Invasive Meningococcal Disease
in England & Wales
Shamez Ladhani, Pauline Kaye and Mary Ramsay
Immunisation Department
Pub...
... on the basis of the available evidence, routine infant or
toddler immunisation using Bexsero is highly unlikely
to be ...
Invasive Meningococcal Disease
Laboratory-confirmed Cases

England & Wales, 1998/99 to 2012/13
3000
Ungrouped
Other
Y
W
C
...
Meningococcal Cases by Age & Year
England and Wales, 2006/07-2012/13
450
2006/2007

Number of cases

400

2007/2008

350

...
Where do these
figures come from?
IMD Surveillance in England & Wales
•

PHE Meningococcal Reference Unit (MRU):
•
•
•
•
•
•

National service for species c...
IMD Surveillance in England & Wales
•

PHE Colindale
•
•

•
•
•

Enhanced national surveillance of IMD
Monitor MenC vaccin...
Alternative Data Sources: LabBase2
Labase2
•

Voluntary electronic reporting of laboratory-confirmed
clinically significan...
PCR Diagnosis for IMD

Number of cases

1400

B

C

W135

Y

Other

•

5,471 lab-confirmed cases by PHE MRU
during 2006/07...
Contribution of PCR-testing to IMD diagnosis
England & Wales, 1998/99-2012/13
3000
PCR ONLY

Number of Cases

2500

CULTUR...
Added Value of PCR-testing to IMD
Surveillance (England, 2009 and 2010)
•

25,379 specimens to MRU for PCR testing:
1,492 ...
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-...
Recent increase in MenW cases
(England & Wales, 2006-2013)

Number of MenW cases

60

Other

50

2a

40
33

30
2

20
10

1...
Are we truly capturing all
invasive meningococcal
cases?
Estimating the total burden of IMD in
England using multiple national data sources

MRU DATABASE

ELECTRONIC LAB REPORTS

...
National Data Sources: HES
•

HES
•

Hospital Episode Statistics for all hospital admissions in
England only
• Data format...
National Data Sources: ONS Deaths
•

Death Registrations
•

ICD10 codes and cause of death available electronically for
al...
ICD10 Codes for Bacterial Meningitis & IMD
ICD10 codes: A39* and G00* expanded
Completeness of case ascertainment
(England & Wales, 2007-2011)
1600

1400
1200
1000

168

433

433 cases: coded as IMD in...
Completeness of case ascertainment
(England & Wales, 2007-2011)
1600

1400
1200
1000

168

433
265

168 cases: coded as IM...
Age distribution of HES cases that were
MRU-confirmed, MRU-negative & unmatched
Conclusions
Current surveillance of IMD in England and Wales relies on PHE MRU
•

National Reference Centre for clinical i...
Pathogens causing Bacterial Meningitis
(LabBase2, England & Wales, 2004-2011)

Adults (≥15 years)
0.3

2
nm

1.6

spn

1.2...
Acknowledgements
MenB Cases
45-64 ≥ 65 NK Total

<1

1-4

5-9 10-14 15-19 20-24

2544

2006/07

274

314

83

28

102

44

53

56

30

3

9...
Disease in <2 year-olds
40
Ungrouped

Number of reports

35
Other groups

30

ACWY

25

B

20
15
10
5

0

0 1 2 3 4 5 6 7 ...
Disease in <24 year-olds
300

Number of reports

Ungrouped
250

Other groups

200

ACWY

150

B

100
50
0
0 1 2 3 4 5 6 7 ...
Current epidemiology of meningococcal disease in the UK and Europe, including issues for surveillance relating to a MenB v...
Current epidemiology of meningococcal disease in the UK and Europe, including issues for surveillance relating to a MenB v...
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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

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Dr Shamez Ladhani's presentation from Meningitis Research Foundation's 2013 conference Meningitis & Septicaemia in Children & Adults

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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. 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. 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....
  3. 3. Invasive Meningococcal Disease Laboratory-confirmed Cases England & Wales, 1998/99 to 2012/13 3000 Ungrouped Other Y W C B 2500 2000 1500 1000 500 0 Epidemiological Year
  4. 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
  5. 5. Where do these figures come from?
  6. 6. 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
  7. 7. 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
  8. 8. 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
  9. 9. 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
  10. 10. 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
  11. 11. 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
  12. 12. 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
  13. 13. 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
  14. 14. Are we truly capturing all invasive meningococcal cases?
  15. 15. Estimating the total burden of IMD in England using multiple national data sources MRU DATABASE ELECTRONIC LAB REPORTS INDIVIDUAL HOSPITAL ADMISSIONS DEATH NOTIFICATIONS
  16. 16. 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)
  17. 17. 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”)
  18. 18. ICD10 Codes for Bacterial Meningitis & IMD
  19. 19. ICD10 codes: A39* and G00* expanded
  20. 20. 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
  21. 21. 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
  22. 22. Age distribution of HES cases that were MRU-confirmed, MRU-negative & unmatched
  23. 23. 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
  24. 24. 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
  25. 25. Acknowledgements
  26. 26. MenB Cases 45-64 ≥ 65 NK Total <1 1-4 5-9 10-14 15-19 20-24 2544 2006/07 274 314 83 28 102 44 53 56 30 3 987 2007/08 274 357 78 32 117 42 74 72 31 5 1082 2008/09 284 335 70 39 111 46 51 82 30 4 1052 2009/10 210 236 53 36 77 41 50 51 27 5 786 1042 1242 284 135 407 173 228 261 118 17 3907 Total
  27. 27. Disease in <2 year-olds 40 Ungrouped Number of reports 35 Other groups 30 ACWY 25 B 20 15 10 5 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 Age (months)
  28. 28. Disease in <24 year-olds 300 Number of reports Ungrouped 250 Other groups 200 ACWY 150 B 100 50 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Age (years)

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