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Prof Kim Mulholland @ MRF's Meningitis & Septicaemia in Adults & Children

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Effectiveness of pneumococcal conjugate vaccines in developing countries
https://www.meningitis.org/mrf-conference-2017

Published in: Health & Medicine
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Prof Kim Mulholland @ MRF's Meningitis & Septicaemia in Adults & Children

  1. 1. Pneumococcal vaccines – impact in the developing world Kim Mulholland Murdoch Children’s Research Institute, Melbourne London School of Hygiene and Tropical medicine University of Melbourne
  2. 2. Pneumococcal vaccines - history • 1911 – 1st pneumococcal vaccine trial in South Africa • 1930-34 – 7-valent pneumococcal vaccine protected miners against types 1,2,3,5,7,12,14 (Pub South African Inst Med Research 1935;37:7) • 1945 – 4-valent vaccine (1,2,5,7) in US Air Force recruits – ↓ pneumococcal pneumonia – ↓ pneumococcal carriage of vaccine types (J Exp Med 1945;82:445-65) – Licensed by Squibb, abandoned in 1951
  3. 3. • 1960s – Robert Austrian argued that pneumococcus remained an important cause of death • 1977 – 14-valent PS vaccine licensed by Merck • 1983 – 23-valent PS vaccine licensed • 1986 – Trial of PS vaccine in Papua New Guinea children published (I Riley et al) • 1988 – work begins on pneumococcal conjugate vaccine (NIH-Praxis Biologics) • 1990 – Hib conjugate vaccine licensed for use in infants
  4. 4. • 2000 – Gavi Alliance launched • 2000 – 1st PCV licensed (PCV7 or Prevnar-7®, Wyeth Vaccines) – $57/dose – ST1 and ST5 excluded – PCV9 (with 1 & 5) produced and used in key trials in Gambia and South Africa • Around 2003 – PCV11 (Sanofi Pasteur) abandoned midway through Philippines trial • 2003 – Initiatives to make PCVs available – PneumoADIP – Advance Market Commitment – International Finance Facility for Immunization
  5. 5. • 2009 – PCV7 introduced into South Africa, Gambia and Rwanda
  6. 6. • 2009 – PCV7 introduced into South Africa, Gambia and Rwanda ES Donkor et al. Vaccination against pneumococcus in West Africa Int J Gen Med 2013;6:757-764 Invasive pneumococcal disease in West Africa
  7. 7. • 2009 – PCV7 introduced into South Africa, Gambia and Rwanda • 2009 – PCV10 licensed (Synflorix®, GSK) • 2010 – PCV13 licensed (Prevnar-13®, Pfizer) • 2011 – PCV13 introduced Gambia, S Africa • 2012 (April) – PCV13 introduced Ghana • 2016 – January-February major meningitis outbreak in Ghana – Most pneumococcus ST1
  8. 8. Ghana meningitis outbreak 2016 • Dec 2015 – March 2016 • Over 12 weeks: • 567/886 suspected cases had LP • 135 confirmed meningitis • 104 pneumococcal meningitis Brenda Kwambana-Adams et al. BMC Infectious Diseases 2016;16:575
  9. 9. Ghana meningitis outbreak 2016 Brenda Kwambana-Adams et al. BMC Infectious Diseases 2016;16:575
  10. 10. Ghana meningitis outbreak 2016 Kwambana-Adams BA et al. BMC Infectious Diseases 2016;16:575
  11. 11. Ghana pneumococcal meningitis cases Kwambana-Adams BA et al. BMC Infectious Diseases 2016;16:575 PCV introduced April 2012 6,10,14 weeks
  12. 12. Do PCVs protect against ST1 in Africa? • Gambia and SA PCV9 trials (combined) – Vaccinees – 5 – Controls – 5 • Is a late (booster) dose preferable to just a primary series? – Is 2+1 superior to 3+0? • OPA data suggests much better ST1 response after booster, so…
  13. 13. POET study (PCV11, GSK) OPA data 1 10 100 1000 10000 ST1 ST6B ST19F ST23F Chart Title post-primary pre-boost post-boost Vaccine 25 (2007) 1962–1968
  14. 14. UK Serotype 1 disease 2+1 schedule
  15. 15. Ghana pneumococcal meningitis cases Kwambana-Adams BA et al. BMC Infectious Diseases 2016;16:575 PCV introduced 4 years earlier
  16. 16. Unasnwered questions • Do PCV10 and PCV13 protect individuals/communities against ST1 disease? – Is 2+1 schedule better than 3+0? • Is there a role of monovalent type 1 PCV for controlling outbreaks? – Or combined with Mening. conjugate vaccine?
  17. 17. Pneumococcal conjugate vaccines • 7-valent Pnc-CRM (Prevnar7®, Wyeth/Pfizer) licensed in US, 2000 • 9-valent Pnc-CRM trialed in South Africa and Gambia, but never licensed (includes 1&5) • 11-valent vaccine from Sanofi Pasteur trialed in Philippines, but never licensed • 10-valent Pnc-Protein D (Synflorix®, GSK) licensed in Europe 2009 • 13-valent Pnc-CRM (Prevnar13®, Pfizer) licensed in US 2010
  18. 18. Pneumococcal vaccines under development • Conjugate vaccines – PCV10 – Serum Institute of India (in Phase 3) – PCV10 – Panacea, India – PCV11, PCV12 – GSK – PCV15 – Merck – PCV16 – Sanofi – PCV20 – Pfizer • Other vaccines – Whole Cell vaccine (BioFarma Indonesia) – Various protein vaccines
  19. 19. Pneumococcal Conjugate Vaccine national immunization programmes, 2017 * Includes partial introduction Data source: WHO/IVB Database, as of 14 April 2017 Map production Immunization Vaccines and Biologicals (IVB), World Health Organization The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. ©WHO 2017. All rights reserved. Introduced* to date (133 countries or 68.6%) Planned introductions in 2017 (4 countries or 2.1%) Not Available, Not Introduced/No Plans (57 countries or 29.4%) Not applicable
  20. 20. PCV impact studies • Options – Pre and post – ecological approach • Surveillance • Routine data (eg. UK) – Case control study • OK for IPD • Probably not OK for pneumonia – Phased introduction • Eg. Mongolia
  21. 21. Pneumonia hospitalizations - USA
  22. 22. PCV introduction
  23. 23. Ongoing PCV impact studies in Asia • Laos – PCV13 impact study • Mongolia – PCV13 pilot introduction in 2 districts of Ulaanbaatar (June 2016) • Fiji – PCV10 impact study • Nepal – PCV13 impact study • Pakistan – PCV10 impact study • India – PCV13 impact on pneumonia
  24. 24. PDR Laos • Introduced PCV13 in 2013 • Pneumonia burden high – 20% of paediatric admissions • Evaluation started around the time of PCV introduction – Community carriage surveys – Monitor pnc carriage in pneumonia cases – Monitor % of IPD cases due to PCV13 types – Compare vaccinated and unvaccinated cases
  25. 25. Laos – early findings • Hypoxic pneumonia was less common in vaccinated than unvaccinated children with pneumonia (12.6% vs 22.3%, p= 0.0001) • Pneumococcal carriage rates were similar between vaccinated and unvaccinated children with pneumonia (p=0.757)
  26. 26. IPD cases in children under 5
  27. 27. Bacterial meningitis in Beijing Children’s Hospital, China Data from Prof H Yang
  28. 28. PCV impact in Mongolia
  29. 29. Pre-vaccination IPD data for Mongolia 0 5 10 15 20 25 30 35 40 45 50 2010 2011 2012 2013 2014 2015 Chart Title VT non-VT Dominant serotypes: 19F – 23; 6A/B/C – 17; 9V – 11; 14 – 9; 19A – 6;
  30. 30. Fiji • Population of 840,000 • Hib vaccine – 1998 • PCV – 2012 • Since 2012 meningitis remains a problem • Antibiotic abuse minimal
  31. 31. In Fiji since 2012… • 13/16 meningococcal meningitis Group B • 1/14 pneumococcal meningitis cases VT 0 1 2 3 4 5 Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov Jan Mar May Jul Sep Nov Jan 2013 2014 2015 2016 2017 No.ofmeninogococcalcases Meningococcal Cases at CWMH
  32. 32. Conclusions • Pneumococcal vaccines have major potential benefits • IPD surveillance – possible in selected sites in Africa – very difficult in Asia • Impact demonstration will be demanded by the community and politicians • To be valid must be done very carefully and well in selected sites

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