Fungal Meningitis- Cryptococcus Flashcards
Cryptococcus
Ubiquitous (unencapsulated or encapsulated?) (yeasts or molds?) belonging to the division __________.
_______________ are inhaled from environment
The fungus (can or cannot?) spread from person to person
encapsulated; yeasts
Basidiomycota
Fungal spores
Cannot
Cryptococcus
Over _____ species of Cryptococcus are known, however, Cryptococcus _______ and C._____ are the two main species implicated in nearly all cases of human cryptococcosis.
70
neoformans; gattii
Cryptococcus
C. neoformans has 2 distinct varieties:
C. neoformans var. _________
C. neoformans var. ________
Other species of less clinical significance includes:
C. ________ , C._______, C. _______, etc.
neoformans
grubii
laurentii; adeliensis; albidus
Cryptococcus
Yeast: ______ or ______ shaped
• _______ in diameter
•Surrounded by ___________________
•20-30mm thick
round or oval
4-6mm
polysaccharide capsules
Cryptococcus
“_______” cells
~90-100 mm
___________
______vely stains with India Ink and nigrosin
Stains with ______ and ___________
Titan
Melanised
Negati
PAS and mucicarmine
C. neoformans
Frequently isolated from _______ contaminated with ______ or other ______ and NOT in _________________.
soil; pigeon
bird droppings
fresh wet droppings
C. neoformans
The precise link between C. neoformans and birds to date remains ________.
unclear
Birds get infected with C. Neoformans
T/F
F
They do not
C. gattii
Isolated from _______ in the _____ group of _________ trees, cedar, oak and other native trees.
decaying wood
red gum
eucalyptus
C. gattii has been isolated from bird droppings.
T/F
F
C. gattii has not been isolated from bird droppings.
C. gattii affects _________________ patients
C. neoformans affects _____ patients (98% _________ patients, Rarely ___________)
Immunocompetent
HIV; Immunocompromised; immunocompetent
C. neoformans var neoformans affects _______________ patients
Immunocompromised; rarely immunocompetent
Cryptococcosis refer to infections caused by any species of the genus __________.
Cryptococcus spp. are capable of causing diseases in ______________________________________ individuals.
Cryptococcus
both immunocompetent and immunocompromised
_________ is the most common clinical manifestation of cryptococcosis.
Cryptococcal meningitis
Disseminated cryptococcal disease is largely associated with ______/_____
HIV/AIDS.
__________ —————- disease is largely associated with HIV/AIDS.
Disseminated cryptococcal
Virulence factors of cryptococcus
Polysaccharide capsule formation
Comprised of _________________ (GXM) and _____________ (GalXM)
glucuronoxylomannan
galactoxylomannan
Virulence factors
Polysaccharide capsule formation
Key roles
Anti-_________
Antibody _____________
Inhibition of ______________
Deregulation of _______________
Interference with ___________________
L-selectin & tumor necrosis factor loss
phagocytic
unresponsiveness
leucocyte migration
cytokine secretion
antigen presentation
Virulence factors of cryptococcus
Major virulence
__________ formation
________ pigment production
Ability to grow well at ___0C
____________ ————
Polysaccharide capsule
Melanin; 37
Phenotypic switching
Virulence factors of cryptococcus
Other virulence
Secreted _________________
______ production
Enzymes associated with ________ against _____________
phospholipase B
Urease
protection
oxidative stresses
Who are at risk?
C. neoformans
_____(80-90%)
Idiopathic CD4 ______
________ malignancies and disorders
Long-term ________ and /or immunosuppressive therapy
_______ and _______ transplant recipients
___________
HIV; lymphopenia
Lymphoproliferative
corticosteroid
Solid organ & bone marrow
Sarcoidosis
Who are at risk?
C. neoformans
Treatment with _______ antibodies
____________ diseases
Hyper-Ig___ or Hyper-Ig__ syndromes
Decompensated _______disease
_____ failure and /or peritoneal _____
Adult-onset immunodeficiency
monoclonal
Rheumatological
M; E
chronic liver
Renal; dialysis
Virulence factors of cryptococcus neoformans
Melanin pigment production
Catalyzed by the enzyme ________________
Phenol oxidase
Virulence factors
Melanin pigment production
Key Roles
Anti________
Cell wall _______ and _______
Interference with ____-cell response
Reduction of susceptibility to antifungal agents
__________ of antibody mediated phagocytosis
Protection from extreme ________
oxidant
support and integrity
T
Abrogation; temperature
Virulence factors: Phenotypic switching
Occurs during ______ infection
Common in serotype ____ and ____ strains of C. neoformans
Associated with differential ______ and _______ changes in virulence
“_______” cell formation
chronic
A and D
gene expression and capsule
Titan
Cryptococcus are _______ encapsulated _____.
C.______ and C.____ are the two main species implicated in clinical
disease.
ubiquitous; yeasts
neoformans; gatti
C. neoformans var. grubii (serotype ___) is the most common cause of ______ disease in HIV/AIDs patients.
A
disseminated
C.________ var. ——— (serotype ___) is the most common cause of disseminated disease in HIV/AIDs patients.
neoformans
grubii
A
Who are at risk: C. gattii
Predominantly immuno__________ individuals
competent
Who are at risk: C. gattii
Other risk factors1
•HIV (___-___%)
•Current ______
•Age (>___ years)
•History of ________
10-20
Smoker
50; invasive cancers
Cryptococcus & HIV
Cryptococcus is the ____________ leading opportunistic infection in patients with HIV/AIDS.
Patients with CD4 <____ are the most at risk.
2nd or 3rd
100
Cryptococcus & HIV
Cryptococcus is responsible for up to ____% (13-44%) of the HIV/AIDS deaths.
6% of the global HIV/AIDS population with under _____ CD4 cells are CrAg positive, with substantial geographical variability
100
Cryptococcal disease
Cryptococcal infection is associated with a range of illness.
In some people, the fungus causes a lung infection similar to ———-, or it can cause ______________.
The incubation period is _______, but it is thought that the infection can ____________________________.
tuberculosis; no symptoms at all.
not known
remain dormant in the body for many years
Cryptococcal disease
In immunosuppressed people , particularly HIV-infected people with CD4 counts under 100, the infection can _____ and ____________________.
Cryptococcal _______, most common presentation.
reactivate
spread throughout the body
Meningitis
Clinical Presentations
Cryptococcal Meningitis
Typical :
_______ onset of fever and headache
________ and/or meningeal signs in only 25%
Subacute
Photophobia
Clinical Presentations
Cryptococcal Meningitis
Less typical
•_______
•__________
• Progressive _______
• __________ impairment
• FUO
Seizures
Confusion
dementia
Visual or hearing
Investigations of CNS Cryptococcal infection
Csf sample
______ ml volume needed
____eased yield if multiple CSF samples
3 - 5
incr
Investigations of CNS Cryptococcal infection
Csf examination
Measure opening pressure (OP):
• 50% of HIV+ patients have OP >_____ cmH20
• (Raised Or Lowered?) lymphocytes
•(Raised or Lowered?) protein
•(Low or High?) glucose
Indian Ink & fungal culture & CRAG
25
Raised
Raised
Low
Summary of Diagnostic Options
Culture
____________ colonies within 48hours
_______ cultures often (+) in immunosuppressed patients
2/3rds with _________
• Tissue
_______ or ______ stain
________ for CSF
•Cryptococcal antigen
Serum and CSF are 99% sensitive in _____ patients
Serum is (more or less?) sensitive in normal hosts
White mucoid
Blood
Meningitis
Silver or mucicarmine
India ink
AIDS
Less
Cryptococcal meningitis is a common cause of death among HIV/AIDS patients
T/F
T
In some areas of the world, cryptococcal meningitis is estimated to cause more deaths than tuberculosis (TB)
T/F
T