Systemic Mycosis

Prof. Dr. Gamal El Sawaf

Head of Microbiology Department
Medical Research Institute
Prof. Dr. Gamal El Sawaf 2010
Prof. Dr. Gamal El Sawaf 2010
Comparison of medically important
organisms
Characteristic Viruses Bacteria Fungi
Cells No Yes Yes

(Diameter(µm 0.2 – 0.02 1-5 (yeast (3-10

Nucleic acid Either DNA or RNA Both DNA &RNA Both DNA &RNA

Type of nucleus None Prokaryotic Eukaryotic

Ribosomes Absent S 70 S 80

Mitochondria Absent Absent Present

Nature of outer ,Protein Rigid wall containing Rigid wall containing

,capsid peptidoglycan chitin
surface
lipoprotein envelope

Motility None Some None

Replication Not binary fission binary fission Budding or mitosis

Prof. Dr. Gamal El Sawaf 2010

Eukaryotic Cell
Prof. Dr. Gamal El Sawaf 2010
 Yeasts
• Yeasts are eukaryotic micro-
organisms classified in the kingdom
Fungi.

• Most reproduce asexually by

budding.

• Yeasts are unicellular, although some

species may become multicellular
(pseudohyphae, or false hyphae)

• Yeast size typically measuring 3–

4 µm Ø, although some yeasts can
reach over 40 µm.
Prof. Dr. Gamal El Sawaf 2010
 Molds

Mold on Bread Mold on an Orange

Molds are microscopic, plant-like organisms, composed of

long filaments called hyphae. Mold hyphae grow over the
surface and inside nearly all substances of plant or animal
origin.
Prof. Dr. Gamal El Sawaf 2010
 Moulds are composed of numerous,
microscopic, branching hyphae known
collectively as a mycelium.

Prof. Dr. Gamal El Sawaf 2010

 Dimorphic fungi
Dimorphic fungi are fungi which can exist
as mold/ hyphal /filamentous form.or as yeast.

At room temperature, it grows as a mold.

At body temperature, it grows as a yeast.

Prof. Dr. Gamal El Sawaf 2010

 General Characteristics of
Fungi
. Fungi include moulds, yeasts and higher fungi

• All fungi are eukaryotic and have sterols but not peptidoglycan
in their cell membrane.

• They are chemoheterotrophs (requiring organic nutrition)

and most are aerobic.

• Many fungi are also saprophytes (living off dead organic matter)
in soil and water and acquire their food by absorption.

• Characteristically they also produce sexual and asexual spores.

• There are over100,000 species recognised, with 100 infectious

agents of man Prof. Dr. Gamal El Sawaf 2010
What are systemic
?mycoses
• Systemic mycoses are fungal infections
affecting internal organs.

• In the right circumstances the fungi enter the

body via the lungs, through the gut, paranasal
sinuses or skin.

• The fungi can then spread via the bloodstream

to multiple organs including the skin, often
causing multiple organs to fail and eventually
resulting in the death of the patient
Prof. Dr. Gamal El Sawaf 2010
What causes systemic
?mycoses

1- True pathogenic fungus infections

( endemic respiratory infections)

2- Opportunistic Fungus Infections

Prof. Dr. Gamal El Sawaf 2010

 1- True pathogenic fungus infections
(endemic respiratory infections)
In true pathogenic fungus infections, the fungus is
virulent regardless of the constitutional adequacy of the
host.
Source of infection :
• Inhalation of the spores of dimorphic fungi that have their mold forms in the soil.

• Within the lungs, the spores differentiate into yeasts or other specialized forms.

• Most are asymptomatic and self-limited.

• If the disease is disseminated, the organisms grow causing destructive lesions, and
may result in death.

• Infected persons are not communicable

• Resolution of the infection is accompanied by a strong specific resistance to

reinfection

• Very restricted geographic distribution ofElfungus

Prof. Dr. Gamal Sawaf 2010
1- True pathogenic fungus infections
(endemic respiratory infections)

include:
• Histoplasma capsulatum
(causing histoplasmosis)
• Coccidioides immitis
(causing coccidioidomycosis)
• Blastomyces dermatitidis
(causing blastomycosis)
• Paracoccidioides brasiliensis
(causing paracoccidiodomycosis)
These fungi are found in soil and wood debris.

Prof. Dr. Gamal El Sawaf 2010

 Histoplasmosis
• Histoplasma capsulatum a dimorphic fungus exists as a mold in soil and as
a yeast in tissues.
• It forms 2 types :
- Macroconidia (finger like projection) imp. In diagnosis
- Microconidia (smooth wall spores) if inhaled transmit the infection

Histoplasma capsulatum
microconidia & macroconidia Histoplasma capsulatum yeast form

Prof. Dr. Gamal El Sawaf 2010

 Coccidioidomycosis
• C. immitis is a dimorphic fungus that exist as mold in soil and as a spherule in tissue

Prof. Dr. Gamal El Sawaf 2010

 Blastomyces dermatitidis
(causing blastomycosis)

Yeast phase, KOH •One-celled blastoconidia

preparation produced on short
conidiophores are typical
of Blastomyces
dermatitidis at 25°C

Prof. Dr. Gamal El Sawaf 2010

 PARACOCCIDIOIDOMYCOSIS
P. Brasiliensis is a dimorphic fungus that exist as a mold in soil and
as a yeast in tissue, the yeast is thick walled with multiple buds

Prof. Dr. Gamal El Sawaf 2010

The balance determining the probability of fungal
infection and disease

Prof. Dr. Gamal El Sawaf 2010

Major factors affecting the host’s ability to resist fungal
infection and disease .

Prof. Dr. Gamal El Sawaf 2010

OPPORTUNISTIC FUNGUS- 2
INFECTIONS
Opportunistic Fungus Infections are caused by organisms that are
inherently of low virulence, and disease production depends on
diminished host resistance to infection.
Common etiologic agents are

1- Yeasts
• Candida spp.
• Cryptococcus spp.

2- Mycelial or Filamentous Fungi

• Aspergillus spp.
• Zygomycetes
• Rhizopus

3- Protozoan-like fungi
• Pneumocystis carinii
Prof. Dr. Gamal El Sawaf 2010
General Properties
•Very low inherent virulence.

•Recovery from an infection does not establish a specific

immunity .

•Reinfection may occur if general resistance is lowered

again.

•Fungus does not convert from one form to another.

Prof. Dr. Gamal El Sawaf 2010

 Candidiasis
•Candida albicans, the most important sp. of candida is an oval yeast with a
single buds, it is a part of the normal flora in the upper respirator tract,
gastrointestinal tract, femal genital tracts.
•In tissues may appear as yeast or pseudohyphae
•Pseudohyphae are elongated yeast that resemble hyphae but are not true
hyphae

Prof. Dr. Gamal El Sawaf 2010

Candidiasis may be caused by:
• Candida albicans
• C. tropicalis
• C. krusei
• C. pseudotropicalis
• C. albicans var. stellatoida
• C. parapsilosis
• C. guilliermondii
• C. glabrata (Torulopsis glabrata)

Prof. Dr. Gamal El Sawaf 2010

Clinical manifestation of
Candidiasis
A. Mucocutaneous involvement
1. Oral Candidiasis (thrush)
• Appearance of milk curds as they crumble
• Common in older people, diet deficiencies.
• Premature babies, first sign of clinical AIDS
• 2. Vaginitis
• Predisposing factors
– pregnant women (growth promoted by secretion of glycogen and progesterone)
– obesity
– diabetes (high sugar content in urine)
– may be sexually transmitted but rarely infects the penis (balanitis).
3. Bronchial and pulmonary (not common)
• Difficult to diagnose because organism is common in most chronic lung
conditions
4. Alimentary candidiasis
• Infection resides in the esophagus, intestine and anus.

Prof. Dr. Gamal El Sawaf 2010

B. Cutaneous involvement

• often associated with skin that is

kept moist and where abrasions
occur
• interdigital - between the fingers
groin, axillary regions (underarms),
umbilicus, feet and nails
• bacteria may be involved in a
secondary invader nail infections -
onychomycosis
• diaper rash may be caused by a
species of Candida
Prof. Dr. Gamal El Sawaf 2010
C. Systemic involvement
1. Endocarditis - heart
Predisposing conditions:
drug addicts using unclean needles
preexisting valvular disease
people treated with antibiotics
intravenous infusion = gets into tubes of machine

2. Urinary Tract
Bladder and kidney included
more common in women then men
yeast can be found in urine with no obvious infection present

3. Meningitis
relatively rare.

4. Septicemia
in blood and potentially fatal patients often predisposed through antibiotic
therapy or a result of having leukemia

Prof. Dr. Gamal El Sawaf 2010

D- Allergic Diseases

• Candidids
- similar to the dermatophytid reaction caused by
dermatophytes
• Eczema
- Reddening and itching of skin, may become crusty
and scaly
• Gastritis

Prof. Dr. Gamal El Sawaf 2010

 Cryptococcosis
Cryptococcus neoformans
• Cryptococcosis is the most common life threatening fungal disease in AIDS patient
• C. neoformans Is an oval budding yeast surronded by a wide polysaccharide capsule
• Causes cryptococcal meningitis
• It is not dimorphic

Prof. Dr. Gamal El Sawaf 2010

 Mycelial or Filamentous
Fungi
• Opportunistic pathogens that do not convert from
a filamentous form to another phase of growth
(e.g., yeast phase) when pathogenesis occurs.

• Aspergillus spp.

• Zygomycetes

• Rhizopus

Prof. Dr. Gamal El Sawaf 2010

 Aspergillosis
• Aspergillus sp. exist only as molds, they are not
dimorphic, They have septate hyphae

• Aspergillus sp. cause infection of skin, eyes, ears, and

other organs.

• Etiologic Agents
• Aspergillus fumigatus
• A. niger
• A. flavus (produces aflatoxin - most potent carcinogen
known)

Prof. Dr. Gamal El Sawaf 2010

 Aspergillus
Aspergillus clinical finding
1- Pulmonary
• Symptoms similar to TB
• Fungus can be found in sputum (Hyphae or spores)
• Aspergilloma - "fungus ball“
2- Allergic - sensitization reaction
occurs in bronchi and causes blockage in the lung
fungi growing in secretions of lung causing strong asthmatic reaction to these function
3- Systemic
disseminated form from a primary lung infection ==> gets through the blood system or
lymphatic system, may cause infection in the heart (endocarditis), meninges.
4- Localized
the orbit of the eye, in the conjunctive, eyeball, or nasal sinuses Otomycosis (ear)
nail infection - onychomycosis

Prof. Dr. Gamal El Sawaf 2010

 .
Underlying Nosocomial Risk Factors for Fungal Infection

Prof. Dr. Gamal El Sawaf 2010

 Protozoan-like fungi
Pneumocystis carinii
•Pneumocystis is an infection of the lung caused by Pneumocystis
carinii.

•The organism is a common cause of fatal pneumonia in AIDS

patients. An intracellular parasite, with a life cycle of trophozoite and
cyst, it was formerly considered to be a protozoan.

•The cysts contain 8 nuclei which can be seen in smears of

pulmonary aspirates.

• P. carinii is a commensal of many wild and domestic animals and

evidence suggests that human infection is commonly derived from
dogs.

Prof. Dr. Gamal El Sawaf 2010

Protozoan-like fungi
Pneumocystis carinii

Prof. Dr. Gamal El Sawaf 2010

Who is at risk of systemic
?mycoses
• Immune compromised people are at risk of
systemic mycoses.
• Immune compromise can result from:
1. Human immunodeficiency virus(HIV) infection
2. Systemic malignancy (cancer)
3. Neutropaenia (low white blood cell count)
4. Organ transplant recipients
5. After a major surgical operation
6. Poorly controlled diabetes mellitus
7. Very old or very young.

Prof. Dr. Gamal El Sawaf 2010

Underlying Causes of Impaired Host Defense

Prof. Dr. Gamal El Sawaf 2010

What are the clinical
?features
• The clinical features of the illness depend on the
specific infection and which organs have been
affected.
• Infections in people with normal immune function may
result in very minor symptoms or none at all (this is
called subclinical infection).
- General symptoms of illness may include:
• Fever
• Cough
• Loss of appetite

Prof. Dr. Gamal El Sawaf 2010

Prof. Dr. Gamal El Sawaf 2010
Purpuric lesions

Prof. Dr. Gamal El Sawaf 2010

Pyoderma gangrenosum

Prof. Dr. Gamal El Sawaf 2010

Cellulitis

Prof. Dr. Gamal El Sawaf 2010

Erythema multiforme

Prof. Dr. Gamal El Sawaf 2010

erythema nodosum

Prof. Dr. Gamal El Sawaf 2010

.Infection Related to Intravascular Devices

Prof. Dr. Gamal El Sawaf 2010

 What tests can be done to
?diagnose systemic mycoses

• The most reliable tests to confirm infection

are skin biopsy for histological
(microscopic) analysis, and fungal culture.
Blood can also be cultured.

Prof. Dr. Gamal El Sawaf 2010

Diagnostic Methods of Fungal Detection

Prof. Dr. Gamal El Sawaf 2010

What treatment is
• available
? Once a diagnosis of systemic mycoses has been established the
immune compromise should be reversed if possible, for example
by discontinuing immune suppressing medications or at least
reducing their dose.

• Systemic antifungal medications can also be given.

• Suitable drugs include:

- Amphotericin B
- Fluconazole
- Itraconazole
- Voriconazole
Caspofungin -
The prognosis depends on the patient’s immune function and the
extent of infection when treatment is started.

Unfortunately, despite treatment many patients die of their infection.

Prof. Dr. Gamal El Sawaf 2010
Fungal cell structure. Established and emerging antifungal agents are
classified according to specific cellular target.

Prof. Dr. Gamal El Sawaf 2010

Prof. Dr. Gamal El Sawaf 2010