John Manaloor MD, FAAP - Pediatric Infectious Diseases

October 5th, 2011

PediatricVaccineUpdate

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

~ 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.”

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

Vaccines preventable diseasesAnthrax

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)

WHO Region Total number of cases

Countries Genotype Identified

African 2 Kenya (1), Nigeria (1) B3 (2)

Eastern Mediterranean

2 Pakistan (1), Jordan (1) D4 (1)

European 25 France (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)

Americas 1 Dominican Republic†(1) D4 (1)

South-East Asia 16 India (15), Indonesia (1) D8 (5), D4 (1)

Western Pacific 7 China (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

Measles – Outbreak 2011

MMWR May 24, 2011

Measles – Outbreak 2011

MMWR May 24, 2011

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

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 (3rd) will be necessary

• Varicella: 2 doses, same time as MMR

MMRV and Febrile Seizure

Vaccine Safety Datalink (VSD),* a collaboration between CDC and eight MCOs

Febrile Sz 7-10 days post

1st dose

Febrile Sz 7-10 days post

2nd dose

MMR + V 4.2/10,000 0/64,663

MMRV 8.5/10,000 1/84,653

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

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

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

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

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

Quadrivalent Conjugate Vaccine

Meningococcus - group B

Rappuoli R F1000 Medicine Reports 2011, 3:16 (doi:10.3410/M3-16)

Incidence of Meningococcal Disease in Infants <12 months,United States, 1998-2007

*Other includes serogroups W-135, nongroupables, other, and unknownABCs cases from 1998-2007 and projected to the U.S. population

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

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

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

Infant Meningococcal VaccinationACIP 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)

Infant Meningococcal VaccinationACIP 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 yearsa. in a community with a serogroup C or Y

meningococcal outbreakb. traveling to areas with high endemic rates of

serogroups C or Y meningococcal diseases (Does not protect against serogroups A and W-135)

Rate of Meningococcal Disease by Single Age Year: All Serogroups

NETTS data, average annual rate, 2003 - 2006

11-12 year old recommendation

2 yr

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

Serogroup B- BlueBlue

Serogroups A,C,Y,W-135- YellowYellow

Rates of Meningococcal Disease(A/C/Y/W-135) by Age, 1998-2007

0

0.5

1

1.5

11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

Age (years)

Rate

per

100

,000

Active Bacterial Core surveillance (ABCs), 1998-2007

Meningococcal Disease Among Young Adults, United States, 1998-1999

•18-23 years old 1.4/100,000

•18-23 years old not college students 1.4/100,000

•Freshmen 1.9/100,000

•Freshmen in dorm 5.1/100,000

Bruce et al, JAMA 2001;286;688-93

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)

–MenACWYD (Menactra)

–MenACWYCRM (Menveo)

Coverage of Meningococcal Vaccination among 13-17 year-olds, NIS-Teen, 2006-2008

0

10

20

30

40

50

13 14 15 16 17

Age (years)

Per

cen

t C

ove

rag

e

20062007

2008

National Immunization Survey

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)

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

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

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

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

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)

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

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

PLoSOne March 2011, 6:(3) e17616

C

• 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

• 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

• 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

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

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)

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

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

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?

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