Download Brain Abscess

Lecture 18 – Infectious Agents of CNS Disease
Types of CNS Infection
 Meningitis
o Inflammation of the meninges surround the brain
 Encephalitis
o Inflammation of the brain parenchyma
 Meningoencephalitis
o Inflammation of brain and meninges
 Myelitis
o Inflammation of the spinal cord
 Abscess
o Necrotic lesion encapsulated by collagen fibers
Common Causes of Bacterial Meningitis in CHILDREN
Listeria monocytogenes
E. coli
Ages: 0-6 months
Streptococcus agalactiae (main one)
Neisseria meningitides
Haemophilus influenza type b
Ages: 6 months – 6 years
Streptococcus pneumoniae (main one)
ADULTS
Always think Enterovirus 1st  then bacteria
 Ages: 6-50 years
Neisseria meningitides
 military recruits; dorm residents
Streptococcus pneumonia (main one)
Listeria monocytogene
Haemophilus influenza
Ages: >50 years
CNS infection indicators:
1. WBC numbers (normal = 0-5/microL)  will be high >5; w/ PMN predominance
(bacterial meningitis)
2. Protein (15-45 mg/dL)  will be high (>45)
3. Glucose (40-70 mg/dL)  will be low (50 of time), but no change for viruses
4. CSF opening pressure  >250 mmH2O = increased intracranial pressure = meningitis,
intracerebral hemorrhage, or tumors
Bacterial meningitis in children: altered cry (or absence); lethargy; vomiting (after fever); neck stiffness;
seizures (w/in 1st few days); HA/irritability
Bacterial Meningitis
Streptococcus pneumonia (6mos-6yrs)*****
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Presentation & Labs: 6-month old female; ER; overnight hx of lethargy. In ER 3 days
ago w/ fever & URI sx so diagnosed w/ otitis media & given ABs  now irritable; less
active; vomiting; urine output decreased & no diarrhea
- Temp: 104; questionable neck stiffness (grimacing on movement)
- high WBC (high in PMN; normal CT
Diagnostic work-up: ****
- Lumbar puncture: CSF: high WBC (mostly PMN), low glucose, high protein
 gram + cocci in pairs/chains (strep/staph)
 alpha-hemolysis on blood agar
 catalase negative (so not staph)
 optochin-sensitive (strep. pneumonia)
Micro: virulence
- Polysaccharide capsule: blocks phagocytosis & complement activation
- Pneumolysin: release caused by peroxide build-up; cytotoxic to endothelial cells;
inhibits phagocytosis & adaptive response; inhibits ciliary axn; stimulates chemotaxis of
PMN (promotes inflamm.)
Upper respiratory tract colonization (URT)
Streptococcus agalactiae (GBS) – 0-6mos***
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Presentation & labs: 1-month old female; in ER w/ 24hr hx of fever, poor feeding &
irritability; seizure prompted ER visit
- Temp: 100.8; high pulse; slightly low BP; nuchal rigidity
- Blood: high WBC (mostly PMNs); normal CT
Diagnostic Work-up:
- Lumbar puncture: CSF: high WBC; low glucose; high protein
 gram + cocci in chains (strep/staph)
 beta-hemolysis on blood agar
 catalase negative (so not staph)
 Bacitracin-resistant (so it’s a group B strep)
 Positive CAMP test (this is only used to confirm group B strep-GBS)
o Synergistic rxn  enhanced & very visible zone (clear zone) of
hemoplysis in region b/t 2 cultures (never in groups A,C, or G
strep)
- Blood bacteremia (blood culture same as CSF)
- Direct detection of capsular Ags
- PCR  rule out viruses
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Micro: Leading cause of death among US infants
- Early onset neonatal disease (usu. from mom during birth): 1st wk of life;
pneumonia & bacteremia
- Late-onset disease (usu. from hospitals): 1wk-3mos; meningitis (+/- bacteremia);
hearing loss, brain injury may occur (goes straight into brain)
- Virulence:
 Cell surface pore-forming toxins:
o Beta-hemolysin/cytoplasm  invasion of epithelia/endothelia &
BBB; promotes neuro damage
o CAMP factor  cytolysin; binds Fc of IgG
 Polysaccharide capsule (capsules provide protection from phagocytes)
Neisseria meningitides (meningococcus)
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Presentation & labs: 19-yr old college student, December  to ER w/ 12hr hx of high
fever, chills, & severe HA; vomiting upon arrival
- Temp: 103.8; high pulse; low BP; can’t answer questions or follow commands; nuchal
stiffness; “purple” rash on extremities******(rash means the infection has
disseminated; pt probably now septic)
- Blood: low WBC (mostly PMN); normal CT
Dx Work-up:
- Lumbar puncture: CSF: high WBC (mostly PMNs); low glucose; high protein
 gram – cocci in prs (THERE IS ONLY 1 GRAM – COCCI!!!)(neisseria)
 growth on chocolate or sheep blood agar
 oxidase-positive (blue color)
 no lactose fermentation (red); + for glucose & maltose
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- Blood (bacteremia)  culture (same as CSF)
- Direct detection of capsular Ags
Micro: Leading cause of bacterial meningitis in children & young adults in US
(cold, dry months) ****
- Virulence:
 Lipooligosaccharides (LOS): 10x more tosic than LPS; Ag variation; inhibits
complement deposition (when sialyated)
 Polysaccharide capsule
 Intracellular survival in PMN (allows infection of inflamed tissue as PMN
migrate to those sites
 Fimbriae & porins
URT colonization: rapid replication  dissemination (bacteremia, shock, purpura,
petechia) & enters brain; slow replication  into brain, heart, & joints
Septic shock (TNF alpha; IL-1)
 Induces endothelial expression of tissue factor (TF)
o TF  thrombin  fibrin clots in microvasculature
 Induces expression of plasminogen activator inhibitor-1 (PAI-1)
o PAI-1  prevents fibrinolysis
 Inhibits activation of protein C (or activated protein C, APC)
o APC  blocks PAI-1 production, prevents thrombin production (cleaves factors V, VIII)
Listeria monocytogenes
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Presentation & labs: 61-yr old  to ER w/ 5 day hx of fever, HA, confusion; had a 2
day bout of diarrhea that resolved a few days before current sx; hx of dail prednisone
for rheumatoid arthritis
- fever & high pulse; unable to answer questions; NO nuchal rigidity
- Blood: high WBC (lots of PMN); normal head CT
Dx work-up:
- Lumbar puncture: CSF: high WBC w/ mostly PMNs; normal glucose; high protein
 gram + bacilli
 sheep agar growth (weakly beta-hemolytic)
 growth @ 4 degrees C (or high salt media) – done b/c of diarrhea hx
 Wet mount  “tumbling motility”  positive motility test*****
Micro: Foodborne illness in adults & meningitis in newborns
- high risk: pregnant women; neonates; immune-compromised pts; elderly
- Virulence:
 Listeriolysin O & Phospholipase B  induces uptake by epithelia &/or
phagocytes; enzymes activated in endosome/phagosome; escape into cytosol & replicate
 ActA & Actin tails  propel bact into host cell memb & into adjacent cells
(flagella created as the bact moves; get into adjacent cells to avoid immune response)
Ingestion of contaminated meat/diary: successful Tx requires T1/T17 response
Haemophilus influenzae type B (Hib)
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Presentation & labs: 20-month old male  ER after seizure; 3 day hx cough &
congestion & low-grade fever; fussy & inconsolable; has not received all immunizations
- fever & high pulse; nuchal rigidity
- Blood: high WBC (lots of PMN); normal head CT
Dx work-up:
- Lumbar puncture: CSF: high WBC w/ mostly PMNs; low glucose; high protein
 gram – coccobacilli?
 chocolate agar growth (@ 5% CO2)
 growth on heart infusion/trypticase soy agar (+Hemin, +NAD)
 Oxidase positive (purple in organisms w/ cytochrome C in respiratory chain)
 Serotype capsule (a-f)
Micro: Unencapsulated strains colonize 75% of healthy children & adults
- Virulence: Polyribital phosphate (PRP) capsule (adherence, blocks phagocytosis & complement
activation, inhibits ciliary axn); Fimbriae; IgA protease
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URT colonization
Subacute/Chronic Meningitis
Cryptococcus neoformans
Mycobacterium tuberculosis
Treponema pallidum
Histoplasma capsulatum
Coccidioides immitis/posadasii
Cryptococcus neoformans
 Presentation & labs: 42 y.o. white male  ER b/c 2 wk hx fever, severe HA, NV, and changes in
mental status; previous dx of HIV 2 yrs ago & currently not taking antiretroviral therapy
- fever, high pulse, nuchal rigidity, positive Hernig sign (flexing of neck when knee is flexed)
- Blood: low WBC (mostly PMNs); normal head CT
 Dx work-up:
- Lumbar puncture: CSF: high WBC (mostly lymphocytes); normal glucose; high protein
 gram stain not revealing
 India ink
 latex agglutination test (polysaccharide capsule)
- CSF/Blood culture:
 growth on Sabouraud-dextrose agar (mucoid, creamy white colonies)
 Niger Bird Seed agar (dark brown, smooth colonies)
 Urease-positive
 Micro: most common pathogen causing fungal meningitis
- opportunistic infection
- virulence: polysaccharide capsule; melanin production (stable populations of free radicals)
 Pathogenesis: replication in bird feces & eucalyptus trees  fungemia
Mycobacterium tuberculosis, Treponema pallidum, Histoplasma capsulatum, Coccidioides
immitis/posadasii
 Presentation:
- unrelenting HA
- stiff neck
- low-grade fever
- lethargy for wks
- cranial nerve abnormalities & night sweats
Mycobacterium tuberculosis
 Micro: 1/3 of world population infected
- virulence: Lipoarabinomannan (LAM) (blocks lysosome-phagosome fusion; inhibits Agpresentation)
 Transmission: Inhalation of contaminated respiratory droplets (viable for hours on objects) 
Tuberculosis meningitis in 5% of cases (mostly pulmonary disease)
 Pathogenesis:
- Inflammation at base of brain  compromised CSF flow  increased intracranial pressure
(coma possible)
- Granulomas & inflammation around cranial nerves can cause malfunction
 Dx work-up: Tuberculosis meningitis
- Night sweats
- Lumbar puncture: CSF: acid fast bacillus (red, mycolic acid wall); lymphocyte pleocytosis
(increased cell count)
 Culture: growth on Lowenstein-Jensen egg media
Treponema pallidum
 Micro  3-stage disease
1. Primary syphilis: painless papule (chancre); 4-6 wk duration
2. Secondary Syphilis: rash (macular, popular, pustule); also on palms of hands and feet; 2 wk
duration
3. Latent Syphilis: lesion (gumma) development in multiple organs; 1-20 yrs after secondary
syphilis
- asymptomatic neurosyphilis (CSF abnormal): increased protein; pleocytosis
- symptomatic neurosyphilis: meningitis <1 yr after infection; meningitis + cerebral
vasculitis; widespread brain parenchymal damage (delusions, hallucinations, memory &
speech & balance loss, altered personality)
 Dx work-up: Neurosyphilis  CSF exam
- Venereal disease research lab test
- FTA-ABS (fluorescent treponemal Ab absorption)
- Serodia TP-PA test (indirect agglutination for Ig against microbe)
Histoplasma capsulatum
 Micro: most prevalent endemic mycosis in N. America
(Ohio & Mississippi river valleys)
- soil enriched w/ bird/bat droppings  fungal growth 
cases from spelunking, excavation, cleaning chicken
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coops, demolition/remodeling buildings, or cutting down dead trees
- Virulence: prevent acidification of phagolysosome in macrophages; iron-acquisition enzymes
Pathogenesis: inhalation of microconidia
Dx work-up: Histoplasmosis
- Lumbar puncture: CSF: hitoplasma polysaccharide antigen detection w/ enz. Immunoassay
(EIA)
- Blood exam: positive for Ag/Ab; complement fixation for Ab to H or M Ags; EIA
- Bone marrow: Aspirate  gets here via migratory infected macrophages; infects cells of
reticuloendothelial system (culture on SDA)
Coccidioides immitis/posadasii
 Micro:
- immitis: endemic in Southwest US
- posadasii: remaining central and western US
- soil enriched w/ bat/rodent droppings  Fungal growth
- Virulence: induction of arginase I in phagocytes (block NO production); urease promotes
ammonia production @ infection site (tissue damage)
 Dx work-up: Coccidioidomycosis
- Lumbar puncture: CSF exam
 complement fixation/EIA for Abs to coccidioides Ags
 culture only successful 50% of time
- Blood exam: complement fixation for Abs to cocc. Ags
Brain Abscess
Presentation (usu. 11-12 days after sx onset)
 HA (constant, dull, aching; hemicranial or generalized)
 Fever (50% pts at dx)
 Seizure (reason for visit)
 Focal neuro deficits (dependent on lesion location)
- Frontal lobe  hemiparesis
- Temporal  dysphasia
- Cerebellum  ataxia
- Occipital  visual field defects
Predisposing conditions: Otitis media; sinusitis; feverish infections of chest, penetrating head
wound, trauma, neurosurgery, dental infections
Pathogenesis:
 Must be pre-existing areas of ischemia, necrosis, or hypoxia in brain tissue
- Early stage (1-3d): inflamm. cell infiltration (surround central core of necrosis
- Late stage (4-9d): pus forms enlarging necrotic center; surrounded by macrophages &
fibroblasts
- Capsule formation (10-13d): collagenous capsule initiates
- Late capsule formation (>14d): well-formed necrotic center & surrounding capsule
 Dx work-up:
- MRI & CT; needle aspiration (stain and culture); peripheral leukocytosis, elevated Creactive protein & ESR
Immunocompetent pts:
Streptococcus spp. (40%)
Enterics [Proteus spp., Escherichia coli, Klebsiella spp.] (25%)
Anaerobes [Bacteroides spp., Fusobacterium spp.] (25%)
Staphylococcus spp. (10%)
Immunosuppressed pts
Nocardia spp.
Toxoplasma gondii
Aspergillus spp.
Candida spp.
Cryptococcus neoformans
Taenia solium (pork tapeworm)
 Neurocysticercosis is most common parasitic disease
of CNS worldwide
 Increased intracranial pressure:
- HA; NV; vision difficulites; dizziness & atazia
 Seizures, hydrocephalus, altered mental status, chronic
meningitis (cysticerci in subarachnoid)
 Dx work-up: Neurocysticercosis
- Clinical presentation
- Imaging: cysticerci lesions
- Blood: ELISA detection of Abs against cystcerci
- Therapy: resolution of disease albendazole or
praziquantel alonw
- Detection of lesions in other sites of body (along w/ the CNS ones)
Toxoplasma gondii
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Micro: see pathogenesis image
- Nonfeline stage (human, intermediate host): primary replication
sites are CNS & mm
- Feline stage: cat consumption of infected animals (rodents) and
harbor bradyzoites  carry out sexual phase in cat  produce
oocytes (these are ingested by humans)
- By adulthood: 50% Americans = seropositive for T. gondii
Clinical presentation:
- Immunocompetent:
 Cervical lymphadenopathy; HA; fever & myalgia; sore
throat; abd pn; meningoencephalitis
- Immunosuppressed:
 Principle CNS
infection of AIDS
pts; altered mental
status; seizures; Has;
mass lesions (basal
ganglia, brain stem,
pituitary); focal
lesions (motor
deficits, cranial n
palsies, movement
disorders, visual
field loss, aphasia)
Dx work-up: Toxoplasmosis
- CSF: PCR detection of
toxoplasma DNA
- Blood: ELISA/EIA to
detect Abs against
Toxoplasma Ags