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section 10: Bacterial Meningitis
Terms in this set (89)
the membranes that envelop the central nervous system (brain and spinal cord)
3 layers of the meninges from the brain out
pia mater, arachnoid mater and dura mater
cerebral spinal fluid position
between the arachnoid and pia maters
cerebral spinal fluid function
cushion for the brain
an infection of the meninges
what is meningitis often due to?
viral or bacteria infection
difference between viral and bacterial meningitis
- viral meningitis= less severe and usually resolves without specific treatment
- bacterial meningitis = rapid and life-threatening
blood brain barrier BBB
a protective cellular structure that restricts passage of chemicals, toxins, and microorganisms from the blood to the central nervous system (CNS)
secondary function of BBB is to protect CNS from...
peripheral immune system
what is the BBB made of?
what are the endothelial cells in the BBB stitched together with?
what is in between the BBB endothelial cells and the brain?
which experiment shows that endothelial cells in BBB prevent things from moving back and forth?
blue dye injected in animal and saw major organ system, everything would stain blue except the brain
If dye was injected in brain, only the brain no other organs were stained
astrocytes and pericytes
provide support for other cells of the CNS including the BBB
"tissue macrophages" of the CNS
what cells and proteins are typically not present in the CNS
white blood cells and antibodies
how bacterial meningitis occurs (10 steps)
1. nasopharyngeal colonization
2. invasion into blood
3. multiplication in blood
4. crossing of the blood brain barrier (BBB)
5. invasion of the meninges
6. production of proinflammatory cytokines/chemokines
7. recruitment of leukocytes into CNS
8. edema, increased cranial pressure
10. neuronal damage
3 mechanism of transversing the BBB
- microorganism can invade endothelial cell and come out from other side
Bacteria go through tight junctions
Can live within macrophage which can bring them in
which method of transversing the BBB is most common?
how does lyme disease bacteria transverse BBB?
how does TB transverse BBB to cause menangitis?
a rare but very dangerous disease, kills in days
issue with bacterial menangitis signs
early signs may be non-specific
in an outbreak, who are most likely to die?
first people to develop bacterial menangitis
mortality for bacterial menangitis
survivors of bacterial menangitis may have irreversible damage such as... (4)
brain damage, blindness, hearing loss, learning disabilities
list clinical symptoms of bacterial menangitis for adults and children (9)
vomiting or nausea
sleepiness or difficulty waking up
photophobia - sensitivity to light
skin rash in cases of meningococcal meningitis
which 2 symptoms do most people have for bacterial menangitis
headache and stiff neck
clinical symptoms of bacterial menangitis in infants (8)
excessive sleepiness or irritability
inability to maintain eye contact
a bulge in the 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
difference between infant and adult symptoms of menangitis
can be subtle, variable and non-specific in infants
risk factors of bacterial menangitis (6)
lack of vaccination= critical
young age (infants)
living in a community setting
immunocompromised individuals due to disease or chemotherapy
diagnosis methods for bacterial menangitis (4)
- history and symptoms
- blood tests for inflammatory markers, culture
- lumbar puncture (spinal tap)
- imaging (CT or MRI)
main diagnostic method for bacterial menangitis
lumbar puncture (spinal tap)
spinal needle inserted between 3rd and 4th lumbar vertebrae, and cerbrospinal fluid is taken out
how does the spinal tap say if menangitis is present (4)
Gram stain and culture
presence of white cells (neutrophils= bacterial, t-cells=viral)
3 physical signs of bacterial menangitis
Inability to flex the head forward
Severe neck stiffness causes a patient's knees to flex when the neck is flexed
Severe stiffness of the hamstrings
causes an inability to straighten the leg
when the hip is flexed to 90 degrees
3 treatment methods of bacterial menangitis
- intravenous antibiotics (prior to culture analysis) immediately
- corticosteroids (dexamethasone) to reduce swelling in the meninges
- supportive therapies (monitoring, oxygen, fluids etc)
in what instance is giving immediate antibiotic without culture analysis not missue?
because it's needed immediately
major bacteria that cause menangitis (4)
- Neisseria meningitidis
- Streptococcus pneumoniae
- (Haemophilus influenzae)
- Listeria monocytogenes
major bacteria that cause menangitis in infants (0-2 months) (2)
Streptococcus agalactiae (Group B Streptococcus)
Escherichia coli K1
What do the bacteria that cause menangitis have in common (except for listeria)?
produce a capsule as a major virulence factor
- a loose, relatively unstructured network of polymers that cover the surface of some bacteria
- composed of polysaccharides
role of capsules in menangitis
protect bacteria from the complement system eg. C3b
(encapsulated bacteria are less likely to be opsonized by through the complement system)
how can capsules be used as vaccines?
- generate antibodies from B cells that can recognize the capsule
- antibodies that recognize the capsule promote opsonization and phagocytosis
- conjugate vaccine: polysaccharide conjugated to protein carrier
this vaccine will be T cell-dependent
Neisseria meningitidis name, shape and gram
where does N. meningitidis colonize in humans?
colonizes the nose and throat -
asymptomatic carriage is common
is N. meningitidis human only pathogen?
which capsules does N. meningitidis produce?
antigenic variants (i.e. serotypes)
A, B, C, W135 and Y
Why is N. meningitidis termed invasive meningococcal disease?
It's a leading cause of bacterial meningitis and meningococcemia
N. meningitidis infectious capability
highly contagious and may cause local epidemics in college dormitories, boarding schools and on military bases
meningitis occurs after bacteria
enter the bloodstream and cross the BBB
endotoxin (LPS) can lead to septic shock
disseminated intravascular coagulation symptoms
- widespread blood clotting
- clotting factors are used up which leads to small skin bleeds = purpuric rash
- rash does not fade under pressure ("glass test")
problem with seriotypes
if you have antibodies against A, you don't against B,C, etc.
list, on average the highest to lowest infection causing serogroups in Canada
B, Y, C, W-135
Menactra (Sanofi Pasteur)/Menveo (Novartis)
quadrivalent conjugate capsule vaccine from 4 serotypes of meningococcus (serogroup A, C, Y, W-135)
why is menactra not for serogroup B if it causes most diseases in Canada?
capsule is poorly immunogenic, too similar to our own tissues
contains 4 recombinant protein antigens that targets serogroup B- now licensed (as of 2014) for use in Canada
the african meningitis belt
up to ~500/100,000
mostly caused by serogroup A
Streptococcus pneumoniae common name
streptococcus pneumoniae, gram and shape of growth
Gram-positive cocci, grows in chains
where in the body does streptococcus pneumonia reside?
commonly resides asymptomatically in the nasopharynx
what diseases does streptococcus pneumonia create?
causes pneumonia, ear infections, sinusitis and many other diseases
the leading cause of bacterial meningitis in infants and young children
how does the pathogen infect in streptococcus pneumoniae?
produces a polysaccharide capsule
many different serotypes exist
how many deaths globally does streptococcus pneumoniae cause?
> 700,000 deaths per year globally
vaccine for streptococcus pneumoniae
- Prevnar 13 (Pfizer)
- Canada for children
- a capsule vaccine from the 13 most prevalent serotypes of pneumococcus
Haemophilus influenzae type b common name
hib shape, gram, mode of pathogenicity
Gram negative, coccobacillus, produces a polysaccharide capsule
who does hib affect most?
primarily causes meningitis in children under 5
when menanigitis occurs, hib tends to follow what diseases?
an upper respiratory infection, ear infection or sinusitis
conjugate, routine childhood immunization schedules has reduced 99% of invasive Hib disease to low levels (<1 per 100,000)
before the 1990s, what was the leading cause of menangitis?
Listeria monocytogenes gram and shape
why is listeria not your 'typical' meningitis pathogen ?
it's a food-borne pathogen
can range from gastroenteritis -> bacteremia meningitis
who does listeria cause high rates of mortality in ?
immunocompromised individuals including neonates and the fetus
listeria optimal environment
able to grow at 4°C (a psychrotroph) - important for a food-borne pathogen (soft cheeses often implicated)
where does Listeria invade?
intestinal epithelial cells and replicates within the cytosol (actin-based motility and cell-to-cell spread)
how much of meningitis cases are caused by listeria?
method of cell invasion of lysteria
Not using flagella
a) Pushing against host membrane and trying to escape
b) Will go inside phagosome
c) damage membrane (lysis) and get in cytosol
d) produce F-actin
e) Can push out of one cell into another cell and form double membrane vacoule in cytosol
f) lysis of the vaccuole and repeat
Not an aggressive pathogen, but in pregnant women, can get into fetus cells
Streptococcus agalactiae name
"Group B Streptococcus" GBS
GBS shape and gram
Gram positive cocci, grows in chains
method of pathogenicity of GBS
produces a capsule
many women carry S. agalactiae in the ...and can be passed on to child during...
women are usually tested for GBS at...
women pos for GBS are treated via...
antibiotics during labour to prevent infection of the newborn
E. coli 1K
E. coli expressing the K1 antigen (capsule) is a leading cause of infant meningitis
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