Bacterial Meningitis Flashcards
What is meninges?
- the membrane that envelops 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 pis mater
what is meningitis?
- an infection of the meninges
- usually due to viral or bacterial infection
- 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
- a protective cellular structure that restricts the passage of chemicals, toxins, and microorganisms from the blood to the central nervous system
- protect CNS from the peripheral immune system
- endothelial cells are stitched together by structures called “tight junctions”
- astrocytes and pericytes provide support
for other cells of the CNS including the BBB - microglia cells are the “tissue macrophages” of the CNS
- white blood cells and antibodies are not normally present in the CNS
What does infection look like for bacterial meningitis?
- nasopharyngeal colonization
- invasion into blood
- multiplication in blood
- the crossing of the BBB
- invasion of the meninges
- production of proinflammatory cytokines/chemokines
- recruitment of leukocytes into CNS
- edema increased cranial pressure
- inflammation
- neural damage
How to traverse through the BBB
Transcellular traversal
- through endothelial cells
Paracellular transversal
- force between endothelial cells
Trojan horse mechanism
- an infected macrophage passes through endothelial cells
What is bacterial meningitis?
- rare and very dangerous
- death in days
- early signs may be non-specific
- in an outbreak, 1st people to develop disease are most at risk
- morality rate is high
- survivors may have irreversible damage
What type of irreversible damage can survivors have when recovering from bacterial meningitis
- brain damage
- blindness
- hearing loss
- learning disabilities
What are the 4 main clinical symptoms in children and adults
- high fever
- severe headache
- stiff neck
- confusion
What are the clinical symptoms in infants?
- 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 baby’s head
- stiffness in body and neck
- skin rash in cases of meningococcal meningitis
What are some of the risk factors of bacterial meningitis?
- lack of vaccination
- young age (infants)
- living in a community setting
- uni dorms
- military personnel
- boarding schools
- child care facilities
- prisons
- immunocompromised individuals due to disease or chemotherapy
- cranial surgery
Diagnosis of bacterial meningitis
- history and symptoms
- blood test for inflammatory markers
- lumbar punction
- imaging
Lumbar punction
- cloudy CSF
- gram stain and culture
- presence of white cells
- low glucose
What are some of the physical signs for bacterial meningitis?
- Nuchal rigidity
- Brudzinski’s sign
- Kernig’s sign
What is nuchal rigidity?
The inability to flex the head forward
What is Brudzinski’s sign?
Severe neck stiffness causes a patient’s knees to flex when the neck is flexed
What is Kernig’s sign?
Severe stiffness of the hamstrings causes an inability to straighten the leg when the hip is flexed to 90 degrees
Treatments for bacterial meningitis
- must be sought immediately
- intravenous antibiotics
- corticosteroids to reduce swelling in the meninges
- supportive therapies (monitoring O2, fluids, etc.)
What are the major causes of bacterial meningitis?
- Neisseria meningitidis
- streptococcus pneumoniae
- Haemophilus influenzae
- listeria monocytogenes
- streptococcus agalactia (in infants)
- group B streptococcus
- these diverse pathogens (except listeria) produce a capsule as a major virulence factor
Capsules as vaccines?
effective host response against capsules in the generation of antibodies from B cells that recognize the capsule
- antibodies recognize capsule and promote opsonization and phagocytosis
- polysaccharide vaccines do not provide long-term memory (T cell-independent)
- T cells respond to proteins/polypeptides not sugars
- conjugate vaccines have polysaccharide conjugated to protein carriers
- this vaccine will be T- cell-dependent
Neisseria meningitids “meningococcus”
- gram-negative, diplococcus
- human-specific pathogen
- colonizes the throat and nose
- a symptomatic carriage is common
- produces a polysaccharide capsule
- antigenic variants (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 dorms, boarding schools and on military bases
Meningococcal disease
- meningitis occurs after bacteria enter the bloodstream and cross BBB
- endotoxin (LPS) can lead to septic shock
- disseminated intravascular coagulation
- widespread blood clotting
- ischemia
- clotting factors are used up which leads to small skin bleeds
- purpuric rash
- the rash does not fade under pressure (“glass test”
Vaccines for meningococcus
- Menactra/menveo - quadrivalent conjugate capsule vaccine from 4 serotypes of meningococcus
- serogroup B most common for invasive disease in Canada but the capsule is poorly immunogenic
- Bexsero contains 4 recombinant protein antigens
What is the African Meningitis Belt
- highest burden of the disease in the world
- mostly caused by serogroup A
Streptococcus pneumoniae “pneumococcus”
- Gram-positive cocci that grow in chains
- commonly reside asymptomatically in the nasopharynx
- cause pneumonia, ear infections, sinusitis and other diseases
- a leading cause of bacterial meningitis in children
- produces a polysaccharide capsule
- many different serotypes exist
- a major global pathogen
Vaccines for pneumococcus
- has been licensed for use in Canada
- previously a 7 serotype vaccine
- now Prevnar 13
- a conjugate capsule vaccine from the 13 most prevalent serotypes of pneumococcus
- use of the vaccine is associated with decreasing rates of invasive pneumococcal disease all around the world
- 23 valent polysaccharide vaccine for high-risk adults, but poorly immunogenic in children (T-cell-dependent)
Haemophilus influenzae type b “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
- Hib conjugate vaccine available as part of the routine childhood immunization schedules has reduced 99% of invasive Hib disease to low levels
- H. influenzae type b was the leading cause of bacterial meningitis
Listeria monocytogenes
- Gram-positive rods
- not your ‘typical’ meningitis pathogen
- a foodborne pathogen
- “listeriosis” can range from gastroenteritis -> bacteremia -> meningitis
- high rates of mortality in immunocompromised individuals including neonates and the fetus
- can grow at 4 degrees Celcius
- this is important for a foodborne pathogen
- listeria invades intestinal epithelial cells and replicates within the cytosol
- listeria makes up less than 5% of meningitis cases
Streptococcus agalactiae “Group B streptococcus”
- Gram-positive cocci and grows in chains
- produces a capsule
- many women carry S. agalactiae in the urogenital tract as a commensal
- GBS can be passed from 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
