Similar a Current epidemiology of meningococcal disease in the UK and Europe, including issues for surveillance relating to a MenB vaccine costs of meningitis
Similar a Current epidemiology of meningococcal disease in the UK and Europe, including issues for surveillance relating to a MenB vaccine costs of meningitis (20)
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Current epidemiology of meningococcal disease in the UK and Europe, including issues for surveillance relating to a MenB vaccine costs of meningitis
1. Invasive Meningococcal Disease
in England & Wales
Shamez Ladhani, Pauline Kaye and Mary Ramsay
Immunisation Department
Public Health England Colindale
E-mail: shamez.ladhani@phe.gov.uk
2. ... on the basis of the available evidence, routine infant or
toddler immunisation using Bexsero is highly unlikely
to be cost-effective ...
... if the vaccine had no impact on ...carriage ....
adolescent immunisation is also unlikely to be costeffective....
4. Meningococcal Cases by Age & Year
England and Wales, 2006/07-2012/13
450
2006/2007
Number of cases
400
2007/2008
350
2008/2009
2009/2010
300
2010/2011
250
2011/2012
2012/2013
200
150
100
50
0
<1
1-4
5-9
10-14
15-19
20-24
Age Group (years)
25-44
45-64
≥
>=65
7. IMD Surveillance in England & Wales
•
PHE Meningococcal Reference Unit (MRU):
•
•
•
•
•
•
National service for species confirmation and capsular
grouping of invasive Neisseria meningitidis isolates
~ “Real-time” PCR-testing of clinical samples for molecular
diagnosis of IMD
Routinely requests clinical isolates for PCR-positive cases
Molecular characterisation of a proportion of isolates annually
Clinical & diagnostic support for IMD clusters & outbreaks
Laboratory support for meningococcal vaccine trials
8. IMD Surveillance in England & Wales
•
PHE Colindale
•
•
•
•
•
Enhanced national surveillance of IMD
Monitor MenC vaccination programme –
impact, effectiveness, replacement disease, population
immunity
Follow-up of clinical cases (when needed)
Public health advice and national guidance for management
of cases and contacts, including outbreaks
Modelling, carriage studies, vaccine trials, health economic
analyses and other relevant studies to inform national
immunisation policy
9. Alternative Data Sources: LabBase2
Labase2
•
Voluntary electronic reporting of laboratory-confirmed
clinically significant pathogens by NHS hospital
microbiology departments in England & Wales
• Proportion of laboratories reporting to LabBase2 has been
increasing over the past decade
• Currently ~ 83% of cases reported through LabBase2
• BUT:
- Only laboratory-confirmed cases
- No clinical data
- Variable quality and timing of reporting by laboratories
10. PCR Diagnosis for IMD
Number of cases
1400
B
C
W135
Y
Other
•
5,471 lab-confirmed cases by PHE MRU
during 2006/07-10/11 (5 years)
800
•
Average annual incidence: 1.8/100,000
600
•
Incidence in infants: 38.6/100,000
•
1,034 lab-confirmed cases in 2010/11
•
Only 14 cases in LabBase2 were not
reported to PHE MRU
1200
1000
400
200
0
Epidemiological year
11. Contribution of PCR-testing to IMD diagnosis
England & Wales, 1998/99-2012/13
3000
PCR ONLY
Number of Cases
2500
CULTURE ONLY
CULTURE AND PCR
2000
1500
1000
500
0
Epidemiological Year
12. Added Value of PCR-testing to IMD
Surveillance (England, 2009 and 2010)
•
25,379 specimens to MRU for PCR testing:
1,492 patients (6.8%) tested positive
•
Of 1,924 IMD cases:
1099 (57%) were confirmed by PCR only
432 (23%) by culture only
393 (20%) by both tests
•
Multiple PCR Specimens:
Of 2827 patients with multiple PCR-samples
submitted, only one patient had a discordant result
between two EDTA samples submitted on the same day.
•
PCR sensitivity against cultures:
Comparing PCR-negative/culture-positive samples taken
on the same day (n=5) to cases confirmed by both
methods (n=393), the sensitivity of PCR was 99%
•
Comparison with LabBase2:
Only 47/509 (10%) isolates not submitted to PHE MRU
Heinsbroek et al. Journal of Infection (2013); 67: 385-90
But 36/47 (77%) had already been tested PCR-positive
13. Changing epidemiology of MenY disease
(England & Wales, 2006-2013)
40
A <1
B 1-4
C 5-9
D 10-14
E 15-19
F 20-24
G 25-44
H 45-64
I >=65
Number of MenY cases
35
30
25
20
15
10
5
0
2006/2007
2007/2008
2008/2009
2009/2010
2010/2011
Epidemiological Year
2011/2012
2012/2013
14. Recent increase in MenW cases
(England & Wales, 2006-2013)
Number of MenW cases
60
Other
50
2a
40
33
30
2
20
10
18
11
1
20
5
20
15
15
17
15
10
0
2a
Other
2006/2007
2007/2008
1
18
2
20
2008/2009
2009/2010
2010/2011
2011/2012
2012/2013
15
5
15
11
15
20
10
33
17
Epidemiologocal Year
15. Are we truly capturing all
invasive meningococcal
cases?
16. Estimating the total burden of IMD in
England using multiple national data sources
MRU DATABASE
ELECTRONIC LAB REPORTS
INDIVIDUAL
HOSPITAL
ADMISSIONS
DEATH
NOTIFICATIONS
17. National Data Sources: HES
•
HES
•
Hospital Episode Statistics for all hospital admissions in
England only
• Data format requires complex analysis, especially if linking
with other data sources
• Diagnosis based on ICD-10 codes at discharge
• BUT
- Only includes hospitalised cases
- Coding may be non-specific (e.g. meningitis, pneumonia)
- No laboratory-confirmation (clinically diagnosed cases vs.
petechial rash treated with 7 days of IV antibiotics)
18. National Data Sources: ONS Deaths
•
Death Registrations
•
ICD10 codes and cause of death available electronically for
all death registrations in England
• May identify non-hospitalised cases at post-mortem (although
usually still need laboratory-confirmation)
• Allows assessment of timing and cause of death for
laboratory-confirmed IMD cases
• BUT:
- Least specific data source for pathogen-specific disease
- Pathogen may not be known at the time of registration
- Pathogen may not be reported even if known (“meningitis”)
21. Completeness of case ascertainment
(England & Wales, 2007-2011)
1600
1400
1200
1000
168
433
433 cases: coded as IMD in HES, but not linked to MRU
265
22
293
22 cases: coded in ONS as IMD but not linked to MRU or
HES
800
293 cases: MRU-positive, infection-related ICD10 code in
HES for most (~87.5%) cases
600
400
787
200
787 cases: MRU Positive & coded as IMD in HES
0
IMD Cases
22. Completeness of case ascertainment
(England & Wales, 2007-2011)
1600
1400
1200
1000
168
433
265
168 cases: coded as IMD in HES but no lab-confirmation
265 cases: Coded as IMD in HES but MRU-negative
22
HES cases that were PCR-negative
400
800
600
400
787
200
Number of Cases
293
300
200
100
0
0
5
10
15
20
25
Interval (days) between admission and testing
0
IMD Cases
30
23. Age distribution of HES cases that were
MRU-confirmed, MRU-negative & unmatched
24. Conclusions
Current surveillance of IMD in England and Wales relies on PHE MRU
•
National Reference Centre for clinical isolates and PCR-testing
•
Standardised methodology – consistent over time
•
Allows molecular surveillance of meningococci causing IMD
PHE monitors completeness of case ascertainment at regular
intervals using multiple alternative national datasets
•
Currently surveillance captures >90% of laboratory-confirmed cases
•
Redundancy in free PCR-testing service ensures high case ascertainment
PHE working to develop standardised methodology for routinely
linking multiple national datasets to enhance IMD surveillance
•
Particular emphasis on cases without laboratory confirmation
25. Pathogens causing Bacterial Meningitis
(LabBase2, England & Wales, 2004-2011)
Adults (≥15 years)
0.3
2
nm
1.6
spn
1.2
gbs
0.8
ecoli
0.4
hi
0
2004 2005 2006 2007 2008 2009 2010 2011
Year
Incidence per 100,000
Incidence per 100,000
Children (<15 years)
nm
0.2
spn
gbs
0.1
ecoli
hi
0
2004 2005 2006 2007 2008 2009 2010 2011
Year