THE LATEST AND GREATEST IN THE WORLD OF VACCINES

Nikki Turner

University of Auckland

June 2013

Only clean water and antibiotics

have had an impact on childhood

death and disease that is equal to

that of vaccines World Health Organization

Analysis of US 2009 birth cohort - effect of the routine childhood immunisation programme

Prevent 421,000 early deaths

Prevent 20 million cases of disease

Net savings – $ US 13.5 billion in direct costs

– $ US 68.8 billion in indirect costs

3 Zhou F et al Pediatrics 133:4. March 2014

• Schedule changes 2014

• Current challenges with VPDs

• Influenza

• Pregnancy vaccination

• Private market vaccines

• Future of the national schedule

• Immunisation coverage

• Communication issues

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Routine schedule changes 1 July 2014

2014 Schedule Change Vaccine For whom

Introduction of rotavirus

vaccine

Rotateq® All children at 6wk, 3mth and

5mth

Change from PCV10 to

PCV13

Prevenar13® Replaces PCV10

Use of DTaP-IPV or Tdap in

catch up schedules

Boostrix®

Infanrix-IPV®

Incompletely immunised

children aged up to 17 years

Post immunosuppression.

Rotavirus

• Death rare

• 1 in 43 children hospitalised by 5 yrs in NZ

• For each hospitalisation 8 children seen in primary care

• > 90% children have RV by 3 yrs

– no strong ethnic or se gradient, a universal bug!

Lepage P. Pediatr Infect Dis J 2006;25:S5−S6.

Grimwood K, Lambert SB. Hum Vaccine 2009;5:57−69

Milne RJ, Grimwood K. Value Health 2009;12:888−898

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Rotavirus vaccine

Available from 1st July 2014

• RotaTeq® vaccine (MSD)

• Live Pentavalent vaccine

• 3 oral doses

– 1st dose before 15 wks of age

– 3rd dose no later than 8 months of age

Viral shedding

• Occurs less with RV5 than RV1

• Stress good hand washing after nappy changing and careful disposal of nappies

Intussusception

• Vaccine-attributable risk estimate 5.6 additional cases/100 000 vaccinated infants – Based on increased incidence in 1-21 days post dose 1 and 1-

7 days post dose two

• Estimated 14 extra IS cases and >6500 fewer gastroenteritis hospitalisations annually in Australia.

Carlin JB et al. Clin Infect Dis. 2013; 57:1427-34.

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Vaccine Percentage of cases prevented

Risk ratio (95% confidence interval)

Number of participants (number of trials)

Quality of evidence

Severe rotavirus diarrhoea: infants aged under one year

RV1 86 0.14 (0.07–0.26)

40,631 (6)

high

RV5 87 0.13 (0.04–0.45)

2344 (3)

moderate

Severe rotavirus diarrhoea: children aged under two years

RV1 85 0.15 (0.12–0.2)

32,854 (8)

high

RV5 82 0.18 (0.07–0.5)

3190 (3)

moderate

Severe all-cause diarrhoea: infants aged under one year

RV1 40 0.60 (0.5–0.72)

17,867 (1)

moderate

RV5 72 0.28 (0.16–0.48)

1029 (1)

low

Severe all-cause diarrhoea: children aged under two years

RV1 37 0.63 (0.56–0.71)

39,091 (2)

moderate

RV5 96 0.04 (0.00–0.70)

5916 (1)

low

Source: Adapted from: Soares-Weiser K, MacLehose H, Bergman H, Ben-Aharon I, et al. 2012. Vaccines for preventing rotavirus diarrhoea: Vaccines in use. Cochrane Database of Systematic Reviews (11). 10.1002/14651858.CD008521.pub3 (accessed 12 August 2013).

Table from Cochrane review: percentage of severe rotavirus and all cause diarrhoea cases

prevented in children by RV1 and RV5, compared to placebo in low mortality rate countries

Rotavirus vaccine introduction in Australia

Special Risk Groups Schedule Change Vaccine For whom

Targeted varicella vaccine

for high risk groups

Varilrix® Targeted programme for high risk

groups and close contacts

Meningococcal conjugate

vaccines replaces

polysaccharide

meningococcal vaccine

Menactra® for 2 years

of age and older.

Neisvac-C® for under 2

years of age.

Pre- and post-splenectomy, functional

asplenia

Post solid organ or bone marrow

transplant

Post immunosuppression

Close contacts of meningococcal cases

Hepatitis A vaccine Havrix® and Havrix

Junior®

Transplant patients

Children with chronic liver disease

Close contacts of hepatitis A cases

On recommendation of a local MOH

Introduction of a higher

dose Hepatitis B vaccine

HBvaxPRO® 40mcg Dialysis patients

Liver or kidney transplant patients

Change to eligibility criteria

for HPV vaccine

Gardasil® Patients aged under 25 years with HIV

Transplant patients

The high risk groups for funding

categories are likely to change in future,

check the latest Pharmaceutical Schedule

for clarification.

Varicella vaccine Varilrix (2 doses) will be funded under set criteria:

For non-immune patients:

with chronic liver disease who may in future be candidates for transplantation; or

with deteriorating renal function before transplantation; or

prior to solid organ transplant; or

prior to any elective immunosuppression.

For patients 2 years after bone marrow transplantation

For patients at least 6 months after completion of chemotherapy

For HIV positive non immune to varicella.

For household contacts of paediatric patients who are immunocompromised

Current challenges

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• High degree of suspicion:

– Generalised maculopapular rash

– Fever (>380C)

– Cough, coryza, conjunctivitis or Koplik’s spots

– Suspicion of sporadic case want diagnosis:

• Blood for serology

• NP swab

• Vaccination +++

– anyone born since 1969 needs 2 recorded MMR

– MMR < 1 year not counted

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Pertussis: New Zealand notifications and hospitalisations

https://surv.esr.cri.nz/PDF_surveillance/PertussisRpt/2013/Pertussisreport

Oct-Dec2013.pdf

Pertussis control….tricky

• Unable to eradicate from whole community

– aP vaccines have limited duration of action, minimal/no herd immunity

• Most severe in younger children

– Main target of immunisation strategies

• KEY: High coverage and timeliness of delivery

• Other strategies – Immunising pregnant women

– Immunising older children

– cocoon strategies

– Immunising HCPs/ECC occupations

FLU

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Recent TIV vaccine efficacy and effectiveness studies conducted in adults under 65 years of age. Adapted from Plotkin 6th edition 2012 and updated.

Study Population age Study design Study years Outcomes and VE

Jefferson 2010 [14] 16-65 Meta-analysis NA 30% (17%-41%) VE

against ILI

73% (CI 54%-84%) VE

against influenza

symptoms

Osterholm 2012 [74] 18-65 years Systematic review

and meta-analysis

N/A 59% (CI 51%-67%) VE

against influenza

Monto 2009 [75] 18-49 RPCT 2007-2008 68% VE against LCI

Beran 2009 [76] 18-64 RPCT 2006-2007 62% VE against LCI

67% VE against vaccine

matched strains

Jackson 2010 [77] 18-49 RPCT 2005-6 2006-7 49% VE against CCI

63% VE against C or SCI

Barrett 2011 [78] 18-49 RPCT 2008-2009 78% VE against matched,

CCI

Study Population age Study design Study years Outcomes and VE

Jefferson 2012 [15] Under two

years

Systematic review N/A Insufficient data to support

VE

Cochran 2010 [69] 6-23 months Retrospective cohort 2003-2006 76% VE against LCI 2005-6

No effectiveness in 2003-4

or 2004-5

Heinonen 2010 [70] 9 months to 3

years

Prospective cohort 2007-2008 66% VE against ILI

Kelly 2011 [71] 6-59 months Case-control 2008 58% VE against medical

visits;

Vesikari 2011 [72] 6-71 months RPCT 2007-8 and

2008-9 43% (CI 15-61%) VE against

PCR-confirmed influenza

Jefferson 2012 [15]

[73]

Under 16 years Systematic review

and meta-analysis

N/A 59% (41% - 71%) efficacy

against LCI

36% (24% - 46%)

effectiveness against ILI

Recent TIV vaccine efficacy and effectiveness

studies conducted in infants and children. Adapted from Plotkin 6th edition 2012 and updated.

SARI and influenza hospitalisations by age groups

NZPHSR 2013;11(2):5-6

<1 1-4 5-19 20-34 35-49 50-64 65-79 80+

SARI 4,636 935 94 128 137 320 860 1,445

Influenza 411.7 107.8 18.9 28.7 29.3 62.3 130.5 222.7

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Eligible funded ....includes

• “children under the age of 5 years who have been hospitalised for a respiratory illness, or have a history of significant respiratory illness”

Vaccines

• TIV (trivalent inactivated vaccines) – The only current NZ vaccines – Quadrivalents (QIV) on the way

• Adjuvanted – Expected to have stronger immune response – Was used effectively in some pandemic vaccines – Likely better immune response in elderly ,young children – Safety issues – local reactions, ?narcolepsy

• LAIV (Live Attenuated Intranasal) – Broader immune response – Likely better for children – ?safety issues in children <2 yrs – Likely better for herd immunity – To be introduced to UK all children > 2 , 2014

Strategies

• Targeted Individual protection

• Pregnancy – individual protection and fetal/infant protection

• Cocoon protection (not funded)

– Infants

– Elderly

– High risk patients

• Herd immunity

– Universal childhood vaccination

Pregnancy and Vaccination

Flu vaccine

- Start of flu season

• Reduces maternal morbidity/mortality

• Reduces fetal mortality – Reduces fever

• Reduces flu in newborn – Ab protective for around

8 weeks

– 91% effective in reducing flu in infants

Pertussis-containing vaccine

- 28 to 38 weeks gestation

• Reduces maternal morbidity

• Reduces risk of transfer to newborn

• Some passive protection to newborn

– Higher Ab transfer if later in pregnancy

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Effectiveness of flu vaccine given during pregnancy in preventing hospitalisation for flu in infants 91% effective

Benowitz I, Esposito DB, Gracey KD, Shapiro ED, Vazquez M. Influenza vaccine given to pregnant women

reduces hospitalization due to influenza in their infants. Clinical Infectious Diseases 2010 Dec

15;51(12):1355-61.

Private Market Vaccines

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• Cory has been brought in for his 6 week immunisations. His Mum wants to give him all the full protection she can. Should she have the ‘better’ pneumococcal vaccine that she was told about in her antenatal group.

• Cory’s brother is 8 years old and the mum wants him to have the meningococcal protection because he missed the MeNZB vaccination programme

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• Cost can be high

• Consumers want to be given the choice

• We are not effectively or systematically offering private market vaccines in GP

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Groups with the highest rates of meningococcal disease in New Zealand

by age and ethnicity over 2008–20125

Meningococcal group B

disease (no vaccine available)

Meningococcal group C

disease (vaccines available)

By ethnicity

Infants under 1 year of

age

Children aged 1–4 years

Children aged 1–4 years

Adolescents aged 15–19

years

Maori

Pacific peoples

A, Y , W135 strains rare in NZ context: useful for travellers

Meningococcal vaccines

Polysaccharides – quadrivalent A, C, Y, W-135

Mencevax® ACYW, Menomune® ACYW-135

• Ineffective in younger children

• Short duration of immunity

• Possible hyporesponsiveness with multiple use

• Cheap , traditional travel vaccines

Conjugates

C: Meningitec®, NeisVac-C™

Quadrivalent A, C, Y & W135: Menactra®

• Effective in younger children

• Herd immunity effects

– B vaccine.....not yet (NB unlikely to be any individual protection left now in NZ community from MeNZB vaccine) 34

Varicella • 2 dose from 9m or ?one dose from a year of age (assume wild boosting)

• Adolescents/adults with no history of disease 2dose

Meningococcal • Conjugate C 2 (to infants) + 1 booster (>1 year)

• Conjugate C or quadrivalent at mid teenager

• Every 5 year if high risk/concerns

Pneumococcal • PCV13 followed by PPV23 for high risk respiratory COPD etc

Pertussis and influenza: pregnancy (funded)/cocoon

HPV • boys, particularly MSM

Shingles • Elderly ?>60 yrs…..or older

At risk occupations/travellers – hepatitis B, hepatitis A, flu

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Shingles - Zostavax

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• VE – Zoster reduction 51%

– Post herpetic neuralgia reduction 67%

• Contraindications – Anaphylaxis to any components, neomycin

– Immunodeficiency/ immunosuppressed

– Pregnancy

– Active untreated Tb

• Who to advise

– Elderly …..

Aims

– Keep independent living

– Reduce increased frailty with onset of zoster

NZ Immunisation Schedule

? the future....

Vaccines: What is next............

• Always the possibility of future flu pandemics

• Next vaccines recommended for the schedule

– Varicella

• To consider after that

– Meningococcal Vaccines

• Conjugates C and quadrivalent

• B (Bexsero licensed in Australia)

– Better flu vaccines: live attenuated (kids), adjuvanted(elderly)

– HPV for boys/men

– Shingles vaccines (elderly)

– Pertussis vaccines in older age groups…

Immunsation coverage progress…..

A celebration of how fabulous General Practice can be!

1995 Strategy

Priorities for Action Report

National Strategy Parliamentary Enquiry

National Health Targets

2012 targets

NIR

NHC report

PHC report

Turner N, unpublished; using combined data from national surveys and the NIR

Percentage fully immunised by two years of age

Data sourced from NIR

Why are we improving • Commitment at all levels – national target

• Feedback loops – DHBs and PHOs

• General Practice engagement and confidence – More focus , higher priority

– Less missed opportunities

• SYSTEMS – Early ENROLMENT! - and follow up

– Precalls/recalls/audits

– PMS/NIR

– Providers to OIS : effective interface

• Confident health sector spills over to confident public – Less anti-science in the media

Areas to continue focus: Missed opportunities

True contraindication

• Anaphylaxis to any component of the vaccine

• Acutely unwell: high fever, toxic etc

Immunocompromised with a live vaccine (MMR, Varicella)

Evolving neurological conditions with pertussis

Anaphylaxis to egg with flu vaccine

False….

• MMR vaccine causes autism

• Egg allergy cannot vaccinate with MMR

• Availability of single vaccines eg tetanus

• 3 injections at 15 months is too hard

• Can’t vaccinate while breast feeding

X

Communication challenges

Coincidence vs. Causality

“Regardless of what the research tells us, I know what I saw.”

Dr. Kathy Pratt, April 25th, 2001, during a hearing by the Office of

Government Reform to investigate MMR and autism

Anecdote trumps science any day hero, victim and villain

“He plunged the needle into my son and I watched his soul leave

his body”

Jenny McCarthy

Assessing Risk

Thank you

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(466863)

www.immune.org.nz