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Micro- Winter > CNS Infections- Cryptococcosis > Flashcards

CNS Infections- Cryptococcosis Flashcards

1
Q

Cryptococcal meningitis caused by ________ is usually a subacute or chronic disease which is fatal if not treated.

A

the fungus, Cryptococcus neoformans

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2
Q

C. neoformans (Cn) - Opportunistic pathogen that predominantly infect __________

A

immunocompromised persons

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3
Q

variation grubii (CnVG; serotype A)

A
  • Cn variety (var)

* *major causative agent worldwide

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4
Q

variation neoformans (CnVN; serotype D)

A

prominent in central Europe

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5
Q

variation AD

A

a hybrid diploid

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6
Q

C. gattii (Cg; serotype B and C; AKA Cryptococcus bacillisporus), a primary pathogen that predominantly infects ___________

A

immunocompetent persons

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7
Q

Location/habitat of CnVN and CnVG

A
  • 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.
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8
Q

Location/habitat of Cg (C. gattii)

A
  • 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
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9
Q

The infectious and pathogenic form for humans is the _________

A

asexual yeast form

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10
Q

Description of Cryptococcus spp.

A
  • Not thermally dimorphic, like other agents of systemic mycosis.
  • Possess a sexual cycle, but hyphae & spores are NOT involved in infection or disease
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11
Q

Virulence factors

A
  1. Capsule- Glucuronoxylomannan GXM
    (antiphagocytic, prevents antigen processing)
  2. Phenoloxidase (laccase) production
    (antiphagocytic, results in increased resistance to amphotericin B, may also be responsible for agent’s neurotropism)
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12
Q

3rd most common cause of CNS infection in __________________

A

advanced HIV/AIDS patients

after HIV and Toxoplasmosis

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13
Q

4th most common opportunistic infection in advanced HIV/AIDS patients after _________

A

P. jiroveci, CMV, and M. avium complex

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14
Q

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

A

person-to-person

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15
Q

Primary POE is the ____ with hematogenous spread to CNS

A

RT

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16
Q

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.

A

tropical/subtropical regions (e.g., California in the US)

advanced HIV/AIDS pt (explanation unknown).

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17
Q

CnVN AND CnVG (grubii and neoformans) have a distribution that is __________. They rarely causes disease in __________, however will cause cryptococcosis in _____________.

A

sporadic & worldwide

immunocompetent patient

immunocompromised or immunosuppressed individuals

18
Q

Cryptococcosis in immunocompromised or immunosuppressed individuals occurs via

A

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.
19
Q

For var. grubii and var. neoformans, primary POE is the respiratory tract with __________

A

hematogenous spread to CNS

20
Q

For grubii and neoformans, ______ are primary sites of infection

A

Lungs and CNS

21
Q

In immunocompetent patients asymptomatic pulmonary infection (grubii/neoformans) are __________

A

common

22
Q

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 __________

A

variable, ranging from mild, sustained febrile illness with normal radiographs to fulminant course with shock and/or ARDS

23
Q

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:

A

fever, cough, dyspnea, weight loss, headache, CXR reveals interstitial infiltrates (focal or diffuse)

24
Q

Infections with grubii/neoformans can also cause Meningoencephalitis, which is a progressive infection mostly involving _________

A

basal ganglia & cortical gray matter

25
Q

Meningoencephalitis from c. grubii/neoformans causes _______

A

Elevated Intracranial pressure (ICP) >250 mm H2O is common and a significant cause of mortality in these patients

26
Q

Meningoencephalitis is usually subacute with insidious onset, within 2-4 weeks, symptoms develop

A

-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

27
Q

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 _________

A

any organ, especially skin (every kind of lesion is possible)

eye, bone, urinary tract

28
Q

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 __________

A

sentinel finding of disseminated disease

29
Q

Another condition seen in advanced HIV/AIDS and severe T-cell compromised patients is Cryptococcal polysaccharidemia/antigenemia, which is characterized by

A
  1. positive serum Ag assay W/O detection of fungi from any body site (i.e., negative results by visualization or growth or histochemical staining).
  2. Occurring with increasing frequency in advanced HIV/AIDS infected patient due to increased antigen testing.
  3. There is no data on how many persons with antigenemia will develop disease
  4. Since this is a fatal disease and treatment is available, all patients with positive serum antigen MUST be treated
30
Q

C. grubii/neoformans are facultative intracellular pathogens of __________

A

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.
31
Q

Differential meningoencephalitis for an AIDS patient

A
  1. HAD
  2. Primary or metastatic brain tumor; EBV associated primary CNS lymphoma.
  3. Toxoplasmosis encephalitis
  4. PML
  5. Cryptococcal meningoencephalitis
  6. CMV polyradiculopathy, encephalitis, myelopathy, etc.
32
Q

Serologic tests (latex agglutination test, ELISA) are used to detect presence of _________

A

capsular antigen: serum CrAg

Its presence is highly predictive of development of CM within 1yr

33
Q

Can be detected via culture on ___________

A

routine mycological or bacteriological media (blood agar)

34
Q

Microscopic examination of sedimented CSF with India ink preparation reveals ________

A
  • 5→7 μm spherical, capsulated yeasts forms

- cells of macrophage/monocyte lineage

35
Q

Microscopic examination of sedimented CSF by by Gram-stain reveals ________

A

-Gram-positive eucaryotic cells

All yeast, including cryptococcus, stain Gram-positive by Gram stain

36
Q

Other stains that can be used to examine CSG (3)

A
  1. Mucicarmine stain
  2. Papanicolaou prep
  3. Hematoylin and eosin (H & E)
37
Q

Use CXR or CT for _________

Use CT or MRI for ________

A

pulmonary involvement

meningitis

38
Q

Treatment

A
  1. High dose amphotericin B (0.7mg/kg IV) with 5-fluorocytosine (100mg/kg/day) for 2 weeks
  2. Fluconazole (400mg PO) or itraconazole for 8 weeks
  3. Maintain with fluconazole (200mg PO daily) life-long unless relapse occurs

Drug resistance is rare

39
Q

MUST remember to treat

A

elevated ICP

40
Q

Prognosis is poor in the absence of ________

A

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

Micro- Winter (26 decks)

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