Meningococcus

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pathogen

  • Neisseria meningitidis
  • gram negative diplococci
  • carriage in nasopharynx
  • 12 identified capsular serogroups
  • common pathogenic serogroup A, B, C, W, X, Y
  • seasonal epidemics by group A, C
    • meningitis belt
  • sporadic cases by e.g. group B
    • Latin America
    • Norway
    • New Zealand
  • immunity generated by polysaccharide capsule except B
    • may be the reason that herd immunity development relatively slow and sporadic outbreaks continue in above countries

epidemiology

  • highest < 2 y/o and adolescent
  • annual outbreak during dry season in meningitis belt
    • dry winds make people's nose drier resulting in easier capture and membrane breakthrough
  • wide range difference of nasopharynx carriage between countries
    • reason totally unknown
    • NZ & 3%
    • Nigeria muslim boarding school 30-40%
  • 日本で戦後急速に発生が減ったのは,抗菌薬の導入普及と発熱早期での過剰投与,および住宅環境の改善による小児の集蔟が減少したためかもしれない

transmission

  • aerosol
  • fomite
  • adolescent activity

clinical picture

  • fever
  • distinctive petechiae anywhere in whole body
    • apparent pain accompanies with petechia in contrast to dengue
    • in earlier stage rashes are inflammation, not petechiae
  • no fading by pressure with glass tumbler - "tumbler test"
  • resulting in purple bruising of skin
  • photophobia
  • headache, neck stiffness, vomiting
  • irritability and/or confusion

vaccine

development history

  • 1960s - purified PS vaccines for A and C
    • immunity short term due to lack of T-cell involvement
  • 1990s - conjugated vaccines for A and C after success of Hib conjugate vaccine
  • 2000s - monovalent A vaccine for Africa
    • "MenAfriVac"

Development history of meningococcal vaccine.jpg

current vaccines

  • A polysaccharide
    • MenAfriVac
  • C conjugate
  • A,C,Y,W135 conjugate
    • Menactra (Sanofi Pasteur)
    • Menveo (GSK)
    • Nimenrix (Pfizer)
  • B protein (not polysaccharide)
    • Bexsero (GSK)
    • Trumenba (Pfizer)
    • VA-MENGOC-BC (Finlay Institute of Cuba)

issues of men B vaccine

  • polysaccharide of B is relatively low immunogenic
    • the reason is considered because of interaction between B polysaccharide and fetal brain tissue, resulting in possible immunotolerance
      • interaction is observed as antibodies against B-PS have also affinity to fetal brain tissue
    • it means B-PS vaccine has potential of neurological damage for young infants
  • currently available men B vaccines are protein-based vaccine, not PS vaccine
    • proteins expressed on the surface of N. meningitidis group B are purified through bacterial culture

Interactions of MenACWY conjugate vaccines and other vaccines

MenACWY-DT
  • conjugated with diphtheria toxoid
  • メナクトラ Menactra
MenACWY-TT
  • conjugated with tetanus toxoid
  • メンクアッドフィ MenQuadfi
PCV7
  • conjugated with DT
  • In a clinical trial of Menactra1)
  • Concomitant administration of Menactra+PCV7 at 12 months of age showed unmet non-inferiority criteria of pneumococcal IgG in 3 serotypes out of 7 in PCV7
PCV13
  • conjugated with DT
  • MenQuadfi+PCV13 can be administered concomitantly2), though SBA of serogroup A was lower of unknown clinical relevance
Td
  • In an RCT1)
  • Serum bactericidal assay (SBA) titers of serogroups C, W and Y in 11-17 years of age were higher in concomitant administration of Menactra+Td than single Menactra
DTaP
  • containing DT & TT
  • In an RCT1)
  • SBA titers of all 4 serogroups in 4-6 years of age were lower in [DTaP (DAPTACEL) → 30days → Menactra] than in [Menactra → 30days → DTaP (DAPTACEL)]
Tdap
  • containing DT & TT
  • MenQuadfi+Tdap can be administered concomitantly2), though antibody titer against pertussis antigen PT was non-inferior whereas titers against pertussis FHA, RPN and FIM were lower of unknown clinical relevance