Pediatric
Vaccine
Update
John Manaloor MD, FAAP - Pediatric Infectious Diseases
October 5th, 2011
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
“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.”
~ Benjamin Franklin
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 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)
Measles, United States, January – June 17, 2011
Source of Importations
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 – 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
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
Vaccine Safety Datalink (VSD),* a collaboration between CDC and eight MCOs
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 2448 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 unknown
ABCs 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 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)
Infant Meningococcal Vaccination
ACIP Recommendations
(Pending Approval)
3.
4.
HibMenCY is recommended for infants <2 years at
increased risk for meningococcal disease, e.g.
persistent complement deficiencies; anatomic or
functional asplenia, (HIV?)
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)
Rate of Meningococcal Disease by
Single Age Year: All Serogroups
2 yr
11-12 year
old
recommend
ation
NETTS data, average annual rate, 2003 - 2006
Estimated Annual Number of Cases of
Meningococcal Disease, United States:
Age 0 - 21 years
Serogroup B- Blue
Serogroups A,C,Y,W-135- Yellow
Active Bacterial Core surveillance (ABCs) cases from 19962005 and projected to the U.S. population
Rates of Meningococcal Disease(A/C/Y/W-135)
by Age, 1998-2007
Rate per 100,000
1.5
1
0.5
0
11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
Age (years)
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
50
Percent Coverage
40
30
2006
2007
2008
20
10
0
13
14
15
16
17
Age (years)
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.
C
PLoSOne March 2011, 6:(3) e17616
Trivalent inactivated Influenza virus
vaccines for children 2011-2012
• 2011-12 U.S. seasonal influenza vaccine virus
strains are identical to those contained in the 201011 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
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)
Influenza Vaccine and Egg Allergy
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
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