400 100 · PDF file30 40 50 60 70 80 90 100 0 50 100 150 200 250 300 ... provide maximal protection to every infant; ... et al. Lancet Neurol. 2012;11:774-783. Meningococcal

1

www.ncirs.usyd.edu.au

Maternal immunisation and infant

immunisation: core business for GPs

What’s new in 2016?

Peter McIntyre

Director, National Centre for Immunisation Research &

Surveillance

Senior Staff Specialist, Children’s Hospital at Westmead

Professor, University of Sydney

Recommended vaccines

- Free and user pays

Children:

• Free – National Immunisation Program (Commonwealth)

• 18 month pertussis

• Influenza for children with increased risk of severe disease

• User pays - Recommended in Handbook, not in NIP

• Meningococcal B

• Influenza for all children especially those < 5 years

• 2nd dose varicella

Maternal – in pregnancy

• Free - NIP (Commonwealth) – influenza

• Free - funded by State Governments – pertussis

2

Outline

Pertussis and Influenza

• Preventing death/severe disease in children

• Maternal immunisation

• Child immunisation

• Safety monitoring

Meningococcal B

• How much and how severe?

• Meningococcal B vaccine recommendations

3 www.ncirs.usyd.edu.au

Pertussis

4

ICD-coded pertussis hospitalisations in infants aged <12

months, Australia, July 1998 - June 2012

0

10

20

30

40

50

60

70

80

90

100

0

50

100

150

200

250

300

350

400

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50

Cu

mu

lati

ve

pe

rce

nta

ge

of

ca

se

s

No

. o

f h

os

pit

alis

ed

ca

se

s

Age at onset (weeks)

First DTPa dose from 6 weeks

Source: AIHW National Hospital Morbidity Database

~30% of hospitalisations

before 6 weeks

Pertussis deaths

and

ICU with

ventilation:

80% < 6 weeks

Strategies to protect infants from severe

disease

Earlier vaccination of infant

• 6 weeks recommended from 2009

• Australian neonatal trial

Vaccination of contacts

• Vaccination of siblings: 18 month dose

• “Cocoon” vaccination of adult contacts

Maternal vaccination

6

2

Unexpected problem: rapid waning of

immunity with acellular pertussis vaccines

Without 18 month booster:

• From 2 years – Australian study (Quinn et al Pediatrics

2014)

With boosters at 18 months and 5-6 years:

• From 7-8 years – US study (Misegades et al JAMA 2013)

Australian study 2010 (NSW)

• Source: siblings 36%, parents 24%

• Most sibling sources aged 3-4 years and vaccinated

Australian study 2015 (WA)


• Most sibling sources aged 3-4 years and vaccinated

US study 2015


• Mother more important in youngest infants

• Average sibling age ~ 8 years and vaccinated

Source of infection for infants –

siblings and waning immunity

1. Jardine A, et al. CDI 2010; 34:116-21.2. Bertilone C, et al. CDI 2015;38:195-200

3. Skoff et al Pediatrics 2015; 136: 635-41.


The cocoon strategy

- incomplete cocoons

- incomplete coverage

- incomplete vaccine effectiveness

Deaths from whooping cough

in infants, England, 2001-2012

Sources: lab confirmed cases, certified deaths, Hospital episode statistics, GP registration details

Game changer : Maternal pertussis vaccine

12

3

Case control study – protection against pertussis in

infants under 8 weeks of age – UK

Vaccine effectiveness estimated at 91-93%

• Infants < 8 weeks old

13

California – infants born to vaccinated mothers can

still get pertussis but less severe than in unvaccinated

mothers


Safety of ante-natal pertussis

vaccination

Reassuring data – studies of 20,000

pregnancies (UK) and 120,000 (US)

dTpa vaccine is recommended as a single dose during the

third trimester of each pregnancy (see refer to 3.3 Groups

with special vaccination requirements). Vaccination during

pregnancy has been shown to be more effective in reducing

the risk of pertussis in young infants than vaccination of the

mother post partum.

Vaccination is recommended with each pregnancy to

provide maximal protection to every infant; this includes

pregnancies which are closely spaced (e.g. <2 years).

March 2015 Pertussis chapter update

Prepared for ATAGI # 57

Optimum timing in pregnancy

• Death in UK when dTpa given < 2 weeks pre-delivery

• Recent evidence that 2nd trimester (from 21 weeks) is

ok and may even be preferable1,2

• Co-administration with influenza vaccine?

• Should be fine, no data

1. AbuRaya Vaccine 2014 2 Eberhardt et al Clin Inf Diseases 2016

UK pertussis deaths post program – no “herd”

protection for infants of non-immunised mothers

4

Coverage, coverage – it’s all about the baby……


18 m dose

Recommended in Handbook since 2010

Funded from April 2016 (and required for no jab,

no pay)

• Reduce sibling infections

• Should eliminate any concern about lower infant

antibodies post maternal immunisation

AusVaxSafety

National active SMS-based

surveillance

2016 – 2019: Pertussis vaccines

• Children 12 months – 7 years

• Monthly reporting

• AESI: extensive limb swelling


Influenza

22

0

20

40

60

80

100

120

140

160

180

200

0-5m 6-23m 2-4y 5-11y 12-17y 18-64y ≥65y

Incidence(per 100,000)

Age group

Hospitalisation ICU

Influenza vaccine

not indicated

ICD-coded hospitalisation for influenza 2002–2013

Influenza vaccine fundedonly with risk factors

Vaccine funded for all > 65 years

Children <18y + significant comorbidities x 2 chance of admission to ICU

Deaths per year vs. Years of Life Lost per death 2006-13

24

0.6 1.0 1.7 0.9 0.6

22.4

60.4

81 83 7976

68

37

8

0

10

20

30

40

50

60

70

80

90

0–5m 6–23m 2–4y 5–11y 12–17y 18–64y ≥65y

Nu

mb

er

of

de

ath

s p

er

year

, o

r n

um

be

r o

f Y

LL p

er

case

Average number of deaths per year

Annual number of YLL per case of death

* based on ABS Cause of Death data (influenza being any cause of death)

5

+ = ?

Influenza in pregnancy

2009 Pandemic = 42 ICU admissions and

3 deaths in pregnant women in Australia

Influenza immunisation in pregnancy-it’s all about the baby!

Influenza and pertussis vaccines in pregnancy

– important findings from WA1-4

Safety

• N=2885 women

• 14% self-reported AEFI

• 1.4% medically attended1

• More local reactions with dTpa than influenza

Uptake4

• 35% private O&G; 20% GP; 44% antenatal; 2% private midwife

• Most important reasons not to have flu vaccine:

- not recommended + concern re side effects

• Most important reason to have flu vaccine: “for baby”

1. Regan et al ANZJOG 2014; 2. Regan et al BMC Preg and Childbirth 2015;

3. Regan et al Women and Birth 2016; 4. Regan et al Vaccine 2016

Influenza immunisation for children

Free on NIP for children from 6 months with pre-

disposing illness

• In these children, especially important for all

household members to also receive vaccine

High hospitalisations < 2 years

• < 6 months only preventable by maternal vaccination

• Need 2 doses in first year

• Vaccine effectiveness higher in children

29

RCH Melbourne

Dr Margie Danchin:

Influenza vaccine for kids

April 2016

> 300,000 views

Facebook responses

from parents

6


Meningococcal B

Uncommon but…..

High severity

31

Significant mortality despite appropriate

treatment

• ~5-10% of cases are fatal2,3

Significant morbidity despite appropriate

treatment

• ~10% of MenB child survivors experience major

sequelae, including limb amputations, seizures

and hearing loss4

• More than 30% of MenB child survivors

experience other deficits such as psychological

disorders, digit amputations and unilateral

hearing loss4

Top image: Courtesy of Centers for Disease Control and Prevention and Dr. Gust. Bottom image: Courtesy of Meningitis Research Foundation UK. Available

at www.meningitis.org.

1. Thompson MJ, et al. Lancet. 2006;367:397-403; 2. Meningococcal meningitis factsheet No 141. World Health Organization website.

http://www.who.int/mediacentre/factsheets/fs141/en/index.html; 3. Rosenstein NE, et al. N Engl J Med. 2001;344:1378-1388; 4. Viner RM, et al. Lancet

Neurol. 2012;11:774-783.

Meningococcal B and C disease compared

33

MenB disease <2 years

10.1

17.218.6

16.8

11.0

6.4 6.2

0.0

5.0

10.0

15.0

20.0

25.0

0-2 3-4 5-6 7-8 9-11 12-17 18-23

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an a

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ear

s

Age (months)

Meningococcal vaccines

Serogroup-specific

Registered/ in use in Australia:

• Serogroup C: Meningococcal C (MenC) conjugate vaccine

• Serogroups A/C/W/Y: 4-valent conjugate vaccine

• Serogroups A/C/W/Y: 4-valent polysaccharide vaccine

• Serogroup B: multi-component recombinant MenB vaccine

» NOT capsular polysaccharide

Meningococcal B

– a number of surface proteins associated with

immunity

36

http://f1000.com/prime/reports/m/3/16/fig-002

7

Recombinant multicomponent Meningococcal B vaccine:

4CMenB

37 Source:

McIntosh D. Presented at: 2013 Vaccine Preventable Diseases Conference; April 2013; Dublin, Ireland. Available at:

www.immunisation.ie/en/Conferences/2013VPDConference/PDFFile_17228_en.pdf (accessed Mar 2014)

Registered in

Australia

August 2013

Available on

private

market since

March 2014

4CMenB schedule

Multiple doses

• 4 doses starting @ 2 months

• 3 doses starting @ 6 months

• 2 doses starting > 12 months

38

Age in months

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 …. x x+1 x+2

Young infants

Older infants

Toddlers

Others

3 instead of 4 doses

in infants

Early results of use in

UK look promising for

2 or more doses

4CMenB: Reactogenicity – infants

Systemic reactions in an phase 2 study in infants given 4CMenB at

age 2, 4, 6, and 12 months (concurrent with ‘routine’ vaccines):

40Source of figure: Borrow R. Public Health England. Issues in evaluating the impact of a new meningococcal B vaccine

http://www.slideshare.net/meningitis/issues-in-evaluating-the-impact-of-a-new-meningococcal-b-vaccine

Source of study: Findlow et al. Clin Infect Dis 2010;51:1127-37

Paracetomol recommended

( 3 doses)

Early reactogenicity data

from UK do not suggest

any major problems

Varicella Breakthrough

varicella

2 doses of varicella vaccine are recommended

only one dose is “free”

Breakthrough varicella is usually mild

• can be severe occasionally

• ? increases risk of zoster

• school absence

Second dose is VV alone

• MMR+V at 18 months

• Can give VV @ 12 months with MMR separate

42

8

Summary

Maternal immunisation

Exciting potential to prevent severe disease in infants

less than 6 months of age

High coverage is key

• Partnership with other antenatal care providers

Main motivators for high coverage

• Dr recommendation + baby welfare

Child immunisation

User pays but recommended (influenza, Men B, 2nd

varicella)

• “ask and it shall be given” ….including influenza

• Take opportunities to inform parents 43

Acknowledgements

44

Helen Quinn Kevin Yin

Nick Wood Sanjay Jayasinghe

Frank Beard Cyra Patel

Kristine Macartney Clayton Chiu

Sami Carlson

NCIRS is supported by the Australian Government

Department of Health, the NSW Ministry of Health and the

Sydney Children’s Hospitals Network.

Documents

400 100 · PDF file30 40 50 60 70 80 90 100 0 50 100 150 200 250 300 ... provide maximal protection to every infant; ... et al. Lancet Neurol. 2012;11:774-783. Meningococcal