B. Influenza

1. Impact of influenza in young children

Dr. Uyeki reviewed attack rates of 35%-36% in Houston in preschoolers, 13.5%-27% in Vanderbuilt.
Glezen AJE 1980;111:13-22 overall 40% absenteeism from school.
Quach Peds 2003:112:e197-201 70% of hospitalized children <2 years old; 70% previously healthy.

Neurological complications of influenza include febrile seizures, encephalitis in Japan
CID 2002;35:512-7: acute encephalopathy in Japan; 85% previously healthy; 32% died
US passive surveillance on influenza-associated encephalopathy showed 23 cases, 2 of which were fatal and 26% had neurological sequelae.

MMWR 2003; 52:837-40 reported 14 cases of severe influenza associated illness in Michigan; 4 cases fata; 10 serious non-respiratory illness.
9 influenza-associated sudden explained deaths reported to CDC this year.

Dr. Thompson reviewed disease burden.
New CDC data show 115 hospitalizations per 100,000 among 0-4 year olds.
For children <2 years of age, 240 hospitalizations per 100,000 among 0-2 year olds.
Among children <5, 92 estimated deaths annually in US
Among children <2 years of age 17,000 estimated hospitalizations annually.

2. Influenza Hospitalizations in Children

Dr. Griffin discussed the New Vaccine Surveillance Network.
Population based surveillance for burden of disease in children
Inpatient surveillance if admitted for acute respiratory illness (ARI) or fever without cause
Culture and RT-PCR were done.
1037 hospitalizations for ARI.
Influenza as cause in 7% of hospitalizations
1.8 influenza admissions per 1000 children. Among 6-23 month olds, rate 1.75 per 1000.

3. Vaccine safety and efficacy in young children

Medline search of articles and searching references
Old studies show no safety problems
a. Safety and immunogenicity studies - small rates of local and systematic reaction b. RCT
Gruber 1990 showed 83% efficacy
Edwards 1994 44-48% seroconversion based efficacy; when culture confirmed, was higher.
Heikkinen AJDC 191;145:445. Efficacy was 83% by culture
Clements Arch Ped Adol Med 1995 OR=.69 against AOM
Hurwitz JID 2000;182:1218 and JAMA 2000;284:1 45% efficacy

Hoberman JAMA 2003;290:1608 no reduction in AOM but 66% efficacy in year 01.

4. Children’s Hospital of Pittsburgh Influenza Trial

RCT of TIV, using diluent as placebo. 90% seroconversion among vaccinees. 66% efficacy in Year 01 with none in Year 02 though only 3.3% culture + rate in placebo recipients showing low attack rate.
No serious SAE
Influenza associated AOM effectiveness was 62% in Year 01

5. Safety Databases

VAERS data
Fever was reported in 34% of reports.
VSD screening analyses
Self-control methodology with control period 15-28 days after vaccination.
8,476 doses in 6-23 month olds.
No neurological outcomes identified in the 2 weeks following vaccination and no serious AE

6. IOM report on Neurologic Consequences of Influenza Vaccine

Influenza vaccine in 1976 (swine flu) favors acceptance of a causal relationship with GBS
All other years inadequate for GBS
Favors rejection of a causal relationship between influenza vaccine and MS relapse in adults
Virtually no evidence in the 6-23 months age group
Biologic direct neurotoxic effect is only theoretical
Weak evidence that a biologic mechanism could exist for molecular mimicry to cause a demylinating disorder

7. Economic evaluation

1st model
Total vaccination costs estimated at $64.77 for 6-23 month olds (including 2 doses) including lost work time for parents
Range varies from $<1000 to $8000 per QALY

2nd model - Monte Carlo
death rate is the major impact on cost
cost depends on vaccination price
79% of savings are indirect
Threshold for 90% healthy group is $48/dose administered

8. Feasibility studies were reviewed including the University of Pittsburgh study which showed that vaccination rates increased in the inner city when a tailored approach was used; this presentation was given by myself.

9. Influenza Vaccine is not covered by VICP unless full recommendation.

10. AAP COID perspective: Disease burden is moderately high. Inactivated vaccine is safe. Modest efficacy of the vaccine. They think Aencouragement@ is confusing and the VICP coverage is needed. AAFP perspective was also given.

11. ACIP voted, effective Fall 2004, to recommend annual influenza vaccine to children 6-23 months of age.

C. Dr. Sloan reviewed the IOM report on vaccine financing. The IOM recommends a vaccine coverage mandate for all public and private health plans, a new federal subsidy to cover mandated vaccine costs and administration fees, a voucher system for uninsured for vaccines and administration fees, a process to distinguish between vaccines that have a strong and weak societal benefits, a process to calculate subsidy levels based on estimated societal benefits for future vaccines, ACIP procedures and membership to include societal benefits and costs, and NVPO to convene stakeholder deliberations on this financing strategy and CDC to initiate a research program on the societal value of vaccines.

D. Smallpox vaccine

38,542 civilian vaccinees; 92% take rate.
Military vaccinated 504,000. Take rate 96%
Military only used 2 VIG treatments thus far which is less than expected..
Encephalitis occrred in one who recovered
58 myopericarditis cases
80% complete recovery at 8 weeks
10 HIV inadvertently vaccinated; all took.
Inflammatory cardiac disease - DOD data suggest a causal association from smallpox vaccine
no eczema vaccinatum, no progressive vaccinia, and no nosocomial contact transmission
4 cases of dilated cardiomyopathy; recognized 3-5 months after vaccination; severe cardiomyopathy resulted.
VAERS deaths: 4 cardiac deaths and no causal association identified; 1 PE, 1 illicit drug overdose, 1 unexplained
Vaccinia transmission to contacts in family members or bed partners (intimate or sexual contact)
No nosocomial transmission.
Rates of spontaneous abortion in amount anticipated in general literature when vaccine inadvertently given during early pregnancy.
Good evidence for persistence of long-term antibody and cell-mediated immunity

E. Pediatrician’s knowledge and Adherence to ACIP PCV7 Shortage Recommendations

Most pediatricians experienced a shortage and shortage recommendations. They vaccinated publicly and privately financed children similarly. Half gave 4th dose despite recommendations not to give it. Over one third did not track deferred children.

F. PCV Effectiveness

ABCs data show effectiveness at 94%. Effectiveness against related serotypes varies: 6B in vaccine, 6A is not; efficacy against 6A is 87%. Effectiveness against 19A is 40% with wide CI that includes 0; not in vaccine but 19F is.
Invasive disease has dropped dramatically and herd immunity for serotypes in vaccine appears to be affecting older age groups including the elderly.

G. Pediatrician clinical practices and adherence to national immunization guidelines after introduction of PCV

15% reported adding at least 1 well child visit after PCV
381 respondents reported following 209 different schedules for giving all of the recommended childhood vaccines. 36% were not adherent to national recommendations for at least 1 vaccine
These data were before Pediarix.

H. 2004 Childhood Immunization Schedule

The schedule will cover January to June, 2004. After AAP and AAFP approve influenza vaccine for use in 6-23 month old children, the schedule will be revised for the later portion of the year. 24 weeks was adopted as the earliest age for hepatitis B#3 (though routinely recommended at 6 months).

I. Meningococcal Working Group

The group is working on education about the polysaccharide vaccine. An application for licensure for a conjugate vaccine may be submitted later in 2003 and 5 companies are working on conjugate vaccines. The working group is planning on reviewing the epidemiology and new vaccines.

J. Hepatitis B VFC Resolution Corrections
Small corrections were made.

K. HIV Working Group

VaxGen gp120 showed no overall efficacy. An uxexpected sub-analysis showed apparent efficacy in blacks, Asians, and other groups. US government sponsored group is re-analyzing results. VE could be due to chance 8% among minorities and 22% among blacks by chance. Randomization appeared to work. Loss to follow-up was examined. VaxGen gp120 trial in Thailand is ongoing.

ALVAC Thai phase III trial by US Army using a recombinant canarypox from Aventis on a 0,1,3,6 month schedule with a VaxGen B/E boost at 3, 6 months. Several vaccines in pipeline.

L. Yellow Fever vaccine safety

5 more reports of serious yellow fever vaccine safety; two cases fatal.

M. NIH

New anthrax vaccine in development.
NIAID launches malaria vaccine trial in Mali.

N. NVPO

NVAC is working on IOM=s vaccine financing group

O. VICP

>300 lawsuits about thimerosal including class action suits.
Types include traditional tort, medical monitoring class action suit, and derivative claims from parents or spouses. Litigants claiming thimerosal is an adulterant.

P. NIP Update

Steve Cochi is the new deputy director.
Measles outbreak in the Republic of the Marshall Islands occurred due to low coverage (<75%), importation, and high population density. 752 confirmed cases, 84 hospitalizations, and 3 deaths.

Respectfully submitted,