Prospects for preventing bacterial meningitis Prospects for preventing bacterial meningitis

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Prospects for preventing bacterial meningitis Prospects for preventing bacterial meningitis

  1. 1. Prospects for preventing bacterial meningitis Elizabeth Miller Immunisation Department Centre for Infections Health Protection Agency, Colindale, London
  2. 2. The Clinical Spectrum of Pneumococcal Disease Bacteraemia Soft Tissue Infection Arthritis Sinusitis Otitis Media Meningitis Pneumonia Peritonitis
  3. 3. Outcomes of bacterial meningitis by causative organism Meta-analysis of prospective cohort studies from developed countries: Baraff et al. % of children
  4. 5. *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
  5. 6. Meningococcal Disease
  6. 7. Annual meningococcal cases and deaths by serogroup and year: E&W 1998-2004 Cases Deaths
  7. 8. Number of deaths by age group from meningococcal serogroup B disease, 1998-2004 Age (years) Total identified deaths 442 Mean 63/yr
  8. 9. Ideal requirements for a Men (B) vaccine <ul><li>Able to be licensed on basis of correlate of protection </li></ul><ul><ul><li>Agreed protective level of serum bactericidal antibody </li></ul></ul><ul><ul><li>International standardisation of SBA assay </li></ul></ul><ul><ul><li>Supportive evidence from other assays e.g. OPA, CMI </li></ul></ul><ul><li>High coverage of prevalent strains </li></ul><ul><li>Long-term persistence of SBA above protective threshold </li></ul>
  9. 10. 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.
  10. 11. Ideal requirements for a Men B vaccine <ul><li>Able to be licensed on basis of correlate of protection </li></ul><ul><ul><li>Agreed protective level of serum bactericidal antibody </li></ul></ul><ul><ul><li>International standardisation of assays </li></ul></ul><ul><ul><li>Supportive evidence from other assays e.g. OPA, CMI </li></ul></ul><ul><li>High coverage of prevalent strains </li></ul><ul><li>Long-term persistence of SBA above protective threshold </li></ul><ul><li>Reduce carriage and thus able to induce herd immunity: </li></ul><ul><ul><li>Continuing protection for vaccinated if efficacy wanes </li></ul></ul><ul><ul><li>Able to protect the unvaccinated </li></ul></ul>
  11. 12. 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
  12. 13. % 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
  13. 15. Serogroup distribution of IMD by year, all European countries in EU IBIS scheme
  14. 16. 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
  15. 17. Serogroups A, C, Y and W135 Serogroup B Conclusion
  16. 18. Acknowledgements <ul><li>Rob George and staff of the HPA Respiratory & Systemic Laboratory, Colindale </li></ul><ul><li>Usha Gungabissoon and Mary Ramsay, HPA, Immunisation Department, Colindale </li></ul><ul><li>Ray Borrow, Ed Kaczmarski and staff at the HPA Meningococcal Reference Unit </li></ul><ul><li>MRF for funding our trials with OMV vaccines </li></ul>

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