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

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. 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. • 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. • 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. • 2009 – PCV7 introduced into South Africa,
Gambia and Rwanda

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. • 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. 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. Ghana meningitis outbreak 2016
Brenda Kwambana-Adams et al. BMC Infectious Diseases 2016;16:575

10. Ghana meningitis outbreak 2016
Kwambana-Adams BA et al. BMC Infectious Diseases 2016;16:575

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. 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. 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. UK Serotype 1 disease
2+1 schedule

15. Ghana pneumococcal meningitis cases
Kwambana-Adams BA et al. BMC Infectious Diseases 2016;16:575
PCV introduced 4 years earlier

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. 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. 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. 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. 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. Pneumonia hospitalizations - USA

22. PCV
introduction

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. 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. 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. IPD cases in children under 5

27. Bacterial meningitis in Beijing
Children’s Hospital, China
Data from
Prof H Yang

28. PCV impact in Mongolia

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. Fiji
• Population of 840,000
• Hib vaccine – 1998
• PCV – 2012
• Since 2012 meningitis
remains a problem
• Antibiotic abuse minimal

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. 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