sputum (this test provides the clearest diagnosis of
histoplasmosis, but results can take 6 weeks)

Histoplasma capsulatum:-
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Histoplasma capsulatum is found in soil, often associated with decaying bat

guano or bird droppings. Disruption of soil from excavation or construction can
release infectious elements that are inhaled and settle into the lung.
People can get histoplasmosis after breathing in the microscopic fungal spores from
the air. Although most people who breathe in the spores don’t get sick, those who do
may have a fever, cough, and fatigue. Many people who get histoplasmosis will get
better on their own without medication, but in some people, such as those who have
weakened immune systems, the infection can become severe.

A dimorphic fungus species of worldwide distribution that causes histoplasmosis in h

umans and other mammals; its

LABORATORY DIAGNOSIS
Serologic tests for antibodies form the basis for diagnosis in most patients with
mild infections, while cultures, stains, and tests for antigens are more useful in those
with more severe disease. Biopsy of the involved organ for histopathology and culture
may be required in some patients in whom test for antibodies in serum and CSF, test
for antigens in urine, serum and other body fluids, and cytological analysis are
negative or in severely ill patients in whom an immediate diagnosis is judged to be
necessary to begin antifungal therapy before antigen results can be obtained.

Serologic Tests
Antibodies to H. capsulatum measured by immunodiffusion or complement
fixation develop in most patients. H. precipitin bands can be demonstrated in less than
25% of patients and clear during the first 6 months following exposure . M bands
occur in over three-quarters of cases and persist for years in some patients.
Complement fixation titers of 1:8 or more are found in most patients with
histoplasmosis while titers of 1:32 or higher are more suggestive of active infection..

Culture
Cultures are most useful in patients with disseminated or chronic pulmonary
histoplasmosis. Culture is a particularly reliable diagnostic method for patients with
disseminated histoplasmosis and HIV/AIDS. The sensitivity is only l0 to 15% in
patients with other forms of histoplasmosis . In disseminated histoplasmosis, the
highest yield is from bone marrow or blood, positive in over 75% of cases
. Organisms can be found in sputum or bronchoscopy specimens in 60 to 85% of
cases of cavitary histoplasmosis . Due to their time consuming nature, fungal cultures
cannot be relied up for a rapid diagnosis of histoplasmosis especially in patients with
severe disease where timely initiation of antifungal therapy might be lifesaving.

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Antigen Detection
Sensitive methods for rapid diagnosis of histoplasmosis in patients with severe
manifestations are essential to allow prompt initiation of therapy. Fungal stain is rapid
but insensitive. Detection of antigen offers a valuable approach to the rapid diagnosis,
especially in patients with the “epidemic” form of acute pulmonary, which follows
within a week or two of a heavy exposure and is characterized by diffuse infiltrates
and for disseminated histoplasmosis .

Fungal Stains
Silver stain of tissue sections or Wright stain of peripheral blood smears permits rapid
diagnosis but with a lower sensitivity than culture or antigen detection. Fungal stains
of tissues are positive in about half of cases of disseminated histoplasmosis . Candida
glabrata, Cryptococcus neoformans, Blastomyces dermatitidis, Penicillium marneffei,
Pneumocystis carinii, Toxoplasma gondii, Leishmania and staining artifacts may be
misidentified as H. capsulatum.

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Lecture 10:Antifungal
An antifungal medication is a pharmaceutical fungicide used to treat and
prevent mycoses such as athlete's foot, ringworm, candidiasis (thrush), serious
systemic infections such as cryptococcal meningitis, and others.

Classes:-
Polyene antifungals:-
A polyene is a molecule with multiple conjugated double bonds. A polyene
antifungal is a macrocyclic polyene with a heavily hydroxylated region on the ring
opposite the conjugated system. This makes polyene antifungals amphiphilic.
The polyene antimycotics bind with sterols in the fungal cell membrane,
principally ergosterol. This changes the transition temperature of the cell membrane,
thereby placing the membrane in a less fluid, more crystalline state. (In ordinary
circumstances membrane sterols increase the packing of the phospholipid bilayer
making the plasma membrane more dense.) As a result, the cell's contents including
monovalent ions (K+, Na+, H+, and Cl−), small organic molecules leak and this is
regarded one of the primary ways cell dies. Animal cells contain cholesterol instead
of ergosterol and so they are much less susceptible. However, at therapeutic doses,
some amphotericin B may bind to animal membrane cholesterol, increasing the risk of
human toxicity. Amphotericin B is nephrotoxic when given intravenously. As a
polyene's hydrophobic chain is shortened, its sterol binding activity is increased.
Therefore, further reduction of the hydrophobic chain may result in it binding to
cholesterol, making it toxic to animals.

 Amphotericin B
 Candicidin
 Filipin – 35 carbons, binds to cholesterol (toxic)
 Hamycin
 Natamycin – 33 carbons, binds well to ergosterol
 Nystatin
 Rimocidin

Imidazole, triazole, and thiazole antifungals:-

Azole antifungal drugs (except for abafungin) inhibit the enzyme lanosterol 14
α-demethylase; the enzyme necessary to convert lanosterol to ergosterol. Depletion of
ergosterol in fungal membrane disrupts the structure and many functions of fungal
membrane leading to inhibition of fungal growth.
Imidazoles:-
 Bifonazole  Butoconazole  Clotrimazole

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 Econazole Luliconazole Sertaconazole

 Fenticonazole  Miconazole  Sulconazole
 Isoconazole  Omoconazole  Tioconazole
 Ketoconazole  Oxiconazole
 

Triazoles:-
 Albaconazole  Isavuconazole  Ravuconazole
 Efinaconazole  Itraconazole  Terconazole
 Epoxiconazole  Posaconazole  Voriconazole
 Fluconazole  Propiconazole
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Thiazoles:-

 Abafungin

Allylamines:-
Allylamines inhibit squalene epoxidase, another enzyme required for ergosterol
synthesis. Examples include Amorolfin, Butenafine, Naftifine, and Terbinafine.
Echinocandins:-
Echinocandins may be used for systemic fungal infections in immunocompromised
patients, they inhibit the synthesis of glucan in the cell wall via the enzyme Beta (1-3)
glucan synthase:
 Anidulafungin
 Caspofungin
 Micafungin

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Echinocandins are poorly absorbed when administered orally. When

administered by injection they will reach most tissues and organs with
concentrations sufficient to treat localized and systemic fungal infections.
Others:-

 Benzoic acid – has antifungal properties, but must be combined with

a keratolytic agent such as in Whitfield's ointment
 Ciclopirox – (ciclopirox olamine) – is a hydroxypyridone antifungal that
interferes with active membrane transport, cell membrane integrity, and
fungal respiratory processes. It is most useful against tinea versicolour.
 Flucytosine or 5-fluorocytosine – an antimetabolite pyrimidine analog
 Griseofulvin – binds to polymerized microtubules and inhibits
fungal mitosis
 Haloprogin – discontinued due to the emergence of more modern
antifungals with fewer side effects
 Tolnaftate – a thiocarbamate antifungal, which inhibits fungal squalene
epoxidase (similar mechanism to allylamines like terbinafine)
 Undecylenic acid – an unsaturated fatty acid derived from natural castor
oil; fungistatic, antibacterial, antiviral, and inhibits Candida
morphogenesis
 Crystal violet – a triarylmethane dye, it has antibacterial, antifungal,
and anthelmintic properties and was formerly important as
a topical antiseptic.
 Balsam of Peru has antifungal properties.

Adverse effects:-
Apart from side-effects like liver damage or affecting estrogen
levels, many antifungal medicines can cause allergic reactions in people.
For example, the azole group of drugs is known to have
caused anaphylaxis.
There are also many drug interactions. Patients must read in detail the
enclosed data sheet(s) of the medicine. For example, the azole antifungals
such as ketoconazole or itraconazole can be both substrates and inhibitors
of the P-glycoprotein, which (among other functions) excretes toxins and
drugs into the intestines. Azole antifungals also are both substrates and
inhibitors of the cytochrome P450 family CYP3A4, causing increased
concentration when administering, for example, calcium channel blockers ,

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immunosuppressants , chemotherapeutic drugs, benzodiazepines, tricyclic

antidepressants, macrolides .
Before oral antifungal therapies are used to treat nail disease, a
confirmation of the fungal infection should be made. Approximately half of
suspected cases of fungal infection in nails have a non-fungal cause. The
side effects of oral treatment are significant and people without an infection
should not take these drugs.

Mechanism of action:-
Antifungals work by exploiting differences between mammalian and
fungal cells to kill the fungal organism with fewer adverse effects to the
host. Unlike bacteria, both fungi and humans are eukaryotes. Thus, fungal
and human cells are similar at the biological level. This makes it more
difficult to discover drugs that target fungi without affecting human cells.
As a consequence, many antifungal drugs cause side-effects. Some of these
side-effects can be life-threatening if the drugs are not used properly.

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