JAMUR

BLOK
PUSAT TRANSFORMASI ILMU
PENGETAHUAN BERBASIS MEKANISME DASAR PENYAKIT
PERADABAN ISLAM DEPARTEMEN MIKROBIOLOGI
Fungal Infections
 Once exotic and rare
 Now increasingly
common
 Fungi are not “virulent”
 But they are good at
taking advantage
 “Opportunistic”
Fungal biology
 Eukaryotes
 Non-motile
 Aerobic
 Saprophytic or parasitic
 Cell wall contains glucan and chitin
 Cell membrane contains ergosterol
Fungal cell structure
 Yeasts (unicellular,
budding)
 Molds (mycelial,
spores)
 Dimorphs (both)
Pathogenesis
 Toxins: produced but not relevant to
human infections
 Disease from:
◦ Bulk of organisms
◦ Immune response to them or their
byproducts
Overview of fungal infections
 Superficial (skin or mucosa)
 Subcutaneous
 Systemic:
◦ “True pathogens” – infect healthy hosts,
although disease worsens with
immunocompromise
◦ “Opportunists” – disease almost exclusively
in immunocompromise
Superficial Fungal Infections
Dermatophytes:
Molds producing keratinase
Saprophytes on skin/nails; inflammation below

Diseases:
tinea corporis
tinea capitis
tinea cruris
tinea pedis
tinea unguum
Superficial fungal infections
 Malassezia furfur
Lipophilic yeast

Disease:
Tinea versicolor (itch, pigment changes)
Occasionally, fungemia with lipid infusions
Subcutaneous fungal infections
Pathogenesis: introduced through skin,
grow in subcutaneous tissues, spread via
lymphatics. May reach distant organs
especially bone, joints in path.
Most common in nonindustrialized world
(“Madura foot”)
Subcutaneous: sporotrichosis
 Organism: Sporothrix schenkii
◦ Dimorphic soil organism
◦ Worldwide distribution
 Pathogenesis: splinters or thorns
inoculate organism into subcutaneous
tissues
Sporotrichosis
Pathophysiology: Clinical:
 Yeast travel along  Gardners and persons of
lymphatics sport
 Ulcerating nodules along
hard cord
 Elicit mixed pyogenic/  Bone and joint
granulomatous destruction
reaction  Occasional
dissemination
Systemic fungal infections:
the “true pathogens”
Histoplasmosis, Coccidioidomycosis and
Blastomycosis
 Dimorphic
 Respiratory acquisition
 Restricted geographic distribution
 Infect normal hosts
 Disease reminiscent of TB
Histoplasmosis
 Organism: Histoplasma capsulatum
◦ Dimorphic soil organism
 Habitat: soils with high N content
 Ohio-Mississippi valley; Puerto Rico, Central and S.
America
 Guano of bats, birds, poultry (chicken coops and
caves)
 Pathogenesis: inhalation of spores
Histoplasmosis
Pathophysiology: Clinical: mimics TB
 Spores transform to  May disseminate
yeast in lung, elicit early (infancy,
cellular immunity as immunodef.)
per TB  May cause acute
◦ Hematogenous nodular/cavitary lung
dissemination disease
◦ skin test reactivity  May reactivate years
(histoplamin)
later
Coccioidomycosis
 Organism: Coccoides immitis
◦ Dimorphic soil organism with spherules and
endospores in host
 Habitat: the lower Sonoran life zone
(arid)
◦ Southwest US, Mexico, Central and South
America
 Pathogenesis: inhalation of spores
Cocci
Pathophysiology: Clinical:
• Spores transform to Acute self-limited flu-like
spherules in lung, elicit seroconversion (Valley
cellular immunity as fever)
per TB
• Hematogenous Dissemination (pregnancy, dark
skin, immuno-compromised)
dissemination
 Skin
• Skin test reactivity
(coccoidin)  Bone
 CNS
Blastomycosis
 Organism: Blastomyces dermatitidis
◦ Dimorphic soil organism
 Habitat: humid woodlands
◦ MidAtlantic countryside
◦ Beaver dams, peanut farms
◦ Organic debris
 Pathogenesis: inhalation of spores
Blastomycosis
Pathophysiology: Clinical:
 Spores transform  Acute or chronic
into yeast in lung, lung disease
disseminate. (nodular/cavitary)
 No good antigen test  Disseminated disease
to describe exposed ◦ skin
population ◦ bone
◦ urinary tract
Systemic fungal infections: the
“opportunists”
“True pathogens” “Opportunists”
 geographic restriction  Omnipresent
 Dimorphic  Yeasts or molds
 Infection by inhalation
 Varies routes
 Pyogenic/granulo-matous
 Host response varies
host response
 Similar to TB
 Infection ~= immunity  Widely variable
 No lasting immunity
Cryptococcosis
 Organism: Cryptococcus neoformans
◦ yeast with thick polysaccharide capsule
 Habitat:
◦ Bioterrorism of a sort, worldwide
 Pathogenesis: inhalation of yeast
Cryptococcosis
Pathophysiology: Clinical:
 transient Meningoencephalitis
colonization  acute or chronic
 fever, headache, stiff neck,
OR
loss of vision
 acute/chronic lung
 complicated by
disease hydrocephalus
OR  cryptococcal antigen for
 CNS invasion diagnosis
Candidiasis
 Organism: Candida albicans et al
 Habitat: normal human flora
 Pathogenesis:
◦ colonized areas: overgrowth
◦ noncolonized areas: invasion
Candidiasis
Pathogenesis: Clinical settings:
 Breach in  Moisture, antibiotics,
 Skin or mucosal
pregnancy
integrity  HIV infection
 Intravenous
 Normal bacteriologic
catheters
flora
 Chemotherapy or
 Neutrophil function marrow ablation
or CMI
Candidiasis
Diagnosis:
 Gram stain may help
 Infection and colonization may be difficult
to distinguish
Treatment:
 Remove the breach in defenses, if possible
Aspergillosis
 Organism: Aspergillus fumigatus and
others
◦ Mold without a yeast phase
 Habitat:
◦ everywhere, worldwide
 Pathogenesis:
◦ Inhalation of spores
Aspergillosis
Pathophysiology: Clinical:
Spores in lung may  Allergic broncho-
 elicit allergy pulmonary
 grow in preexisting
aspergillosis
cavity  Aspergilloma
 invade vasculature,  Invasive, with
disseminate pneumonia, other
(neutrophils key) end-organ disease
Mucormycosis
 Organism: species of Mucorales, genera
Rhizopus and Mucor
◦ Mold without a yeast phase
 Habitat:
◦ Everywhere, worldwide
 Pathogenesis:
◦ Inhalation of spores
Mucormycosis
Pathophysiology: Clinical:
 Alveolar MPH/PML clear  The most acute and
organisms fulminant fungal infection
BUT known
 Acid  Pneumonia progressing
 Sugar to infarction
 Neutrophil dysfunction  Sinusitis progressing to
 May enable relentless brain abscess
growth
LEARNING AND PERFORMANCE OBJECTIVES

to learn about the most frequent opportunistic fungi

and to understand main risk factors for developing
infection

to be able to predict the most probable agent of

invasive fungal infection in a particular compromised
patient state and to be able to act preventively
FUNGI
 EUCARIOTIC ORGANISMS
 TWO BASIC FORMS:
- YEASTS

- MOLDS
MYCOSES

1. SUPERFICIAL
2. CUTANEOUS
3. SUBCUTANEOUS
MYCOSES
ENDEMIC (PRIMARY,
SYSTEMIC):
Histoplasma capsulatum,
Coccidioides immitis,
Blastomyces
dermatitidis,
Paracoccidioides
brasiliensis
MYCOSES
OPPORTUNISTIC
endogenous
- Candida (different
species)
- Pneumocystis carinii
(?)
MYCOSES
OPPORTUNISTIC
exogenous
- Cryptococcus neoformans
- Aspergillus (different
species)
- Zygomycetes
- MANY OTHER FUNGI
 Candida albicans and other
Candida species

 Harmless inhabitants of
the skin and mucous
membranes of all humans
 Normal immune system
keeps candida on body
surfaces
 MAIN DEFENSE
MECHANISMS AGAINST
CANDIDA I.

 skinand mucous
membranes integrity
 presence of normal
bacterial flora
 MAIN DEFENSE
MECHANISMS AGAINST
CANDIDA II.

 phagocytosis
 killing,mostly in
polymorphonuclear cells,
less in macrophages
 T-cells (CD4)
THE MOST IMPORTANT RISK
FACTORS
1. Neutropenia
2. Diabetes mellitus
3. AIDS
4. SCID
5. Myeloperoxidase defects
6. Broad-spectrum
antibiotics
 THE MOST IMPORTANT RISK
FACTORS
7. Indwelling catethers
8. Major surgery
9. Organ transplantation
10. Neonates
11. Severity of any illness
12. Intravenous drug addicts
CLINICAL FORMS OF
CANDIDIASIS

1. Cutaneous and
mucosal
candidiasis
 CLINICAL FORMS OF
CANDIDIASIS

2. Invasive (systemic,
disseminated,
hematogenous)
candidiasis
INVASIVE CANDIDIASIS

 Usually begins with

candidemia (but in only
about 50% of cases
candidemia can be proven)
 If phagocytic system is
normal, invasive infection
stops here
INVASIVE CANDIDIASIS
 If phagocytic system is
compromised, infection
spreads to many organs
and causes focal
infection in these organs
 mortality of candidemia
is 30-40%
 DIAGNOSIS OF INVASIVE
CANDIDIASIS
 Gram stain and isolation
from blood, CSF or
peritoneal fluid
 isolation and/or pathology
positive of organ involved
 other tests are of lower
significance for the diagnosis
EPIDEMIOLOGY
Although candidiasis is
endogenous in most
cases, cross infections
are described, especially
in intensive care unit
patients.
 Pneumocystis carinii

• Present in lungs of many

mammals, including humans,
in persistent but harmless
infection
 Pneumocystis carinii
• Main defense mechanism is
T-cell mediated
• causes interstitial
pneumonitis in compromised
patients
• treatment and prevention:
cotrimoxasole or pentamidine
 Cryptococcus neoformans
 Occurs worldwide in soil and
in bird droppings
 Prominent feature: thick
polysaccharide capsule,
which causes evasion from
phagocytosis
MAIN DEFENSE MECHANISMS
AND PATHOGENESIS

 T-cellsresponsible for
defense
 Cryptococcus reaches
humans by inhalation of
aerosolized yeast cells
CHRONIC MENINGITIS IN
AIDS-PATIENTS
 The most important
clinical syndrome
 treatment: amphotericin
B+/-flucytosine
 recurrence prevention:
fluconazole
EPIDEMIOLOGY OF
CRYPTOCOCCOSIS

Infection is always
exogenous, is not
transmitted from human
to human
Aspergillus species
 Aspergilliare worldwide
occurring saprophytes,
living in soil and on
plants; they have small
conidia that form
aerosols
• Main defense mechanism is
phagocytosis
• Main risk factors are
hematological malignancy,
bone marrow transplantation
and corticosteroid therapy
The most frequent syndromes
are: - aspergilloma
- invasive aspergillosis
(high mortality rate)
Treatment: amphotericin B,
itraconazole, flucytosine
and surgery
Prevention: avoid exposure

to conidia (new buildings in the hospital!)

 ZYGOMYCETES
 Zygomycetes are ubiquitous
saprophytes
 main host defense is
phagocytosis
 main risk factors are diabetes,
hematological malignancies,
corticosteroid therapy
Major clinical syndrome is:

Rhinocerebral mucormycosis
(infection of nasal passages,
sinuses, eyes, cranial bones
and brain)
Treatment: surgery and
amphotericin B
Prognosis: very poor
OPPORTUNISTIC FUNGAL
INFECTIONS ARE:
 difficult to diagnose
 difficult to treat
 difficult to prevent
 more and more frequent
 a great challenge for a
future work in all fields