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Prof Martin Antonio @ MRF's Meningitis and Septicaemia 2019

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PCV impact and the paediatric meningitis surveillance in West Africa

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Prof Martin Antonio @ MRF's Meningitis and Septicaemia 2019

  1. 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. 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. 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 24 35 D 23B 11C 12F 10 A 35D 23B 12F 12F 17F 12F 24 29 24 9L/9N 35B 12F 38 13 10A 12B 12F 29 15B/15C 35B 24 12F 15 B/15C 15 B/15C 22F 16F 24 2 11C 33F 15B/15C 12F 15B/15C 15B/1 5C 33F 12F 34 1 7F 1 1 1 1 5 5 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 5 5 1 1 1 5 1 1 1 5 7F 7F 1 1 1 1 1 1 5 1 1 7F 1 1 5 1 1 5 5 5 5 5 7F 5 5 6A 6A 6A 6A 19A 6A 6A 6A 6A 19A 3 6A 6A 6A 6B 23F 14 6E(6B) 19F 23F 6E(6B) 14 23F+ 19F 6E(6B) 6E(6B) 23 F 19F 19F 14 14 19F 23F 6E(6B) 6B 23F 14 23F 19F 14 6E(6B) 23F 14 6E(6B ) 9V 9V 19F 4 14 14 14 23F 14 14 14 23F 19F 19F 18C 14 14 23F 19F 14 23F 23F 18C 23F 6E(6 B) 6E (6B) 14 23F 14 18C 18C Nov el 6849 33 24 303 33 24 303 915 303 3404 802 340 4 4194 2447 6851 9931 2818 6850 3804 2174 6848 2211 68 57 3081 4194 4194 63 63 4194 9905 202 95 09 9488 361 5547 172 3207 3207 9929 9534 63 4187 9498 9490 9914 9929 9489 217 4194 2174 63 2208 273 33 29 6856 3081 260 303 618 618 61 8 618 618 61 8 618 618 618 618 618 61 8 61 8 618 618 618 618 618 618 612 33 24 2942 3339 63 34 04 2208 217 4103 8052 217 280 303 9500 280 10810 205 172 63 3339 63 63 1526 63 303 63 4187 303 12239 3081 2174 12 24 0 10 811 289 12241 3544 12725 3081 12726 5521 10812 989 3324 21 7 1233 30 3 63 63 217 802 2942 4194 63 5547 172 3081 3081 28 9 373 802 2208 172 1233 989 303 802 3081 6844 30 3 3544 3544 217 2160 1348 6847 3081 30 3 3339 217 217 5547 3207 55 42 55 42 12388 289 8949 63 2818 6856 3404 915 74 3804 3404 34043404 3544 289 10608~ 10161 11645 989 9498 910 10 60 8~ 3404 41 03 989 1778 11645 2010 2012 2009 2011 2009 2010 2010 2010 2010 2011 2010 2011 2010 2011 2010 2010 2010 2010 2010 2010 2010 2010 2010 2011 2011 2012 2011 2012 2012 2012 2012 2012 2011 2013 20122012 2013 2012 2012 2011 2012 2012 2011 2013 2012 2012 2012 2012 2012 2013 2011 2011 2007 2011 2011 2010 2010 2007 2010 2010 2010 2010 2011 2011 2011 2009 2010 2010 2008 2009 2009 2010 2011 2010 2009 2010 2011 2011 2011 2011 2011 2012 2011 2011 2011 2011 2011 2010 2012 2012 2011 2011 2012 2011 2010 2012 2012 2012 2013 2011 2011 2011 2011 2011 2012 2010 2011 2010 2013 2013 2011 2011 2012 2011 2011 2012 2012 2011 2012 2011 2009 2011 2013 2011 2011 2011 2011 2011 2011 2012 2010 2010 2013 2010 2013 2013 2013 2011 2011 2013 2013 2012 2011 2012 2010 2011 2011 2012 2012 2010 2009 2010 2010 2010 2012 2012 2012 2012 2015 2015 2015 2012 2010 2007 2010 2010 2010 2015 2015 2015 2016 2015 2015 2016 2015 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. 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. 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. 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. 7. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine Standardized Structure
  8. 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. 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. 10. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
  11. 11. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
  12. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 22. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine 22 PCV vaccine introduction and coverage in WA 2018 ( WUENIC)
  23. 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. 24. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine Love them or loathe them
  25. 25. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine Martin Antonio, Isaac Adewole, Chikwe Ihekweazu
  26. 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. 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. 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. 29. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine
  30. 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. 31. MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine Acknowledgements

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