Bacterial Meningitis (9)

Question 0

How do the causative agents get into the CNS… where do they colonize first?

Answer 0

Colonize the nasopharynx and then travel via the blood into the CNS

Question 1

What is meningitis?

Answer 1

Inflammation of the pia mater

Question 2

Other than bacterial culture, what are 3 ways of identifying the causative agents of suspected bacterial meningitis?

Answer 2

1. Gram stain of CSF
2. Rapid antigen Detection (of capsular material in CSF)
3. PCR testing for specific species in CSF

Question 3

What are the 3 characteristic CSF findings in meningitis due to bacteria?

Answer 3

1. Elevated white count (especially of neutrophils)
2. Decreased glucose
3. Elevated protein

Question 4

What are the 3 most common agents of bacterial meningitis in the age range of Birth to 3 months of age?

Answer 4

1. Group B Strep (most common, colonizes the vagina)
2. Gram negative enterics–> E. Coli commonly (is 2nd most common)
3. Listeria monocytogenes (can be gotten if mother eats soft cheeses, deli meats that are infected)

Question 5

What are the three most common causative agents of bacterial meningitis in the age of 3 months to 2 years?

Answer 5

1. Streptococcus pneumoniae
2. Neisseria meningitides
3. H. influenzae (type B)–> usually only in areas without immunizations against

Question 6

What are the 2 most common causative agents of bacterial meningitis in people from age 2 - 18?

Answer 6

1. Neisseria meninigitides

2. Streptococcus pneumoniae

Question 7

In older patients (18+ - 50)what are the common causes of bacterial meningitis?

Answer 7

1. Strp pneumoniae
2. N. meningitides
3. H. flu
4. Gram neg enterics (gram neg rods and Pseudomonas)
   * Basically all the agents possible

Question 8

What three agents are responsible for bacterial meningitis in the immunocompromised?

Answer 8

1. Staph
2. Gram neg enterics (rods)
3. Psuedomonas

Question 10

What is the most common cause overall of bacterial meningitis?

Answer 10

S. pneum, aka pneumococcus–> is a normal inhabitant of the upper respiratory tract in 5-40% of population

Question 12

What is the Rx used to treat bacterial meningitis? (2 drugs)

Answer 12

3rd generation cephalosporin + dexamethasone

Question 13

What drug needs to be added to treatment if S. pneum infection is suspected?

Answer 13

Vancomycin (add to 3rd gen ceph and dexamethasone)

Question 14

When should dexamethasone be administered if its going to be given along with Abx?

Answer 14

always give BEFORE abx

Question 15

What drug needs to be added to treatment if infection with Listeria is suspected?

Answer 15

Ampicillin

Question 17

What morphology do Streptococcus pneumoniae have (gram stain and shape)? What about catalase?

Answer 17

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)

Question 19

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?

Answer 19

Choline-binding proteins–> CbpA especially

*CbpA deficient pneumococci are defective in binding to the nasopharynx and fail to bind to human cells in vitro

Question 20

What enables pneumococci to colonize the upper respiratory tract?

Answer 20

Pili–> allows them to attach to the epithelium in the nasopharynx

Question 21

How specifically does the pneumococcal capsule work as a virulence facter?

Answer 21

Interferes with phagocytosis–> blocks complement C3b from binding to the bacterial surface

*encapsulated strains are ~100,000 times more virulent than unencapsulated strains

Question 22

How specifically can pneumococci invade the BBB?

Answer 22

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

Question 23

What hemolysin do S. pneum have?

Answer 23

Pneumolysin–> protein that can cause lysis of host cells and activate complement

Question 24

What causes the inflammatory response caused by pneumococci?

Answer 24

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

Question 25

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?

Answer 25

Pnemovax–> has 23 capsule types and is a multivalent, non-conjugated vaccine

Question 26

What two virulence factors are important in invasion of host cells and blocking the immune response? (other than of pili, capsule, and CbpA)

Answer 26

1. Neuraminidase

2. IgA protease

Question 27

What is one short-coming of Pneumovax, other than it being generally ineffective in the young pt population?

Answer 27

Immunity only lasts 5-7 years

Question 28

What is an issue with Prevnar?

Answer 28

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

Question 29

Which vaccine is given to children and infants to prevent pneumococcal meningitis? How many capsule types does it contain?

Answer 29

Prevnar--> contains 13 capsule types; is a heptavalent, conjugated vaccine *can gen. Abs in children as young as 2 months

Question 31

What are the gram stain and morphological characteristics of Neisseria meningitides?

Answer 31

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)

Question 32

What are 5 risk factors for Strep pneum infection?

Answer 32

1. Splenic dysfunction (apslenic, trauma, sickle cell) 2. Skull fracture 3. Cochlear implant 4. Recurrent otitis media 5. Immunocompromised (AIDS, etc)

Question 33

What is conditions are conducive to contracting N. meningitides (meningococcus)? Why?

Answer 33

Crowded places--> jails, military barracks, DORMS * spread via respiratory droplets, so high probability of spread in close quarters

Question 34

What is mortality rate for meningitis due to N. meningitides? What % of survivors have serious sequlae?

Answer 34

10-15% will die, despite treatment 10% may lose limbs, become deaf, suffer seizure/stroke, or become mentally retarded

Question 35

What 3 serotypes of N. meningitides are responsible for most sporadic (small number of related cases) outbreaks?

Answer 35

B, C, Y

Question 36

What serotype of N. meningitides is usually responsible for larege, epidemic outbreaks (large area, large # of cases)?

Answer 36

A

Question 37

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?

Answer 37

Mental changes (agitation, confusion, coma)

Question 38

What general complication is usually responsible for the makority of deaths due to N. meninigitides?

Answer 38

Fulminant meningococcemia--> occur in 10-15% of patients with meningococcal disease

Question 39

What is a late sign of meningococcal meningitis that would signal bad sepsis?

Answer 39

Sudden appearance of widespread petechial and purpuric skin rash

Question 40

What is the usual cause of death in patients with severe meningococcal meningitis with meningococcemia?

Answer 40

Pulmonary insufficiency--> pts usually die w/in 24 hrs of hospitilization despite Abx and intensive therapy

Question 41

What is the ony known reservoir for N. meningitides?

Answer 41

Human nasopharynx --> attach to nonciliated columnar epithelial cells via pili

Question 42

What mechanism do N. meningitides employ that allow for invasion of mucosal cells?

Answer 42

Phase Variation (can turn off capsular genes, then turn back on again once back in the bloodstream)

Question 43

What is the major virulence factor for N. meningitides other than its anti-phagocytic capsule?

Answer 43

Lipooligosaccharide (LOS)--> is an endotoxin

Question 44

Why is routine vaccination against N. meningitides not reccomended?

Answer 44

Risk of infection is low; vaccines are usually ineffective in children as well * A, C, AC, and ACYW135 capsular vaccines do exist however

Question 45

What does no vaccine currently exist for group B polysaccharide serorypes of N. meningitides?

Answer 45

Because it is a homopolymer of human sialic acid--> normal human cell constituent so is not immunogenic

Question 46

What is DOC for meningococcal meningitis and meningococcemia?

Answer 46

Penicillin (plus dexamethasone)

Question 47

Which N, meningitides vacine is recommended for all children 11-12 years old? What is different about it compared to the other?

Answer 47

Menactra--> conjugated to a toxin, so produces an anamnestic response *licensed for use in 11-55 year olds

Question 48

What is Phase Variation? By what two mechanisms do meningcocci do this?

Answer 48

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)

Question 49

Which meningococcus vaccine is non-conjugated (no memory response) and given to high risk patients and military personnel?

Answer 49

Menomune--> is a carbohydrate vaccine *also given to cochlear transplant patients and those travelling to subsaharan africa (known as the meningitis belt)

Question 50

What is the gram stain and morphological characteristics of H. flu?

Answer 50

Gram negative rods

Question 51

What three diseases can H. flu cause?

Answer 51

1. otitis media 2. respiratory dz 3. meningitis (especially in children)

Question 52

What is Antigenic Variation? What do meningococci use this mechanism to alter?

Answer 52

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)

Question 53

What is Hib, the current H. flu vaccine conjugated to?

Answer 53

Is type b capsular polysaccharide conjugated to a diptheria toxin

Question 54

What age children should receive Hib, the H. flu vaccination?

Answer 54

Infants between the ages of 2 and 15 months

Question 55

Which serotype of H. flu is the most important human pathogen?

Answer 55

Serotype b

Question 56

What is H. flu the second most common cause of?

Answer 56

Otitis media (2nd to S. pneum)

Question 57

What special medium does H. flu need to grow in culture?

Answer 57

CAP--> contains Factor V and Factor X * V = NAD/NADP * X = Hemin

Question 58

What causes most of the rare (~300 cases in U.S. per year) of H. flu related meninigitis?

Answer 58

Cases are in non-immunized children or due to non-typable H. flu (so vaccine wouldnt confer protection)

Question 59

What is special about Listeria's life cycle?

Answer 59

It is a facultative intracellular parasite

Question 60

In what two specific populations is Listeria a fairly significant cause of meningitis or other serious disease?

Answer 60

1. Pregnant women (associated with vaginal colonization; stereotypically due to pregnant women eating soft cheeses like feta, etc.) 2. AIDS patients (get listeria @ 300x the incidence rate of normal population 3. Older patients (also have poor immune function) * really any immunocompromised state (pregnancy is also one of these)

Question 61

What are the gram stain and morphological characteristics of Listeria monocytogenes?

Answer 61

Gram positive rod

Question 62

How can Listeria grow even on things that have been pasteurized?

Answer 62

Pasteurization is not 100%; any surviving Listeria actually grow well at refrigerator temps, so cold storage may actually amplify Listeria populations

Question 63

What bacterial protein does Listeria have that mediates entry into non-phagocytic cells?

Answer 63

Internalin--> binds to E-cadherin

Question 64

What two places in the body can Listeria colonize?

Answer 64

1. G.I. tract | 2. Vagina

Question 65

What bacterial product allows Listeria to escape the phagolysosome once endocytosed?

Answer 65

Listeriolysin O

Question 66

Why can't macrophages destroy Listeria?

Answer 66

They require cytokine activation so need the immune sytem's help

Question 67

What bacterial protein allows Listeria to directly spread cell-to-cell?

Answer 67

F-actin

Question 68

Which strep are group B strep, the most common cause of bacterial meningitis in children form birth to 3 months?

Answer 68

Streptococcus agalactiae

Question 69

What is used to determine the specific serotype of S. pneumoniae?

Answer 69

Capsular polysaccharide

Question 70

What two drug options should be used to treat meningococcus if a person is allergic to penicillin?

Answer 70

Chloramphemicol or a 3rd gen. cephalosporin (cefotaxime or ceftriaxone)

Question 71

What is a main difference between N. meningitides and N. gonarrhoeae (the two main pathogenic strains of Neisseria)?

Answer 71

N. meningitides (aka meningococcus) has a prominent antiphagocytic polysaccharide capsule, other doesn't * MC serogroups are A, B, C, Y, and W135

Question 72

Which strep are Group A strep?

Answer 72

Streptococcus pyogenes