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 AsThanks to GSK for their kind permission to

use content from some of their slides.

2011 NZ Immunisation Schedule DTaP-IPV-HepB/Hib

PCV Hib MMR DTaP-IPV dTap HPV Td Influenza

6 weeks Infanrix hexa®

Synflorix®

3 months Infanrix hexa®

Synflorix®

5 months Infanrix hexa®

Synflorix®

15 months Synflorix® Act-HIB™ MMR II®

4 years MMR II® Infanrix® -IPV

11 years Boostrix®

12 years 3 dosesGardasil®

45 years ADT-Booster™

65 years ADT - Booster®

Fluvax® or

Fluarix®

Schedule changes: summary

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

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

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.

Pharynx

Larynx

Nasopharynx

Eustachiantube

Nasal cavity

Trachea

Primarybronchi

Lungs

Lower respiratory

tractinfections

Upper respiratory

tractinfections

Meningitis

Sinusitis

Otitis media

Pneumonia

Parapneumonicempyema

Bacteraemia/septicaemia

Invasivedisease

Colonisation

Pneumococcal bacteria cause disease when they spread beyond the nasopharynx

S. pneumoniae

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

InvasivePneumococcalDisease

Vaccination drivers

SeverityDeaths

HospitalisationCosts

Volume of casesEconomic costs

Antibiotic use and resistance

Adapted from Melegaro et al. J Infection 2006, 52(1):37–48. Silfverdal et al. Vaccine 2009; 27: 1601–1608. WHO. The global burden of disease. 2008. O’Brien et al. Lancet 2009;374:893–902.

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;8:281–300.

Impact of pneumococcal vaccines

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

IPD in children younger than 5 years worldwide by serotype

Year

Cas

es p

er 1

00,0

00 p

opul

atio

n

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

Adults ≥65 years

97% decrease

76% decrease

PCV7 programme

Children ≤5 years

PCV7 immunisation programmes in the USA have reduced IPD

Overall decline in IPD >75%

Rate of invasive pneumococcal disease caused by PCV7 serotypes in the USA

PCV7 immunisation in New Zealand has reduced IPD

Incidence of invasive pneumococcal disease in children younger than 2 years

PCV7 serotypes

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

Ref: Figure 9.2 NZ Immunisation Handbook 2011

Pneumococcal vaccines in NZ

The VaccinesPCV10: 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 Serotypes

PCV7 4,6B,9V,14,18C,19F,23F

PCV10All serotypes in PCV7 + 1,5,7F

PCV13All serotypes in PCV10 + 3,6A,19A

23PPVAll serotypes in PCV13 + 2,8,9N,10A,11A,12F15B,17F,20,22F,33F

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

PolysaccharideAnd lipid (LPS)

Pneumococcalbacterium

LipidCRM197 Protein Carrier

ChemicalReaction

Purificationprocess

Polysaccharide-proteinconjugate

Conjugate vaccine

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;136:352–359.

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):602–607. 5Hausdorff et al. Vaccine 2007;25:2406–12. 6Ruckinger et al. Pediatr Infect Dis J 2009;28:118–22. 7Torzillo et al. Vaccine 2007;25:2375–78.

Composition of Synflorix – designed as a dual-pathogen vaccine

S. pneumoniae

Polysaccharides

Non-typeable H. influenzae

Main carrier protein: Protein D

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

NTHi Protein D1, 5, 7F4, 6B, 9V, 14, 18C, 19F, 23FDTTT

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

1GSK NZ. Synflorix® Data Sheet. 2010. 2Wysocki et al. Pediatr Infect Dis J 2009;28:S77–88. 3Hausdorff et al. BMC Pediatr 2010;10:4. 4Prymula et al. Lancet 2006;367:740–748. 5Schuerman. Vaccine 2009;27:5748-5754. 6GSK. COMPAS (Clinical Otitis Media & Pneumonia Study). 2007. 7GSK. Pneumococcal Conjugate Vaccine 1024850A (FinIP). 2009.

National immunisation programmes:

2 + 1 schedule•Colombia (Bogotá) •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

• First registered in December 2008

• Now approved in 83 countries

Global use of Synflorix (April 2011)

• 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

3 + 0 schedule• Kenya

1GlaxoSmithKline.Data on file. 2010. 2WHO prequalification of Synflorix. 2009..

Synflorix is generally well toleratedCombined 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 >38°C 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:S109–118.

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 2–8°C

• Do not freeze

• 3-year shelf-life

• Protect from light

• Shake well before useGSK NZ. Synflorix Data Sheet, 2010.

Administration of prefilled syringe1. 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)

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 μg of pneumococcal purified capsular

polysaccharides for serotypes 1,3,4,5,6A,7F,9V,18C,19A,19F, 23F and 4.4 μg 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

• 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

Schedule for high risk children

More information on Prevenar 13

• Phone the Immunisation Advisory Centre on 0800 IMMUNE (0800 466 863)

• Refer to Prevenar 13 datasheethttp://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 changesNeonatal 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: 1339–50

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, ESRMeningococcal disease rates, all ages, by year

0

2

4

6

8

10

12

14

16

18

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Year

Rate per 100,000

Total casesB otherCEpidemic

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;8:281–300. 4Stanhope et al. NZ Med J 1978;88:5–8. 5Ministry of Social Development. Wellington;MSD:2007. 6NZ Health Technology Assessment. Wellington:NZHTA; 1998.

An 11-valent prototype for Synflorix was effective against AOM

*Statistically significant effect

**

100

80

60

40

20

0

-20

-40

-60

-80

-100

All-cause All

pneumococcal serotypes

Non-vaccine serotypes

Cause of AOM:

Adapted from: 1Prymula et al. Lancet 2006;367:740–748. 2GSK. Synflorix Data Sheet. 2010.