Meningitis Flashcards
What are the meninges?
What is meningitis (viral vs. bacterial)?
- 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
What is the blood brain barrier?
What 4 cells are involved?
- 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!
- Endothelial cells make up the structure
- Astrocytes, pericytes = support
- Microglia cells = “tissue macrophages” of CNS but mostly rid necrotic tissue (poor with bacteria)
Describe the pathogenesis of bacterial meningitis
- We are colonized by the pathogens asymptomatically in the nasopharyngeal
- They invade the bloodstream
- Multiply in blood (bacteremia)
- Cross the BBB
- Invade the meninges
- Our receptors detect this; inflammation occurs (cytokines, chemokines production)
- Recruitment of leukocytes like neutrophils enter the CNS
- Not good to have inflammation in the brain but no choice; recruitment leading to edema (increased cranial pressure)
- Inflammation damage
- Neuronal damage
Describe the 3 proposed mechanisms for how a microorganism crosses the BBB
Which do most meningitis pathogens use?
- Transcellular traversal
- Microorganism invades endothelial cells and egress out other side
- Most meningitis pathogens use this mechanism
- Paracellular traversal
- Microorganism goes between cells
- Trojan-horse mechanism
- Intracellular pathogen lives in macrophage, macrophage brings that cell across
Describe the lethality and risk factors for bacterial meningitis
- Rare, dangerous, kills in days (10-25% lethality)
- Survivors may have irreversible damage (brain, blindness, hearing loss, learning)
Risk factors
- In an outbreak, the first to develop disease are most at risk due to unawareness
- Lack of vaccine
- Infant
- Community settings (ex., dorms, prison, military)
- Immunocompromised
- Surgery (cranial)
Describe the physical sings of meningitis
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
Describe the symptoms of meningitis in children, adults
- High fever
- Severe headache
- Stiff neck
- Confusion
- “Classic 4”
- Vomiting
- Seizure
- Sleepiness
- Light sensitivity (photophobia)
- Skin rash (in cases of meningococcal meningitis) that fails glass test
Describe the symptoms of meningitis in infants
- Fever
- Constant crying
- Sleepiness/irritability
- Poor feeding
- Inability to maintain eye contact
- 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)
- Stiffness in the baby’s body and neck
- Skin rash (in cases of meningococcal meningitis) that fails glass test
How is meningitis diagnosed?
- 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
- Needle inserted between 3rd and 4th lumbar vertebrae
- Imaging (CT)
How is meningitis treated?
- 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
List the bacterial pathogens that commonly cause meningitis
What is shared between them?
- Neisseria meningitidis
-
Streptococcus pneumoniae
- Most common for adults
-
Haemophilus influenzae
- Not a huge problem
- Listeria monocytogenes
-
Streptococcus agalactiae (Group B Strep)
- Most common for infants; pediatric
Except Listeria, all have capsule as major virulence factor
How does the capsule of the meningitis pathogens function?
- 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
Describe the meningitis vaccine
- Antibodies can recognise the capsule, enabling phaocytosis
- Therefore we can use capsules as vaccines
- Polysaccharides are T-cell independent so we use a conjugate
Neisseria meningitidis
Describe pathogen: (1) Neisseria meningitidis (“meningococcus” –> rash)
- 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)
Neisseria meningitidis
Describe meningococcal disease
- 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
Neisseria meningitidis
Describe the Neisseria meningitidis vaccine
-
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
- Bexsero (GSK): vaccine that contains 4 recombinant protein antigens (NOT capsules) that can protect against B
Neisseria meningitidis
What is the African meningitis belt?
Hot spot of the disease, infected with meningitis by serogroup A
Vaccine nearlt wiped out group A
Streptococcus pneumoniae
Describe pathogen: (2) Streptococcus pneumoniae (“Pneumococcus”)
- 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
Streptococcus pneumoniae
Describe the Streptococcus pneumoniae vaccine
- 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
Streptococcus pneumoniae
Why is it a problem that not all serotypes are covered in the Streptococcus pneumoniae vaccine?
- We introduce a selective pressure
- 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
Describe pathogen: (3) Haemophilus influenzae type b (“Hib”)
- Gram negative
- Coccobacillus
- Follows an upper respiratory infection
- Reduced 99% by vaccine
Describe pathogen: (4) Listeria monocytogenes
- 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
How does Listeria monocytogenes move in the intestine?
- Actin-based motility
- Comet tails
- Invades, enters cell, produces toxins that destroy the membrane, free it to infect others
- Invades immune system
- Comet tails
Describe pathogen: (5) Streptococcus agalactiae (“Group B Streptococcus - GBS”)
- 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
- This can be passed to the infant during child birth
