1. John Manaloor MD, FAAP - Pediatric Infectious Diseases October 5 th, 2011 Pediatric Vaccine Update

2. Disclosure I have never had a significant financial interest or other relationship with the manufacturer(s) of the product(s) or provider(s) of the service(s) that will be discussed in this presentation. John Manaloor MD, FAAP

3. ~ Benjamin Franklin “I long regretted bitterly, and still regret that I had not given it to him by inoculation. This I mention for the sake of parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it, my example showing that the regret may be the same either way, and that therefore, the safer should be chosen.”

4. Sources of GOOD Information www.cdc.gov/vaccines/recs/ACIP www.aap.org www.cispimmunize.org www.fda.gov/cber www.immunize.org www.immunizationinfo.org www.vaccinesafety.edu

5. Vaccines preventable diseases Anthrax Diphtheria Hemophilus Influenzae type b Hepatitis A Hepatitis B Human Papillomavirus Influenza Japanese Encephalitis Lyme Disease Measles Meningococcal Disease Mumps Pertussis Pneumococcal Disease Polio Rabies Rotavirus Rubella Tetanus Tuberculosis Typhoid Fever Varicella (Chickenpox) Yellow Fever Zoster (Shingles) Anthrax Diphtheria Hemophilus Influenzae type b Hepatitis A Hepatitis B Human Papillomavirus Influenza Japanese Encephalitis Lyme Disease Measles Meningococcal Disease Mumps Pertussis Pneumococcal Disease Polio Rabies Rotavirus Rubella Tetanus Tuberculosis Typhoid Fever Varicella (Chickenpox) Yellow Fever Zoster (Shingles)

7. WHO RegionTotal number of cases CountriesGenotype Identified African2Kenya (1), Nigeria (1)B3 (2) Eastern Mediterranean 2Pakistan (1), Jordan (1)D4 (1) European25France (12), Italy (4), Poland (1), Romania (1), Spain (1), United Kingdom (4), France/United Kingdom*(1), France/Italy/Spain/Germany *(1) D4 (11), G3 (1) Americas1Dominican Republic†(1)D4 (1) South-East Asia16India (15), Indonesia (1)D8 (5), D4 (1) Western Pacific7China (2), Philippines (4), Philippines/Vietnam/Singapore /Malaysia*(1) H1 (1), D9 (2) 70% of importations among U.S. residents traveling abroad *Patient visited more than 1 country during the incubation period † Likely acquired disease from French tourist Measles, United States, January – June 17, 2011 Source of Importations

8. Measles – Outbreak 2011 MMWR May 24, 2011

9. Measles – Outbreak 2011 MMWR May 24, 2011

10. Measles – Exposure Management Exposure: 6-11 mos Community outbreak or travel to endemic provide extra dose School or day care: give vaccine if <2 doses Household exposure: provide IG* if not vaccinated,+ vaccine at appropriate interval *IG 0.25 mL/kg; 0.5 mL/kg immunocompromised

11. MMR and VZV: Previously Recommended Schedule 1st dose @ 12-15 months 2nd dose @ 4-6 years May be given as early as 4 weeks after first 6-11 month old may receive MMR if at increased risk Extra dose (3 rd ) will be necessary Varicella: 2 doses, same time as MMR

12. MMRV and Febrile Seizure Vaccine Safety Datalink (VSD),* a collaboration between CDC and eight MCOs Febrile Sz 7-10 days post 1 st dose Febrile Sz 7-10 days post 2 nd dose MMR + V4.2/10,0000/64,663 MMRV8.5/10,0001/84,653

13. Klein NP, et al. Pediatrics 2010;126:e1-8.

14. MMRV and Febrile Seizure “ One additional febrile seizure occurred among every 2,300 children vaccinated with a first dose of MMRV vaccine compared with children vaccinated with a first dose of MMR vaccine and varicella vaccine administered at the same visit.” … “…Postlicensure data do not suggest that children who received MMRV vaccine as a second dose had an increased risk for febrile seizures after vaccination compared with children who received a second dose of MMR vaccine and varicella vaccine at the same visit.” MMWR May 7, 2010

15. MMRV First dose(12-47 months): MMR + Varicella Unless the parent or caregiver expresses a preference for MMRV Second dose: MMRV generally preferred. Personal or family (i.e., sibling or parent) history of seizures of any etiology is a precaution for MMRV vaccination. Children with a personal or family history of seizures of any etiology generally should be vaccinated with MMR vaccine and varicella vaccine. MMWR May 7, 2010

16. Neisseria meningitidis Aerobic gram-negative bacteria At least 13 serogroups based on characteristics of the polysaccharide capsule Most invasive disease caused by serogroups A, B, C, Y, and W-135 Relative importance of serogroups depends on geographic location and other factors (e.g. age) Aggressive illness that can lead to death within 24- 48 hours of the first symptoms

20. Rosenstein N et al. N Engl J Med 2001;344:1378-1388

21. Quadrivalent Conjugate Vaccine

22. Meningococcus - group B Rappuoli R F1000 Medicine Reports 2011, 3:16 (doi:10.3410/M3-16)

24. Incidence of Meningococcal Disease in Infants <12 months, United States, 1998-2007 *Other includes serogroups W-135, nongroupables, other, and unknown ABCs cases from 1998-2007 and projected to the U.S. population

27. Meningococcal disease Conclusions: Amount of potentially preventable disease among infants is low –Currently at nadir in disease incidence –Low proportion of serogroup C+Y disease –Declining incidence after first 6-8 months of life Morbidity and mortality in infants is lower than in other age groups

28. Meningococcal Vaccines for Infants and Toddlers Hib-MenCY (GSK) –3 dose priming (2,4,6m) –+ 12-15 mo booster MCV4 (Menactra  -Sanofi) – 9, 12-15 mo 2 dose series Men4 (Menveo  -Novartis) –3 dose priming (2,4,6m) –+ 12-15 month booster

29. Working Group Interpretation: HibMenCY HibMenCY is an effective vaccine for Hib and serogroup C and Y meningococcal disease after the second or third dose and for one year after the fourth dose Evidence of waning immunity, especially for serogroup Y, indicates vaccine, unlikely to provide protection until age 11-12 years

30. Infant Meningococcal Vaccination ACIP Recommendations (Pending Approval) 1.NO routine recommendation for infant meningococcal vaccination 2.HibMenCY is safe and immunogenic. HibMenCY could be used to complete routine Hib vaccination series (4 doses of HibMenCY required for at least one year of persistence of functional antibody)

31. Infant Meningococcal Vaccination ACIP Recommendations (Pending Approval) 3.HibMenCY is recommended for infants <2 years at increased risk for meningococcal disease, e.g. persistent complement deficiencies; anatomic or functional asplenia, (HIV?) 4.HibMenCY can be given to infants <2 years a.in a community with a serogroup C or Y meningococcal outbreak b.traveling to areas with high endemic rates of serogroups C or Y meningococcal diseases (Does not protect against serogroups A and W-135)

32. Rate of Meningococcal Disease by Single Age Year: All Serogroups NETTS data, average annual rate, 2003 - 2006 11-12 year old recommend ation 2 yr

33. Estimated Annual Number of Cases of Meningococcal Disease, United States: Age 0 - 21 years Active Bacterial Core surveillance (ABCs) cases from 1996- 2005 and projected to the U.S. population Blue Serogroup B- Blue Yellow Serogroups A,C,Y,W-135- Yellow

34. Rates of Meningococcal Disease(A/C/Y/W-135) by Age, 1998-2007 Active Bacterial Core surveillance (ABCs), 1998-2007

35. Meningococcal Disease Among Young Adults, United States, 1998-1999 18-23 years old1.4/100,000 18-23 years old not college students1.4/100,000 Freshmen1.9/100,000 Freshmen in dorm5.1/100,000 Bruce et al, JAMA 2001;286;688-93

36. Adolescent Meningococcal Vaccination Program ACIP Recommendation, Oct 2007: –11-12 year-olds at their pre-teen vaccination visit –13-18 year-olds who have not been previously vaccinated Two licensed vaccines (MCV4) –MenACWY D (Menactra  ) –MenACWY CRM (Menveo  )

37. Coverage of Meningococcal Vaccination among 13-17 year-olds, NIS-Teen, 2006-2008 National Immunization Survey

38. Adolescent Meningococcal Vaccine: Antibodies wane prior to peak incidence of disease Breakthrough cases as severe as in those who never received vaccine Anamnestic response occurs but is not rapid enough to prevent invasive disease (7-10 days)

39. Will a single dose early adolescent vaccination program meet our prevention goals? Goals –Protection through the peak in risk during late adolescence –Protection for college students, especially freshmen living in dormitories Strategy –Vaccinate prior to period of increased risk

40. Adolescent Meningococcal Vaccine Options 1.Stay the course – no change; assess frequency of disease Waning immunity results in lack of protection at period of greatest risk 2.Move timing of single dose  15 to 16 years Same cost 11-15 year olds vulnerable 3.Booster dose (11-12 years and 16 years) greatest number of cases prevented cost per case prevented better than current policy

41. Antigenic Drift and Shift Drift – frequent Minor changes within subtypes Point mutations Occurs in both A and B subtypes May cause epidemics (2003-2004 : A / H3N2/ Fujian emerged in instead of the previously predominant strain A /H3N2 / Panama

42. Antigenic Drift and Shift Shift – infrequent Major change Development of new H or N antigen Exchange of gene segments between influenza stains in mammals Occurs in A subtypes only May cause pandemic

43. Antigenic Drift and Shift Pandemics: 1918-19, “Spanish flu”: A (H1N1). >500,000 deaths in the U.S. ~50 million deaths globally 1957-58, “Asian flu”: A(H2N2). 70,000 deaths in the U.S. 1968-69, “Hong Kong flu”: A (H3N2). 34,000 deaths in the U.S. 2009-2010, “Swine flu”: A (H1N1). 2,117 deaths in the U.S. (282 pediatric deaths)

44. Interpandemic attack rate ~30% Interpandemic hospitalization rate <2yo ~ 50%

46. Quote or statistic could go here. Either the same one throughout, or change from page to page.

47. PLoSOne March 2011, 6:(3) e17616 C

48. 2011-12 U.S. seasonal influenza vaccine virus strains are identical to those contained in the 2010- 11 vaccine Only fourth time in 25 years the vaccine has stayed the same in a consecutive season/year A/California/7/2009 (H1N1)-like A/Perth/16/2009 (H3N2)-like B/Brisbane/60/2008 Trivalent inactivated Influenza virus vaccines for children 2011-2012

49. Annual vaccination is recommended even for those who received the vaccine for the previous season Post-vaccination antibody titers decline over the course of a year Trivalent inactivated Influenza virus vaccines for children 2011-2012

50. Children aged 6 months through 8 years require 2 doses of influenza vaccine (administered a minimum of 4 weeks apart) during their first season of vaccination to optimize immune response In previous seasons, children aged 6 months through 8 years who received only 1 dose of influenza vaccine in their first year of vaccination required 2 doses the following season. As vaccine strains are unchanged between this and the previous season, children in this age group who received at least 1 dose of the 2010-11 seasonal vaccine will require only 1 dose of the 2011-12 vaccine Trivalent inactivated Influenza virus vaccines for children 2011-2012 MMWR August 26, 2011

51. http://aapredbook.aappublications.org/flu/

52. Influenza Vaccine and Egg Allergy Anaphylaxis and severe allergies (angioedema, respiratory distress; urticaria) following egg exposure are still a contraindication for influenza vaccine For other egg allergies/reactions: –Skin testing is no longer necessary –Use the lowest ovalbumin – containing influenza vaccine (Ovalbumin content is listed in package inserts and/or Table 1 of http://www.aaaai.org/professionals/administering_influenza _vaccine.pdf)

53. Vaccine Administration Options: –Two-step graded challenge: 1/10 of vaccine followed in 30 minutes with remainder –Single dose – observe 30 minutes Appropriate resuscitative equipment should be available Influenza Vaccine and Egg Allergy

54. http://aapredbook.aappublications.org/flu/

55. Questions About the Risk of Febrile Seizures After TIV 1. Was the risk in 2010-11 higher than in past influenza seasons? 2. What was the role of concomitant vaccines? 3. What age groups were affected? 4. What is the attributable risk? 5. What is the effect of 1st vs. 2nd dose TIV?

56. Observation for the possible Risk of Febrile Seizures After TIV Largest excess risk was in 12-23 mo old children who received concomitant 1st dose TIV + PCV13 (+/- other vaccines) Attributable risk: 61 (95% CI 13 to 109) per 100,000 vaccinees ~1 in 1,640 vaccinees