(B): Lecture 15: Bacterial Meningitis Flashcards
Meninges
- membranes that envelope the CNS (brain + spinal cord)
- includes pia mater (closest to brain), arachnoid mater and dura mater
- Cebrospinal fluid (CSF) is btwn arachnoid and pia maters
Meningitis
- infection of meninges
- meningitis is usually due to viral or bacterial infection
Viral meningitis is generally less severe + resolves w/o specific treatment
Bacterial meningitis can be rapid + life-threatning
BBB
Blood Brain Barrier
- protective cellular structure that restricts passage of chemicals and toxins from blood to CNS
- also protects CNS from peripheral immune system
- endothelial cells are stitched together by tight junctions
- astrocytes and pericytes support cells
- microglia
- WBCs and antibodies are NOT normally present in CNS (don’t want inflammatory response in brain)
Microglia
tissue macrophages of CNS
Bacterial meningitis Action
- nasopharyngeal colonization
- upper resp. tract colonizer - invasion into blood
- multiplication in blood
- crossing of BBB
- invasion of meninges
- producing of pro-inflammatory cytokines/chemokines
- recruitment of leukocytes into CNS
- caused by chemokines and leads to + feedback loop - edema = increased cranial pressure
- inflammation
- neuronal damage
Mechanisms of Traversing the BBB
- Transcellular traversal
- Paracellular traversal
- Trojan-horse mechanisms
Transcellular traversal
MAJOR mechanism most cells use to get into CNS
microorganisms invades inside endothelial cell and enters brain
Paracellular traversal
squeezes btwn TIGHT JUNCTIONS and endothelial cells to get into CNS
Trojan-horse mechanism
bacteria gains access to a phagocyte
- lives IN phagocytes (ex. macrophage)
Bacterial meningitis
- rare but very dangerous (kills in days)
- early signs may be non-specific
- first ppl to develop disease are most at risk in outbreak
- high mortality rate (10-25%)
- survivors may have irreversible damage (brain damage, blindness, hearing loss, learning disabilities)
Bacterial meningitis symptoms in children and adults
MAIN 4 (95% have 2+ of these)
- high fever
- severe headache
- stiff neck
- confusion
Other symptoms
- vomiting or nausea
- seizures
- sleepiness or difficulty waking up
- photophobia = sensitivity to light (due to nerve inflammation)
- skin rash in meningococcal meningitis
Bacterial meningitis symptoms in infants
Can be subtle, variable, non-specific
- fever
- constant crying
- excessive sleepiness or irritability
- poor feeding
- inability to maintain eye contact
- bulge in soft spot on top of baby’s head (fontanel)
- stiffness in baby’s body + necl
- skin rash in meningococcal meningitis
Risk factors for bacterial meningitis
- lack of vaccination
- young ages (infants)
- living in a community setting
- immunocompromised individuals (due to disease or chemo)
- cranial surgery/invasive surgery
Diagnosis of bacterial meningitis
MAIN DIAGNOSTIC: LUMBAR PUNCTURE (SPINAL TAP)
- cloudy CSF (should be clear)
- gram stain + culture
- presence of white cells (neutrophils) - good indication
- low glucose (bacteria using glucose to grow)
- history and symptoms
- blood tests for inflammatory markers, culture
- imaging (CT)
What does presence of T cells or neutrophils mean?
T cells = viral infection
Neutrophils = bacterial infection
Physical signs of bacterial meningitis
NOT sensitive
- Nucal rigidity
- Brudzinki’s sign
- Kernig’s sign
Nucal rigidity
Physical sign of bacterial meningitis
Inability to flex head forward
Brudzinki’s sign
Physical sign of bacterial meningitis
severe neck stiffness = patients KNEES FLEX when the neck is flexed
Kernig’s sign
Physical sign of bacterial meningitis
severe stifness of HAMSTRINGS = inability to straighten leg when hip is flexed to 90 degrees
Treatment of bacterial meningitis
- must be immediate
intravenous (IV) antibiotics (prior to culture analysis
- empiric use but NOT a misuse b/c outcome can be so devastating
- corticosteroids to reduce swelling in meninges
- supportive therapies (oxygen, fluids)
Causes of bacterial meningitis
almost all bacterial pathogens have potential to cause meningitis
MAJOR causes of bacterial meningitis (create CAPSULE as a virulence factor to survive in blood)
- Neisseria meningitidis
- Streptococcus pneumonia
- Haemophilus influenza
- Listeria monocytogenes
Main cause of bacterial meningitis in infants (0-2 months)
GBS (Group B Streptococcus)
Main cause of bacterial meningitis in adults
Streptococcus pneumoniae
Main cause of bacterial meningitis in children + adolescents
Streptococcus pneumoniae + Listeria monocytogenes
Capsule
- loose, unstructured network of polymers that cover surface of some bacteria
- most are made of POLYSACCHARIDES
- main role in meningitis: PROTECT BACTERIA FROM COMPLEMENT SYSTEM
encapsulated bacteria are less likely to be opsonized thru complement system
Can capsules be used as vaccines?
Effective host response against capsules is generation of antibodies from B cells that can recognize the capsule
- promotes opsonization + phagocytosis to kill the capsule
Polysaccharide vaccines do NOT provide long-term memory b/c they are T-cell independent = no memory
- T cells provide help to B cells = long-term memory
BUT T cells respond to proteins not sugars
Conjugate vaccines
Conjugate vaccine
Polysaccharide conjugated to protein carrier
- makes vaccine T cell-dependent
No class switching, primarily IgM response
B cell activates T cell by presenting the carrier protein on the sugar chain to MHC Class II
Neisseria meningitidis
- meningococcus
- gram-NEGATIVE, diplococcus
- human-specific
- colonizes nose + throat (often asymptomatic carriage)
- produces POLYSACCHARIDE CAPSULE
(serotypes are all antigenically unique) - leading cause of bacterial meningitis and meningococcemia (INVASIVE meningococcal disease)
- highly contagious and may cause local epidemics
Invasive meningococcal disease
isolated from a space you’d expect to be sterile
Ex. meningococcemia
Meningococcal disease
- occurs after bacteria enters the bloodstream and crosses the BBB
- ENDOTOXIN (LPS) can lead to SEPTIC SHOCK (drop in b.p)
- gram-NEG
Disseminated intravascular coagulation
- widespread clotting = DIC
- ischemia = loss of O2 to tissues
- clotting factors are used up = PURPURIC rash
- rash does not fade under pressure (glass test)
Vaccines for Neisseria meningitidis
- Menactra/Menveo
- Serogroup B: most common in Canada
- Bexsero
African Meningitis Belt
- highest burden of the disease in world
- 1 person per 1000
- most caused by serogroup A
Streptococcus pneumoniae
- “Pneumococcus”
- gram-POSITIVE cocci
- grows in chains
- commonly lives asymptomatically in nasopharynx
- causes pneumonia, ear infections, etc
- leading cause of bacterial meningitis in CHILDREN > 2 YEARS and adults
- produces polysaccharide capsule
- major global pathogen (top 5 mortality)
Vaccine for Streptococcus pneumoniae
Prevnar 13 (PCV13)
- conjugate capsule vaccine from the 13 most prevalent serotypes
Use of vaccine = decreasing rates of invasive pneumococcal disease
23-valent polysaccharide (NOT conjugate) is recommended for ppl w/ respiratory issues
- T-cell independent
Incidence of pneumococcal disease
Vaccines against serotypes
- Incidence decreases over time
- serotypes are targeted by immune system
When serotypes are not in the vaccine there is an increase in incidences
Haemophilus influenzae type b
- “Hib”
- bacteria NOT virus
- gram NEGATIVE, coccobacillus
- produces a polysaccharide capsule
- mainly meningitis in CHILDREN UNDER 5 (used to be #1 cause)
- usually after an upper resp. infection, ear infection or sinusitis
- Since conjugate vaccine, incidence dropped
Listeria monocytogenes
- OPPORTUNISTIC pathogen
- gram-POSITIVE, rod
- food-borne pathogen
- listeriosis can range from gastroenteritis –> bacteremia –> meningitis
- high mortality rate in immunocompromised especially pregnant women and the fetus
- cold-tolerant (can grow more than other bacteria)
How does Listeria monocytogenes invade the cell?
intracellular
- gets into macrophage
- invades intestinal epithelial cells
- enters phagosome
- L. mono. lyses phagosome and replicates in the cytosol
- F. actin pushes themselves into adjacent cells
- enters vacuole in adjacent cell
- breaks out of vacuole
- can cross placenta
Streptococcus aglactiae
Group B Streptococcus – GBS
- gram-POSITIVE cocci
- produces a capsule
- many women carry S. aglactiae in urogenital tract as a commensal - don’t cause disease in vagina
- can be passed from mother to infant during labour
- women are usually tested at 36 weeks
- women who are positive for GBS are treated with antibiotics during labour to prevent infection of newborn
