prospects for preventing bacterial meningitis prospects for preventing bacterial meningitis
TRANSCRIPT
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Prospects for preventing bacterial meningitis
Elizabeth Miller
Immunisation Department
Centre for Infections
Health Protection Agency,
Colindale, London
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Bacteraemia
Soft Tissue Infection
Arthritis
Sinusitis
Otitis Media
Meningitis
Pneumonia
Peritonitis
The Clinical Spectrum of Pneumococcal Disease
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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
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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
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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)
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Meningococcal Disease
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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
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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
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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
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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.
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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
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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
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% 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
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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
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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
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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
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Serogroups A, C, Y and W135 Serogroup B
Conclusion
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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