Childhood Vaccines: Why we vaccinate, when we vaccinate

1. Childhood Vaccines:Why we vaccinate, when we vaccinate ACIC 9th Annual Conference Marian Michaels MD, MPH Professor of Pediatrics Children’s Hospital of Pittsburgh Division of Pediatric Infectious Diseases

2. 2014 AAP Vaccine Schedule 0-18 years

3. Immunizations • Aside from improved sanitation nothing has done as much to improve the health of children as immunizations • Effective vaccine • Induces a strong long lasting protective responsive in a safe fashion • Decreases death and disease from the natural infection

4. Change in Vaccine Preventable Diseases Immunization Action Coalition 12/13

5. Childhood VaccinationWhy we vaccinate when we vaccinate • Vaccinate individuals at risk • Vaccinate a population to protect others • Vaccinate an available population to protect them later • As we discuss examples will address rationale for using particular types of vaccines

6. Vaccinate to protect the person at risk when they are at risk:Example – HiB Meningitis

7. Invasive HiB by Age Pre Vaccine

8. Haemophilus influenza B (HiB) • This bacteria caused most of the meningitis in children between 2 and 56 months of age • Highest risk for severe disease is 2-12 mo • Ab against polysaccharide capsule is protective • Don’t respond to polysaccharide (either as vaccine or natural disease until > 2 years of age • First vaccine (1985) polysaccharide • Variable efficacy < 2 years of age • Too little too late to impact on group at risk for disease • Newer vaccines (1987) conjugated the polysaccharide to a carrier Ag so T cell dependent to be effective in children under 1 year of age

9. Before vaccination ~ 20,000 cases/year with ~ 1000 deaths/year Polysaccharide vaccine -1985 Conjugate vaccine -1987 Invasive HiB Disease, USA 1990-2007 3 cases of HiB at CHP in 2013 (all unvaccinated) Year *Rate per 100,000 children <5 years of age (CDC data)

10. S pneumoniae • Pre-vaccine era • 17,000 invasive cases S pneumoniae < 5 years • 700 cases meningitis • 200 deaths • Similar to HiB < 2 years of age = highest risk • Antibody to polysaccharide offers protection • Unlike HiB many different serotypes • 7 associated with most pediatric invasive dz. • 2000- first conjugate vaccine –PCV 7 Types 4, 9V, 14, 19F, 23F, 18C, and 6B

11. S pneumoniae vaccine • After initial great success started to see increases in invasive disease with non PCV7 strain • 2010 added 1, 3, 5, 6A, 7F, 19A (PCV13)

12. Vaccinate to protect the person at risk: Polio during the 1950’s ~ 20, 000 cases paralytic polio/year

13. Poliomyelitis: Historical Events • 3700 BC: Earliest recorded history-Egyptian Mummy • 1793: Underwood described unequivocal cases of polio • 1949: Propagation of poliovirus in human embryonic tissue • 1955: Inactivated vaccine licensed (Salk) • 1961: Live attenuated vaccine licensed (Sabin) • 1962: US nationwide mass vaccination program

14. Poliovirus • Enterovirus • Fecal – oral spread • Replicates locally • Secretory Ab • Viremia +/- CNS • Humoral Ab

15. Polio • > 90% asymptomatic • < 10% symptoms: • Fever, pharyngitis, malaise • Anorexia, mylagias • CNS symptoms develop • 1% of children • 10% adolescents or adults

16. IPV • Salk vaccine, 1955 • Formalin killed, Types 1,2,3 • Neutralizing Ab in 95% • Protects individual from polio • Shedding of wild type polio can still occurs if infected • Enhanced version licensed 1982

17. OPV • Sabin vaccine, 1962 • Attenuated, live oral Types 1,2,3 • Replicates like w. polio • Secretory and neutralizing Ab • No shedding of wild type poliovirus • Vaccine virus shed in stool • Immunizes contact • Contact-associated VAPP

18. Salk vaccine 1955 Poliomyelitis—United States, 1950-2007 Western Hemisphere Polio free- 1994 So why continue to vaccinate for polio Parts of Africa, Asia never free Fall 2013-13 cases Syria (last seen 1999) Virus also found in Israel Oral Sabin vaccine Last indigenous case

19. Sabin - OPV • Practically perfect • Inexpensive, easy to administer • Mimics natural infection • IgA and IgG antibody • Herd immunity • Susceptible individuals protected

20. Polio • Global eradication occurring • Last wild type polio • U.S.A. 1979 • Americas 1991 • Western hemisphere “polio-free” 1994

21. Vaccine-Associated Polio • 6-10 cases every year • 50% vaccinee; 50% contact • Usually after 1st dose • Unique susceptibility of host • Wild type polio absent • eIPV introduced 1982

22. Comparison of Vaccine Types In era of no wild type polio, 6-8 cases VAPP too many Polio Vaccine schedule altered 2000 to eIPV

23. Vaccinate to Protect and at Risk Population: Congenital Rubella • Mild disease • Infection during pregnancy • Miscarriage • Fetal death • Congenital rubella syndrome Vaccinate children to prevent disease in pregnant women to protect the unborn baby

24. Sunday Rubella CampaignPittsburgh, PAMay 17, 1970 • Over 2,000 volunteers • 106 sites (mostly schools) • 130 hypospray jet injectors • 190,845 children immunized • (58% of susceptibles 1-12 yr)

26. Vaccinate to Protect and at Risk Population: Whooping Cough

27. Whooping cough/ Pertussis • Bacteria Bordetella pertussis • Outbreaks every 2-5 year cycles • Very easy to transmit • >90% attack rate in susceptible household contacts • Infants can have very severe disease • Pneumonia, periods of inability to breathe, seizures, brain damage, death • Nov 2013 & Aug 2014 two newborns died at Children’s due to pertussis

28. PertussisThree phases • Catarrhal phase – seems like a simple cold • Can transmit to others • Treatment can work • Paroxysmal phase – cough, whoop, emesis • Can transmit • Treatment doesn’t work but prevents transmission • Convalescent phase- 100 day cough • Exacerbations • Adults and older children = reservoir

29. Whole Cell Pertussis Vaccine • Introduced in 1940’s • Adverse reactions occurred • Non-serious reactions common • Low grade fever in ~45 % of infants • Fever > 101 in 16% • Moderate to severe fussiness or pain in ~ 40% • More serious reactions very rare

30. Pertussis Vaccine • People who were against the vaccine claimed that the vaccine caused • SIDS, Seizures, Brain Damage • They also believed that • Decrease in pertussis due to improved sanitation • Believed natural disease wasn’t a big deal

31. Pertussis Vaccine • Large epidemiologic studies comparing DT to DPT (>15000 children studied) • No true association of vaccine with severe disease symptoms • Temporal association • Vaccine is given at 2, 4, 6 months • This is often an infant’s first cause of a fever • Also a time when many seizure syndromes show up naturally

32. Japanese outbreak of whooping cough 1976-1981

33. Rationale for developing the acellular pertussis vaccine • Concern about adverse effects with DTwP • Public perception of severe risk • Improvements possible • Decrease reaction to vaccine • Large studies conducted to show that rates of fever and fussiness and pain decreased • Low grade fever 45% DTwP vs 16-30% DTaP • High fever 16% DTwP vs. <5% DTaP • Mod/severe Pain 40% DTwP vs. 4-11% DTaP

34. Acellular pertussis vaccine • Desire to protect those too young to be vaccinated by vaccinating others “cocooning” • Tdap – adolescents and adults • Repeat towards end of each pregnancy to give passive Ab to infant (and immunity to mother) • Likely will use in future for booster as well for all adults

35. Vaccinate an Available Population to Protect Them Later • Example of HPV, Hepatitis B • Controversial for parents • “My child isn’t at risk”

36. Hepatitis B vaccine • Given during infancy • Prevents much of maternal transmission • Asia uses it alone without HBIG • Maternity hospitals are considering not giving due to cost • Step backwards • When shortage occurred Hepatitis transmission • Works well in young age group • Protects those who will develop risks later • Not just Drug users • Policemen, Firemen, Nurses, Cardiac surgeons • Accident victims requiring emergency transfusions

37. Human Papillomavirus (HPV) • DNA virus- causes warts: > 100 types • Genital HPV is most common STD in US • Types 6 and 11 cause 90% genital warts • Types 16, 18 cause 70% cervical cancers • HPV associated > 70% oropharyngeal CA • Type 16 associated most prominently • 2006 quadrivalent HPV vaccine approved for girls and young women; bivalent vaccine approved for girls in 2009 • 2009 HPV4 approved for males as well • 2011 HPV4 recommended for males

38. HPV recommendations • Not beneficial after wild type infection • Desire vaccine before sexual debut • ACIP recommends age 11-12 • HPV 4 or HPV 2 for girls • HPV 4 for boys • Can start as young as 9 years, Catch up till age 26 • Poor uptake by community • a lack of knowledge, • a belief that the vaccine was not needed, • concerns about vaccine safety or side effects • the vaccine not being recommended by their provider

39. HPV: Combatting Myths • Pre-licensure studies: blinded:control • > 20,000 women and > 4,000 males • Post licensure non controlled VAERS report • > 60 million HPV4 and > 700,000 HPV2 doses • Most AE non SAE • Systemic: nausea, dizziness, headache, syncope, urticaria • Local symptoms: injection-site redness, swelling, and induration • No association found with autoimmune disease, Guillain Barre syndrome, stroke

40. On line Vaccine Resources • Center for Disease Control and Prevention • http://www.cdc.gov/vaccines/ • Immunization action coalition • http://www.immunize.org/aboutus/ • Children’s Hosp of Phil. vaccine service • http://www.chop.edu/service/vaccine-education-center/