Meningitis Flashcards

1
Q

What are the meninges?

What is meningitis (viral vs. bacterial)?

A
  • Membranes that envelop CNS (brain, spinal cord)
  • 3 layers: pia mater, arachnoid mater, dura mater
    • Cerebral spinal fluid located between arachnoid and pia
  • -itis; inflammation of meninges caused by infection
    • Viral = resolves without treatment
    • Bacterial = rapid, life-threatening
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2
Q

What is the blood brain barrier?

What 4 cells are involved?

A
  • Cellular structure between blood/brain; restricts passage from blood to CNS
  • Keeps peripheral immune system OUT of CNS; not much immunity (tradeoff)
    • Immune response = inflammation in brain = bad, but also, no immunity in brain!
  1. Endothelial cells make up the structure
  2. Astrocytes, pericytes = support
  3. Microglia cells = “tissue macrophages” of CNS but mostly rid necrotic tissue (poor with bacteria)
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3
Q

Describe the pathogenesis of bacterial meningitis

A
  1. We are colonized by the pathogens asymptomatically in the nasopharyngeal
  2. They invade the bloodstream
  3. Multiply in blood (bacteremia)
  4. Cross the BBB
  5. Invade the meninges
  6. Our receptors detect this; inflammation occurs (cytokines, chemokines production)
  7. Recruitment of leukocytes like neutrophils enter the CNS
  8. Not good to have inflammation in the brain but no choice; recruitment leading to edema (increased cranial pressure)
  9. Inflammation damage
  10. Neuronal damage
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4
Q

Describe the 3 proposed mechanisms for how a microorganism crosses the BBB

Which do most meningitis pathogens use?

A
  1. Transcellular traversal
    • Microorganism invades endothelial cells and egress out other side
    • Most meningitis pathogens use this mechanism
  2. Paracellular traversal
    • Microorganism goes between cells
  3. Trojan-horse mechanism
    • Intracellular pathogen lives in macrophage, macrophage brings that cell across
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5
Q

Describe the lethality and risk factors for bacterial meningitis

A
  • Rare, dangerous, kills in days (10-25% lethality)
    • Survivors may have irreversible damage (brain, blindness, hearing loss, learning)

Risk factors

  1. In an outbreak, the first to develop disease are most at risk due to unawareness
  2. Lack of vaccine
  3. Infant
  4. Community settings (ex., dorms, prison, military)
  5. Immunocompromised
  6. Surgery (cranial)
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6
Q

Describe the physical sings of meningitis

A

Nucal rigidity: inability to flex the head forward

Brudzinski’s sign: severe neck stiffness causes patient’s knees to flex when the neck is flexed

Kernig’s sign: severe stiffness of the hamstrings causes inability to straighten leg when hip is flexed 90 degrees

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7
Q

Describe the symptoms of meningitis in children, adults

A
  1. High fever
  2. Severe headache
  3. Stiff neck
  4. Confusion
    • “Classic 4”
  5. Vomiting
  6. Seizure
  7. Sleepiness
  8. Light sensitivity (photophobia)
  9. Skin rash (in cases of meningococcal meningitis) that fails glass test
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8
Q

Describe the symptoms of meningitis in infants

A
  1. Fever
  2. Constant crying
  3. Sleepiness/irritability
  4. Poor feeding
  5. Inability to maintain eye contact
  6. A bulge in the soft spot of the top of a baby’s head (called fontanel - skull hasn’t fused yet -, which swells to produce the bump)
  7. Stiffness in the baby’s body and neck
  8. Skin rash (in cases of meningococcal meningitis) that fails glass test
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9
Q

How is meningitis diagnosed?

A
  • History (is there an outbreak?) and symptoms
  • Blood testing for inflammatory markers, blood culture (time consuming)
  • Lumbar puncture (spinal tap)
    • Needle inserted between 3rd and 4th lumbar vertebrae
      • Cloudy CSF = organism growing
    • Gram stain and culture (check Gram negative/positive for treatment specificity)
    • Neutrophils and low glucose = indicative of infection as organisms use sugar for food
  • Imaging (CT)
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10
Q

How is meningitis treated?

A
  • Immediate intravenous antibiotics (prior to culture analysis!)
    • This is not a misuse due to the severity
  • Anti-inflammatories (corticosteroids like dexamethasone) are given to reduce swelling of meninges
  • Supportive therapies
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11
Q

List the bacterial pathogens that commonly cause meningitis

What is shared between them?

A
  1. Neisseria meningitidis
  2. Streptococcus pneumoniae
    • Most common for adults
  3. Haemophilus influenzae
    • Not a huge problem
  4. Listeria monocytogenes
  5. Streptococcus agalactiae (Group B Strep)
    • Most common for infants; pediatric

Except Listeria, all have capsule as major virulence factor

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12
Q

How does the capsule of the meningitis pathogens function?

A
  • Capsule (polysaccharide, sugar) let them survive in blood (protects from complement system)
  • C3b attaches to surface of bacteria for C3b receptor; binding is blocked by capsule
    • Therefore less likely to be opsonized
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13
Q

Describe the meningitis vaccine

A
  • Antibodies can recognise the capsule, enabling phaocytosis
  • Therefore we can use capsules as vaccines
    • Polysaccharides are T-cell independent so we use a conjugate
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14
Q

Neisseria meningitidis

Describe pathogen: (1) Neisseria meningitidis (“meningococcus” –> rash)

A
  • Gram negative, diplococcus (2 cells joined)
  • Human specific, human reservoir (asymptomatically colonizes nose, throat)
  • Capsule serotypes; each strain has different antibodies (A, B, C, W135, Y serotypes)
  • Causes bacterial meningitis and menigococcemia (invasive)
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15
Q

Neisseria meningitidis

Describe meningococcal disease

A
  • Produces endotoxins (LPS) (it is Gram negative) leading to septic shock
  • Causes DIC (disseminated intravascular coagulation) - widespread blood clotting by immune system in response to LPS
    • Purpuric rash (small bleeds)
    • Ischemia (low blood to heart) = organ failure
    • Necrotic fingers, toes
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16
Q

Neisseria meningitidis

Describe the Neisseria meningitidis vaccine

A
  1. Menactra (Sanofi Pasteur)/Menveo (GSK): quadrivalent conjugate capsule vaccines from 4 serotypes of meningococcus (A, C, Y, W135)
    • No B because that capsule is poorly immunogenic
  2. Bexsero (GSK): vaccine that contains 4 recombinant protein antigens (NOT capsules) that can protect against B
17
Q

Neisseria meningitidis

What is the African meningitis belt?

A

Hot spot of the disease, infected with meningitis by serogroup A

Vaccine nearlt wiped out group A

18
Q

Streptococcus pneumoniae

Describe pathogen: (2) Streptococcus pneumoniae (“Pneumococcus”)

A
  • Number 4 disease in terms of mortality (700,000 deaths/yr)
  • Gram positive
  • Cocci, grows in chains, colonizes nasopharynx asymptomatically
  • Causes pneumonia, ear infections, sinusitis, many other diseases
  • Leading cause of bacterial meningitis in children > 2 years and adults
  • Produces a polysaccharide capsule with a huge number of serotypes
19
Q

Streptococcus pneumoniae

Describe the Streptococcus pneumoniae vaccine

A
  • Prevnar 13 (PCV13) covers 13, previously 7
    • Conjugate capsule from 13 most prevalent serotypes
  • 23 valent polysaccharide vaccine for high risk adults
    • T cell independent
20
Q

Streptococcus pneumoniae

Why is it a problem that not all serotypes are covered in the Streptococcus pneumoniae vaccine?

A
  1. We introduce a selective pressure
  2. If we track the serotypes, vaccine eliminates the strains it covers but the strains it does not cover rise
    • Similar to ABx problem –> we have to use them, but we are placing selection pressures
21
Q

Describe pathogen: (3) Haemophilus influenzae type b (“Hib”)

A
  • Gram negative
  • Coccobacillus
  • Follows an upper respiratory infection
  • Reduced 99% by vaccine
22
Q

Describe pathogen: (4) Listeria monocytogenes

A
  • Gram positive
  • Food borne pathogen (unusual)
  • Causes listeriosis: gastroenteritis, bacteremia, and/or meningitis (trojan horse mechanism)
  • Dangerous for immunocompromised or pregnant women and fetus (can invade placenta)
  • Psychotroph - cold tolerant, grows in fridge (unpasteurised cheeses)
  • Invades intestinal epithelial cells, replicates inside
23
Q

How does Listeria monocytogenes move in the intestine?

A
  • Actin-based motility
    • Comet tails
      • Invades, enters cell, produces toxins that destroy the membrane, free it to infect others
      • Invades immune system
24
Q

Describe pathogen: (5) Streptococcus agalactiae (“Group B Streptococcus - GBS”)

A
  • Gram positive
  • Cocci, rows in chains
  • Many women carry group B in the urogenital tract as a commensal (mutualistic) organism
    • This can be passed to the infant during child birth
      • Women who test positive are given ABx during labour to prevent this