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bacterial meningitis Flashcards

1
Q

what are meninges?

A

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

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2
Q

what is meningitis?

A

an infection of the meninges usually due to viral or bacterial infection

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3
Q

differentiate between viral and bacterial meningitis

A

viral meningitis is generally less severe and usually resolves without specific treatment

bacterial meningitis can
be rapid and life-threatening

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4
Q

what is the blood brain barrier (BBB)

A

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

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5
Q

describe the structure of the blood brain barrier (BBB)

A

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

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6
Q

describe how bacterial meningitis infects one (thru the blood brain barrier)

A

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

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7
Q

what are the 3 ways in which microorganisms can traverse the blood brain barrier? describe them

A

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)

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8
Q

describe the severity of bacterial meningitis?

A

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

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9
Q

what are the classic 4 clinical symptoms of bacterial meningitis demonstrated in children and adults? what about infants?

A

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

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10
Q

what’s a symptom unique to meningococcal meningitis?

A

skin (purpuric) rash

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11
Q

what are risk factors for bacterial meningitis?

A

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

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12
Q

how is bacterial meningitis diagnosed?

A

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)

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13
Q

when diagnosing bacterial meningitis, what physical signs do we look for?

A

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

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14
Q

describe the treatment of bacterial meningitis

A

must be sought immediately

intravenous antibiotics (prior to culture analysis)

corticosteroids (dexamethasone) to reduce swelling in the meninges

supportive therapies (monitoring, oxygen, fluids)

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15
Q

what bacteria causes bacterial meningitis? the major causes?

A

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

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16
Q

what’s the major cause of bacterial meningitis in infants?

A

streptococcus agalactiae (group B streptococcus)

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17
Q

which pathogen responsible for bacterial meningitis does not produce a capsule as a major virulence factor?

A

listeria monocytogenes

18
Q

what is a capsule? what is it composed of? what is it’s main role in meningitis?

A

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)

19
Q

describe capsules as vaccines

A

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

20
Q

what is the issue with capsules as vaccines? and the solution?

A

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

21
Q

describe neisseria meningitidis, what type of bacteria is it? what is it the leading cause of?

A

aka meningococcus

gram- , diplococcus (spheres in pairs)

a human specific pathogen

leading cause of bacterial meningitis and meningococcemia, an invasive meningococcal disease

22
Q

what type of capsules does neisseria meningitidis produce?

A

polysaccharide capsules

with antigenic variants aka serotypes
—- A, B, C, W135, Y

23
Q

what are the different serotypes of neisseria meningitidis?

A

A

B

C

W135

Y

24
Q

what is meant by invasive when referring to bacteria?

A

bacteria in site that should normally be sterile (e.g. blood, liver or meninges)

25
Q

what is the meningococcal disease?

A

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

26
Q

what’s ischemia?

A

inadequate blood supply to organs

27
Q

what’s disseminated intravascular coagulation (DIC)?

A

widespread blood clotting

28
Q

what are the main serotypes that cause invasive meningococcal disease in Canada?

A

B (major cause!)

C

W135

Y

29
Q

what are the vaccines for neisseria meningitidis? any problems?

A

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

30
Q

what is the African meningitis belt?

A

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!

31
Q

describe streptococcus pneumoniae, what type of bacteria is it? where is it generally found? what does it cause?

A

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

32
Q

what type of capsules does streptococcus pneumoniae produce?

A

polysaccharide capsule with many different serotypes (OVER 90!)

— so for vaccines, we can’t protect against all but we can introduce selective pressure

33
Q

describe the streptococcus pneumoniae vaccines (2). are there any concerns?

A

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

34
Q

describe haemophilus influenzae type b, what type of bacteria is it? what does it cause?

A

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

35
Q

how effective were Hib (Haemophilus influenzae type b) vaccines? when was the vaccine introduced in Canada?

A

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)

36
Q

describe listeria monocytogenes, what type of bacteria is it? what does it cause? which demographic is more vulnerable?

A

gram+ rod

“listeriosis” can range from gastroenteritis, bacteremia, and meningitis

high rates of mortality in immunocompromised individuals including neonates and the fetus

37
Q

how is listeria monocytogenes different from other meningitis causing bacteria?

A

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)

38
Q

where in humans does listeria monocytogenes infect and how?

A

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

39
Q

what portion of meningitis cases is caused by listeria monocytogenes?

A

less than 5%

40
Q

on a cellular level, how does listeria monocytogenes infect humans?

A

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

41
Q

describe streptococcus agalactiae, what type of bacteria is it? what does it cause? where is it found?

A

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

microimm (30 decks)

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