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Prospects for preventing bacterial meningitis
Elizabeth Miller
Immunisation Department
Centre for Infections
Health Protection Agency,
Colindale, London
Bacteraemia
Soft Tissue Infection
Arthritis
Sinusitis
Otitis Media
Meningitis
Pneumonia
Peritonitis
The Clinical Spectrum of Pneumococcal Disease
Outcomes of bacterial meningitis by causative organism
Meta-analysis of prospective cohort studies from developed countries: Baraff et al.
0
5
10
15
20
25
30
Mortality Retardation Spasticity/paresis Deafness Seizure Disorder
% o
f C
hild
ren
S.pneumoniae
N.meningitidis
H.influenzae
% o
f ch
ildre
n
Pneumococcal Meningitis - Proportion of cases infected with a conjugate vaccine serotype1998-2004
0.0%
20.0%
40.0%
60.0%
80.0%
100.0%
a. <2m b. 2-5m c. 6-11m d. 1-4y e. 5-9y f. 10-79y g. 80+Age Group
7valent 9valent 11valent
Age group Annual no. (mean 1998-04)
No.with 7 valent serotype
Annual cases in 1st year with
<2 m 5 2 5
2-5 m 30 18 21
6-11 m 46 37 10
1-<2 yrs 25 21 6
2-4 yrs 17 14 17
5-14 yrs 10 5 10
15-44 yrs 43 18 43
45-64 56 23 56
65+ yrs 49 25 49
Total* 281 163 217*excludes 13 with age NK
Predicted effect in 1st year on number of pneumo meningitis cases of a 7 valent conjugate catch-up to 2 years, (no herd immunity,
100% instant uptake)
Meningococcal Disease
Annual meningococcal cases and deaths by serogroup
and year: E&W 1998-2004
0
200
400
600
800
1000
1200
1400
1600
1800
1998 1999 2000 2001 2002 2003 2004
BC
0
20
40
60
80
100
120
1998 1999 2000 2001 2002 2003 2004
Cases Deaths
Number of deaths by age group from meningococcal serogroup B disease, 1998-2004
0
20
40
60
80
100
120
140
160
1 2 3-4 5-8 9-10 11-14 15-19 20-24 25+
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 11-15No. men tested 36 5 11 6 5 9No. 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:P1.1510 - 14 years
83%
4:P1.153 months - 6 years 47-74%
Norway 15:P1.1611 - 16 years 57%
Chile 15:P1.31 - 21 years 51%
Year Age group VaccineCuba
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-3rd dose) against
homologous and heterologous strains
0
10
20
30
40
50
60
70
80
90
Vaccinestrain
NewZealandstrain
UK strainMO1
240013
UK strainMO1
240101
UK strainM01
240149
UK strainM01
240185
UK strainM01
240355
SBA
Anti-OMV IgG
J Findlow et al – unpublished
The top 90%, PHLS MRU meningococcal group B serosubtype data, 01/10/2000 to 31/10/2001
0
20
40
60
80
100
serosubtype
Cumu
lative
plot of
each
serosu
btype
as a %
of all
menin
gococc
al B iso
lates
Serogroup distribution of IMD by year,all European countries in EU IBIS scheme
0%10%20%
30%40%50%60%70%
80%90%
100%
1999 2000 2001 2002 2003 2004
otherCB
Potential maximal coverage of serogroup B OMV vaccines in Europe, all countries and years combined
0%10%20%30%40%50%60%70%80%90%
100%
Cuban (P1.15) Walter Reed(P1.13)
Norwegian(P1.7,16)
NZ (P1.7,4) RIVM nonavalent
Potential coverage No coverage
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