Dr Emma Best Paediatric Infectious Diseases Consultant

Starship Children’s Hospital

Vaccine preventable diseases

Acknowledgements for slides Dr. Cameron Grant, Associate Professor, Paediatrics, University of Auckland Paediatrician, Starship Children’s Hospital, Auckland Dr Nikki Turner, Director, Immunisation Advisory Centre, University of Auckland Dr Anusha Ganeshalingham PICU fellow intensive care for pertussis info Google Images

Dr Emma Best

Senior Lecturer, Department of Paediatrics, University

of Auckland

Paediatric Infectious Diseases Specialist

Starship Children’s Hospital

Immunisations again…

Declarations

Today am invited speaker by GSK who have paid my travel and accommodation

Do not accept honoraria

Participant in research groups with consumables funded by Wyeth (Pfizer) and GSK

Member of the Anti-infectives committee of Pharmac

Outline

Describe vaccine preventable diseases which I still see

Using presentations and complications

To help understand importance of vaccinating still and the public health significance

Discuss aspects of prevention of the disease and vaccine uptake

Immunology made simple

Vaccines stimulate body’s defence mechanisms (immune system) against an infection

Help immune system detect and destroy infection when encountered in the future without development of significant symptoms or complications of that disease

www.science.org.au/immunisation.html

Some vaccines can provide herd immunity

Indirect protection from infection caused by immune individuals

Exposure to antigens?

Will use Photos to introduce some vaccine preventable diseases and some of their complications

Name the vaccine preventable disease

Explain what caused the bleeding

Coughed so hard that she has burst the blood vessels on the surface of her eyes

“100 day

cough”

Whooping cough

Pertussis

Illness with paroxysms of coughing, plus whoop, apnoea and vomiting.

Presentation of pertussis varies with age .. and immunisation status

Infant

Apnoea and/or cyanosis and/or paroxysmal cough

Children

Non-immunised cough increasing in severity over several weeks rapidly repeated, forceful coughs followed by desperate gasps

Well between paroxysms

Immunised – milder disease – still cough, less forceful

Presentation of pertussis varies with age

Adult

Persistent cough,worse at night and often paroxysmal

Awoken by a ‘choking sensation’

scratchy throat, sweating attacks

Post-tussive vomiting and whoop

Every 3-5 years escalating epidemics at the end of 2011 – it was that time again, and proving to be a record

breaker

Number of pertussis notifications by week

reported, 2010 - 2013

ESR, Pertussis Report: April 2013.

NZ epidemic statistics are being mirrored around the world – in the

UK

USA..

Australia

34 Admissions to SSH PICU…and

counting

3 deaths

And cohorting up to 4 apnoeic babies per bay (4 times this epidemic)

Critical Pertussis

Malignant or fulminant

Infants

6/10 will be hospitalized in <6 mth age group

Reservoir is adults/adolescents

Factors associated with fulminant

pertussis – unimmunised or partly,

age< 6 months

To control pertussis you have to do immunisation well

Increase coverage from < 80% to 80- 90% and you decrease disease burden 10 fold,

Increase coverage to 95% or greater and you get another 10 fold reduction

Pertussis hospital discharge rate in NZ per 100,000 person years

J Paed Child Health 2007 Somerville, Grant et al

Vaccination has changed pertussis epidemiology

Booster vaccination: Prolonged protection 6-10 years

No additional booster: immunity wanes Susceptible adults:

reservoir of pertussis

Unvaccinated or partly vaccinated infants: susceptible

Primary vaccination: 4-6

Why are pertussis outbreaks occurring worldwide?

Vaccination does not change the periodicity of epidemics

Immunity wanes – perhaps faster than imagined

The current vaccine is not perfect and needs very good coverage

Why is pertussis in NZ so bad?

Very infectious and imperfect vaccine

+ NZ has not achieved good coverage

+ NZ has not achieved timeliness

+ NZ has changed our schedule several times (including dropping a dose in 1970’s)

+ NZ has poverty and crowded housing issues

Protect the young immunise …

Pregnant women, post partum

Older siblings/school aged children

Close contacts – fathers, grandparents

Early childcare workers

Healthcare workers (!)

Give vaccines on time and boosters

Name the Vaccine preventable disease affecting this newborn baby?

What is this complication from the same vaccine preventable disease?

Congenital cataracts – opaque lenses

Rubella

Was a common childhood illness -mild symptoms

Transmission by respiratory secretions

Rash is similar to many other infections

enlarged lymph nodes (back of neck, behind ears)

Cataracts Nerve deafness Heart defects

Microcephaly (small brain) Mental retardation Behavioural problems

Inflammation • Liver • Lungs • Bone marrow

But for newborns whose mothers acquire rubella in the first trimester …..

Blueberry muffin baby - due to bone marrow failure

Rubella in New Zealand

New Zealand Immunisation Handbook 2011

Rubella in New Zealand

Not common

Between 2005 and 2010, 49 cases of rubella were notified.

43 cases in children < 9 year

Worldwide, less developed countries offer only monovalent measles vaccine (India, Indonesia, Timor) so no control/monitoring of rubella

Measles Conjunctivitis, rash (cough) look miserable/sick!

Measles Transmission by respiratory secretions

Highly infectious

Rash is similar to many other infections

Measles

Days 2-4: Fever, red eyes, runny nose, Koplik spots

Day 3-7: Maculopapular rash (confluent)

Child most unwell day 1-2 of rash

Complications in 10%

Diarrhoea and dehydration

Otitis media, pneumonia, croup

Encephalitis 1:1,000 cases

Deaths in early 90’s and one in 1997 outbreaks

1969-1970 introduced

1990 MMR

Two dose schedule 1992,

changed to 15 mths in 1996

Measles in New Zealand

Epidemics still occur but immunisation has increased the time between them and many less cases

To prevent epidemic 95% of the population must be immune

Vaccine efficacy of 90-95%

Hence 2 dose schedule needed

WHO global eradication goal

Name vaccine preventable disease and country where these resurgent cases still seen

Poliomyelitis NZ 1915-2000

Western pacific polio free since 2000

Imported Case of Poliomyelitis, Melbourne, Australia, 2007- 22-yr-old

Pakistani student who had travelled home to Nthern Pakistan on holiday

Measles, rubella and polio are examples of herd immunity

and how we are part of both a mobile and global community

Polio will be eradicated but is not yet!

South East Asia is aiming for measles eradication ..but it is years away

Millions receive monovalent measles vaccine (M not MMR) so areas with little rubella control

Tetanus

u Clinical term for muscular rigidity caused by the toxin produced by Clostridium tetani

u Spores found everywhere in environment particularly manure/soil, not “infectious” or passed between people

u Easily introduced to a wound at time of injury especially deep penetrating dirty wounds

New Zealand, tetanus

New Zealand Immunisation Handbook 2011

New Zealand tetanus

Last 15 years, 30 cases of tetanus (2 cases per year in NZ) notified*

Mostly older adults - vaccinated ‘years ago’, no booster

Children – all unimmunised (4)

Starship experience with tetanus

Difficult to achieve full immunisation in families with fixed anti-immunisation beliefs

Publicity around cases increases discussion and may help some reconsider stance

Tetanus - a good reminder that for some diseases there is no herd immunity

Haemophilus influenzae type b (Hib) causes meningitis, periorbital cellulitis or epiglottitis

Epiglottitis

Fever, breathing difficulties, to

painful swallowing, drooling and then

complete airway obstruction

Haemophilus influenzae type b…………

used to be the paediatrician’s bread and butter

0

10

20

30

40

50

60

1st 4th 3rd 2nd 1st 4th 3rd 2nd 1st 4th 3rd 2nd 1st 4th 3rd 2nd 1st 4th 3rd 2nd 1st 4th 3rd 2nd 1st 4th 3rd

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 20092010

Ca

se

s

Hib laboratory confirmations 1990 - 1995 and notified cases 1996 - 2010

Source: Immunisation Advisory Centre, University of Auckland

Pre immunisation was the commonest cause of bacterial meningitis in children

1 in 350 NZ children aged < 5 years had an episode of invasive Hib infection

Hib epidemiology

Transmission by direct contact and respiratory secretions

Immunisation reduces carriage of bacteria in nose

Preschool children are ones affected so immunisation works very well - provide immunity for crucial age

If 80% of population vaccinated disease virtually disappears

Leung B , Best EJ et al ‘Haemophilus influenzae type b disease in Auckland children during the Hib vaccination era, 1995–2009.’ NZ Med Journal, Nov 2012

1-2 cases per year, disease still same spectrum, most unimmunised

Neisseria meningitidis Meningococcaemia Meningococcal meningitis (brain inflammation)

Meningococcal epidemiology

Asymptomatic colonisation

5 to 15% of population

Carriage increased by smoking (also

passive), crowding, viral infections

Respiratory droplet and secretion spread,

then infection in those at increased risk

Not as simple

as Hi type b

5 serogroups

that cause

disease

A, B, C, W135

and Y

Meningococcal bacteriology

Which New Zealanders?

Those in crowded houses Doubling of risk with the addition of 2 adolescents or adults to

a 6-room house (Baker PIDJ 2000;19 )

Age < 5 years, especially age 6 to 12 months

Maori and Pacific children (2 to 3x increased risk)

Household contacts 600x risk in week after index case

Students in hostels (adolescence the other risk group)

…anyone ..

Meningococcal disease

Meningococcal Vaccines available No longer MenzB

Conjugate meningococcal C

Polysaccharide quadrivalent A,C,W135 Y

Menactra conjugate A,C,W135,Y

Age range

Any but not long

lasting protection

particularly in infants

All ages and long

lasting

Over 2 years and

lasts about 5 years

Over 9months and

long lasting

Otitis media Pneumonia (and empyema) Meningitis pus and inflammation in the membrane

around the brain

Streptococcus pneumoniae

Pneumococcal disease

Pneumococcal epidemiology

Also not simple

90 (!) serotypes

Some more

invasive than

others

Pneumococcal bacteriology

Asymptomatic

colonisation in 30-

60% of young

children

Changed by season,

viral illness, antibiotic

prescribing,

socioeconomic

status

Invasive disease for

some

<2 yrs, >65yrs,

medical conditions

Non invasive disease

Ear infections,

pneumonia

S. pneumoniae substantial burden of disease Estimated annual hospital admissions per

100,000 in NZ children aged <5 years1*

23

295

808

*Before implementation of PCV7 immunisation in NZ

1. Milne, Vander Hoorn. Appl Health Econ Health Policy 2010;8:281–300

Paediatric pneumococcal disease in New

Zealand

Life threatening

Each year ≈ 150 cases of pneumococcal meningitis

and bacteraemia in children under 5 years old

10-11 deaths

13-26 cases of severe long-term disability

Pneumonia

3000 admissions per year

20 to 40% due to pneumococcal infection

Otitis media

A large proportion of antibiotic prescriptions

Pneumococcal vaccines

23 valent polysaccharide vaccine

Not immunogenic in children < 2 years old

Conjugate vaccines

Antigens from most invasive pneumococcal serotypes

Joined (conjugated) to a carrier protein

More complex molecule - creates an immune response in infants

Seroptypes causing IPD in Children <2 years and Adults ≥65 years

Laboratory Surveillance NZ 1998-2005

0

5

10

15

20

25

30

14 6B 19F 4 23F 9V 18C 19A 6A* 7F 8 3 22F 12F 1

Included in PCV-7 Not in PCV-7

Pneumococcal Serotypes

Pe

rce

nta

ge o

f S

ero

typ

es I

sola

ted

<2 years

≥65 years

Serotypes Causing IPD in Children <2 years and Adults ≥65 years - Laboratory Surveillance NZ 1998-2005

Jackson C Serious Pneumococcal Disease in NZ 2007 IMAC , University of Auckland

PCV vaccines Serotypes

Prevenar13™

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

1, 5, 7F 3, 6A, 19A

CRM197 Diphtheria carrier protein

Serotypes

Serotypes

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

CRM197 Diphtheria carrier protein

Prevenar™

PCV7 licensed in

2000

Introduced NZ June

2008

NTHi protein D

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

1, 5, 7F

NTHi protein D T D

Synflorix™ Switched

to PCV 10

June 2011

3 + 1 schedule

6wks, 3mths, 5mths and 15 mths

New Zealand IPD rates

90% reduction in VT IPD

70% reduction in overall IPD Heffernan et al INVASIVE PNEUMOCOCCAL DISEASE IN

NEW ZEALAND, 2010

Young girl with a rash

Varicella – common childhood illness

COMMON YES – 90% have had chicken pox by age 14 yrs

So common that complications also common!

What is this common associated skin complication?

Cellulitis

What is this rare complication of this VPD?

Necrotising fasciitis – “flesh eating bug”

Typically Streptococcus pyogenes

Not so benign - severity of chicken pox

Mild disease 50 lesions (most breakthrough disease in vaccinated children is <50 lesions)

Moderate 200-400 lesions (most wild type)

Severe >1000 lesions

Although more severe in immunocompromise most deaths and hospitalisations occur in healthy people/children

SSH PICU again; varicella admissions

10 years review – 2-3 children per year

4 deaths

Currently looking at all hospitalisations due to varicella across New Zealand over 2 years in <15 yr olds

For every hospitalisation 90-150 GP visits

Varicella vaccine

• Varicella vaccine available since 1996 (live attenuated vaccine)

• Recommended but not funded, (about 17% uptake)

• Vaccines available in New Zealand:

• Varilirix Varivax

• Quadrivalent MMRV vaccine (Priorix-Tetra or ProQuad)

• Zostavax (herpes zoster vaccine for adults ≥ 50 years of age)

• Recommended for children from age 12m to 12yrs 1 dose effective for 80%, very effective at reducing serious infection

• Administered at 15m (with MMR, Hib & PCV10)

• Second dose (debatable) at 4yrs with MMR (effectiveness 2 doses >95%)

USA AUSTRALIA USA since 1995 Australia –

recommended 2003,

funded since 2005

Varicella vaccine

Common questions raised when talking about vaccinating chicken pox

Why – common childhood disease and better immunity from wild infection?

Vaccine immunity only lasts 20 years?

More shingles

2 doses?

Use MMRV or MMR + V ?

Common questions raised when talking about vaccinating chicken pox

Why? common and nasty

Vaccine immunity only lasts 20 years – no reason to believe this – live viral vaccine and antibody should present lifelong but without wild virus may need other boosting

More shingles? Less shingles after vaccine – theoretical concern of increased shingles in those whilst we “eradicate varicella with vaccine” – development of zostavax Reid S NZMJ 2012 125; 1354

• Give the varicella vaccine or the MMRV??

• So 1 jab (MMRV) or 2 jabs (MMR + V) at 15 months?

• NZ MOH recommends MMR+V at 15 months due to risk of febrile seizures

• What is the risk for febrile seizures?

• 1 additional febrile seizure is expected per 2500children vaccinated with MMRV when compared with MMR + V (if receive it aged 1-2 yr)

• No increased risk seen in those aged 4-6yrs who received MMRV

• Weigh up with other costs – pain of extra injection, risk of falling behind schedule, missing opportunity of vaccinating

Varicella vaccine or MMRV

A very current vaccine preventable disease -

Global community, herd immunity and not

Bacterial vaccines - the old’ish and new’ish

HIB, MENINGOCOCCAL AND PNEUMOCOCCAL

What’s in store?

PERTUSSIS

Polio, rubella Measles Tetanus

Varicella

Key messages

VPD -a reality in NZ and cause morbidity and death

Improved coverage and timeliness will change this

We are part of a global community of people (measles) and microbes (tetanus)

Effective bacterial vaccines give new invasive disease priorities - surveillance is important

Pertussis control is complicated

New vaccines such as varicella likely to impact positively both at population and individual level