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An Update on Immunisation and Infectious diseases in Australia: 2013

An Update on Immunisation and Infectious diseases in Australia: 2013. Prof Robert Booy National Centre for Immunisation Research (NCIRS) Many thanks: Dr Rashmi Dixit, Dr Greg Rowles, Profs Peter McIntyre & Kristine MaCartney. Nigeria polio vaccinators shot dead in Kano. 8 February 2013

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An Update on Immunisation and Infectious diseases in Australia: 2013

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  1. An Update on Immunisation and Infectious diseases in Australia: 2013 Prof Robert Booy National Centre for Immunisation Research (NCIRS) Many thanks: Dr Rashmi Dixit, Dr Greg Rowles, Profs Peter McIntyre & Kristine MaCartney

  2. Nigeria polio vaccinators shot dead in Kano 8 February 2013 http://www.bbc.co.uk/news/world-africa-21381773 Nine female polio vaccinators have been killed in two shootings at health centres in northern Nigeria Some Nigerian Muslim leaders have previously opposed polio vaccinations, claiming they could cause infertility One cleric told people that new cases of polio were caused by contaminated medicine Nigeria is one of only three countries where polio is still endemic

  3. Outline of talk • Some qanda at beginning and end • Pertussis: a real curly one.. • Influenza: always something new under the sun • Rotavirus vaccine: yet again, the haves have more • HPV: the wizardry of Oz Ian Frazer • Measles: what, that old chestnut? • Varicella and Shingles.. On the downhill run • Pneumococcal disease • Polio • Meningitis, encephalitis: no time except #qanda

  4. Five year-old Behnam went from a sniffle and a headache at a birthday party on Saturday to intensive care by Monday morning….. Kids Research Institute Annual Report 2011 - 2012 The cause of encephalitis, or swelling of the brain, is still unknown in more than half of cases. It can kill in hours and leaves many others with brain damage and other major complications

  5. Baby Button and Mother

  6. The Herald Sun Deadly whooping cough warning March 14th, 2012. “3 week old infant caught pertussis from 2 year old fully vaccinated sister”…… Learning points: suspect pertussis in neonates & test; prolonged cough in older child, even if vaccinated

  7. Weekend Gold Coast Bulletin - Saturday, 02 April 2011

  8. Bordetella pertussis: whooping cough • Vaccination began 1950s but pertussis still prevalent • 1990-2008 data consistent with outbreaks every 3-5 years • Prior to vaccine: every 2-3 years present epidemic c.f. epidemics in 1997 & 2002: • Longer & many more infections were reported 2009-12 • fewer deaths BUT same number of hospitalisations • Australia had record 38,000 cases diagnosed in 2011 • Seven infant deaths in Australia 2008-11 • Notifications falling in 2012/3 • Bordetella parapertussis: A related GNB • Clinically milder • Pertussis vaccine not effective • Europe: up to 1/3 of “whooping cough cases”; less in Aus

  9. Pertussis symptoms • Neonatal apnoea +/- cough/whoop • If older child/adult1 may resemble URTI, bronchitis, sinusitis, asthma • Consider if prolonged coughing: B. pertussis3 • Cherry et al. Pediatr Infect Dis J 2005; 24(5 Suppl): S25–34; • 2. Brooks, Clover. J Am Board Fam Med 2006; 19: 603–11; 3. Wirsing von König et al. Lancet Infect Dis 2002; 2:744–50

  10. Reasons for recent outbreak • Vaccine refusal • Refusal clusters promote spread • However: • in Australia 94% of 2y-olds UTD with vaccines • Cases not confined to these communities • most pertussis cases >one dose dTPa, many UTD! • More / better testing • Increased clinical recognition • Use of PCR testing much increased last 5 years McIntyre and Wood: Pertussis Prevention in early infancy. Current Opinion in Infectious Diseases. 2009; 22; 215-223

  11. Reasons for recent outbreak • Shorter period of protection / Waning immunity • Neither natural nor vaccine immunity is lifelong   • Adults (?teens) & sibs are source of infection to infants • Recent outbreak: pre-schoolers and primary schoolers • ? Vaccine less effective: mutations in pertussis toxins • No evidence of this (but looking: NCIRS study 2012) 2 doses required before significant protection • Currently: significant immunity from 18/52 age (2/52 post dose 2) • One dose probably ↓ death / ventilation • Most deaths < 12/52 age McIntyre and Wood: Pertussis Prevention in early infancy. Current Opinion in Infectious Diseases. 2009; 22; 215-223

  12. J Infect Dis. 2012; 205:1220-4 (Lan: senior author)Newly Emerging Clones of Bordetella pertussis Carrying prn2 and ptxP3 Alleles Implicated in Australian Pertussis Epidemic 2008-2010 Octavia et al • A total of 194 Bordetella pertussis isolates collected 2008-10 were typed by single-nucleotide polymorphism (SNP) analysis • Strains with 2 closely related SNP profiles carrying prn2 and ptxP3 from the recently emerged SNP cluster I predominated • The data suggest but don’t prove increasing selection among the B. pertussis population in Australia in favour of strains carrying prn2 and ptxP3 under the pressure of acellular vaccine-induced immunity

  13. But • "The vaccine is still the best way to reduce transmission of the disease and reduce cases, but it appears to be less effective against the new strain and immunity wanes more rapidly….” said Dr Lan

  14. Pertussis vaccination: benefits and risks • Opponents (“Anti-vaccinists”) argue pertussis vaccine ‘ineffective’ +/or ‘risky’ • The DTPa vaccine: overwhelmingly safe and effective • Pre-vaccine 1940s: hundreds died, now death rate v low • Encephalopathy (‘brain damage’) • Dravet’s syndrome: genetic condition = explanation for most cases of encephalopathy post whole-cell pertussis vaccine Berkovic SF. et al. De-novo mutations of the sodium channel gene SCN1A in alleged vaccine encephalopathy: a retrospective study. Lancet Neurology. 5(6):488-92, 2006 Jun  Tro-Baumann B. et al.A retrospective study of the relation between vaccination and occurrence of seizures in Dravet syndrome. Epilepsia. 52(1):175-8, 2011 Jan.  McIntosh AM. Et al. Berkovic SF.Effects of vaccination on onset and outcome of Dravet syndrome: a retrospective study. Lancet Neurology. 9(6):592-8, 2010 Jun.

  15. Effects of vaccination • For vaccinated person: • Reduction in susceptibility to infection • Reduction in disease severity • ? Effect on transmissibility • Reduction in infectiousness • For unvaccinated person: • Reduced proportion of contacts infected • Herd immunity

  16. Index case: vaccinated vs unvaccinated 0.25 0.2 0.15 Secondary attack rate 0.1 0.05 0 Vaccinated Unvaccinated Status of index case Evidence of vaccine on transmission. Senegal household study The unvaccinated who acquire pertussis are more infectious, with a higher secondary attack rate, than the vaccinated. Halloran ME, Préziosi MP, Chu H. Estimating vaccine efficacy from secondary attack rates. Journal of the American Statistical Association. 2003;98:38–46.

  17. US Data • Pertussis deaths US 2000 – 2005: (N = 140 deaths) • Majority (n = 131) of fatalities were in infants • Too young (<4 m) to be vaccine protected (n = 126) • Of deaths: • 97% unvaccinated • 1% had one dose of vaccine against pertussis • 2% had 2 or more doses against pertussis • Conclusion: Vaccine protects against death. Tiwari T. Reported pertussis-related deaths to the National Notifiable Diseases Surveillance system and the CDC in the United States, 2000-2005. #82. Presented at: the 42nd National Immunization Conference; March 17-20, 2008; Atlanta.

  18. Pertussis hospitalisations < 1 yr old: 1994 - 2008 Well over 60% cases by 16 weeks of age

  19. Strategies for Infant Pertussis: Indirect protection • 4 year old booster: • ?4 yrs  3.5 yrs: as many pre-schoolers in recent outbreak* • Not categorically shown to reduce infant pertussis • Universal adolescent / adult vaccine • Recent data USA / Australia: adolescents do not transmit to infants, unless teen parents • mathematical models in American / European context demonstrate pertussis spreads child-to-child, not often child-to-adult • Immunity wanes after 5 yrs with DTPa/ dTpa: may need 10 yr boosters Kandola K, Lea A, White W, Santos M. A comparison of pertussis rates in the Northwest Territories: pre and post acellular pertussis vaccine introduction in children and adolescents. Can J Infect Dis Med Microbiol 2005; 16:271–274 Rohani P et al., Contact Network Structure Explains the Changing Epidemiology of Pertussis. Science magazine. 330 (6006): 982-985 Quinn H and McIntyre P. The Impact of adolescent pertussis immunisation 2004-2009: lessons from Australia. Bull World health Organ. 2011; 89: 666-674 Skoff TH et al. early Impact of the US Tdap Vaccination Program on Pertussis Trends. Archives PaediatrAdolesc Med Online January 2 2012

  20. Strategies to address Pertussis: Indirect protection • Cocoon: mother (father +/- grandparents +/- childcare workers) • Parents (mother) commonest source, but source often hard to identify • APERT trial: reduced pertussis in adults • Expected  lower transmission; no field data • Modelling: cocooning + regular / single booster ↓ infant pertussis • Poor uptake despite parental support • Funding / implementation support required • Maternity hosp for mums; GPs for fathers /family [before delivery] • HCW vaccination ↓ intensive care nursery outbreaks / cost effective • Current NCIRS study on effect of cocooning McIntyre and Wood: Pertussis Prevention in early infancy. Current Opinion in Infectious Diseases. 2009; 22; 215-223 Ward JI et al. Bordetella Pertussis Infections in Vaccinated and Unvaccinated Adolescents and Adults, as Assessed in a National Prospective Randomized Acellular Pertussis Vaccine Trial (APERT). Clin Infect Dis. (2006) 43; 151-157.

  21. USA experience with cocooning: Key Points • “Cocooning can be Successful” in short-term.. • Demonstration projects • Houston, TX – Ben Taub General Hospital • Nevada - 18 birthing hospitals • Important success factors • “Champion” for the cause • Donated healthcare provider time • Free dTPa Clark, Thomas. Centers for Disease Control and Prevention; NCIRS Pertussis Meeting; August 26, 2011 • Clark, T. CDC. NCIRS Pertussis Meeting, August 2012

  22. Five years later, is cocooning working in the USA? • Not at a national level • Limited success vaccinating fathers / family • Poor uptake of dTpa at birthing hospitals • No demonstration of program sustainability or scale-up • No program of support at Federal level • Cf States in Aus cutting back…. SLIDE BORROWED FROM Clark, Thomas. Centers for Disease Control and Prevention; NCIRS Pertussis Meeting; August 26, 2011 4

  23. www.6minutes.com.au25 June 2012 • New mothers are the latest target for pertussis vaccination as cocooning programs are discontinued • “In NSW, a 3 year pertussis vaccination campaign that provided free vaccine to carers of new babies was halted from end of June 2012, but new mothers are still eligible for vaccine; most states stopping entirely • BUT parents/g’parents can still PAY for vaccination

  24. Potential source of pertussis transmission to infants – who? • Parents and siblings were common sources of infection • (Mother > Sibling, Father) *Groups includes aunts and uncles NCIRS, National Centre for Immunisation Research and Surveillance 1. Bisgard et al. Pediatr Infect Dis J 2004; 23: 985–98; 2. Elliot et al.Pediatr Infect Dis J, 2004; 23: 246–52; 3. Chuk et al.Commun Dis Intell 2008; 32: 449–56; 4. Jardine et al. Commun Dis Intell 2010; 34: 116–21; 5. Wendelboe et al. Pediatr Infect Dis J 2007; 26: 293–9; 6. Wiley. Presentation at NCIRS Pertussis workshop 25 August 2011, Sydney, Australia

  25. The Cocoon Effectiveness Study: Australia NCIRS + NSW Health Peter McIntyre, Helen Quinn, Clayton Chiu, Andrew Habig, Paula Spokes • Matched case-control study (1:3 ratio) • Telephone Survey (CATI): • Size of ‘cocoon’ • Frequency of care (if non-household carer) • Pertussis vaccination status • Childcare attendance, demographics, illness- associated costs • Statistical analysis (Odds Ratio & Vaccine Effectiveness) • estimates effect of cocoon on risk of infant pertussis disease

  26. Infant Pertussis: Direct Protection • Passive (transplacental) or active (immunisation) • Accelerate the first dose to 6/52: • USA study: reduced infant deaths / hospitalisations 9% • Plus: improve on-time administration of 3 doses* • Aus estimate: accel’n to 6 weeks reduces notific’ns & hosp’ns by 8-9% (Foxwell et al PIDJ 2011) • Pertussis vaccination from 20 weeks of pregnancy • Protect until 10 series complete in infant McIntyre and Wood: Pertussis Prevention in early infancy. Current Opinion in Infectious Diseases. 2009; 22; 215-223

  27. Pertussis vaccination pregnancy: Pros • Mother protected from 20 weeks of pregnancy • Covers infants before start of 10 series: highest incidence disease first weeks of life • Vaccine highly immunogenic in adults • 2-5x higher levels after first dose than in infants • Well tolerated in pregnancy • Recommended!

  28. Pertussis vaccine in pregnancy: Cons • ?uptake / liability • Protection not perfect from passive maternal ab transfer • Data from pre-vaccine era: transfer of natural abs • Maternal abs wane after 6-8/52 of age • Not detectable after 2-6/12 age • Interfere with response to active immunisation, DTPa • Abs neutralise antigens in vaccine • Demonstrated with wP vaccine trials • Mum’s Abs wane after about 5 years, ?boost next pregnancy

  29. USA: ACIP Conclusions 2012 • Recommend vaccinating all contacts of infants • Nonetheless, cocoon insufficient national strategy to prevent infant pertussis • Recommendation for pregnancy immunisation ACIP Published 2012 Bridges CB , ACIP Recommended Adult Immunization Schedule: United States, 2012*Ann Intern Med. 2012;156:211-217. SLIDE BORROWED FROM Clark, Thomas. Centers for Disease Control and Prevention; NCIRS Pertussis Meeting; August 26, 2011

  30. NCIRS RCT Study: aP vaccine to infants • Pa vaccine, measured ab levels up to 8/12 • Earlier ab response in birth-dose group • (As per studies from Italy and Germany) • Non significant difference at 7-8 months • As per study from Germany • Contrary Italy and USA: reduced abs in birth dose group • ‘immune tolerance’ • Reactogenicity: Sydney • Birth dose • Nil fever >38C • Nil injection site reactions >10mm after birth Pa dose PIDJ 2010. Acellular Pertussis vaccine and 0 and 1 months induces antibody responses by 2 months” NCIRS study Wood et al

  31. Australian dTpa booster recommendations The Australian Immunisation Handbook 9th edition recommends: Australian immunisation handbook, 9th edition: http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook-pertussis (accessed June 2011)

  32. Pertussis: national public campaign • Public campaign: brochure Nov 2011: • Identify, protect, prevent?? • Infant: • keep people with a cough away from baby • emphasise timeliness of 2, 4 and 6 months • Dose 1 can be given at 6 weeks • Vaccine can fail to protect esp. before dose 2 • Clinicians / parents need to consider pertussis in respiratory infections • Older children / adolescents • vaccine @ 3.5 yrs & high school: direct & indirect benefits • Vaccinated kids can still get infection

  33. Influenza • 3 strains: • pH1N1 Influenza A 2009 California: swine flu (now ‘seasonal’ flu) • H3N2 Flu A : Victoria strain • Flu B Wisconsin (likely 2 B strains in future) • 2012 season increased numbers esp’ly H3N2 in Oz; also 2013 H3N2 surge in USA etc • More rain and colder so people remain more indoors • First line of defence: Hand-washing, masks, isolation, cough/sneeze etiquette, smile: don’t shake hands is my motto http://www.health.gov.au/internet/main/publishing.nsf/content/cda-surveil-ozflu-flucurr.htm

  34. Figure 3.5.2: Influenza notification rates, Australia, 2006 to 2007, and hospitalisation rates, 2005/2006 to 2006/2007,* by age group * Notifications – diagnosis between January 2006 and December 2007 Hospitalisations – separation between July 2005 and June 2007

  35. Who is at increased risk of complications from influenza infection? Older aged and Aboriginal and Torres Strait Islanders • Individuals aged ≥ 65 years • Aboriginal and Torres Strait Islanders ≥ 15 years of age

  36. Influenza: High-risk groups • Funded vaccines also available for: • Chronically ill: comorbidities • Respiratory / cardiac / renal / diabetes (metabolic) / neurological/ hepatic/ immune deficiency • Asthma?? Pregnant women • (particularly badly affected by swine flu pandemic)

  37. Influenza Vaccine • Fever & seizures in children CSL Fluvax® 2010 • processing error during manufacture? • Excess RNA/short gene fragments; insufficient splitting.. Excessive immune response • Fluvax® no longer recommended for < 5 yr olds • Safe for older children and adults • Other flu vaccines safe: data - Australia/ NZ/ OS http://www.tga.gov.au/safety/alerts-medicine-seasonal-flu-100702.htm http://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con103051.pdf

  38. Horvath Review 10/ 2010 (former CMO) Of Public Health response to the adverse events to Fluvax • Australian system similar to passive AE surveillance systems in comparable countries • Able to detect safety signal with 2010 vaccine • take appropriate action • Reporting of adverse events could be more timely http://www.tga.gov.au/safety/alerts-medicine-seasonal-flu-100702.htm http://www.mhra.gov.uk/home/groups/pl-p/documents/websiteresources/con103051.pdf http://immunise.health.gov.au/internet/immunise/publishing.nsf/Content/11DFBB4FD968D072CA25789400172DA1/$File/adverse-event-march-2011.pdf

  39. Monovalent H1N1 vaccine delay • A/California/09/2009 • Detected in Apr 09 • The monovalent pandemic H1N1 vaccines • Now known as A(H1N1)pdm09 vaccines • Available from late Sept 09 in small numbers

  40. Vaccine May 2012 Impacts on influenza A(H1N1)pdm09 infection from cross-protection of seasonal trivalent influenza vaccines and A(H1N1)pdm09 vaccines: Systematic review and meta-analyses Yin JK, Chow MY, Khandaker G, King C, Richmond P, Heron L, Booy R

  41. UK (1) 7 Europe countries (1) Canada (2) U.S. (1) Spain (1) U.S. (5) Hong Kong (1) Mexico (2) Australia (3) Argentina (1) Australia (2) Argentina (1) New Zealand (1) Risk of H1N1 infection after : increased, decreased, no different seasonal influenza vaccination

  42. Endpoints: 14 days after the vaccination Laboratory-confirmed A(H1N1)pdm09 2009 illness Sickness absenteeism

  43. Results Cross-protection (CP) of TIV • Confirmed illness • 1 RCT (7,334 subjects): 38% (19 to 53%) protection • 13 case-control studies

  44. TIV, case-controls studies: confirmed illness Excluding studies with moderate or high risk of bias Cross-protection=34% (95% CI=9 to 52%), I2=91%

  45. Bird Flu (H5N1 Influenza A) in 2013 • Kills up to 60% of victims • Indonesia: our nearest neighbour.. Canoe ride away • 200 + cases reached • Overall >150 deaths in Indonesia (global total >350) • Currently no licensed vaccine… but progress underway and mock-ups are licensed

  46. Indonesian bird markets on cusp of avian flu (H5N1) outbreak Saturday, 06 October 2012 06:00 www.sciencewa.net.au NEW research has revealed an urgent need to improve biosecurity in live bird markets in Bali and Lombok to prevent future outbreaks of the Highly Pathogenic Avian Influenza (HPAI or H5N1) “The level of biosecurity practiced at markets is extremely low. In our field observations, we saw little segmentation of bird species and frequent mixing of birds in cages, including ducks, which may have no symptoms of HPAI, and chickens,” said Ms Kurscheid of Murdoch Uni

  47. “In one market in Lombok we saw birds being slaughtered in the open, which is not good practice in terms of infectious disease control, as the main way humans have contracted HPAI is through slaughter of infected birds and handling of dead birds “Basically, all traders engaged in a number of practices that could sustain virus circulation in live bird markets.” Rotterdam Experiment a big worry

  48. Science 2012; 336:1534-41Airborne transmission of influenza A/H5N1 virus between ferrets Fouchier RA • Department of Virology, Rotterdam, The Netherlands • To address the concern that the virus could acquire transmission ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The virus acquired mutations ultimately becoming airborne transmissible in ferrets.. • Risk for human pandemic influenza

  49. Not as bad as we thought… • None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses • Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses • The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains

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