bacterial meningitis Flashcards
what are meninges?
the membranes that envelop the central nervous system (brain and spinal cord)
includes the pia mater, arachnoid mater and dura mater
cerebral spinal fluid is between the arachnoid and pia maters
what is meningitis?
an infection of the meninges usually due to viral or bacterial infection
differentiate between viral and bacterial meningitis
viral meningitis is generally less severe and usually resolves without specific treatment
bacterial meningitis can
be rapid and life-threatening
what is the 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)
also protects your CNS from
the peripheral immune system
describe the structure of the blood brain barrier (BBB)
endothelial cells are stitched together by structures called “tight junctions”
—- astrocytes and pericytes provide support for other cells in the CNS (including BBB)
microglial cells serve as the “tissue macrophages” of the CNS
— bc WBCs and antibodies are not normally present in the CNS
describe how bacterial meningitis infects one (thru the blood brain barrier)
bacteria colonizes host asymptomatically - typically in the nasopharynx (nasopharyngeal colonization)
invasion and multiplication in bloodstream
crosses the blood brain barrier (BBB)
invades the meninges
production of pro-inflammatory cytokines and chemokines
recruitment of leukocytes into CNS
edema (fluid build up), inflammation, increased cranial pressure
neuronal damage
this continues, it’s a positive feedback loop
what are the 3 ways in which microorganisms can traverse the blood brain barrier? describe them
transcellular traversal
— microorganism invades cell, then exists out other side
— believed that most pathogens causing meningitis travel this way
paracellular traversal
— pathogen goes between cells
trojan-horse mechanism
— intracellular pathogen brings cell across (via immune cells, e.g. macrophages)
describe the severity of bacterial meningitis?
a rare but very dangerous disease – can kill in days
early signs may be non-specific
in an outbreak, the first people to develop disease
are most at risk - they don’t know what’s going on
mortality rate has remained high (10-25%)
survivors may have irreversible damage
—– brain damage, blindness, hearing loss, learning disabilities
what are the classic 4 clinical symptoms of bacterial meningitis demonstrated in children and adults? what about infants?
high fever
severe headache
stiff neck confusion
confusion
symptoms in infants can be subtle, variable, and non-specific
bulge in the soft spot on top of a baby’s head because the skull not yet fused and inflammation (fontanel)
in the case of meningococcal meningitis they will develop skin rash
what’s a symptom unique to meningococcal meningitis?
skin (purpuric) rash
what are risk factors for bacterial meningitis?
lack of vaccination
young age (infants)
living in a community setting (e.g. dormitories, prisons, childcare facilities)
immunocompromised individuals due to disease of chemotherapy
cranial surgery
how is bacterial meningitis diagnosed?
history and symptoms
blood tests for inflammatory
markers, culture
lumbar puncture (aka spinal tap) – inserting spinal needle and drawing cerebral spinal fluid
—– cloudy CSF (want it to be clear)
—– gram stain and culture (+ or -, knowing this is important for treatment)
—– presence of white cells (neutrophils are indicative of bacterial infection and T-cells are indicative of viral infection)
—– low glucose (organism uses sugar as food source, therefore glucose levels drop)
imaging (CT) to look for inflammation
physical signs (lack of physical signs does not mean there is no meningitis)
when diagnosing bacterial meningitis, what physical signs do we look for?
nucal rigidity
— inability to flex the head forward
brudzinski’s sign
— severe neck stiffness causes a patient’s knees to flex when the neck is flexed
kernig’s sign
— severe stiffness of the hamstrings causes an inability to straighten the leg when the hip is flexed to 90 degrees
describe the treatment of bacterial meningitis
must be sought immediately
intravenous antibiotics (prior to culture analysis)
corticosteroids (dexamethasone) to reduce swelling in the meninges
supportive therapies (monitoring, oxygen, fluids)
what bacteria causes bacterial meningitis? the major causes?
almost all known bacterial pathogens have the potential to cause meningitis but relatively few account for most cases
major causes of bacterial meningitis
—- neisseria meningitidis
—- streptococcus pneumoniae
—- haemophilus influenza
—- listeria monocytogenes
these diverse pathogens (except Listeria) produce a
capsule as a major virulence factor
what’s the major cause of bacterial meningitis in infants?
streptococcus agalactiae (group B streptococcus)
which pathogen responsible for bacterial meningitis does not produce a capsule as a major virulence factor?
listeria monocytogenes
what is a capsule? what is it composed of? what is it’s main role in meningitis?
a loose, relatively unstructured network of polymers that cover the surface of some bacteria
most are composed of
polysaccharides
main role in meningitis is to
protect bacteria from the
complement system. they block the complement cascade
encapsulated bacteria are less likely to be opsonized by through the complement system
complement: innate immune
system serum proteins (e.g. C3b)
describe capsules as vaccines
an effective host response against capsules is the generation of antibodies from B cells that can recognize the capsule
antibodies that recognize capsule promote opsonization phagocytosis
capsules can therefore be used as vaccines
what is the issue with capsules as vaccines? and the solution?
polysaccharide vaccines do not provide long-term memory because they are T cell-independent
T cells provide are required for B cells (long-term memory) BUT, T cells only respond to
proteins/peptides, not sugars
SOLUTION
conjugate vaccine: polysaccharide conjugated to protein carrier
—- this makes the vaccine T cell-dependent
linkage to protein carrier allows B cell to recognize polysaccharide, endocytose it, and present the conjugated protein on MHC II
—- the T cell epitope is on the protein and the B cell epitope is on the polysaccharide
this allows us to produce memory T/B cells against capsule bacteria
describe neisseria meningitidis, what type of bacteria is it? what is it the leading cause of?
aka meningococcus
gram- , diplococcus (spheres in pairs)
a human specific pathogen
leading cause of bacterial meningitis and meningococcemia, an invasive meningococcal disease
what type of capsules does neisseria meningitidis produce?
polysaccharide capsules
with antigenic variants aka serotypes
—- A, B, C, W135, Y
what are the different serotypes of neisseria meningitidis?
A
B
C
W135
Y
what is meant by invasive when referring to bacteria?
bacteria in site that should normally be sterile (e.g. blood, liver or meninges)
what is the meningococcal disease?
meningitis occurs after bacteria enters the bloodstream and crosses the blood brain barrier
lipopolysaccharides aka endotoxins can lead to septic shock
the purpuric rash is caused by disseminated intravascular coagulation (DIC), which is widespread blood clotting – this leads to ischemia, inadequate blood supply to the organ - especially the heart
clotting factors are all used up, leads to small skin bleeds, which result in purpuric rash – this rash does not fade under pressure (this is the glass test!)
in DIC, extremity tissues often go necrotic
— if this occurs in organs, it can lead to “multi organ failure” and it’s very difficult to recover from
what’s ischemia?
inadequate blood supply to organs
what’s disseminated intravascular coagulation (DIC)?
widespread blood clotting
what are the main serotypes that cause invasive meningococcal disease in Canada?
B (major cause!)
C
W135
Y
what are the vaccines for neisseria meningitidis? any problems?
menactra/menveo
—- quadrivalent conjugate capsule vaccines from 4 serotypes of meningococcus (A, C, W135, Y)
—- problem: serotype B is the most common for invasive diseases in Canada, but the capsule is poorly immunogenic (so it is not in the menactra/menveo vaccine)
bexsero (GSK)
—- contains 4 recombinant protein antigens, not a capsule vaccine (designed to cover serotype B)
—- licensed in Canada
what is the African meningitis belt?
where the highest burden of the disease is in the world
more than 1000/100000 people infected
mostly caused by serotype A
—- vaccine not used there bc companies can’t make a lot of money in Africa – but Bill Gates helped get the vaccine there
serotype A in Chad has now been mostly wiped out (Herd Immunity) — colonization was blocked!
describe streptococcus pneumoniae, what type of bacteria is it? where is it generally found? what does it cause?
aka pneumococcus
gram+ cocci, grows in chains
commonly resides asymptomatically in nasopharynx
causes pneumonia, ear infections, sinusitis, and many other diseases
— the leading cause of bacterial meningitis in children over 2 years and adults
what type of capsules does streptococcus pneumoniae produce?
polysaccharide capsule with many different serotypes (OVER 90!)
— so for vaccines, we can’t protect against all but we can introduce selective pressure
describe the streptococcus pneumoniae vaccines (2). are there any concerns?
a pneumococcal vaccine
licensed for use in Canada
previously a 7-serotype vaccine but now Prevnar 13 (PCV13), meaning it now has 13 of the most prevalent serotypes of pneumococcus
use of the vaccine is associated with decreasing rates of invasive pneumococcal disease in Canada and elsewhere
a 23 valent polysaccharide vaccine for high-risk adults
— mostly used in older adults with respiratory problems
poorly immunogenic in children (T cell independent)
however, strains not in the vaccine are INCREASING in number
continuous cycle of creating selective pressures, then making new vaccines to cover
more serotypes
describe haemophilus influenzae type b, what type of bacteria is it? what does it cause?
aka “hib”
gram-, coccobacillus
primarily causes meningitis in children under the age of 5 – when it occurs, it tends to follow an upper respiratory infection, ear infection, or sinusitis
how effective were Hib (Haemophilus influenzae type b) vaccines? when was the vaccine introduced in Canada?
hib conjugate vaccine available as part of the routine childhood immunization schedules has reduced 99% of invasive hib disease to low levels (1/100000)
before the 1990s, H. influenzae type b was the leading cause of bacterial meningitis (the vaccine was introduced in 1988)
describe listeria monocytogenes, what type of bacteria is it? what does it cause? which demographic is more vulnerable?
gram+ rod
“listeriosis” can range from gastroenteritis, bacteremia, and meningitis
high rates of mortality in immunocompromised individuals including neonates and the fetus
how is listeria monocytogenes different from other meningitis causing bacteria?
it’s a food-borne pathogen
it’s able to grow at 4 degrees celsius (a psychrotroph, bacteria capable of growing at low temperatures), this is important for a food-borne pathogen (soft cheeses often implicated)
where in humans does listeria monocytogenes infect and how?
invades intestinal epithelial cells and replicates in the cytosol — it can also invade meninges
may use the trojan-horse mechanism
can also invade the placenta – very dangerous for fetuses
it has actin-based motility, a tail to move around within host cell – it uses this movement to evade immune system
it also spreads from cell to cell
what portion of meningitis cases is caused by listeria monocytogenes?
less than 5%
on a cellular level, how does listeria monocytogenes infect humans?
listeria invades and enters phagosome
releases toxins to lyse membrane (of vacuoles or phagosomes)
exits into the cytosol
uses actin based motility to move around and push into an adjacent cell
can enter macrophages and other cells
describe streptococcus agalactiae, what type of bacteria is it? what does it cause? where is it found?
group B streptococcus (GBS) that can be passed from the mother infant during labour
gram+, cocci
produces a capsule
leading cause of meningitis in children less than 2 months old
many women carry it in their urogenital tract as a commensal
