Schedule Changes 2011

Outline
Main changes to the schedule: 2011 Pneumococcal disease Impact of pneumococcal vaccines New PCV vaccines
Synflorix (PCV10) Prevenar 13 (PCV13)

High risk programme New Hib vaccine brand: Act-Hib BCG

New brand New eligibility criteria

Common Qs and As

Thanks to GSK for their kind permission to use content from some of their slides.

2011 NZ Immunisation Schedule

DTaP-IPVHepB/Hib
6 weeks 3 months 5 months 15 months 4 years 11 years 12 years 45 years 65 years

PCV

Hib

MMR

DTaP-IPV

dTap

HPV

Td

Influenza

Infanrix Synflorix hexa Infanrix Synflorix hexa Infanrix Synflorix hexa Synflorix Act-HIB MMR II MMR II Infanrix -IPV Boostrix 3 doses Gardasil ADTBooster ADT Booster Fluvax or Fluarix

Schedule changes: summary

Synflorix (PCV10) replaces Prevenar (PCV7) at 6 weeks, 3, 5 & 15 months

High risk children only: Prevenar 13 (PCV13) followed by Pneumovax 23 (23PPV)

Summary cntd.
MeNZB vaccine is no longer available.

Change in BCG brand and eligibility criteria

Act-HIB replaces Hiberix The date the new vaccines are available will be later than 1 July while existing vaccine stocks are used up The Immunisation Handbook 2011 will be available online during May and hardcopies will be sent to practices in June Rubella antibody levels to indicate protection are now recommended to be 15IU/mL (previously it was 10 IU/mL)

Pneumococcal disease

Pneumococcal disease is caused by Streptococcus pneumoniae

S. pneumoniae is a gram-positive diplococcus with a polysaccharide capsule1,2 >90 serotypes with different polysaccharide chains1,2 Normal inhabitant of human nasopharynx2
not found in animals3

Use of antibiotics has caused resistant strains to emerge1-3

1World

Health Organization. Pneumococcal vaccines: 2003. 2US CDC. Epidemiology and prevention of vaccine preventable diseases. 2009. 3EU CDC. Factsheet for healthcare professionals. 2008. Photo credit: Image of pneumococcal serotype 19F; Rob Smith.

Pneumococcal bacteria cause disease when they spread beyond the nasopharynx
S. pneumoniae

Meningitis
Upper Sinusitis respiratory tract Otitis media infections

Nasal cavity

Eustachian tube Nasopharynx

Pharynx Larynx

Invasive disease

Trachea

Lower respiratory Pneumonia tract infections

Primary bronchi

Bacteraemia/ septicaemia

Lungs

Parapneumonic empyema

Streptococcus pneumoniae causes a spectrum of invasive and non-invasive disease

Vaccination drivers
Invasive Pneumococcal Disease
Severity Deaths

Hospitalisation Costs Volume of cases Economic costs Antibiotic use and resistance

Adapted from Melegaro et al. J Infection 2006, 52(1):3748. Silfverdal et al. Vaccine 2009; 27: 16011608. WHO. The global burden of disease. 2008. OBrien et al. Lancet 2009;374:893902.

Pneumonia and otitis media also cause a substantial burden of disease in NZ

Cases per 100,000*

23

295
808

*Disease in children younger than 5 years before implementation of PCV7 immunisation in NZ.
Milne, Vander Hoorn. Appl Health Econ Health Policy 2010;8:281300.

Impact of pneumococcal vaccines

IPD in children younger than 5 years worldwide by serotype

Adapted from Pneumo-ADIP. Geneva: WHO; 2007.

PCV7 immunisation programmes in the USA have reduced IPD

Rate of invasive pneumococcal disease caused by PCV7 serotypes in the USA
Cases per 100,000 population PCV7 programme

Overall decline in IPD >75%

Adults 65 years 76% decrease Children 5 years 97% decrease

Year
Adapted from Hicks et al. J Infect Dis. 2007;196:1346-54.

PCV7 immunisation in New Zealand has reduced IPD

Incidence of invasive pneumococcal disease in children younger than 2 years
100 90 80 70 60 50 40 30 20 10 0 2007
PCV7 serotypes

Rate per 100,000

2008
Year

2009

Adapted from ESR. NZ Public Health Surveillance Report 2010; 8 (4) 4-5.

Rates of invasive pneumococcal disease caused by serotypes 4,6B,9V,14,18C,19F,23F by age group 2004 2009, NZ
100
80

Rate per 100,000

60 40 20 0 <2 years 2004 2005 2-4 years 5-64 years 2008 65+ years 2009 Age group 2006 2007

Ref: Figure 9.2 NZ Immunisation Handbook 2011

Pneumococcal vaccines in NZ

The Vaccines
PCV10: Synflorix - Routine childhood programme
Contains the 7 types and 3 extra Conjugated to Protein D(non-typable H influenza)

PCV13: Prevenar 13 - High risk children

Contains the 7 types and 6 extra conjugated to CRM197 (non-toxin diphtheria)

23PPV: Pneumovax 23 - High risk adults /children

A polysaccharide vaccine Less immunogenic, shorter duration of immunity Poorly immunogenic in children under 2 years

Summary of pneumococcal vaccine serotype content

Vaccine PCV7 PCV10 PCV13 23PPV

Serotypes 4,6B,9V,14,18C,19F,23F

+ 1,5,7F All serotypes in PCV10 + 3,6A,19A All serotypes in PCV13 + 2,8,9N,10A,11A,12F15B,17F,20,22F,33F

All serotypes in PCV7

Polysaccharide vaccines
Made from polysaccharide from the capsule surrounding the bacteria Works in adults Two major problems Not immunogenic in babies No immune memory
String of sugars = polysaccharide

Conjugate vaccine
Pneumococcal bacterium Polysaccharide And lipid (LPS) Polysaccharide-protein conjugate

Purification process

Chemical Reaction CRM197 Protein Carrier

Lipid

PCV10 (Synflorix)

Synflorix increases coverage of IPD worldwide

IPD in children younger than 5 years worldwide by serotype

Adapted from: 1Pneumo-ADIP. Geneva: WHO; 2007. 2GSK. Synflorix Data Sheet. 2010 .

Serotypes that cause invasive pneumococcal disease can vary over time
Serotype 1 has increased in NZ in recent years1 and is one of the most prevalent serotypes in IPD globally2 In 2009 in NZ, serotype 1:
was the most prevalent cause of IPD (153 cases, 16%) in the total population1 was the most prevalent cause of IPD in children younger than 2 years (12 cases, 22%)1 was the second most prevalent serotype (15 cases, 16%) after serotype 14 (17 cases, 18%) in children under 5 years of age1

The incidence of 19A has been steady in NZ over recent years, with no increase observed since the introduction of PCV71,3,4
8 cases in children younger than 2 years in 20091
1ESR.

Invasive pneumococcal disease in New Zealand, 2009. 2010. 2Pneumo-ADIP. WHO; 2007. 3ESR. NZ Publ Health Surveill Rep 2010;8(4):4-5. 4Heffernan et al. Epidemiol. Infect 2008;136:352359.

Synflorix extends coverage against IPD

The WHO required that future vaccines contain serotypes 1 and 5, since they cause a large proportion of severe disease.1
Serotypes 1, 5, and 7F together account for about 15% of global pneumococcal morbidity and mortality.2 In NZ in 2009, serotypes 1 and 7F caused 17% of IPD in children younger than 5 years.3 These serotypes were included in Synflorix because compared with other serotypes they cause more:
invasive disease (1 and 5)4 complicated pneumonias and empyemas (1, 5, and 7F)5 severe disease and deaths (7F)6 outbreaks of meningitis (1 and 5)7

1WHO.

Target Product Profile for the Pneumococcal AMC. 2008. 2Pneumo-ADIP. WHO; 2007. 3ESR. Invasive pneumococcal disease in New Zealand, 2009. 2010. 4Shouval et al. Pediatr Infect Dis J 2006;25(7):602607. 5Hausdorff et al. Vaccine 2007;25:240612. 6Ruckinger et al. Pediatr Infect Dis J 2009;28:11822. 7Torzillo et al. Vaccine 2007;25:237578.

Composition of Synflorix designed as a dual-pathogen vaccine

S. pneumoniae Non-typeable H. influenzae

Polysaccharides
TT DT

Main carrier protein: Protein D

4, 6B, 9V, 14, 18C, 19F, 23F

1, 5, 7F

NTHi Protein D

8 serotypes conjugated to protein D 18C conjugated to tetanus toxoid (TT) 19F conjugated to diphtheria toxoid (DT)

GSK NZ. Synflorix Data Sheet. 2010.

Summary: the design of Synflorix

Synflorix protects against invasive pneumococcal disease, pneumonia, and acute otitis media1 Synflorix extends protection by inclusion of serotypes 1, 5, and 7F1 Additional design features: Inclusion of 6B and 19F stimulates cross-reactive functional immune responses to pneumococcal serotypes 6A and 19A.1,2 Inclusion of Protein D enables immune responses against not only S. pneumoniae but also NTHi (these two bacteria cause up to 80% of acute otitis media)1-5 Note: Data on immune responses to cross-reactive serotypes and NTHi are reviewed in the Synflorix Data Sheet.1 Synflorix is only indicated against disease caused by vaccine serotypes.1 Large-scale effectiveness studies are ongoing.6,7
NZ. Synflorix Data Sheet. 2010. 2Wysocki et al. Pediatr Infect Dis J 2009;28:S7788. 3Hausdorff et al. BMC Pediatr 2010;10:4. et al. Lancet 2006;367:740748. 5Schuerman. Vaccine 2009;27:5748-5754. 6GSK. COMPAS (Clinical Otitis Media & Pneumonia Study). 2007. 7GSK. Pneumococcal Conjugate Vaccine 1024850A (FinIP). 2009.
1GSK 4Prymula

Global use of Synflorix (April 2011)

First registered in December 2008

Now approved in 83 countries
2 + 1 schedule Colombia (Bogot) Finland Mexico Sweden (3 provinces) 3 + 1 schedule Australia (Northern Territories) Austria (high-risk groups) Albania Brazil Bulgaria Cyprus (high-risk groups) Hong Kong Taiwan (Taipei) The Netherlands

National immunisation programmes:

3 + 0 schedule Kenya

Prequalified by World Health Organization in October 2009

Now available in some developing countries as part of advance market commitment an agreement with the GAVI Alliance to improve access to pneumococcal vaccines
file. 2010. 2WHO prequalification of Synflorix. 2009..

1GlaxoSmithKline.Data on

Synflorix is generally well tolerated

Combined analysis of clinical studies of safety in more than 4,000 healthy infants1: The most common adverse reactions observed after primary vaccination were pain, redness, and swelling at the injection site, irritability, fever, and drowsiness.1 Most reactions were of mild to moderate severity and were not long-lasting.1 No safety concerns were identified.1 The safety and tolerability profile of Synflorix is similar to that of PCV7 and commonly co administered vaccines.1 Fever >38C within same range as PCV7 post-primary and booster. Fever >40C was infrequent: 1% of Synflorix doses and 2% of PCV7 doses.1
1Chevallier

et al. Pediatr Infect Dis J 2009;28:S109118.

Synflorix can be co administered with other vaccines available in NZ

Packaging and storage of Synflorix

Packs of 10
No needles Prefilled syringes Store at 28C Do not freeze 3-year shelf-life Protect from light Shake well before use
GSK NZ. Synflorix Data Sheet, 2010.

Administration of prefilled syringe

1. Holding the syringe barrel (not the plunger) in one hand, unscrew the syringe cap by twisting anticlockwise. 2. To attach the needle to the syringe, twist the needle clockwise into the syringe until you feel it lock.

3. Remove the needle protector and administer the vaccine.

GSK NZ. Synflorix Data Sheet, 2010.

More information on Synflorix

Phone the Immunisation Advisory Centre on: 0800 IMMUNE (0800 466 863) Go to www.immune.org.nz or www.moh.govt.nz/immunisation Refer to the Synflorix Data Sheet and Consumer Medicine Information on the Medsafe website:

http://www.medsafe.govt.nz/profs/Datasheet/dsform.asp

For GSK Medical Information in NZ, please call 0800 808 500 or +64 09 367 2900, and ask for the Medical Information Department.

GSK NZ. Synflorix Data Sheet, 2010.

Prevenar 13 and the Pneumococcal high risk programme

Incidence rates of invasive pneumococcal disease by serotype, in children aged less than five years, New Zealand, 1998 2007
(NB prior to introduction of PCV vaccine)

20

PCV-7 serotypes

additional PCV-10

additional PCV-13 types

60

50

15
40

10

30

20

5
10

othe

6B

9V

7F

14

18C

6A

Serotype

Average annual rate

Cumulative average annual rate

19A

19F

23F

Cumulative average annual rate per 100,000 population

Average annual rate per 100,000 population

Prevenar 13 for high risk children

Same vaccine technology and composition as Prevenar, with six additional serotypes Each dose of Prevenar 13 contains: 2.2 g of pneumococcal purified capsular polysaccharides for serotypes 1,3,4,5,6A,7F,9V,18C,19A,19F, 23F and 4.4 g for serotype 6B Each serotype is individually conjugated to non-toxic diphtheria CRM197 protein and adsorbed onto aluminium phosphate (0.565 mg). Each dose contains succinic acid, polysorbate 80, aluminium phosphate and sodium chloride in water for injections. Expected to have the same safety profile as Prevenar

Pneumococcal high risk children: 0 -16 yrs

Offer PCV13 followed by 23PPV Up to 5 years of age: (59 months)
On immunosuppressive therapy or radiation therapy Primary immune deficiencies HIV Renal failure or nephrotic syndrome Immune suppressed following organ transplantation Cochlear implants, intracranial shunts CSF leaks On corticosteroids at least 2mg/kg/day prednisone (or 20mg a day) >2 weeks Chronic pulmonary disease IDDM Down Syndrome Pre or post-splenectomy or functional asplenia Preterm infants born at under 28 weeks

6 16 years:
Pre or post-splenectomy or functional asplenia

Schedule for high risk children

As soon as the child is recognised as high risk, replace the next dose of PCV10 (Synflorix) with PCV 13 (Prevenar 13) at the same schedule visit times If a child has already had a full course of PCV10 offer a single dose of PCV13

8 weeks after the final PCV dose (or at the age of 2 years if under 2) offer 23PPV (Pneumovax 23)
Offer a repeat 23PPV dose in 3-5 years time

More information on Prevenar 13

Phone the Immunisation Advisory Centre on 0800 IMMUNE (0800 466 863) Refer to Prevenar 13 datasheet
http://www.medsafe.govt.nz/profs/datasheet/p/prevenar13inj.pdf

Contact Pfizer:
Phone 0800 734 076 Fax 0800 735 045

Children/Adults high risk: pre or post

splenectomy
The criteria remain unchanged No longer need the recommendation of a secondary care specialist to given in primary care Vaccines now being offered: Prevenar 13 ( children up to 16 years only) Act-HIB Pneumovax 23 Menomune ACYW135
NB Prevenar 13 and Act-HIB are only licensed to 5 years of age, giving to older children and adults is currently outside of licensure. While there are not expected to be any safety concerns, it is important to give full informed consent

Other vaccine changes

Act-HIB
Haemophilus influenza type B vaccine conjugated to tetanus protein Same conjugate as previous vaccine, Hiberix Freeze-dried powder for reconstitution with diluent for injection comes in a vial and separate syringe Expected to act the same as Hiberix Datasheet:
http://www.medsafe.govt.nz/profs/datasheet/a/acthibinj.pdf

BCG key changes

Neonatal BCG offered to infants at increased risk of TB. Those who: Will be living in a house or family/whanau with a person with either currently TB or a past history of TB Have one or both parents or household members or carers, who within the last five years lived for a period of six months or longer in countries with a rate 40 per 100,000 During their first five years will be living for three months or longer in a country with a rate 40 per 100,000 and are likely to be exposed to those with TB List of high-incidence countries: www.moh.govt.nz/immunisation www.bcgatlas.org/index.php

The major change is that fewer Pacific countries are now considered high risk for TB

BCG cntd.
As a general indication, the following global areas have rates of 40/ 100,000
Most of Africa Much of South America Russia and the former Soviet States Indian Subcontinent China including Hong Kong South East Asia (except Singapore) Pacific (except Cook Islands, Fiji, Niue, Samoa, Tokelau and Tonga)

Qs and As

Common Qs and As
Why was PCV10 introduced rather than PCV13? the extra components in PCV10(versus PCV7) provide extra cover against pneumococci The NTHi protein may provide extra protection against otitis media PCV10 is significantly less expensive than PCV13 and more cost-effective
Ref: NZ Immunisation Handbook 2011, Ministry of Health

A child has started on Prevenar and now the practice has only got Synflorix available Switch over to Synflorix

Qs & As cntd.
What about when to use 23 PPV vaccine? Pneumococcal polysaccharide (23PPV) vaccine is recommended, but not funded, for young people and adults aged 16 years and older at special risk, as per the high risk list in the NZ Handbook, and for HIV-infected people. Note that some specialists may recommend PCV13 prior to use of 23PPV (refer Immunisation Handbook 2011).
Do you revaccinate with 23PPV? Revaccination with polysaccharide vaccine (23PPV) should be considered after three to five years in children aged less than 10 years of age when first immunised, and after five years in older children and adults belonging to particularly high-risk groups, who frequently exhibit a poor immune response. Revaccination is recommended five years after the first vaccination post-splenectomy and at 65 years to complete three doses
Ref: NZ Immunisation Handbook 2011 p.196. Refer Table 9.3

Qs & As cntd.
How to enter PCV10 and PCV13 on the PMS PCV will be scheduled for the child The new upgrades should have a drop down box identifying the different types of vaccine: PCV7,PCV10 and PCV13
A child who has started their immunisation programme and has already received some doses of Synflorix then becomes high risk Once the high risk condition has been recognised switch over to PCV13 to complete the programme, and then offer 23PPV 8 weeks after the last dose of PCV13, or when the child reaches 2 years of age If a child has already received 4 doses of PCV10, they should receive one dose of PCV13

Qs & As cntd.
A family is wanting to purchase the private market Prevenar 13 rather than Synflorix to give their child additional protection.
Can switch from Synflorix to Prevenar 13, if they are partially through a schedule they may not get complete protection against the extra 3 serotypes.

Why are conjugates not used routinely in adults?

The conjugates have been specifically designed for the serotypes that are most common in childhood disease, there is a broader spectrum of serotypes that adults are exposed to. There is currently little data on the effectiveness of conjugates in adults. Conjugates are expected to be effective at preventing pneumococcal disease in adults but further data is needed before the precise role of these vaccines is defined in adults.

Qs and As cntd.
What is the PCV programme for a child who needs catch up? Children under 6 months of age need 3 doses at least a month apart Children 6- 12 months need 2 doses at least a month apart Children from 1 to 5 years of age who have never had any PCV need two doses 8 weeks apart Use of medication such as paracetamol for temperature or pain Paracetamol or ibuprofen can be used for children who are in discomfort or pain following immunisation. It is not recommended routinely with immunisations as it may interfere with the immune response.
Ref Prymula R et al Lancet 2009; 374: 133950

Qs and As cntd.
Co administration of Influenza and PCV vaccines Fevers are known to occur after influenza vaccines, and febrile convulsions are a recognised complication of fever. Approximately 24% of all children have a febrile convulsion at some stage in their life. In February 2011 the Center for Disease Control and Prevention (CDC) in the U.S.A. presented findings from the Vaccine Safety Datalink in the U.S.A., which identified there may be a small increase in the risk of fever, and febrile convulsion, in children aged 12 to 23 months of age when an inactivated influenza vaccine was administered at the same time as the pneumococcal conjugate vaccine Prevenar 13 (PCV13). Out of prudence, parents should be advised that there may be a small increase in the risk of fever, and associated febrile convulsion in susceptible children when PCV vaccine is administered with influenza vaccine, over and above having the vaccines separately.
Ref: CDC Feb 2011

Back-up slides

Meningococcal disease rates for selected strains and all cases, by year
Data provisional, ESR
Rate per 100,000
Meningococcal disease rates, all ages, by year

18 16 14 12 10 8 6 4 2 0 2001 2002 2003 2004 2005 Year 2006 2007

Total cases B other C Epidemic

2008

2009

2010

Synflorix and acute otitis media protection

Ear infections are debilitating, affect hearing, and can delay learning
Every year, otitis media in NZ children younger than 5 years accounts for:
83,000 GP consultations1 and 5,000 hospital admissions2 Antibiotics prescribed for at least 50% of cases1

Ethnic disparities in ear health:

Hospital admissions for Maori and Pacific Island children with otitis media are twice those for other children3,4 Maori and Pacific Island children are more than twice as likely as other children to fail new-entrant school hearing checks5,6
1Gribben.

GSK Data on file; 2010. 2Milne, Vander Hoorn. Report to NZ Ministry of Health. 2009. 3Milne, Vander Hoorn. Appl Health Econ Health Policy 2010;8:281300. 4Stanhope et al. NZ Med J 1978;88:58. 5Ministry of Social Development. Wellington;MSD:2007. 6NZ Health Technology Assessment. Wellington:NZHTA; 1998.

An 11-valent prototype for Synflorix was effective against AOM

100

Vaccine efficacy against acute otitis media (95%CI)

80 60 40 20 0 -20 -40 -60 -80 -100

Cause of AOM:

All-cause

All pneumococcal serotypes

Non-vaccine serotypes

*Statistically significant effect

Adapted from: 1Prymula et al. Lancet 2006;367:740748. 2GSK. Synflorix Data Sheet. 2010.