Prospects for preventing bacterial meningitis 	 Prospects for preventing bacterial meningitis
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Prospects for preventing bacterial meningitis Prospects for preventing bacterial meningitis

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Prospects for preventing bacterial meningitis 	 Prospects for preventing bacterial meningitis Prospects for preventing bacterial meningitis Prospects for preventing bacterial meningitis Presentation Transcript

  • Prospects for preventing bacterial meningitis Elizabeth Miller Immunisation Department Centre for Infections Health Protection Agency, Colindale, London
  • The Clinical Spectrum of Pneumococcal Disease Bacteraemia Soft Tissue Infection Arthritis Sinusitis Otitis Media Meningitis Pneumonia Peritonitis
  • Outcomes of bacterial meningitis by causative organism Meta-analysis of prospective cohort studies from developed countries: Baraff et al. % of children
  •  
  • *excludes 13 with age NK Predicted effect in 1 st year on number of pneumo meningitis cases of a 7 valent conjugate catch-up to 2 years, (no herd immunity, 100% instant uptake) 217 163 281 Total* 49 25 49 65+ yrs 56 23 56 45-64 43 18 43 15-44 yrs 10 5 10 5-14 yrs 17 14 17 2-4 yrs 6 21 25 1-<2 yrs 10 37 46 6-11 m 21 18 30 2-5 m 5 2 5 <2 m Annual cases in 1 st year with No.with 7 valent serotype Annual no. (mean 1998-04) Age group
  • Meningococcal Disease
  • Annual meningococcal cases and deaths by serogroup and year: E&W 1998-2004 Cases Deaths
  • Number of deaths by age group from meningococcal serogroup B disease, 1998-2004 Age (years) Total identified deaths 442 Mean 63/yr
  • Ideal requirements for a Men (B) vaccine
    • Able to be licensed on basis of correlate of protection
      • Agreed protective level of serum bactericidal antibody
      • International standardisation of SBA assay
      • Supportive evidence from other assays e.g. OPA, CMI
    • High coverage of prevalent strains
    • Long-term persistence of SBA above protective threshold
  • Invasion can lead within 12 hours to fulminant sepsis Time interval from exposure to onset in UK laboratory workers: Case 1 Case 2 Case 3 Case 4 Case 5 3 days 5 days within 7 days 4 days 5 days Carrier status of military recruits prior to disease Day pre-admission 0 1-2 3-4 5-7 8-10 11-15 No. men tested 36 5 11 6 5 9 No. men +ve NP 36 1 4 0 0 0 Boutet et al . J Hosp Infect 2001;49:282-4. Edwards et al. Scand J Infect Dis 1977;9:105-110.
  • Ideal requirements for a Men B vaccine
    • Able to be licensed on basis of correlate of protection
      • Agreed protective level of serum bactericidal antibody
      • International standardisation of assays
      • Supportive evidence from other assays e.g. OPA, CMI
    • High coverage of prevalent strains
    • Long-term persistence of SBA above protective threshold
    • Reduce carriage and thus able to induce herd immunity:
      • Continuing protection for vaccinated if efficacy wanes
      • Able to protect the unvaccinated
  • Meningococcal OMV vaccine trials (2 doses) Estimated efficacy 1987-89 4:P1.15 10 - 14 years 83% 4:P1.15 3 months - 6 years 47-74% Norway 15:P1.16 11 - 16 years 57% Chile 15:P1.3 1 - 21 years 51% Year Age group Vaccine Cuba Brazil 1989-91 1989-91 1987-89
  • % of adults given Norwegian strain OMV vaccine with > 4 fold rises in SBA and anti-OMV IgG (pre- to post-3 rd dose) against homologous and heterologous strains J Findlow et al – unpublished
  •  
  • Serogroup distribution of IMD by year, all European countries in EU IBIS scheme
  • Potential maximal coverage of serogroup B OMV vaccines in Europe, all countries and years combined Assumptions – any PorA variant that is picked up by monoclonal will be prevented by vaccine containing any variant of the same subtype family, ignoring any PorB protection
  • Serogroups A, C, Y and W135 Serogroup B Conclusion
  • Acknowledgements
    • Rob George and staff of the HPA Respiratory & Systemic Laboratory, Colindale
    • Usha Gungabissoon and Mary Ramsay, HPA, Immunisation Department, Colindale
    • Ray Borrow, Ed Kaczmarski and staff at the HPA Meningococcal Reference Unit
    • MRF for funding our trials with OMV vaccines