Opportunistic Fungal Infections: T-cell mediated immune deficiency – Generally are YEASTS
Name
Cryptococcus
neoformans
Diagnosis
- Grows as an encapsulated budding
yeast in vitro and in vivo
Anamorph: Budding yeast
neoformans –
Telomorph: Basidiospores – filamentous
throughout USA
 Not environmentally controlled
(pigeon shit)
 Not dimorphic
- Suspect in patients with T-cell mediated
gatti – restricted
immune deficiency, especially:
to warmer areas
o AIDS
(Eucalyptus tree o High dose steroids
British Columbia)
o Sarcoid treatment
Two diverse
o Chemotherapy patients
strains mated  Labs
new true
Culture: Bird seed agar
pathogenic strain - Grows as dark colony b/c phenoloxidase
- Candida albicans grows white
Rapid antigen detection test
- Latex agglutination test for capsule
- Especially useful for CSF (meningitis)
Pneumocystis
- Major cause of pneumonia in AIDS
jirovecii
- Thought it was a protozoan initially
Labs
- CANNOT be cultured
Broncioalveolar lavage
- Silver/Giemsa stain: see cysts
- Improved with Calcoflur
Cysts
Micosporidiosis
- Found in AIDS. Probably a parasite
Labs
- Modified gram stain of diarrhea shows
“spores” – improved with
Calcofluor white and acid fast stains
- Electron Micrograph: see coiled polar
Coiled polar tubules
tubule – helps invade cell
- Spore wall contains chitin
Candida albicans - Suspect in patients with T-cell mediated
Superficial
immune deficiency, especially:
Skin/mucosal
o Diabetes, T-cell deficiency
infection ONLY
- In areas where skin remains wet:
o Mouth corners (Dentures), fingers
Symptoms
- Pulmonary infection initially ±
dissemination
- Lung disease may be severe, but usually
inapparent
o Yeasts/basidiospores are infectious
- Dissemination usually to CNS and skin
o Can get meningitis
o Gelatinous growth in meninges will
show capsular polysaccharide
©2009 Mark Tuttle
Pathogenesis
Treatment
Virulence factors
- Amphotericin B and
- Acidic capsular
5-FC (suicide nuc)
polysaccharide
- Azoles
 Negative charge 
repulse
 Antiphagocytic
 T-Independent antigen
 Observable in India Ink
- Phenoloxidase
 Oxidizes phenolics to form
a deep pigment similar to
melanin
 Valuable in invasion of
CNS
Encapsulated Yeast in vivo and in vitro
- Rapid progression of pneumonia over
matter of days
- Human/animal strains not
cross contagious
- Interferes with oxygen
diffusion in alveoli
- Prophylactic
treatment when CD4
is >200 ul
- Trimethoprimsufamethoxazole
- Severe GI disease
- Lung disease
- Other sites
- Multiplies intracellularly
- Coiled polar tubule helps it
enter cells
-
- Release of cytokines from
TH1 cells stimulates
epidermal growth
-
- Mimics cryptosporidium (ie, diarrhea)
- Severe esophageal candidiasis in AIDS 
ulcerative erosions and barium leak
- Vaginitis: satellite lesions and cottage
cheese discharge
- ↑inflammation/erosion vs. Malassezia
Opportunistic Fungal Infections: Neutrophil immune deficiency – Generally are MOLDS
Name
Aspergillus
fumigates,
flavus,
niger
Septate hyphae,
branching at 45°
Zygomycetes
Sporangiospores
Diagnosis
- Mold producing abundant
blastoconidia on conidiophores
- On composts and rotting plant
materials
- Septate branching hyphae; angiotrophic
- Fusarium mimics growth pattern but is
rare (Contact lenses)
- More and more seen post bone marrow
transplant
- Sporegerm tubehyphae/mycelium
Labs
Culture: Grows very well at 45°C
CT scan: Air crescent in lungs (except in
people with absolutely no neutrophils)
Biopsy
Won’t see in blood sample usually!
- Anamorphs: sporangiospores
- Germinate to form hyphae/mycelium
 Wide, aseptate, irregular hyphae
- Much rarer than Aspergillus
- Can get coinfection with Aspergillus
©2009 Mark Tuttle
Symptoms
Pathogenesis
Treatment
- Infects via lungs unless injected somehow
 See air crescent
- Newer azoles
- Pulmonary phagocytes fail to kill spores in with high dose steroid treatment
(Voriconazole/
- Hyphae branch (usually at 45°), expands and penetrates blood vessel walls
Poscaonazole)
 Infarcts follow BV penetration
replacing
- Hyphae in lung present problem of size but normal neutrophils are effective
amphotericin B
at killing them with Reactive Oxygen, H2O2, Myeloperoxidase, and Cl
- Treat on suspicion
Non-neutropenic complications
because of rapid
- Aspergilloma: Grows in a ball in a pre-existing scarred cavity (TB/Sarcoid)
progression
 Corrodes edge – danger of hemoptysis (coughing blood)
 Grows saprophytically outside the reach of the immune system
 Treatment: Need surgery
 See air crescent
- Allergic bronchopulmonary aspergillosis
 Spores germinate in bronchioles and begin to grow
 Allergic mucus response leads to plugging of bronchioles. ABs ↑↑
 Significantly reduced lung capacity
Rhinocerebral zygomycosis
- Infection via nasal turbinates and
sinuses into CNS (lethal in brain)
- ONLY diabetics with ketoacidosis
Bone marrow transplant recipients
- Get zygomacosis when given
voriconazole/posaconazole
prophylactically for Aspergillus
- Usually via lung with
dissemination, but can occur via
GI and wounds
- Hyphae are angiotrophic
- Iron stimulates growth
- Resistant to azoles,
including resistance
to newer azoles:
Voriconazole/
Posconazole
- MUST USE
amphotericin B
Aseptate hyphae
Candida albicans
Invasive
Deep-seated,
systemic
Pseudohyphae
Chlamydospore
Algae!!
- See BOTH yeasts and hyphae in tissues - Serious skin and mucosal infections - NOT respiratory route of infection - Some species
also in Tinea Versicolor (Malassezia) but
do not cause disseminated disease
- Infect via GI and indwelling
resistant to
these are noninflammatory/localized
unless neutropenia develops
catheters
fluconazole  thus
Culture (Sarabound agar)
- Normal Flora of mucosal surfaces
important to identify
- On low Glucose and pCO2↑
Chronic Muscocutaneous Candidiasis
- Dissemination to eye, vitreous
species; based on
yeast converts to filamentous form
- Rare
fluid, heart
patterns of sugar
-5
- Yeast: Pseudohyphae
- Candida on dry skin and nails
Phenotype switching (10 )
assimilation
(Elongated budding yeast)
- Masses of antibodies
- Not a product of mutation
- Filamentous: Chlamydospore**
- Susceptibility is multifactorial
- Switches morphology and
 Diagnostic for Candida albicans
o T-cell anergy for Candida
metabolism
(and Candida dubliniensis)
o Zinc deficiency (Treat w/Zinc!!)
- Enhances ability to thrive in
Germ Tube test (Mix Candida w/serum)
o Endocrinopathy
different environments
- C. albicans (and C. dubliniensis) will
- Can develop resistance to drugs
form germ tubes
- Can develop antiphagocitosis
Diarrhea (profuse bleeding, malodorous, 90% H2O, steatorrhea, similar to anthraxebolaids)