CNS Infections- Cryptococcosis Flashcards
Cryptococcal meningitis caused by ________ is usually a subacute or chronic disease which is fatal if not treated.
the fungus, Cryptococcus neoformans
C. neoformans (Cn) - Opportunistic pathogen that predominantly infect __________
immunocompromised persons
variation grubii (CnVG; serotype A)
- Cn variety (var)
* *major causative agent worldwide
variation neoformans (CnVN; serotype D)
prominent in central Europe
variation AD
a hybrid diploid
C. gattii (Cg; serotype B and C; AKA Cryptococcus bacillisporus), a primary pathogen that predominantly infects ___________
immunocompetent persons
Location/habitat of CnVN and CnVG
- Worldwide distribution (rural and urban)
- Found in soil (especially soil enriched by avian guano, where it exists as a small, minimally encapsulated yeast which is the infectious form)
- Pigeons & other birds are carriers & are important factors in dissemination of the organism in urban settings where the agent grows in droppings around the nest.
Location/habitat of Cg (C. gattii)
- Previously thought to be restricted to tropical and subtropical climates with a special ecologic niche on Eucalyptus trees.
- However, recent outbreaks of Cg infection in healthy humans (pneumonia &/or meningitis) and animals were seen in the temperate climate of Vancouver Island, British Columbia, Canada
- Cg was isolated from several species of trees other than Eucalyptus, as well as soil
- Strong possibility that this fungus might have broader geographic distribution
The infectious and pathogenic form for humans is the _________
asexual yeast form
Description of Cryptococcus spp.
- Not thermally dimorphic, like other agents of systemic mycosis.
- Possess a sexual cycle, but hyphae & spores are NOT involved in infection or disease
Virulence factors
- Capsule- Glucuronoxylomannan GXM
(antiphagocytic, prevents antigen processing) - Phenoloxidase (laccase) production
(antiphagocytic, results in increased resistance to amphotericin B, may also be responsible for agent’s neurotropism)
3rd most common cause of CNS infection in __________________
advanced HIV/AIDS patients
after HIV and Toxoplasmosis
4th most common opportunistic infection in advanced HIV/AIDS patients after _________
P. jiroveci, CMV, and M. avium complex
For any strain of C. neoformans that can produce an infection in any patient population, ________ transmission is NOT believed to occur, even among AIDS patients
person-to-person
Primary POE is the ____ with hematogenous spread to CNS
RT
C. gattii (Cg) causes cryptococcosis in immunocompetent individuals in __________. Incidence of disease is rare, but increasing, it rarely causes disease in __________, and no predisposing factors are known.
tropical/subtropical regions (e.g., California in the US)
advanced HIV/AIDS pt (explanation unknown).
CnVN AND CnVG (grubii and neoformans) have a distribution that is __________. They rarely causes disease in __________, however will cause cryptococcosis in _____________.
sporadic & worldwide
immunocompetent patient
immunocompromised or immunosuppressed individuals
Cryptococcosis in immunocompromised or immunosuppressed individuals occurs via
Impaired cell-mediated immunity:
- advanced HIV/AIDS
- lymphoreticular malignancies
- patient receiving chronic, high-dose corticosteroid
- immunosuppressive therapies for solid organ transplant pt.
- Infection and disease occurs in some (5-10%) of advanced HIV/AIDS patients, causing a persistent infection. Advanced HIV/AIDS pts. that survives initial presentation require life-long therapy.
For var. grubii and var. neoformans, primary POE is the respiratory tract with __________
hematogenous spread to CNS
For grubii and neoformans, ______ are primary sites of infection
Lungs and CNS
In immunocompetent patients asymptomatic pulmonary infection (grubii/neoformans) are __________
common
In immunocompromised patients, especially advanced HIV/AIDS patient, disease is more common and progression of disease tends to be more rapid than in immunocompetent patients. Lung infections are __________
variable, ranging from mild, sustained febrile illness with normal radiographs to fulminant course with shock and/or ARDS
Most commonly in the AIDS patient, S & S of infection with grubii/neoformans are similar to PCP (pneumocystis pneumonia)
Over 2 → 4 weeks, symptoms develop:
fever, cough, dyspnea, weight loss, headache, CXR reveals interstitial infiltrates (focal or diffuse)
Infections with grubii/neoformans can also cause Meningoencephalitis, which is a progressive infection mostly involving _________
basal ganglia & cortical gray matter
Meningoencephalitis from c. grubii/neoformans causes _______
Elevated Intracranial pressure (ICP) >250 mm H2O is common and a significant cause of mortality in these patients
Meningoencephalitis is usually subacute with insidious onset, within 2-4 weeks, symptoms develop
-headache, fever, lethargy, nausea, vomiting, minimal nuchal rigidity
-symptoms progresses on to focal signs: personality change (altered mental status-behavior), impairment of higher mental functions (memory, cognition, language)
-ends with coma and death
In advanced HIV/AIDS and severe T-cell compromised patients, besides the 2 primary sites which are the Lungs and CNS the organism is much more likely to disseminate to _________
any organ, especially skin (every kind of lesion is possible)
eye, bone, urinary tract
Cryptococcus skin manifestations in HIV/AIDS pts [cutaneous cryptococcosis] may mimic many cutaneous disorders, including molluscum contagiousum, acne vulgaris, squamous cell cancer, or even cellulites and can be the __________
sentinel finding of disseminated disease
Another condition seen in advanced HIV/AIDS and severe T-cell compromised patients is Cryptococcal polysaccharidemia/antigenemia, which is characterized by
- positive serum Ag assay W/O detection of fungi from any body site (i.e., negative results by visualization or growth or histochemical staining).
- Occurring with increasing frequency in advanced HIV/AIDS infected patient due to increased antigen testing.
- There is no data on how many persons with antigenemia will develop disease
- Since this is a fatal disease and treatment is available, all patients with positive serum antigen MUST be treated
C. grubii/neoformans are facultative intracellular pathogens of __________
macrophages
- Agent can replicate in the phagosome of macrophages → macrophage lysis and release of the agent.
- An extrusion/expulsion mechanism allows the agent to be released from macropahges without lysing the macrophage and avoiding a host inflammatory responses.
Differential meningoencephalitis for an AIDS patient
- HAD
- Primary or metastatic brain tumor; EBV associated primary CNS lymphoma.
- Toxoplasmosis encephalitis
- PML
- Cryptococcal meningoencephalitis
- CMV polyradiculopathy, encephalitis, myelopathy, etc.
Serologic tests (latex agglutination test, ELISA) are used to detect presence of _________
capsular antigen: serum CrAg
Its presence is highly predictive of development of CM within 1yr
Can be detected via culture on ___________
routine mycological or bacteriological media (blood agar)
Microscopic examination of sedimented CSF with India ink preparation reveals ________
- 5→7 μm spherical, capsulated yeasts forms
- cells of macrophage/monocyte lineage
Microscopic examination of sedimented CSF by by Gram-stain reveals ________
-Gram-positive eucaryotic cells
All yeast, including cryptococcus, stain Gram-positive by Gram stain
Other stains that can be used to examine CSG (3)
- Mucicarmine stain
- Papanicolaou prep
- Hematoylin and eosin (H & E)
Use CXR or CT for _________
Use CT or MRI for ________
pulmonary involvement
meningitis
Treatment
- High dose amphotericin B (0.7mg/kg IV) with 5-fluorocytosine (100mg/kg/day) for 2 weeks
- Fluconazole (400mg PO) or itraconazole for 8 weeks
- Maintain with fluconazole (200mg PO daily) life-long unless relapse occurs
Drug resistance is rare
MUST remember to treat
elevated ICP
Prognosis is poor in the absence of ________
HAART: 10-25% die during initial presentation and 30-60% succumb within 1 year
HAART (highly active antiretroviral therapy) is the use of multiple drugs that act on different viral targets
