ACIC 9 th Annual Conference
Marian Michaels MD, MPH
Professor of Pediatrics
Children’s Hospital of Pittsburgh
Division of Pediatric Infectious Diseases

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

Change in Vaccine Preventable Diseases
Immunization Action Coalition 12/13

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Vaccinate individuals at risk
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Vaccinate a population to protect others
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Vaccinate an available population to protect them later
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As we discuss examples will address rationale for using particular types of vaccines

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

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

Invasive HiB Disease, USA 1990-2007
25
20
15
Before vaccination ~ 20,000 cases/year with ~ 1000 deaths/year
Polysaccharide vaccine -1985
Conjugate vaccine -1987
10
3 cases of HiB at CHP in
2013 (all unvaccinated)
5
0
1990 1992 1994 1996 1998 2000 2002 2004 2005
Year
*Rate per 100,000 children <5 years of age (CDC data)

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

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

~ 20, 000 cases paralytic polio/year

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

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Enterovirus
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Fecal – oral spread
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Replicates locally
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Secretory Ab
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Viremia +/- CNS
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Humoral Ab

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

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

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

Poliomyelitis—United States, 1950-2007
25000
20000
15000
10000
Salk vaccine
1955
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
5000
Last indigenous case
0
1950 1960 1970 1980 1990 2000

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Practically perfect
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Inexpensive, easy to administer
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Mimics natural infection
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IgA and IgG antibody
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Herd immunity
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Susceptible individuals protected

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

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

Vaccine Type
Prevents polio
Neutralizing Ab
Secretory Ab
Good immunity
Herd immunity
VAPP
OPV
Yes
Yes
Yes
Yes
Yes
Yes eIPV
Yes
Yes
No
Yes
No
No
In era of no wild type polio, 6-8 cases VAPP too many
Polio Vaccine schedule altered 2000 to eIPV

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Mild disease
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Infection during pregnancy
• Miscarriage
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Fetal death
• Congenital rubella syndrome
Vaccinate children to prevent disease in pregnant women to protect the unborn baby

Sunday Rubella Campaign
Pittsburgh, PA
May 17, 1970
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Over 2,000 volunteers
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106 sites (mostly schools)
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130 hypospray jet injectors
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190,845 children immunized
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(58% of susceptibles 1-12 yr)

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

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

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

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

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

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

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

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Example of HPV, Hepatitis B
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Controversial for parents
• “My child isn’t at risk”

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

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

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Not beneficial after wild type infection
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Desire vaccine before sexual debut
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ACIP recommends age 11-12
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HPV 4 or HPV 2 for girls
• HPV 4 for boys
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Can start as young as 9 years, Catch up till age 26
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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

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

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