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OPPORTUNISTIC FUNGAL
INFECTIONS
Smilja Kalenic, MD, PhD
Clinical Hospital Centre
Zagreb, Croatia
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
4. ENDEMIC (PRIMARY,
SYSTEMIC):
Histoplasma capsulatum,
Coccidioides immitis,
Blastomyces dermatitidis,
Paracoccidioides brasiliensis
MYCOSES
5. OPPORTUNISTIC
endogenous
- Candida (different
species)
- Pneumocystis carinii (?)
MYCOSES
5. 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.
• skin and 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-cells responsible 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
• Aspergilli are 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