Bacterial Meningitis (9) Flashcards
How do the causative agents get into the CNS… where do they colonize first?
Colonize the nasopharynx and then travel via the blood into the CNS
What is meningitis?
Inflammation of the pia mater
Other than bacterial culture, what are 3 ways of identifying the causative agents of suspected bacterial meningitis?
- Gram stain of CSF
- Rapid antigen Detection (of capsular material in CSF)
- PCR testing for specific species in CSF
What are the 3 characteristic CSF findings in meningitis due to bacteria?
- Elevated white count (especially of neutrophils)
- Decreased glucose
- Elevated protein
What are the 3 most common agents of bacterial meningitis in the age range of Birth to 3 months of age?
- Group B Strep (most common, colonizes the vagina)
- Gram negative enterics–> E. Coli commonly (is 2nd most common)
- Listeria monocytogenes (can be gotten if mother eats soft cheeses, deli meats that are infected)
What are the three most common causative agents of bacterial meningitis in the age of 3 months to 2 years?
- Streptococcus pneumoniae
- Neisseria meningitides
- H. influenzae (type B)–> usually only in areas without immunizations against
What are the 2 most common causative agents of bacterial meningitis in people from age 2 - 18?
- Neisseria meninigitides
2. Streptococcus pneumoniae
In older patients (18+ - 50)what are the common causes of bacterial meningitis?
- Strp pneumoniae
- N. meningitides
- H. flu
- Gram neg enterics (gram neg rods and Pseudomonas)
* Basically all the agents possible
What three agents are responsible for bacterial meningitis in the immunocompromised?
- Staph
- Gram neg enterics (rods)
- Psuedomonas
What is the most common cause overall of bacterial meningitis?
S. pneum, aka pneumococcus–> is a normal inhabitant of the upper respiratory tract in 5-40% of population
What is the Rx used to treat bacterial meningitis? (2 drugs)
3rd generation cephalosporin + dexamethasone
What drug needs to be added to treatment if S. pneum infection is suspected?
Vancomycin (add to 3rd gen ceph and dexamethasone)
When should dexamethasone be administered if its going to be given along with Abx?
always give BEFORE abx
What drug needs to be added to treatment if infection with Listeria is suspected?
Ampicillin
What morphology do Streptococcus pneumoniae have (gram stain and shape)? What about catalase?
Gram positive diplococci (may also grow in chains–> “strips”, so striptococci)
*catalase negative, which dist. them from staph (staph also grow in clusters, not chains)
What, in addition to pili, do pneumococci have that enable them to adhere to epithelium and are also essential for their ability to cross the BBB and cause meningitis?
Choline-binding proteins–> CbpA especially
*CbpA deficient pneumococci are defective in binding to the nasopharynx and fail to bind to human cells in vitro
What enables pneumococci to colonize the upper respiratory tract?
Pili–> allows them to attach to the epithelium in the nasopharynx
How specifically does the pneumococcal capsule work as a virulence facter?
Interferes with phagocytosis–> blocks complement C3b from binding to the bacterial surface
*encapsulated strains are ~100,000 times more virulent than unencapsulated strains
How specifically can pneumococci invade the BBB?
Pili and CbpA allow them to attach to endothelial cells–> they are able to directly invade the cells, so the tight junctions preventing intercellular travel in the BBB dont stop them; transmigrate the capillaries and enter the CSF
What hemolysin do S. pneum have?
Pneumolysin–> protein that can cause lysis of host cells and activate complement
What causes the inflammatory response caused by pneumococci?
Cell wall components–> teichoic acids, lipoteichoic acids containing phosphorylcholine and peptidoglycan
*isolated cells walls (not intact bacteria) produce similar inflammatory response as live cells and recreate many of the symptoms of otitis media, pneumonia, and meningitis, all of which can be caused by S. pneum
Which vaccine for Pneumococcus is recommended for older people and immunocompromised pts and is generally ineffective in the young? How many capsule types does it contain?
Pnemovax–> has 23 capsule types and is a multivalent, non-conjugated vaccine
What two virulence factors are important in invasion of host cells and blocking the immune response? (other than of pili, capsule, and CbpA)
- Neuraminidase
2. IgA protease
What is one short-coming of Pneumovax, other than it being generally ineffective in the young pt population?
Immunity only lasts 5-7 years
What is an issue with Prevnar?
Very expensive, but safe and highly effective (has reduced pneumococcal meningitis in infants by 85%)–> also has an anamnestic response, which is adaptive immunity with memory
*conjugated vaccine= anamnestic response
Which vaccine is given to children and infants to prevent pneumococcal meningitis? How many capsule types does it contain?
Prevnar–> contains 13 capsule types; is a heptavalent, conjugated vaccine
*can gen. Abs in children as young as 2 months
What are the gram stain and morphological characteristics of Neisseria meningitides?
Gram negative, diplococci (are non motile)
*referred to as little pink (aka gram negative) pneumococci, due to morphologocal similarity to S. pneum (which is gram + diplcoccus)
What are 5 risk factors for Strep pneum infection?
- Splenic dysfunction (apslenic, trauma, sickle cell)
- Skull fracture
- Cochlear implant
- Recurrent otitis media
- Immunocompromised (AIDS, etc)
What is conditions are conducive to contracting N. meningitides (meningococcus)? Why?
Crowded places–> jails, military barracks, DORMS
- spread via respiratory droplets, so high probability of spread in close quarters
What is mortality rate for meningitis due to N. meningitides? What % of survivors have serious sequlae?
10-15% will die, despite treatment
10% may lose limbs, become deaf, suffer seizure/stroke, or become mentally retarded
What 3 serotypes of N. meningitides are responsible for most sporadic (small number of related cases) outbreaks?
B, C, Y
What serotype of N. meningitides is usually responsible for larege, epidemic outbreaks (large area, large # of cases)?
A
Other than the usual sings of meningitis type dz (sudden high fever, stiff neck, chills, myalgias, N/V, headache) What other types of issues appear that indicate serious dz?
Mental changes (agitation, confusion, coma)
What general complication is usually responsible for the makority of deaths due to N. meninigitides?
Fulminant meningococcemia–> occur in 10-15% of patients with meningococcal disease
What is a late sign of meningococcal meningitis that would signal bad sepsis?
Sudden appearance of widespread petechial and purpuric skin rash
What is the usual cause of death in patients with severe meningococcal meningitis with meningococcemia?
Pulmonary insufficiency–> pts usually die w/in 24 hrs of hospitilization despite Abx and intensive therapy
What is the ony known reservoir for N. meningitides?
Human nasopharynx –> attach to nonciliated columnar epithelial cells via pili
What mechanism do N. meningitides employ that allow for invasion of mucosal cells?
Phase Variation (can turn off capsular genes, then turn back on again once back in the bloodstream)
What is the major virulence factor for N. meningitides other than its anti-phagocytic capsule?
Lipooligosaccharide (LOS)–> is an endotoxin
Why is routine vaccination against N. meningitides not reccomended?
Risk of infection is low; vaccines are usually ineffective in children as well
- A, C, AC, and ACYW135 capsular vaccines do exist however
What does no vaccine currently exist for group B polysaccharide serorypes of N. meningitides?
Because it is a homopolymer of human sialic acid–> normal human cell constituent so is not immunogenic
What is DOC for meningococcal meningitis and meningococcemia?
Penicillin (plus dexamethasone)
Which N, meningitides vacine is recommended for all children 11-12 years old? What is different about it compared to the other?
Menactra–> conjugated to a toxin, so produces an anamnestic response
*licensed for use in 11-55 year olds
What is Phase Variation? By what two mechanisms do meningcocci do this?
Changes in expression states of a gene leading to “on-off” control—> done via Direct DNA repeats and Slipped strand mispairing (leads to changes in capsule, attachement proteins, LOS, etc)
Which meningococcus vaccine is non-conjugated (no memory response) and given to high risk patients and military personnel?
Menomune–> is a carbohydrate vaccine
*also given to cochlear transplant patients and those travelling to subsaharan africa (known as the meningitis belt)
What is the gram stain and morphological characteristics of H. flu?
Gram negative rods
What three diseases can H. flu cause?
- otitis media
- respiratory dz
- meningitis (especially in children)
What is Antigenic Variation? What do meningococci use this mechanism to alter?
Changes in genes leading to different forms of similar genes–> alter their pili with this; there is a basic conserved region in the pili genes, but a portion of it is variable and changes via RecA mediated recombination)
What is Hib, the current H. flu vaccine conjugated to?
Is type b capsular polysaccharide conjugated to a diptheria toxin
What age children should receive Hib, the H. flu vaccination?
Infants between the ages of 2 and 15 months
Which serotype of H. flu is the most important human pathogen?
Serotype b
What is H. flu the second most common cause of?
Otitis media (2nd to S. pneum)
What special medium does H. flu need to grow in culture?
CAP–> contains Factor V and Factor X
- V = NAD/NADP
- X = Hemin
What causes most of the rare (~300 cases in U.S. per year) of H. flu related meninigitis?
Cases are in non-immunized children or due to non-typable H. flu (so vaccine wouldnt confer protection)
What is special about Listeria’s life cycle?
It is a facultative intracellular parasite
In what two specific populations is Listeria a fairly significant cause of meningitis or other serious disease?
- Pregnant women (associated with vaginal colonization; stereotypically due to pregnant women eating soft cheeses like feta, etc.)
- AIDS patients (get listeria @ 300x the incidence rate of normal population
- Older patients (also have poor immune function)
* really any immunocompromised state (pregnancy is also one of these)
What are the gram stain and morphological characteristics of Listeria monocytogenes?
Gram positive rod
How can Listeria grow even on things that have been pasteurized?
Pasteurization is not 100%; any surviving Listeria actually grow well at refrigerator temps, so cold storage may actually amplify Listeria populations
What bacterial protein does Listeria have that mediates entry into non-phagocytic cells?
Internalin–> binds to E-cadherin
What two places in the body can Listeria colonize?
- G.I. tract
2. Vagina
What bacterial product allows Listeria to escape the phagolysosome once endocytosed?
Listeriolysin O
Why can’t macrophages destroy Listeria?
They require cytokine activation so need the immune sytem’s help
What bacterial protein allows Listeria to directly spread cell-to-cell?
F-actin
Which strep are group B strep, the most common cause of bacterial meningitis in children form birth to 3 months?
Streptococcus agalactiae
What is used to determine the specific serotype of S. pneumoniae?
Capsular polysaccharide
What two drug options should be used to treat meningococcus if a person is allergic to penicillin?
Chloramphemicol or a 3rd gen. cephalosporin (cefotaxime or ceftriaxone)
What is a main difference between N. meningitides and N. gonarrhoeae (the two main pathogenic strains of Neisseria)?
N. meningitides (aka meningococcus) has a prominent antiphagocytic polysaccharide capsule, other doesn’t
- MC serogroups are A, B, C, Y, and W135
Which strep are Group A strep?
Streptococcus pyogenes
