Transcript Slide 1

Vaccine Safety Update
and introduction to
Monash Immunisation
Jim Buttery
Infectious Diseases, MCH
Monash Immunisation, MMC
Director of Research, MCH
SAEFVIC, MCRI
Outline
National
2013 safety initiatives
• Australia TIV 2010
experience
• Flu
• MMRV
• Primary care…
– Signal detection
– Investigations for association
– Investigations for cause
• Changes since 2010 to
improve
–
–
–
–
Surveillance
Signal detection
Investigations
Communication
BCG
• 2012….2013….
Monash Immunisation
Febrile seizures
• Common 2-3% of all children
– Usual trigger minor infection eg URTI, influenza
• Usually 6m-5y of age
– Brief < 5 minutes
– Benign- no neurologic sequalae
• Can recur in 1/3
• Increased risk described following
– MMR, MMRV
– influenza vaccine
Febrile convulsions post influenza vaccines
• Classically 7-11 hours post vaccine
• Febrile convulsion rates:
– USA 0.03 (0.16 over 7 days) per 1,000 doses
• Risk increased if co-administered with PCV13
http://www.cdc.gov/flu/
Leroy et al Vaccine 2012
TIV in Australian Children
Australia
• Funded for special risk groups only
– Contracting/provision administered by states
– Estimated coverage 5%
• Not required on ACIR Immunisation Register
• Coverage hard to determine
• Data mostly held in primary care practices
– Vaccination usually starts March/April
• Inactivated TIV
– CSL Fluvax/ Fluvax Jnr / Panvax (H1N109)
– Other international manufacturers
Chin et al, Eurosurveillance 2012
TIV in Australian Children
Australia
• Funded for special risk groups only
– Contracting/provision administered by states
– Estimated coverage 5%
West Australia
• 3 young children deaths ascribed to flu 2007
• State funding all children 6m-5y from 2008
• Coverage 30-35%
2010 TIV: Pre-licensure safety data
• Seasonal vaccine
– No RCTs for this batch
• Panvax H1N109 trials 2009 with 15µg dose
– 1/82 children <3y severe fever (1.2%, 95%CI 0.2-6.6)
• 4/79 with 30µg dose (5.1%, 95%CI 2-12.3)
Disease Disease
yes
no
Nolan et al JAMA 2010
Vaccine
yes
a
b
Vaccine
no
c
d
2010 timeline
1
8th March: Trivalent vaccine
launched
Fluvax Junior and Fluvax: CSL
Influvac: Solvay Pharmaceuticals
Vaxigrip: Sanofi Pasteur
13th April: TGA
notified
Reports of febrile convulsions
presenting to ED follow TIV
22nd April: WA suspends
preschool influenza
vaccination program
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23rd April: TGA suspends
national flu vaccination
program
Courtesy Chris Blyth, PMH
LESSON 6 : EXPECT THE UNEXPECTED
Princess Margaret Hospital- Perth WA
Influenza
vaccine
2008
2009
2010
0
3
36
31
47
47
(previous 72 hours)
No influenza
vaccine
Slide courtesy Chris Blyth
WA investigations
• State ED database EDIS: 9 Perth EDs
– All admissions coding for febrile seizure r56.0
• TIV delivery estimated using provider
questionnaire for rates
• Reactogenicity of 3 vaccines used determined
by retrospective cohort study from 1 clinic
Armstrong P K et al. BMJ Open 2011;1:e000016
Presentations of children under 5 years of age with febrile convulsions (ICD-10 code R56.0) to
nine Perth hospital emergency departments, 1 January to 2 May 2010.
Armstrong P K et al. BMJ Open 2011;1:e000016
©2011 by British Medical Journal Publishing Group
West Australia Febrile Convulsions
• est max of 18 816 doses of TIV administered
– 63 febrile convulsions recorded
– estimated rate 3.3/1000 doses (95% CI 2.6 to 4.2)
• TGA
– 7/1,000 for FLUVAX (adult) vaccine
– 10/1,000 for FLUVAX JUNIOR
– 0 for INFLUVAC from 1,450 doses administered
• >200 x the only population-based published
estimate
Armstrong P K et al. BMJ Open 2011;1:e000016
www.tga.gov.au
2011-2012: WA influenza vaccination
Number of Doses of TIV Administered in Children <7 by Week, WA, 2008, 2009, 2010
and 2011
6000
No. of TIV Doses in Children <7 years
5000
2008
2009
2010
2011
4000
3000
2000
1000
0
Week
Courtesy CDCD; DoH WA
Febrile seizures following influenza
vaccine in Australian children in 2010
Self controlled case series analysis
N Wood, R Menzies, P McIntyre, H Wang, H Gidding,
M Gold, J Buttery, N Crawford, D Tran, P Richmond, C Blyth
www.ncirs.edu.au
Interval post flu vaccine to febrile seizure
n=38 had febrile seizure within 48 hours
47% aged 12 to 23 months
Days post flu vaccine
SCCS analysis
• CSL seasonal fluvax and FS within 48 hours
compared to non risk period
– IRR = 15.2 (95%CI 7.3-31.4)
• CSL fluvax and FS within 48 hours AND age
adjustment
– <2 years old
• IRR = 15.2 (95%CI 7.3-31.6)
– > 2 years old
• IRR = 0.7 (95%CI 0.17-2.7)
AEFI reporting: Australia
• Differences between states
– Strengths/weaknesses
– Funding
– Clinical links etc
• Relation to TGA
– Communication
– Potential delays
• ACSOM (ADRAC)
– Review cycles
– ‘surge capability’
JURISDICTIONS
NRA
JURISDICTIONS
NRA/Central
2011-2012: finding solutions
FEDERAL INQUIRY: TGA
Professor John Horvath
Former Chief Medical Officer
WA PARLIAMENTARY INQUIRY
Professor Bryant Stokes
Former WA Chief Medical Officer
Recommendations
• States retain reporting
• Harmonise AEFI reporting
for states
– Form
– methods
• User friendly timely internet
reporting
• Increase consumer and
health professional
awareness
• Build flags into internet
reporting for rate changes
• Define surveillance
objectives
• Priority for e-health
– vaccines administered
• Denominator data
– Safety monitoring data
• Establish national vaccine
safety committee
• Establish agreed protocols
for action
– Triggers
– Signal investigation methods
• De-identified AEFI reports
available for open review
Progress
• States retain reporting
• Harmonise AEFI reporting
for states
– Form
– methods
• User friendly timely internet
reporting
• Increase consumer and
health professional
awareness
• Build flags into internet
reporting for rate changes
• Define surveillance
objectives
• Priority for e-health
– vaccines administered
• Denominator data
– Safety monitoring data
• Establish national vaccine
safety committee
• Establish agreed protocols
for action
– Triggers
– Signal investigation methods
• De-identified AEFI reports
available for open review
New for 2013
Flu 2013
• Multicentre comparative
study of paediatric TIV
preparations
– NCIRS led
HPV
• Enhanced surveillance in
schools and LGA
– SAEFVIC
MMRV
• Trial of fever rates postimmunisation from GP
software (pilot) (also Flu)
– SAEFVIC
– Canning tool- interested
practices needed
• MD, BP, Practyx
Safety of environmental
excursions
SS 10 months old
• Healthy term infant
• No significant past history
• BCG Vaccination 16/12/2010
– One week later, travelled to Kerala, India
(23/12/10)
• unwell 3 weeks into trip (10/1/11)
– Fever, cough, rhinorrhea
– Inflamed BCG scar, slight discharge
SS 10 months old
• 2 weeks later
– left anterior axillary lymphadenopathy (21/1/11)
– Ongoing fevers
• Progressive increase in left axillary LNs
– Non-tender
• Returned to Australia at end of Jan 2011
SS 10 months old
History
• Born in Melbourne
• Only child
• Immunised per schedule
• No known TB / chronic cough contacts
ID Clinic Feb 2012
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•
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Firm, possibly fluctuant
Multiple shotty cervial
lymph nodes
No other lymphadenopathy
Unremarkable general
examination
Investigations
• Increased fluctuance on clincal review
Managment
• Excision of lymph node abscess
• 4 month course of daily rifampicin 100mg and
isoniazid 100mg
– Well tolerated
• Histopathology – granulomatous infection
• Mycobacteria PCR positive
• Residual lymphadenopathy resolved over 3/12
• Small LN palpable at end of treatment course
• Notified to SAEFVIC
BCG: History
• BCG is named after the two
French investigators responsible
for developing the vaccine from
an attenuated strain of
Mycobacterium bovis.
• Isolated from a cow with TB
• They presented their results to
the Academie de Sciences in 1908
• Subcultured every 3 weeks for 13
years..
Oils aint oils- from WHO website:
• The BCG vaccines that are currently in use are
produced at several (seven?) sites throughout the
world. These vaccines are not identical. To what
extent they differ in efficacy and safety in humans
is not clear at present. Some differences in
molecular and genetic characteristics are known.
What is not known is if the "BCG" from one
manufacturer is "better" than one produced at
another site. Each BCG is now known by the
location where it is produced.
Current BCG recommendations
• ATSI neonates living in regions of high TB
incidence,
• neonates born to parents with leprosy or a family
history of leprosy,
• children <5 years of age who will be travelling to
live in countries of high TB prevalence for longer
than 3 months
• embalmers,
• healthcare workers involved in conducting
autopsies.
State and Territory guidelines should
be consulted for the following groups
• healthcare workers who may be at high risk of
exposure to drug-resistant cases,
• neonates weighing <2.5 kg,
• children ≥5 years and <16 years of age who
will be travelling or living for extended periods
in countries with a high prevalence of
tuberculosis.
EFFICACY: BCG IS EFFECTIVE IN
PREVENTING SEVERE TB IN CHIDREN
• Protection
• Consistent 60-80% protection against disseminated
tuberculosis (TBM, miliary TB) in HIV-negative and
unexposed young children
• Variable protection: pulmonary TB, limited impact
transmission
• Revaccination: no benefit
• Cost-effective
• Limited efficacy data in HIV-infected infants
• High TB incidence HIV-infected infants (small
subpopulation): 25 fold higher in HIV-infected infants
• HAART: reduces risk of TB in HIV-infected infants
Trunz, Fine, Dye. The Lancet 2006; 367:1173-1180,
Rodrigues, Int J Epi 2002
BCG History: The Lübeck disaster
• Dec 1929 & April 1930
– 251 of 412 infants born
in Lübeck, Germany,
received three doses of
BCG vaccine by the
mouth during the first
ten days of life.
– 72 died of tuberculosis
• most of them in two to
five months, and all but
one before the end of the
first year
BCG History: The Lübeck disaster
• In addition, 135 suffered from clinical
tuberculosis but eventually recovered
• 44 became tuberculin-positive but remained well
• Of 251 children, 207 (82.5%) died or developed
tuberculosis
• later recognized that this batch was accidentally
contaminated with a virulent strain of M.
tuberculosis
REVISED
PAEDIATRIC
DISEASE
CLASSIFICATION
Revised paediatric
BCGBCG
disease
classification
Local disease
Abscess
Dual disease
M. tb and BCG
Regional disease
Adenitis
BCG IRIS
Disseminated
disease
Following HAART
Beyond regional
Hesseling et al, Clin Infect Dis 2006
“SAGE agreed that the BCG position paper should be
updated to reflect this change and provide guidance
to national policy-making bodies, recognizing the
complexity of the decision-making process and the lack of
information as well as the necessary infrastructure to
perform adequate risk assessment in individual children.
Among HIV-infected children, the benefits of potentially
preventing severe TB are outweighed by the risks
associated with the use of BCG vaccine. GACVS therefore
advised WHO to change its recommendation such that
children who are known to be HIV-infected, even if
asymptomatic, should no longer be immunized with BCG
vaccine.”
SAEFVIC: BCG AEFI
9
8
7
Frequency
6
5
4
3
2
1
0
N=59
SAEFVIC BCG AEFI n=59
• male/female : 40/19
• age
– age at vaccination
• mean: 2.66 years
• median: 0.90
• range: 0.06-22.78
•
”Wow
– wonder if there is anything to support
whether men get vaccinated more often and
therefore this is a reflection of vaccine administration
.. or do men just complain about their AEFI more?!!!”
SAEFVIC: BCG AEFI
Primary reaction
2%
2%
7%
3% 2%
5%
Abscess
Lymphadenopathy
Rash
Injection site reaction 49% minor/common/expected
Hypotonic–hyporesponsive
episode - HHE
Urticaria/Hives/Allergic Rash
3%
27%
Drug error (Program error)
Nodule at injection site
BCG withdrawal Sept 2012
• Sanofi-Aventis Australia Pty Ltd has recalled
batches of its Bacillus Calmette-Guerin vaccine
amid concerns its sterility cannot be assured
because of an “environmental monitoring
excursion” during manufacture
BCG recall
• BCG Connaught- 4 batches used since April
• Reviewed SAEFVIC data
– 59 children since 2007
• 21 had batch information available
– 18 since April 2012
• 7 Implicated batches
• 5 x non withdrawn batches
• 6 x no batches available- overseas or not able to be
contacted or no batch number recorded
Pragmatics: BCG
• BCG Connaught strain replaced with BCG
Denmark strain
– Denmark higher rate disseminated disease in HIV
– ?other AE
– 100 dose vials rather than 10 dose
• Distribution now limited to RCH and Monash
– New BCG clinics at Monash Immunisation
• Jo Tully and Tim Davis
Monash Immunisation
An all age immunisation service for
high risk patients
Monash Immunisation
 All age service – established January 2012- first within Australia
 Nurse-led outpatient drop-in centre operating each week day
 Service run by clinical nurses who specialise in immunisation management
and education

Access to specialised adult and paediatric immunisation physicians.
 Provide vaccinations under the National Immunisation Program
 Clinical research
Monash Immunisation
 Immunisation of current inpatients and outpatients
 Provide immunisations to high risk groups
–
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–
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Immunosuppressed patients and patients on immunosuppressive therapies.
Oncology
Respiratory and Cardiac
Transplant
RSV immunoglobulin
Antenatal and Postnatal
Premature babies
Families of high risk patients
 Assist with complex immunisation issues for patients
 Phone support and information.
 Education/advise to health care providers, children, adults and their
families
• AEFI reports
• Clinical support for providers and patients
• How to report?
– Online – www.saefvic.org.au
– Email – [email protected]
– Telephone – (03) 9345 4143
– Fax – (03) 9345 4163
Thank you
Monash Immunisation
• Refer to Monash Immunisation
– Tel 9594 6320
– Fax 9594 6325
– [email protected]
– Need referral
– Level 2 (ground) Jessie Mac rooms area