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bacterial and fungal causes of CNS disease
CBN II
47
Medical
Graduate
01/17/2011

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Term
what are the symptoms of meningitis?
Definition
fever, h/a, n/v, stiff neck, confusion/disorientation, and loss of consciousness (last 2 more common w/bacterial)
Term
what are the consequences of a bacterial infection in the CNS?
Definition
1) influx of PMNs = inflammation = increased BBB permeability, leakage of serum into the CSF, and increased protein in the CSF. 2) edema = increased intracranial pressure. 3) altered glucose transport = decreased glucose in the CSF relative to serum.
Term
what does the CSF analysis consist of for meningitis?
Definition
evaluation of cells (#, type), glucose (CSF glucose is usually 2/3 serum levels), and protein
Term
what does a CSF analysis for a viral CNS infection show?
Definition
lymphocytes (but PMNs initially), normal glucose, and moderately increased protein (<150 mg/dL)
Term
what does a CSF analysis for a bacterial CNS infection show?
Definition
PMNs, low glucose (<25 mg/dL), and elevated protein (150-1000 mg/dL)
Term
what does a CSF analysis for a chronic (TB+mycoses) CNS infection show?
Definition
lymphocytes, low glucose, moderately increased protein (80-500 mg/dL)
Term
what are the most common agents which cause acute bacterial meningitis
Definition
streptococcus pneumoniae (pneumonia, otitis media), neisseria meningitidis (pharyngitis, rash), and haemophilus influenzae (otitis media). all 3 are non-pathogenic strains, part of the nasopharynx normal flora and may transiently colonize the nasopharynx. bacterial meningitis may follow a respiratory infection (otitis media, sinusitis, pharyngitis, pneumonia) which causes a bacteremia, which spreads to the CSF (through choroid plexus or between the cerebral capillary endothelial cells).
Term
what virulence factors do n. meningitidis and h. influenzae have?
Definition
capsule, IgA protease, pili, endotoxin (both are gram negative)
Term
what virulence factors does s. pneumoniae have?
Definition
capsule and IgA protease
Term
what characterizes capsules as virulence factors?
Definition
children do not generate an effective Ab response to polysaccharide Ag until they are 2-3 y/o (Ab to capsular Ag are protective, but no polysaccharide Ag = no opsonization). the sialic acid residues inhibit activation of complement - avoids complement mediated killing/opsonization.
Term
what characterizes the capsules found on n. meningitidis?
Definition
polysaccharide, serotypes: A,B,C,Y, W-135, vaccine: quadrivalent for A,C,Y, W-135 (**not type B).
Term
what characterizes the capsules found on h. influenzae?
Definition
polysaccharide, serotype: b, vaccine: Hib
Term
what characterizes the capsules found on s. pneumoniae?
Definition
polysaccharide, many serotypes, vaccine: pneumovax (23 valent)
Term
what characterizes the capsules found on group B strep?
Definition
polysaccharide rich in sialic acid, serotype: III in neonatal meningitis
Term
what characterizes the capsules found on e. coli?
Definition
polysaccharide rich in sialic acid, serotype: K1 in neonatal meningitis
Term
what characterizes dx of bacterial meningitis?
Definition
can be fatal if untreated, need to start antibx asap then confirm dx: blood+CSF for cx and gram stain. h. influenzae needs to be grown on blood agar/chocolate agar. **obtain cx before starting antibx. gram stain of CSF sediment is both sensitive and specific, but that of the blood is often negative b/c titers are too low. protein + glucose levels should be measured in the CSF. latex agglutination tests for CSF supernate can ID the serotype of the pathogen (even if cx results are negative).
Term
what is the chocolate agar plate/blood agar plate result for n. meningitis?
Definition
CAP+, BAP+, gram negative diplococci
Term
what is the chocolate agar plate/blood agar plate result for s. pneumoniae?
Definition
CAP+, BAP+, gram positive diplococci
Term
what is the chocolate agar plate/blood agar plate result for h. influenzae?
Definition
CAP+, BAP-, gram negative coccobacilli
Term
what characterizes neisseria meningitidis biochemically?
Definition
n. meningitidis is *oxidase positive, oxidizes *glucose and maltose in the cystine trypticase agar (CTA) test, will turn a phenol red indicator from red - yellow (acidic), and agglutination tests can determine serotype. the most common serotypes associated w/neisseria meningitidis are A,B,C,Y, W-135 - B and C of which are the most associated w/meningitis in the US (no vaccination for B [35% of deaths], Y = pneumonia, A = epidemics in asia/africa).
Term
what characterizes transmission of neisseria meningitidis?
Definition
neisseria meningitidis transiently colonizes the nasopharynx of healthy people (no animal reservoir, asymptomatic carriage) via respiratory droplets from asymptomatic carriers. this occurs more commonly in closed populations (schools, military).
Term
who is at higher risk for meningitis due to neisseria meningitidis (essentially, who should be vaccinated)?
Definition
children < 5 (however, vax recommended at 11-18), institutionalized pts, college students, pts w/late complement deficiencies (C5-C9), asplenic individuals, and pts who travel to areas where A+C serogroups are endemic.
Term
who is a lower risk for meningitis due to neisseria meningitidis?
Definition
pts who can produce Ab to the capsule (also other bacteria may have produced an effective cross-reactive Ab)
Term
what characterizes the clinical disease due to neisseria meningitidis?
Definition
*meningitis: abrupt onset of h/a, fever, stiff neck, n/v, photophobia, and altered mental status. in young children symptoms may be non-specific: fever+vomiting. *meningococcemia: lipid oligosaccharide (LOS - gram negative) triggers an inflammatory response which leads to vascular damage, shock, DIC, which may occur w/o meningitis and includes a rash on the trunk/lower extremities (may coalesce), bilateral destruction of the adrenal glands (waterhouse-friderichsen) and leads to a 25% mortality rate (even w/tx). meningitis may occur simultaneously w/meningococcemia - but this is less common. other clinical syndromes include pneumonia w/pharyngitis, arthritis, or urethritis.
Term
what characterizes the MPSV4 or menomune neisseria meningitidis vaccine?
Definition
first developed, covers serotypes A, C, Y and W135. poorly immunogenic in children <2. protection = 3-5 yrs.
Term
what characterizes the MCV4 or menactra neisseria meningitidis vaccine?
Definition
covers serotypes A, C, Y and W135. conjugated to diphtheria (more efficient/effective w/polysaccharide capsules). recommended for pts 11-55 y/o. **preferred vaccine for neisseria meningitidis**
Term
what characterizes the MenACWY-CRM (menveo) neisseria meningitidis vaccine?
Definition
basically the same as the MCV4/menactra - but less studies and therefore not recommended for younger pts.
Term
what characterizes haemophilus influenzae biochemically?
Definition
haemophilus influenzae: gram negative coccobacilli which requires X factor (hematin) and V factor (NAD) to be cultured on blood agar, but will grow on chocolate agar (also can grow in the vicinity of organism that can cause hemolysis).
Term
what types of haemophilus influenzae cause disease?
Definition
the nonencapsulated/typable strains are normal flora of the nasopharynx and are often associated w/sinusitis/otitis media. there are 6 serotypes of haemophilus influenzae, of which type b is the most virulent. the vaccine (Hib) was developed against this and now the serotypes c and f (along w/the nonencapsulated strains) are most common.
Term
what characterizes clinical disease due to haemophilus influenzae?
Definition
children (3-18 mos mostly affected): sinusitis, epiglottitis, and otitis media. adults (elderly/chronic pulmonary): pneumonia. meningitis usually follows a URI. less common now since vaccine.
Term
what characterizes the vaccines available for haemophilus influenzae?
Definition
the early Hib did not induce an Ab response in children less than 18 mos old, which wasn't very useful as this is the most susceptible population. the current Hib has the polyribosylribitol phosphate (PRP, Ag) conjugated to a protein and is either available as PRP-OMP or PRP-TT (booster is necessary though).
Term
what characterizes streptococcus pneumoniae biochemically?
Definition
this alpha hemolytic gram negative is susceptible to optochin (look for zone of inhibition around a P disc on a BAP). s. pneumoniae is soluble in bile salts (deoxycholate) and has multiple serotypes (23 valent vax).
Term
what characterizes clinical disease due to strep pneumoniae?
Definition
most common = pneumonia, sinusitis, otitis media - which if serious enough can lead to bacteremia crossing the BBB and causing meningitis. pts at risk for serious infections: elderly and compromised (esp asplenic) -> should be vaccinated.
Term
what is the most common cause of neonatal meningitis?
Definition
group B streptococci/s. agalactiae (beta hemolytic) which can colonize the genital tract and be transmitted to infants during birth (screen for GBS @ 35-37 wks). the serotypes are determined by the antigenicity of the polysaccharide capsule - w/serotype III most commonly associated w/meningitis.
Term
what characterizes clinical disease due to group B streptococci/s. agalactiae?
Definition
*early onset: <7 days via amniotic fluid/parturition = bacteremia, pneumonia, meningitis w/5% mortality and 15-30% blind/deaf/mentally retarded. risk factors: heavily colonized mother w/o specific Ab, premature rupture of the membranes, pre-term delivery, and prolonged labor/complications. *late onset: 1 wk-3 mos, usually nosocomial (lack of maternal Ab/dirty conditions) = bacteremia and meningitis. mortality is low and less severe neurological complications are possible.
Term
what is the second most common cause of neonatal meningitis?
Definition
e. coli, which occurs in infants < 1 mo, involves the K1 capsular Ag and can be present in the GI tract of the mother and infant.
Term
what is the third most common cause of neonatal meningitis?
Definition
listeria monocytogenes, a gram positive coccobacillus which is widespread in the GI tracts of animals. transmission = contaminated food (grows cold temperatures - dairy, sausage, deli meat), transplacental transmission (early onset neonatal disease), and transmission during birth (late onset neonatal disease).
Term
what characterizes disease due to listeria monocytogenes?
Definition
*early onset neonatal disease: granulomatous infantiseptica, disseminated abscesses/granulomas, high mortality rate. *late onset neonatal disease: 2-3 wks after birth, *meningitis or meningoencephalitis w/bacteremia. *adult: GI/mild flu-like symptoms may occur and bacteremia can disseminate to the CNS - pts at risk for this: immunocompromised pts (renal transplants/Ca) and infants w/late onset neonatal disease.
Term
what characterizes cryptococcus neoformans as a cause of meningitis?
Definition
cryptococcus neoformans, a yeast (not dimorphic) found worldwide in soil contaminated w/pigeon droppings is inhaled and may lead to a subclinical or mild-influenza-like pulmonary infection. disseminated disease involving the CNS occurs more commonly in AIDS pts (disease-defining) usually in the CNS, followed by the skin or bones. symptoms: h/a, fever, stiff neck, and disorientation - but slower onset than bacterial meningitis.
Term
how is cryptococcus neoformans diagnosed?
Definition
CSF cx grows in 3-4 days. india ink prep of CSF (clear zone appears around organism due to capsule) can be done, but requires > 10^5 organisms/mL. latex agglutination test: detects capsular Ag, more sensitive than india ink.
Term
what are the 3 possible sources for brain abscess formation? dx? symptoms?
Definition
hematogenous spread during bacteremia, spread from a sinus/dental/ear infection, and spread following head injury/sx. dx: CT/MRI. symptoms: seizures, progressive loss of consciousness, and focal deficits (depend on location).
Term
what characterizes acute brain abscesses? chronic?
Definition
*acute: mix of aerobes and anaerobic organisms including: staphylococci, anaerobic streptococci, and gram negative bacilli. *chronic: mycobacteria, fungal pathogens, and parasites.
Term
what are the most pathogens associated w/brain abscesses in immunocompetent pts?
Definition
strep (aerobic, anaerobic viridans - endocarditis), enterobacteriaceae (gram neg bacilli - proteus, e. coli, klebsiella), anaerobes (bacteroides, fusobacterium), and staph
Term
what are the most pathogens associated w/brain abscesses in immunocompromised pts?
Definition
nocardia, toxoplasma, aspergillus, candida, and cryptococcus neoformans
Term
where characterizes hematogenous brain abscesses?
Definition
usually multiple and found in the posterior frontal or parietal lobes
Term
what brain absecesses may occur following head trauma?
Definition
MRSA, staph epidermidis, enterobacteriaceae, and pseudomonas aeruginosa
Term
what characterizes nocardia?
Definition
this gram positive filamentous bacteria (appears like fungus/actinomyces) can cause pulmonary disease and may disseminate to the CNS (multifocal lesions) - nocardia asteroids is the most common spp associated w/this presentation. it may also cause a cutaneous lesion - n. brasiliensis.
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