PCV impact and the paediatric meningitis surveillance in West Africa

1. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
PCV Impact and the paediatric meningitis
surveillance in West Africa
Martin Antonio
Medical Research Council Unit The Gambia at
London School of Hygiene & Tropical Medicine
Meningitis Research Foundation’s 12th International Conference
The British Museum, London
6th November, 2019

2. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Africa’s meningitis belts
• Long history (>100 years) of periodic meningitis outbreaks
associated with meningococcus (Greenwood, 2006)
Strategy for managing
meningitis epidemics in
Africa
The WHO strategy for the
control of epidemic
meningitis is based on three
key pillars:
• Surveillance
• Treatment and care
• Vaccination

3. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
• MRCG designated WHO RRL (2010) and WHOCC (2017)
• IBD surveillance in West and Central Africa (2009-2018)
• Supports 17 sentinel sites (largest paediatric hospitals) in ten West and
Central African countries
• WHO CC provides technical support during meningitis outbreaks in West
Africa - Platform for Research
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2010
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20102013
2015
2016
Vaccine type
NVT
PCV serotype
undetermined
Source
Blood
CSF
Lung
Pus
Country
Benin
Cameroon
DRC
Ghana
Ivory Coast
Niger
Nigeria
Senegal
The_Gambia
Togo
Tree scale: 0.1
Phylogeny of S. pneumoniae West Africa (2010-2016)
A maximum likelihood whole genome phylogenetic tree annotated
with serotype, MLST ST (blue), whether serotype is a vaccine type
and year of admission.
MRC Gambia @LSHTM hosts
WHOCC for New Vaccines Surveillance

4. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
IBD surveillance
IBD surveillance is part of:
• The global VP-IBD surveillance network
• Collects data related to the detection of 3 vaccine-preventable
organisms: Haemophilus influenzae, Streptococcus pneumoniae and
Neisseria meningitidis.
The global VP-IBD sentinel surveillance utilizes a 3-tiered
approach:
• Tier 1: surveillance targets children under-five with suspected meningitis
• Tier 2: surveillance also targets children under-five with pneumonia
and/or sepsis
• Tier 3: Population-based Surveillance (seeks to determine incidence
rates of VP-IBD) e.g. MRC Basse, The Gambia

5. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Goal: IBD surveillance
• Production of high quality, local information on the
causes of two major killers of children in West Africa;
Meningitis and Pneumonia.
• Enable decision makers to assess the possible value of
new vaccines using the best local evidence – their own
data not estimates
• Monitor the effect of vaccines post- introduction; sharing
information widely
• All West Africa countries are using PCV-13 except
Nigeria (PCV10)

6. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
WHO Member States that reported data to the Global Invasive Bacterial
Vaccine-Preventable Disease Surveillance Network, 2018

7. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Standardized Structure

8. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Study population
• Sentinel surveillance at the largest paediatric hospitals in
West & Central Africa
• Children <5 years of age admitted to the hospital with
signs & symptoms of probable bacterial meningitis &/or
symptoms of invasive bacterial disease (e.g. sepsis) were
recruited into the study.
• Probable meningitis is a suspected case with examination
of CSF showing at least Turbid appearance or WBC
(>100 cells/mm3) or WBC (10-100 cells/mm3) AND either
an elevated protein (>100 mg/dl) or decreased glucose
(<40 mg/dl)

9. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Summary of specimens received and processed 2010 - 2016
Suspected cases at
sentinel sites
38,404(100%)
CSF samples
collected
18034(48%)
Confirmed & probable
Screened by PCR
1171(7%)
PCR +ve
311(27%)
Serotyped
205(66%)
Suspected Screened
by PCR
7587(42%)
PCR +ve
606(8%)
Serotyped
418(69%)
Bacterial Isolates
327
Confirmed and
serotyped
270(82%)
Whole Genome
sequenced
176(65%)

10. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine

11. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine

12. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
WHO Regional Workshop & Capacity Building at
MRC Gambia @ LSHTM 28thOct -1st Nov 2019
Sheep blood collection for media preparation

13. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Baseline characteristics of suspected meningitis
cases in West & Central Africa: 2010 - 2016
Characteristic Category N %
Age
0-11m 18793 48.7%
12-23m 6570 17.0%
24-59m 12796 33.1%
Unknown 442 1.2%
Sex Female 16969 44.0%
Male 21464 55.6%
Unknown 168 0.4%
Antibiotic before admission
Yes 5516 14.3%
No 17055 44.2%
Unknown 16030 41.5%
Outcome
Discharged Alive 23829 61.7%
Died 2181 5.7%
Unknown 12591 32.6%
Sequelae
No 11758 30.5%
Yes 352 0.9%
Unknown 26491 68.6%
Case type* Confirmed 821 2.1%
Suspected 37780 97.9%

14. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Trends in meningitis and mortality among suspected
cases pre and post PCV in West & Central Africa (2010 –
2016)
200040006000
−4 −3 −2 −1 0 1 2 3 4 5
Years before/after vaccination
Suspectedmeningitis(count) A
100200300400
−4 −3 −2 −1 0 1 2 3 4 5
Years before/after vaccination
Mortality(count)
B
50100150200
−4 −3 −2 −1 0 1 2 3 4 5
Years before/after vaccination
Confirmedcases
C
234567
−4 −3 −2 −1 0 1 2 3 4 5
Years before/after vaccination
Casefatalityrate
D

15. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Trends in confirmed cases pre and post PCV
in West & Central Africa (2010 – 2016)
04080120
−4 −3 −2 −1 0 1 2 3 4 5
Years before/after vaccination
Confirmedcases
A
H. Influenzae
S. Pneumoniae
N. Meningitis
051020
−4 −3 −2 −1 0 1 2 3 4 5
Years before/after vaccination
Mortality(count)
B
H. Influenzae
S. Pneumoniae
N. Meningitis
051525
−4 −3 −2 −1 0 1 2 3 4 5
Years before/after vaccination
Numberofcases
C
PCV−13
Non−PCV13
• Sharp decline in S. pneumoniae
meningitis cases and deaths
• Steady decline in N. meningitidis
cases and deaths
• H. influenzae counts are stable
• Decline in meningitis caused by
PCV13 types

16. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
0100200300400500
2010 2011 2012 2013 2014 2015 2016
Benin
050100150200
2010 2011 2012 2013 2014 2015 2016
Cameroon
05101520
2010 2011 2012 2013 2014 2015 2016
Gambia
050100150
2010 2011 2012 2013 2014 2015 2016
Ghana
020406080
2010 2011 2012 2013 2014 2015 2016
Ivory Coast
050100150
2010 2011 2012 2013 2014 2015 2016
Niger
050100150
2010 2011 2012 2013 2014 2015 2016
Nigeria
051015202530
2010 2011 2012 2013 2014 2015 2016
Senegal
0102030
2010 2011 2012 2013 2014 2015 2016
Sierra Leone
020406080100
2010 2011 2012 2013 2014 2015 2016
Togo
SuspectedMeningitis(Count)
Year Year
• PCV impact appears variable
across different countries
• Benin and Ghana (high)
• Nigeria and Niger (low)
• Short surveillance period
post PCV implementation
Modelling pre and post PCV introduction trends in
suspected meningitis (2010-2016)

17. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
PVC impact by age
(2010 – 2016)
050100150200
2010 2011 2012 2013 2014 2015 2016
Benin
02060100
2010 2011 2012 2013 2014 2015 2016
Cameroon
0246810
2010 2011 2012 2013 2014 2015 2016
Gambia
020406080
2010 2011 2012 2013 2014 2015 2016
Ghana
01020304050
2010 2011 2012 2013 2014 2015 2016
Ivory Coast
020406080
2010 2011 2012 2013 2014 2015 2016
Niger
020406080100
2010 2011 2012 2013 2014 2015 2016
Nigeria
05101520
2010 2011 2012 2013 2014 2015 2016
Senegal
0510152025
2010 2011 2012 2013 2014 2015 2016
Sierra Leone
01020304050
2010 2011 2012 2013 2014 2015 2016
Togo
SuspectedMeningitis(Count)
Year Year
__
__
__
<12months
12−24months
24−59months
• Modelling pre and post PCV
introduction trends in suspected
meningitis by age
• Red: 0-11 months
• Blue: 12-23 months
• Green: 23 – 59 months
• PCV impact appears consistent
across age strata < 5 years old

18. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Trend estimates for PCV impact across West
and Central Africa (2010 – 2016)
RE Model, All
0 1 2 3 4 5
Togo
Nigeria
Niger
Ivory Coast
Sierra Leone
Senegal
Ghana
Gambia
Cameroon
Benin
1.241 [0.854, 1.804]
0.700 [0.362, 1.356]
1.491 [0.740, 3.006]
0.851 [0.547, 1.325]
1.416 [0.412, 4.868]
0.838 [0.652, 1.078]
0.722 [0.637, 0.817]
0.428 [0.303, 0.604]
0.213 [0.166, 0.275]
0.282 [0.206, 0.385]
0.650 [0.430, 0.981]
Long post vaccine follow up
Short post vaccine follow up
A) Suspected Meniningitis Ratio [95% CI]
0.487 [0.290, 0.817]RE Model, Subgroup
1.035 [0.776, 1.381]RE Model, Subgroup
Post/Pre vaccine trend ratio
Long post vaccine follow up
B) Mortality Ratio [95% CI]
Post/Pre vaccine trend ratio

19. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Trend estimates for PCV impact on mortality
across West and Central Africa (2010 – 2016)

20. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Trend estimates for PCV impact on mortality
across West and Central Africa (2010 – 2016)
RE Model, All
0 5 10 15 20
Togo 1.099 [0.448, 2.700]
0.737 [0.464, 1.172]
1.286 [0.719, 2.300]RE Model, Subgroup
Post/Pre vaccine trend ratio
RE Model for All Countries
0 1 2 3 4 5
Togo
Nigeria
Niger
Ivory Coast
Senegal
Ghana
Gambia
Cameroon
Benin
1.265 [0.324, 4.938]
0.367 [0.085, 1.584]
0.032 [0.004, 0.297]
0.534 [0.106, 2.680]
0.836 [0.410, 1.705]
0.707 [0.398, 1.255]
0.133 [0.030, 0.576]
0.886 [0.568, 1.382]
0.989 [0.403, 2.429]
0.728 [0.554, 0.957]
Long post vaccine follow up
Short post vaccine follow up
C) Confirmed Meniningitis Ratio [95% CI]
0.777 [0.581, 1.040]RE Model, Subgroup
0.360 [0.094, 1.379]RE Model, Subgroup
Post/Pre vaccine trend ratio
Post/Pre vaccine trend ratio

21. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
PCV in
15/17 countries except
Guinee: Gavi country
Capo Verde: Non Gavi country
21
PCV vaccine introduction and coverage in WA 2018
( WUENIC)

22. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
22
PCV vaccine introduction and coverage in WA 2018
( WUENIC)

23. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
• PCV has had an impact on suspected meningitis and
mortality among across the sub-region
• The impact is greater in some countries than others
• Short post-PCV surveillance in some countries is a
problem
• Overall, counts of N. meningitidis meningitis have also
declined while H. influenzae has remained stable.
Concluding remarks

24. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Love them
or loathe them

25. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Martin Antonio, Isaac Adewole, Chikwe Ihekweazu

26. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
UK Secretary of State for Foreign and Commonwealth
Affairs Rt Hon Boris Johnson MP visits MRC Unit The Gambia

27. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
UK Secretary of State for Foreign and Commonwealth Affai
Rt Hon Boris Johnson MP visits MRC Unit The Gambia

28. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
UK Secretary of State for Foreign and Commonwealth Affairs
Rt Hon Boris Johnson MP visits MRC Unit The Gambia

29. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine

30. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Acknowledgements
MRC @ LSHTM
• Brenda Kwambana-Adams
• Catherine Okoi
• Sheikh Jarju
• Archibald Worwui
• Research Molecular
Microbiology Team
Countries
• Country Ministries of Health
• WHO Country Offices
WHO
• Jason Mwenda
• Fatima Serhan
• Adam Cohen
NICD
• Anne Von Gottberg
• Linda de Gouveia
• Mignon d Plessis
CDC
• Fernanda Lessa
• Stephanie Schwartz
• Mahamoudou Ouattara

31. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
Acknowledgements