What is meningitis?
infection of the meninges
causes inflammation
What is more sever viral menengitis or bacterial?
Viral usually resolves without specific treatment
Bacterial can be very severe
What are meninges?
Membranes that envelope the central nervous system (brain and spinal cord)
- includes the dura mater, arachnoid, and pia mater
What is the blood brain barrier?
The blood brain barrier is a protective cellular structure that restricts passage of cehmicals toxins and micro-organisms from the blood to the CNS
Why is the BBB immune privliged?
- astrocytes provide syppport for other cells of the CNS including the BBB
- endothelial cells and associated astrocytes are stiched together by structures called “tight junctions” (prevents passage)
- White blood cells are not present in the CNS
- antibodies are not present in the CNS (no normal inflammatory response)
- Microglia cells are the “tissue macrophages” of the CNS
Name the 10 steps of bacterial meningitis?
- nasopharyngeal colonization
- invation
- multiplicatino in blood
- crossing of the BBB
- invasion of meninges and CNS
- increased permeability of the BBB (rare event)
- increased inflammation
- edema, increased cranial pressure, leukocyte migration
- proinflammatory cytokines from white blood cells
- neuronal damage
once inside the brain there is very little immune system to deal with it
How fast can bacterial meningitis kill?
Can kill in days
very dangerous
In an outbreak, first ppl to develop disease are the most likely to die
If an outbreak is occuring people are more wary of initial symptoms
mortality rate has remained high (10-25%)
What effects may bacterial meningitis leave with survivors?
- irreversible neurological damage
- permanent brain damage, blindness , hearing loss, and learning disabilities
What symptoms do bacterial meningitis cause?
95% of patients have 2 of these symptoms
- high fever
- sever headache
- vomiting or nausea
- confusion or difficulty concentrating (in very young = no eye contact)
- seizures
- sleepiness or difficulty waking up
- stiff neck
- sensitivity to light (photophobia)
- lack of interest in drinking and eating
- skin rash in cases of meningococcal meningits
What are symptoms of bacerial meningitis in infants?
Symptoms in infants
- constant crying
- excessive sleepiness or irritability
- poor feeding
- a bulge in teh soft spot on top of a baby’s head (fontanel)
- stiffness in the baby’s body and neck
- skin rash in cases of meningococcal meningitis
What are risk factors of bacterial meningitis?
- lack of vaccination
- age (15 months to 25 years)
- living in a community setting (dorms, prisons, military personnel)
- immunocompromised individuals due to disease or chemotherapy
- cranial surgery
How does one diagnose bacterial meningitis?
History and symptoms
blood test for inflammatory markers
lumbar puncture (spinal tap)
gram stain and culture
presence of white cells
low glucose (organisms use up glucose)
imaging (CT or MRI)
What isNucal rigidity, brudzinski’s sign and kernig’s sign?
Ways to diagnose bacterial meningitis
Nucal rigidity: inability to flex the head forward
Brudzinski’s sign: sever neck stiffness causes a patient’s knees to flex when the neck is felxed
Kernig’s sign: severe stiffness of the hamstrings causes an inability to straighten the leg when the hip is flexed to 90 degrees
What is treatment for bacterial meningitis?
Must be sought immediately
intravenous antibiotics (prior to culture analysis)
coricosteroids (dexamethasone) to reduce swelling in the meninges
supportive therapies (monitoring, oxygen fluids, etc)
despite this mortality is still high
How many pathogens can cause bacterial meningitis? What are the major ones?
Almost all bacterial pathogens have the potential to cause meningitis (but few account for most cases)
Major causes
Neisseria meningitidis
Streptococcus pneumoniae
Haemophilus influenze
LIsteria moncytogenes
In infants (0-2 months)
Streptococcus agalactiae (group B)
Escherichia coli K1
What is the major virulence factor in bacterial meningitis?
capsule (except listeria)
What is a capsule?
- Loose relative unstructured network of polymers that cover the surface of some bacteria
- Composed of polysaccharides
- Protects bacteria from inflammatory responses (complement activation and phagocyte killing)
- Encapsulated bacteria are less likely to be opsonized by C3b using the alternative complement cascade
How can the host effectively respond to capsules?
generation of antibodies that can recognize the capsule promote opsonization and phagocytosis
Are capsules good vaccine candidates?
yes
but. ..
- poly saccharide vaccines do not provide memory because they are T cell independent
- conjugate vaccine = polysaccharide conjugated to protein carrier (mix between sugar and protein)
How is the vaccine T cell dependent?
This vaccine will be processed by APCs and presented to T cells
T cells then provide help to B cells to initiate isotype switching and memory
Describe the pathogen Neisseria meningitidis
- Gram(-), diplococcus
- human specific pathogen
- colonizes the nose and throat (asymptomatic carriage is common)
- produces a polysaccharide capsule
- antigen variants (i.e. serotypes = antigenic variants)
- A, B, C, W135 and Y
What does Neisseria meningitidis cause?
leading cause of bacterial meningitis
also causes meningococcemia (meningococcal disease)
- contagious
- local epidemics in college dormitories
- boarding schools and military bases
Meningococcemia can kill very quickly through what mechanism?
endotoxin (LPS) can lead to Gram (-) shock
disseminated intravascular coagulation (DIC)
Widespread blood clotting
ischemia
clotting factors are used up whichleads to bleeding, skin involvement and finally purpuric rash (glass test)
Can lead to amputation (if clot occurs in hand, it could block off O2 to fingers
What are the most common serogroups of Neisseria meningitidis?
B, C and Y are most common in Americas and Europe
In Canada serogroup C is responsible for outbreaks
