Neisseria meningitidis (meningococcus)

Question 1

Neisseria in general

Answer 1

• paired kidney beans
• contain endotoxin in outer membrane-> consist of lipooligosaccharide(LOS)
• LPS & LOS contain lipid A, but LOS oligosaccharide part ->few sugars; LPS polysaccharide part-> long repeating sugar side chain.
• growth inhibited by toxic
  trace metals & fatty acids found in culture media
  (blood agar plates)-> cultured on chocolate agar containing blood heated to 80°C-> inactivates inhibitors.
• oxidase-positive (possess enzyme cytochrome c).
• lab diagnostic test-> colonies exposed to phenylenediamine turn purple or black as a result of oxidation of reagent by enzyme.

Moraxella catarrhalis-> normal throat flora -> respiratory tract infections
(sinusitis, otitis media, bronchitis, & pneumonia).

Question 2

Important properties

Answer 2

• prominent
  polysaccharide capsule -> antiphagocytic action.
• vaccine immunogen-> induces protective antibodies
• divided into 13 serologic
  groups based on antigenicity of capsular
  polysaccharides.
• 5 -> most cases of meningitis & meningococcemia: A, B, C, Y, and W-135.

A -> epidemic meningitis
worldwide.

B-> not immunogenic polysaccharide, not part of vaccines that contain capsular polysaccharide of
other four groups.
- vaccine against B containing factor H binding protein as immunogen

Question 3

Pathogenesis & Epidemiology

Answer 3

• Humans-> natural hosts
• Transmitted by airborne droplets
• Colonize membranes of nasopharynx & become part of upper respiratory tract transient flora.
• Carriers-> asymptomatic.
• From nasopharynx,
  organism enter bloodstream & spread to meninges, joints, body (meningococcemia).

Carriage rate high-> people who live in close quarters (military recruits, family, dormitories).

• second to S. pneumoniae -> meningitis but common ages 2 & 18 years.

Resistance to disease correlates with presence of
antibody to capsular polysaccharide.
- carriers develop protective antibody titers within 2 weeks of colonization.
- immunity group-specific-> have protective antibodies to one group of organisms, be susceptible to infection by other groups organisms

Complement-> host defenses; people with complement deficiencies, [late-acting complement components (C6–C9)]->
increased incidence.

Question 4

4 virulence factors:

Answer 4

(1) polysaccharide capsule - enables organism
to resist phagocytosis by polymorphonuclear leukocytes (PMNs).
- immunogen capsule in vaccines

(2) Endotoxin
- fever, shock, reproduce

(3) Immunoglobulin A (IgA) protease
- bacteria attach to upper respiratory tract membranes by cleaving secretory IgA.

(4) Factor H binding protein (FHBP)
- binds Factor H(inhibitor of complement factor
C3b).
- presence of Factor H on meningococci surface
reduces opsonizing activity of C3b & amount of membrane attack complex produced
- immunogen FHBP in vaccine against group B.

Question 5

Manifestations of disease:
meningococcemia

Answer 5

severe form -> life-threatening
Waterhouse–Friderichsen syndrome
- high fever, shock, widespread purpura, disseminated
intravascular coagulation, thrombocytopenia, &
adrenal insufficiency.

• Bacteremia -> seeding
  of organs (meninges).

Question 6

Manifestations of disease:
meningitis

Answer 6

• symptoms similar to bacterial meningitis
• fever, headache, stiff neck, & increased level of PMNs in spinal fluid.

Question 7

Lab diagnosis

Answer 7

• meningitis-> gram-negative
  cocci in spinal fluid smear
• grows best on chocolate agar incubated at
  37°C in 5% CO2.
• presumptive diagnosis-> oxidase-positive colonies of gram - diplococci
• Differentiation between N. meningitidis & N. gonorrhoeae -> sugar fermentation: meningococci ferment maltose; gonococci do not (both ferment glucose).
• Immunofluorescence used.
• Serum antibodies not useful.
• Latex agglutination test (rapid test)-> detects capsular polysaccharide in spinal fluid.

Question 8

Treatment

Answer 8

• Penicillin G
• Ceftriaxone (3rd gen cephalosporin)
• penicillin-resistance rare - sulfonamide resistance-> common.
• ciprofloxacin resistant present.

Question 9

Prevention

Answer 9

• Chemoprophylaxis & immunization
• rifampin or ciprofloxacin
  -> prophylaxis in close contact -> efficiently secreted into saliva, in contrast to penicillin G.

Vaccines against groups A, C, Y, and W-135-> polysaccharide capsule as immunogen.
- 3 forms of polysaccharide vaccine

Vaccine against group B ->
Factor H binding protein as immunogen.

Question 10

Prevention: Vaccines against groups A, C, Y, & W-135

Answer 10

• 3 vaccines
• 2 forms of conjugate vaccine:
• Menactra-> 4 polysaccharides conjugated to
  diphtheria toxoid as carrier protein
• Menveo-> 4 polysaccharides conjugated to nontoxic
  mutant of diphtheria toxin as carrier protein.
• 1 unconjugate vaccine
• Menomune-> 4
  polysaccharides (not conjugated to carrier protein).
• conjugate vaccines induce higher titers of children antibodies than unconjugated.
• vaccines induce similar antibody titers in adults.
• No vaccines contain group B polysaccharide because not immunogenic in humans.
• 4th vaccine (Africa) -> MenAfriVac
• conjugate vaccine-> only group A polysaccharide.
• conjugate preferred over
  unconjugated.
• unconjugated prevents meningitis epidemics & reduces carrier rate (military personnel).
• Travelers to epidemic areas & College students in dormitories receive vaccine.
• No booster dose recommended after 16.
• Conjugate vaccine recommended for
  children 11 to 12, reduce disease in teens & young
  adults.
• booster dose recommended prior16.

Question 11

Prevention: Vaccines against group B

Answer 11

• contains immunogen Factor H binding protein
• induces antibody against binding protein inhibiting ability of bacteria to bind factor H.
• enhances complement action (host defense)-> factor H inhibits complement component
  C3b.
• Factor H binding protein in vaccine made by recombinant DNA techniques in Escherichia
  coli.
• 10 to 25 years
• 2nd vaccine -> 4 surface proteins (fHbp, NadA, NHBA, & PorA).