Meningitis (1/18) Flashcards
What makes the CNS different space for infections?
Well defended: BBB, capillary junctions in this specialized endothelial
Priveleged space: little room for inflammation, no complement, minimal immunoglobulin, no PMNs
Overview of bacteria that can cause CNS infection
- What organisms cause meningitis in neonates? Where do they come from?
Organisms that are present in fecal matter that the newborn aspirates during birth
Group B streptococci, E. coli, listeria monocytogenes, enterococci
GBS = Streptococcus agalactiae
Salmonella in developing countries
What is the progression of GBS in neonates?
Colonized mother → aspiration → bacteremia
Early onset → sepsis, pneumonia
Late onset → sepsis, meningitis
What makes neonates susceptible to GBS meningitis?
Complement isn’t as good, TLRs are different, lack of antibody, ET cells in the brain with meningeal receptors → can get endocytosed but not killed, which means that bacteria can replicate
The only antibody they have are IgGs from mother across placenta
This affects treatment – must be treated 2-3 weeks, bc lots of the bacteria are intracellular
What is a polysacchardie capsule?
A common component of bacteria that cause meningitis
If you could make a vaccine against this, it would be really good to prevent meningitis
It helps the organism avoid an immune response: resists phagocytosis, mimics terminal sialic acid galactose= identical to mammalian cell polysaccharide
How is GBS preventable?
Treat mothers known to be carriers before birth
What organism is different from the other ones? Why?
Listeria monocytogenes= present in animal manure/ organic food
Seen in adults who are immunocompromised & causes a flu-like illness
Gram positive rod, catalase positive, characteristic tumbling motility
Can cause neonatal sepsis/meningitis
With CNS infections, what causes pathology in host?
The response, not the bacteria in brain tissue
Pneumococcal virulence factors cause inflammation, apoptosis of neurons, adhesion
Elevated CSF protein & low glucose = indicative of bacterial meningitis
Release of NO → tissue damage
S. pneumo → activation of clotting cascade
ET activation → upregulate ICAM to attract PMNs → tissue damage
Result = stroke, seizure, cardiac failure
What are the goals of therapy of meningitis?
Reduce inflammation with steroids
Penicillin to stop bacterial regulation BUT it can release fragments of the bacteria which causes lots of inflammation (BAD news)
Why is treatment with steroids and antibiotics complicated?
If you give steroids, it treats inflammation
But it also prevents antibiotics from crossing BBB
Vaccines prevent CNS infections in children… but what can cause a vaccine-type meningitis?
If the child is immunocompromised i.e. IRAK4 and NEMO mutations (this was studied in children with recurrent invasive pneumococcal disease)
What is H. influenzae?
A previous cause of bacteremia/meningitis that has gone away due to vaccination in infants
New strains that don’t have capsules can also cause other infections
Adults with liver disease that don’t make appropriate antibody can also get the disease
Treat with corticosteroids before antibiotics- this decreases 2ndary increase in TNF due to release of bacterial cell wall fragments & improved clinical outcome
What is N. meningitidis & what disease does it cause?
Gram negative organism, rapidly taken up by epithelial cells (endocytosis)
Encapsulated – LPS – causes very intense immune response (cardiovascular collapse, clotting cascade activation)
Can cause sepsis due to LPS or meningitis (complex pathophysiology- flu like symptoms+ headache + diffuse petecchiae)
Rare in US (only if you have a compromised immune system), more common in sub-Saharan Africa
