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Vaccine Safety Update and introduction to Monash Immunisation

Vaccine Safety Update and introduction to Monash Immunisation. Jim Buttery Infectious Diseases, MCH Monash Immunisation, MMC Director of Research, MCH SAEFVIC, MCRI. Outline . National. Flu MMRV Primary care…. 2013 safety initiatives. Australia TIV 2010 experience Signal detection

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Vaccine Safety Update and introduction to Monash Immunisation

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  1. Vaccine Safety Update and introduction to Monash Immunisation Jim Buttery Infectious Diseases, MCH Monash Immunisation, MMC Director of Research, MCH SAEFVIC, MCRI

  2. Outline National Flu MMRV Primary care… 2013 safety initiatives • Australia TIV 2010 experience • Signal detection • Investigations for association • Investigations for cause • Changes since 2010 to improve • Surveillance • Signal detection • Investigations • Communication BCG • 2012….2013…. Monash Immunisation

  3. 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

  4. 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

  5. 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

  6. 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%

  7. 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) Nolan et al JAMA 2010

  8. 2010 timeline 13th April: TGA notified 8th March: Trivalent vaccine launched Fluvax Junior and Fluvax: CSL Influvac: Solvay Pharmaceuticals Vaxigrip: Sanofi Pasteur Reports of febrile convulsions presenting to ED follow TIV 22nd April: WA suspends preschool influenza vaccination program 23rd April: TGA suspends national flu vaccination program Courtesy Chris Blyth, PMH

  9. LESSON 6 : EXPECT THE UNEXPECTED

  10. Princess Margaret Hospital- Perth WA Slide courtesy Chris Blyth

  11. 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

  12. 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

  13. 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

  14. 2011-2012: WA influenza vaccination Courtesy CDCD; DoH WA

  15. Febrile seizures following influenza vaccine in Australian children in 2010Self 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

  16. 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

  17. 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)

  18. AEFI reporting: Australia • Differences between states • Strengths/weaknesses • Funding • Clinical links etc • Relation to TGA • Communication • Potential delays • ACSOM (ADRAC) • Review cycles • ‘surge capability’

  19. JURISDICTIONS NRA

  20. JURISDICTIONS NRA/Central

  21. 2011-2012: finding solutions FEDERAL INQUIRY: TGA WA PARLIAMENTARY INQUIRY Professor Bryant Stokes Former WA Chief Medical Officer Professor John Horvath Former Chief Medical Officer

  22. 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 Recommendations

  23. 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

  24. New for 2013 Flu 2013 MMRV Trial of fever rates post-immunisation from GP software (pilot) (also Flu) SAEFVIC Canning tool- interested practices needed MD, BP, Practyx • Multicentre comparative study of paediatric TIV preparations • NCIRS led HPV • Enhanced surveillance in schools and LGA • SAEFVIC

  25. Safety of environmental excursions

  26. 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

  27. 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

  28. SS 10 months old History • Born in Melbourne • Only child • Immunised per schedule • No known TB / chronic cough contacts

  29. ID Clinic Feb 2012 • Firm, possibly fluctuant • Multiple shotty cervial lymph nodes • No other lymphadenopathy • Unremarkable general examination

  30. Investigations • Increased fluctuance on clincal review

  31. 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

  32. 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..

  33. 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.

  34. 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.

  35. 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.

  36. 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

  37. 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

  38. 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

  39. REVISED PAEDIATRIC BCG DISEASE CLASSIFICATION Revised paediatric BCG disease classification Local disease Abscess Dual disease M. tb and BCG Regional disease Adenitis BCG IRIS Following HAART Disseminated disease Beyond regional Hesseling et al, Clin Infect Dis 2006

  40. “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.”

  41. SAEFVIC: BCG AEFI N=59

  42. 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?!!!”

  43. SAEFVIC: BCG AEFI

  44. 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

  45. 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

  46. 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

  47. Monash Immunisation An all age immunisation service for high risk patients

  48. 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

  49. Monash Immunisation • Immunisation of current inpatients and outpatients • Provide immunisations to high risk groups • 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

  50. AEFI reports • Clinical support for providers and patients • How to report? • Online – www.saefvic.org.au • Email – saefvic@mcri.edu.au • Telephone – (03) 9345 4143 • Fax – (03) 9345 4163

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