Immunization Update. Jim Taylor University of Washington

Transcription

1 Immunization Update Jim Taylor University of Washington

2 definition Vaccines biologic agents administered to promote an immune response and treat or prevent disease 2

3 Vaccines One of few medical interventions that actually works One of greatest public health measures in history Triumph of scientific method A victim of their own success

4 Effectiveness of vaccines Deaths from vaccine preventable diseases reduced by > 99% with introduction of immunization programs Estimated that $20 saved for every dollar spent on 9 childhood vaccines

5 Brief history of vaccines: How did we get to here Variolation: administering dried pus from small pox pustules into skin of healthy people Jenner 1797 Observed that milk maids exposed to cowpox (vaccinia) immune to smallpox Led to use of cowpox administration to prevent smallpox (vaccination)

6 History of vaccines Pasteur 1881: anthrax vaccine made using attenuated anthrax bacilli Conducted controlled experiment 24 sheep, 1 goat and six cows given anthrax vaccine, equal numbers of animals used as controls Vaccinated and control animals inoculated with virulent anthrax All control sheep and goat died, no vaccinated animals became ill

7 History of vaccines 1888: Diphtheria toxin discovered Low doses injected into animals who developed antitoxins Antitoxins used to treat children with diphtheria and tetanus Administration of immune serum termed immunization

8 History of vaccines 1923: formalin inactivation of diphtheria and tetanus toxins led to development of toxoids Toxoids didn t cause illness, but led to formation of antitoxins in animals, humans Basis of vaccines for diphtheria and tetanus

9 History of vaccines : killed, whole cell pertussis vaccine developed 1948: combination diphtheria-pertussistetanus vaccine (DPT) released 1996: acellular pertussis vaccine containing immunogenic protein antigens licensed in US--DTaP

10 History of vaccines Development of polio vaccine compelling story involving politics, marketing, professional jealousy, tragedy, ethics and triumph 1955 IPV- formalin inactivated polio virus vaccine licensed with great fanfare 1960 OPV live attenuated polio vaccine 2000 E-IPV main vaccine in use in US

11 History of vaccines 1980 s development of Hib and pneumococcal polysaccharide vaccines Low immunogenicity particularly in young infants Conjugated to protein for improved efficacy Hepatitis B vaccine- first recombinant vaccine Hepatitis B surface Ag gene cloned in yeast to produce New HPV vaccine uses similar technique

12 Modern vaccine era begins 1980 s Explosion of new vaccines developed, licensed, mandated Virtual elimination of many vaccinepreventable diseases in US, elsewhere Realization that not everyone is vaccinated Vaccine controversies real and otherwise

13 Fully vaccinated 2 year old DPT x 4 MMR x 1 OPV x 3 Total of 5 shots

14 Fully vaccinated 2 year old DTaP x 4 MMR x 1 IPV x 3 Hepatitis B x 3 Hepatitis A x 2 Hib x 4

15 Fully vaccinated 2 year old PCV x 4 Varicella x 1 Rotavirus x 3 Total of 23 shots Can be reduced to about 12 shots with combination vaccines

16 Reduction in diseases prevented by old vaccines Disease Annual cases pre-vaccine 2010 cases Reduction Pertussis 147,271 15,216 90% Polio 16, % Measles 152, (593+ in 2014) 99% Mumps 47, >99% Congenital rubella % 16

17 Reduction in diseases prevented by new vaccines Disease Annual rates pre-vaccine 2007 Rate Reduction Hib disease 20, >99% Invasive pneumococcal 77% Varicella deaths % 17

18 Concept of Herd Immunity Even with immunization rates of < 100%, infections are rare because too few susceptible individuals to promote spread Varicella vaccine in NC day cares 1995: 4% vaccinated, 1999: 63% During this period rate of varicella in unvaccinated children fell by 91% Although overall rates of vaccination may be relatively high, in certain populations may be low enough to promote epidemics

19 US measles epidemic : < 5,000 cases/year 1989: 18,000 cases, 41 deaths 1990: 25,000 cases, 60 deaths Majority of cases in children < 5 years old

20 US measles epidemic Minority children disproportionately affected Poor children in inner cities of several metropolitan areas (Chicago, LA, e.g.) Measles vaccine rates in many of these inner-city among 2 year olds < 50% Realization that immunization delivery system in US broken

21 Standards for Pediatric Immunization Practices Remove financial, systematic barriers Assess immunization status of children frequently Multiple provider interventions Limit missed opportunities Only follow true contraindications Give all vaccines for which child eligible at visit Reminder/recall systems

22 Evidence-based interventions to increase childhood immunization Daycare and school mandates for immunizations Removal of financial burden Health insurance coverage of vaccines VFC Universal purchase states 22

23 Evidence-based interventions to increase childhood immunization Provider interventions that work Missed opportunities 23

24 Evidence-based interventions to increase childhood immunization Provider interventions that work Missed opportunities 24

25 Evidence-based interventions to increase childhood immunization Provider interventions that work Limiting contraindications Providing all vaccines for which child is eligible Reminder/recall systems 25

26 Health belief model for preventive services Perceived susceptibility Severity of diseases prevented Perceived benefit Barriers (inconvenience, side effects) Perceived self-efficacy 26

27 Increasing parental concern about safety of vaccines Vaccines controversial since 1885 Increasing concerns since 1970 s, particularly since % parents worried about safety % worried 27

28 More recent parental beliefs

29 Vaccine safety issues Pertussis vaccine encephalopathy MMR and autism Thimerosal 29

30 Reactogenicity of DTP vaccine Fever 46.5% Fever > % Redness 37.4% Anorexia 20.9%

31 Reactogenicity of DTP vaccine Persistent crying 3.1% Unusual high pitched crying 0.1% Hypotonic Hyporesponsive Episode (HHE) 0.06%

32 Pertussis Vaccine encephalopathy First reported in 1948 In 1970 s multiple reports, opposition to vaccine English study estimated incidence at 1/310,000

33 Effects of non-immunization Multiple epidemics, deaths related to pertussis when immunization rate decreased during 70 s in Japan, England Even if neurologic effects of DPT were true, rates of neurologic disease, death higher from disease than vaccine Neurologic illness 4/1 Death 19/1

34 Pertussis Vaccine encephalopathy In part because of safety concerns, work on DTaP Licensure of DTaP in early 1990 s ends most concerns

35 The MMR Autism controversy 1998 Wakefield et al publish paper in Lancet Described 12 children who developed colitis and regressive autism around 1-2 weeks after receiving MMR Children reportedly developmentally normal prior to vaccination

36 Research irregularities 3 of 9 patients described as having autism did not Many of the children not developmentally normal prior to vaccination

37 Research Irregularities Symptoms in some children didn t appear until several months after vaccination Study commissioned and funded to support anti-vaccine litigation

38 Does MMR cause Autism? 2001 Institute of Medicine reviewed evidence could not find causal link Other studies found no link Good evidence that MMR does NOT cause autism

39 MMR rates In England > 90% during late 90 s, fell to about 80% in 2003 Most measles cases reported in London London MMR rates 85% falling to 70% in 2003 In certain ethnic groups in London rates were less than 60%

40 Measles cases England and Wales

41 Thimerosal Thimerosal mercury compound Used as preservative in vaccines to prevent bacterial contamination Ethylmercury metabolite of thimerosal Some data to suggest that small doses of methylmercury can lead to subtle neurodevelopmental abnormalities 41

42 Thimerosal With increasing childhood vaccines, increasing exposure to thimerosal EPA calculated exposure limits to methylmercury 0-6 months 65 to 106 mcg FDA, WHO, others with higher limits Maximum calculated exposure to mercury from thimerosal in vaccines 0-6 months mcg 42

43 Thimerosal 1999 recommendation that thimerosal reduced or eliminated from vaccines Childhood vaccines now contain no/minimal thimerosal No evidence of toxicity from thimerosal in vaccines, no evidence that thimerosal increases the risk of autism 43

44 Thimerosal Suspended birth dose of Hepatitis B vaccine Thimerosal-free Hepatitis B vaccine manufactured, birth dose re-introduced % of babies received birth dose % % 44

45 Advantages and disadvantages of birth dose of Hepatitis B vaccine Maternal Hepatitis B status unknown or wrong: vaccine prevents 75% - 90% of vertical transmission Increases rate of timely completion of 3 vaccine series in babies Complicates documentation of hepatitis B vaccination status

46 Waning Immunization Acceptance: Washington Washington state exemption rates from required school-entry immunizations for personal beliefs: : 3.6% : 4.1% : 5.7% : 6.8% State rank for 15 dose series: 46th

47 Erosion of Vaccine Acceptance: National Data US non-medical exemption rates

48 WA State Non-Medical Exemption Rates: Kindergarten San Juan 13.1% Ferry 11.4% Stevens 9.5% Pend Oreille 8.6% Jefferson 11.7% King 4.3% Lincoln 9.9% Spokane 6.7% <2% 3-3.9% 4-4.9% 2-2.9% 5-9.9% 10% WA State Dept. of Health School Status Reports

49 Vaccine-Hesitant Parents Pro-vaccine Anti-vaccine Acceptors Agree with or do not question vaccines Children fully immunized High trust in provider Interest in vaccine information from child s provider Vaccine-hesitant Are unsure about, delay, or choose only some vaccines Children under-immunized Desire a trustworthy provider Interest in vaccine information from child s provider Rejectors Completely reject vaccines Children unimmunized Low trust in provider No interest in vaccine information 70% 30% <1%

50 Why Parents Change Their Mind % of Parents Information or assurances from child's doctor Just thought more about it 10% 14% 22% 37% Info from some other source Doctor refused to treat/daycare wouldn't admit Discussion with spouse/relative Other Don't know

51 Research Questions Is there a way we can optimize provider-parent vaccine communication by: Improving parental disclosure? Validly identifying who is hesitant? Doing all of this efficiently? What can pediatricians say to hesitant parents that is effective at changing their mind?

52 Percent Days Under-Immunized The Parent Attitudes about Childhood Vaccines (PACV) Survey Self-administered, takes <5 minutes to complete, reads at a 6 th grade level 15 questions under 3 domains Behavior Example item: Have you ever delayed having your child get a shot for reasons other than illness or allergy? Safety and Efficacy Example item: How concerned are you that your child might have a serious side effect from a shot? General Attitudes Example item: It is better for my child to develop immunity by getting sick than to get a shot (ref) N= N= N= N= N=31 Opel et al. Vaccine N= N=15 10 Tier PACV Score Opel et al. JAMA Pediatr N= N= N=3 Opel et al. Human Vaccines 2011

53 Research Plan Use PACV to classify parents Videotape immunization discussions Use conversation analysis to identify themes in communication Associate themes with underimmunization Develop intervention to maximize effectiveness of communication and measure impact

54 Who initiated the vaccine discussion/plan specifically? (N=111) No plan verbalized (3%; N=3) Parent (13%; N=15) Provider (84%; N=93) How does the PROVIDER initiate the vaccine discussion/plan? (N=93) It s time to start all those vaccines we re going to be doing two live vaccines today: the MMR and the chicken pox. Presumptive (74%; N=69) Participatory (26%; N=24) How do you feel about vaccination? How does PARENT respond to the provider s initiation? Accepts (74%; N=51) Accepts (4%; N=1) Provides own plan (13%; N=3) Resists (26%; N=18) Resists (83%; N=20) P<.001; Adjusted OR (95% CI): 17.5 (1.2, 253.4) Opel et al. Pediatrics 2013

55 The Paradox of Taking a Participatory Approach (1.5, (1.5, 200.3)* Increased odds of having a parent rate their visit experience highly.04 (.01,.15)* Decreased odds of having a parent accept all vaccines at the end of the visit *Adjusted Odds Ratios with 95% CI

56 2015 US measles outbreak

57 Measles in California Cases 49 (45%) unvaccinated 12 too young 28 intentionally unvaccinated 1 alternative schedule 5 (5%) 1 dose MMR, 8 (7%) 2+ doses Highlights risk of infection in those vaccinated from exposure to unvaccinated

58 Trends in US Immunization rates in children months old Year % UTD * * 58

59 Conclusions Overall, US immunization program for young children highly effective Concern for geographic pockets were coverage is below what is needed for herd immunity Potential for significant epidemics Unvaccinated, not eligible for vaccination and vaccinated individuals at risk

60 Conclusions Key to preventing this may be VHP (20-30% of US parents) Maximal transparency Continue current programs? Strengthen mandates Effective communication Unknown what this is Likely defies conventional wisdom