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Microimm 2500 > Meningitis > Flashcards

Meningitis Flashcards

1
Q

Meninges

A
  • the membranes that envelop the CNS (brain and spinal cord)
  • includes pia mater, arachnoid mater, and dura mater
  • CSF is between the arachnoid and pia maters
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2
Q

What is meningitis?

A
  • viral or bacterial infection of the meninges
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3
Q

Is viral or bacterial meningitis more sever?

A
  • viral is 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?

A
  • a protective cellular structure that restricts passage of chemicals, toxins, and microorganisms from the blood to the CNS
  • also protects your CNS from the peripheral immune system
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5
Q

What creates the BBB?

A

endothelial cells stitched together by structures called “tight junctions” to prevent things from diffusing across

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6
Q

What is the role of astrocytes and pericytes in the BBB?

A
  • provide support for other cells of the CNS, including the BBB
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7
Q

What is the role of microglia cells in the BBB?

A
  • they are the tissue macrophages of the CNS but not really designed to fight microorganisms - more fore eating up cellular debris
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8
Q

are WBCs present in the CNS?

A
  • no they are normally not present in the CNS, therefore there are no b cells or antibodies.
  • inflammation is not very good here
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9
Q

Bacterial Meningitis Process (10 steps)

A
  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
  9. inflammation
  10. neuronal damage
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10
Q

How do microorganisms transverse the BBB?

A
  • method is not well understood

- three ways: transcellular, paracellular, trojan-horse

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11
Q

Transcellular Transversal

A
  • Invade into endothelial cells and go out through other side
  • Essentially eating through the cell
  • Most meningitis pathogens probably use this pathway
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12
Q

Paracellular Transversal

A
  • Bacteria drive themselves through tight junctions

- e.g. Lyme disease

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13
Q

Trojan-horse Mechanism

A
  • Bacteria gain access to macrophage that is living within a phagocyte and phagocyte crosses through
  • Tuberculosis
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14
Q

The Disease: 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 (because they delay treatment)
  • mortality rate has remained high (10-25%)
  • survivors may have irreversible damage
    brain damage, blindness, hearing loss, learning disabilities
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15
Q

Clinical symptoms of Meningitis in children and adults

A
  • high fever
  • severe headache
  • stiff neck
  • confusion
  • vomiting or nausea
  • seizures
  • sleepiness or difficulty waking up
  • photophobia - sensitivity to light
  • skin rash in cases of meningococcal meningitis
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16
Q

Clinical symptoms of Meningitis in infants

A

can be subtle, variable and non-specific:

  • fever
  • constant crying
  • excessive sleepiness or irritability
  • poor feeding
  • 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
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17
Q

Risk factors for bacterial meningitis

A
  • lack of vaccination
    young age (infants)
  • living in a community setting (university students living in dormitories, military personnel, boarding schools, child care facilities, prisons)
  • immunocompromised individuals due to disease or chemotherapy
  • cranial surgery
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18
Q

Bacterial Meningitis Diagnosis

A
  • history and symptoms
  • blood tests for inflammatory markers, culture
  • CT imaging

Lumbar puncture (spinal tap): spinal needle inserted between 3rd and 4th lumbar vertebrae

  • cloudy CSF
  • Gram stain and culture
  • presence of white cells (neutrophils)
  • low glucose
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19
Q

Physical Signs of Bacterial Meningitis

A

Nucal Rigidity, Brudzinksi’s sign, Kernig’s sign

  • if there were no signs, it is inconclusive (you may or may not have the disease) BUT if the signs are present, you have meningitis
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20
Q

Nucal rigidity

A

inability to flex the head forward

21
Q

Brudzinski’s sign

A

severe neck stiffness causes a patient’s knees to flex when the neck is flexed

22
Q

Kernig’s sign

A

severe stiffness of the hamstrings causes and inability to straighten the leg when the hip is flexed to 90 degrees

23
Q

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 etc)
24
Q

What are the major causes of meningitis?

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 influenzae)
  • Listeria monocytogenes

In infants:
- streptococcus agalactiae (Group b streptococcus)

25
Q

Which virulence factor is mainly produced by meningitis causing bacteria?

A

capsules (except by listeria)

26
Q

What is a capsule?

A
  • a loose, relatively unstructured network of polymers that cover the surface of some bacteria
  • most are composed of polysaccharides
27
Q

What is a capsule’s main role in meningitis?

A
  • to protect bacteria from the complement system
  • complement: innate immune system serum proteins (e.g. C3b)
  • encapsulated bacteria are less likely to be opsonized by through the complement system
28
Q

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 the capsule promote opsonization and phagocytosis
  • capsules can therefore be used as vaccines
29
Q

What is a problem associated with using capsules as vaccines?

A
  • polysaccharide vaccines do not provide long-term memory because they are T cell-independent
  • T cells provide “help” to B cells
  • long-term memory
    BUT, T cells respond to proteins/peptides, not sugars
30
Q

Conjugate Vaccines

A
  • polysaccharide conjugated to protein carrier
  • this vaccine will be T cell-dependent
  • you are essentially tricking the immune system
31
Q

Neisseria Meningitidis

A
  • “meningococcus”
  • Gram-negative, diplococcus
  • a human specific pathogen
  • colonizes the nose and throat – asymptomatic carriage is common
  • produces a polysaccharide capsule
  • antigenic variants (i.e. serotypes)
  • A, B, C, W135 and Y
  • a leading cause of bacterial meningitis and also meningococcemia - termed invasive meningococcal disease
  • this infection is highly contagious and may cause local epidemics in college dormitories, boarding schools and on military bases
32
Q

How are Neisseria meningitidis antigenically different?

A
  • all strains of not make the same capsule (antigenically different)
33
Q

Meningococcal disease

A
  • meningitis occurs after bacteria enter the bloodstream and cross the BBB
  • endotoxin (LPS) can lead to septic shock
  • disseminated intravascular coagulation
  • widespread blood clotting
  • ischemia
  • purpuric rash
34
Q

What is a purpuric rash?

A
  • basically a rsh underneath the skin

- clotting factors are used up which leads to small skin bleeds

35
Q

How do you test if rash is a purpuric rash?

A

rash does not fade under pressure (“glass test”)

36
Q

Vaccines for Neisseria meningitidis

A
  • Menactra (Sanofi Pasteur)/Menveo (GSK) – quadrivalent conjugate capsule vaccine from 4 serotypes of meningococcus (serogroup A, C, Y, W-135)
  • Serogroup B most common for invasive disease in Canada but the capsule is poorly immunogenic
  • Bexsero (GSK) – contains 4 recombinant protein antigens – now licensed (as of 2014) for use in Canada –> now used to go after serogroup B strains
37
Q

The African Meningitis Belt

A
  • the highest burden of the disease in the world
  • up to ~500/100,000
  • mostly caused by serogroup A
38
Q

The pathogen: Streptococcus pneumoniae

A
  • “pneumococcus”
  • Gram-positive cocci, grows in chains
    commonly resides asymptomatically in the nasopharynx
39
Q

What symptoms does streptococcus pneumoniae cause?

A
  • causes pneumonia, ear infections, sinusitis and many other diseases
  • the leading cause of bacterial meningitis in children > 2 years and adults
40
Q

How many people die by Streptococcus pneumoniae globally per year?

A

> 700 000

41
Q

How Streptococcus pneumoniae work?

A

produces a polysaccharide capsule (may different serotypes exist)

42
Q

Vaccine for Streptococcus pneumoniae

A
  • A pneumococcal vaccine has been licensed for use in Canada
  • Previously a 7 serotype vaccine (PCV7)
  • now Prevnar 13 (PCV13)
  • use of the vaccine is associated with decreasing rates of invasive pneumococcal disease in Canada and elsewhere
  • 23-valent polysaccharide vaccine for high-risk adults, but poorly immunogenic in children (T cell-independent)
43
Q

What is prevnar 13 (PCV13)

A
  • a conjugate capsule vaccine from the 13 most prevalent serotypes of pneumococcus
44
Q

What is a trend seen with the vaccines for Streptococcus pneumoniae?

A
  • people are vaccinated for only the most prevalent serotypes
  • as those strains are vaccinated against, others that were less common (and not present in the vaccine), are becoming more prevalent
45
Q

Haemophilus influenzae type B

A
  • “Hib”
  • Gram negative, coccobacillus, produces a polysaccharide capsule
    primarily causes meningitis in children under 5
  • when it occurs, it tends to follow an upper respiratory infection, ear infection or sinusitis
46
Q

Hib Vaccine Effectiveness

A
  • Hib conjugate vaccine available as part of the routine childhood immunization schedules has reduced 99% of invasive Hib disease to low levels (<1 per 100,000)
  • Before the 1990s, H. influenzae type b was the leading cause of bacterial meningitis
47
Q

Listeria monocytogenes

A
  • Gram-positive rod
  • not your ‘typical’ meningitis pathogen
    a food-borne pathogen
  • “listeriosis” can range from gastroenteritis –> bacteremia –> meningitis
  • high rates of mortality in immunocompromised individuals including neonates and the fetus
  • can grow at 4°C (a psychrotroph) – important for a food-borne pathogen (soft cheeses often implicated)
  • Listeria causes <5% of meningitis cases
48
Q

How does listeria escape your immune system?

A
  • Escapes into cytoplasm (intracellular bacteria)
  • There is a protein on its surface that polymerizes actin that drives the bacteria along (NOT FLAGELLA)
  • Can push itself into an adjacent cell
  • Listeria invades intestinal epithelial cells and replicates within the cytosol (actin-based motility and cell-to-cell spread)
49
Q

Streptococcus agalactiae

A
  • Group B Streptococcus” (GBS)
  • Gram positive cocci, grows in chains
  • produces a capsule
    many women carry S. agalactiae in the urogenital tract as a commensal
  • GBS can be passed from the mother to infant during labour
  • women are usually tested for GBS at ~36 weeks
  • women who are positive may be treated with antibiotics during labour to prevent infection of the newborn

Microimm 2500 (8 decks)

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