www.ncirs.usyd.edu.au

Pneumococcal conjugate vaccine impact and schedule arithmetic:

3+0 vs 3+1 vs 2+1

Peter McintyreNational Centre for Immunisation Research AustraliaKids Research Institute and University of Sydney

Arithmetic of PCV schedules - outlineThe 7 valent PCV era: IPD

• The “ 3+0 “ story and Australia’s role in it• Aboriginal and Torres Strait Islander peoples

Non-IPD especially pneumonia

The 10 and 13 valent era: IPD Evolution of 2+1 internationally

Rationale for Australian child pneumococcal vaccine schedule

Conjugate vaccine• 3 doses (2,4,6 months) no risk factors

• Cost-benefit • Meningitis most common under 12 months of age

• 4 doses (2,4,6,12) with risk factors• Lesser immune response

Polysaccharide vaccine • @ 18-24 months for Indigenous children in high

incidence areas (NT, WA, SA, Qld)• Equivalent boosting to 7vPCV• Response to additional serotypes

Potential disadvantages of Australian schedule

No routine conjugate booster• Less impact on vaccine type IPD

- waning/breakthrough • Less protection against non-bacteraemic disease• Less herd immunity

23vPPV booster • Effective vs non 7v types? • Hyporesponsiveness?

www.ncirs.usyd.edu.au

The 7v PCV era

Australian data sources to review schedule – criteria

Trends in incidence of IPD • Long-term • Stable surveillance system • All or most isolates serotyped

Trends in incidence of hospitalisation• ICD coded pneumonia

2012/13 meta-analysis: 7vPCV impact/replacement

Australian studies evaluating impact of 3+0 schedule

IPD – direct and indirect • NSW (greater Sydney) only: Lowbridge et al 2015• Indigenous and non-Indigenous children: Jayasinghe et al 2016

ICD-coded pneumonia • Jardine et al 2009• Menzies et al 2015

Middle ear ventilation tube (MVTI) insertions • Jardine et al 2010

Post program impact economic analysis • Newall et al 2015

IPD impact – comparing Australia, UK and US

Pneumonia Impact – ICD codes

Indigenous children in Northern Australia and the 23 v PPV booster

Indigenous vs non-Indigenous children in 7v+23v eraimportance of 19A

www.ncirs.usyd.edu.au

The 10/13v PCV era

Immunization coverage with PCV3 containing vaccines in infants, 2015

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 2016. All rights reserved

<50% (15 countries or 8%)

50-79% (22 countries or 11%)

80-89% (26 countries or 13%)

>=90% (57 countries or 29%)

Not available / not in national immunization schedule (65 countries or 34%)

Not applicable

PCV in schedule but no coverage data available (9 countries or 5%)Source: WHO/UNICEF coverage estimates 2015 revision, July 2016. Map production: Immunization Vaccines and Biologicals, (IVB). World Health Organization. 194 WHO Member StatesDate of slide: 02 August 2016

PCV Product Use, Globally(June 2017)

PCV10 (33)

PCV13 (100)

PCV10 and PCV13 (8)

Product Gavi Non-Gavi Total

PCV10 14 19 33PCV13 45 55 100

Purchase of PCV = high % of national spending on vaccines

Source: V3P database - www.who.int/immunization/v3p (2015)Note: This graph is calculated using the price and volumes reported by countries for each vaccine type. Both volume and price can therefore influence the share of a vaccine on the expenditure on vaccine purchase. Moreover, particular events such as campaigns, stock replenishment and shortages can influence these percentage. The graph intends to give an indication of the weigh of a vaccine in the overall vaccine purchases and should be used with caution. Only budget sources from the government can give a clear picture of the overall and detail spending on vaccines in a country. The graph only shows countries reporting 5 or more vaccine types for that year and vaccine types with volumes registered as greater than 1.

Median of 37% of spending on vaccines

In MICs median is at 44%.

Share is much higher than for other newer vaccines

(eg. median for Rota: 16%; Penta 16% ; Hexa 29% )

PCVLMIC UMIC

Share of expenditure on each vaccine type over total expenditure on vaccines in each country, 2015In percentage of total national purchases of vaccines

21 | June 12, 2017 |WHO Technical Expert Consultation on Optimization of PCV I

10- year horizon

• Introduction continues at pace• Coverage enhanced, especially in high need

areas• Additional products on market reduce prices• Serotype replacement is limited

• Countries continue investment in PCV• Maximum health benefit is accrued

• Failure to Achieve Optimized Impact• Serotype Replacement Substantial• Subnational Inequity Persists• Supply Challenges

• Weakened country commitment• Withdrawal of PCV

Alternative 10- year horizon

For PCV administration to infants, WHO recommends 3 primary doses (3+0) or as an alternative 2 primary doses plus a booster (2+1).

In choosing between the schedules, countries should consider the epidemiology of the disease, coverage and timeliness of doses.

If disease incidence peaks in young infants (< 32 weeks), a 2+1 schedule might not offer optimal individual protection

In contrast, higher antibody levels are induced by the 3rd dose in a 2+1 schedule. This may be important for duration of protection

If a 2+1 schedule is selected, the 2 primary doses should be given with an interval preferably of 8 weeks or more; one booster dose should be given between 9-15 months of age

CHOICE OF SCHEDULE

24 | June 12, 2017 |WHO Technical Expert Consultation on Optimization of PCV Impact

What may have changed

Additional data availability• On PCV 10 and PCV 13, including large observational

studies• From low and middle-income countries using different

schedules Programmatic issues

• Increasing use of second year of life platform for vaccination

Financing and sustainability issues• Changes in vaccine price and supply

25 | June 12, 2017 |WHO Technical Expert Consultation on Optimization of PCV Impact

Studies evaluating impact of 3+0 schedule

IPD – direct and indirect • NSW (greater Sydney) only: Lowbridge et al 2015• Indigenous and non-Indigenous children: Jayasinghe et al 2016• All ages 2002-2014: Jayasinghe et al 2017

ICD-coded pneumonia • Jardine et al 2009• Menzies et al 2015

Middle ear ventilation tube (MVTI) insertions • Jardine et al 2010

Post program impact economic analysis • Newall et al 2015

Only study Including

PCV 13 era

Impact of PCV7 & 13 2002-2014 – Australia

IPD in NZ in post PCV – ESR report

All IPD: reductions in Australia1 and New Zealand2 by age group

Age group Australia 9 yrs post PCV

NZ8 years post PCV

< 2 years - 82 % - 88%

2-4 years - 69% - 77%

> 65 years - 40% - 28%

All ages - 47% - 40%

1. Jayasinghe et al 2. ESR report to 2015

13vPCV & 7vPCV 3+0 schedule VE – paper in press Sanjay Jayasinghe NCIRS

Albania, Latvia……….Australia Albania introduced PCV universally in March 2011 but

switched from 3+0 to 2+1 in 2015• PCV Coverage 99% reported each year from 2011-15

Latvia introduced PCV universally in 2010 but switched from 3+0 to 2+1 in 2012• PCV2 coverage increased from 76% (2012) to 90%

(2015)

Out of the 13 countries that switched schedules, 11 countries from 3+1 to 2+1

Moving from 3+0 to 2+1 in Australia

7vPCV & 13vPCV breakthrough cases,2006-2016

51

57

5 5 412

28

35

43

53

0

10

20

30

40

50

60

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Coun

t

Diagnosis year

7vPCV 13vPCV

Data source: National Notifiable Diseases Surveillance System

Consultation document

Breakthrough IPD cases due to 13vPCV serotypes

Estimated IPD cases in older age groups: 3+0 vs 2+1

IPD data by ethnicity - NZ

IPD incidence in Indigenous children* < 5yrs of age 2002-2015

In Northern Territory, Queensland, South Australia & Western Australia

IPD incidence in Non-Indigenous children < 5yrs of age, 2002-2015

Incidence of invasive pneumococcal disease notifications (/100,000) for Indigenous Australians by age group 2002-2014

IPD incidence rates (/100,000) for Indigenous and non-Indigenous Australians by age group, 2002-14

42

Summary

PCVs are not one vaccine, but several Schedule appears to make a difference especially

for serotype 19A Move to 2+1 with PCV13 for Australia and major

push for 2+1 PCV schedules internationally NZ moves back to the future with PCV 10

“ We live in interesting times”

Acknowledgements Sanjay Jayasinghe NCIRS Laboratories

• CIDM, Westmead – NSW• ,MDU, Doherty Institute – Victoria• QHPSS, Queensland• Referring laboratories Australia wide

Enhanced IPD Surveillance Working Group• Vicki Krause, Heather Cook, CDC NT• Kristina Barry Surveillance DoHA• Robin Gilmour, Mark Bartlett, NSW Health• David Cole, DHHS Tasmania• Craig Davis, Queensland Health• Ros Holland, DHS SA• Carolien Giele, WA Health• Riemke Kampen, DHCC ACT• James Fielding, DHS Victoria