Herd Protection against Influenza

1
Herd Protection against Influenza
W P Glezen, P A Piedra, M J Gaglani
Houston, Texas
and
SCOTT WHITE Clinic
Temple, Texas
2
Herd Protection against Influenza
it is apparent that progress in the control of
influenza has not been impressive. A reassessment
of the basic assumptions upon which the program
was developed is warranted.
A. D. Langmuir et al 1964 Am J Public Health
54563-71
3
Thompson etal JAMA September 15, 2004292111337
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Problems With TargetingHigh Risk Patients

• High risk patients are not easily accessible
  for vaccination
• Many high risk patients are debilitated or
  immunocompromized and fail to respond optimally
  to vaccine

5
Risk Based Strategies Have Failed

• Universal Recommendations Generally Are More
  Successful
• e.g. gt 65 yr, 6-23 mo., Ontario program
• The most vulnerable persons elderly and infants
  have poor immune responses to vaccines and are
  at the end of the transmission chain
  inefficient use of vaccine.

6
School Children, Preschool childrenand Working
adults have the

• highest attack rates for influenza,
• are the spreaders in the community
• and the introducers into the household.
• They also are most accessible for rapid
  deployment of vaccine.

7
Shift in Age Distribution of Persons with
Culture-Positive Illness Presenting to Sentinel
Clinics during Influenza Epidemics, Houston,
1974-1981

• Epidemic stage
• Age
• (yr) Early () Peak () Late ()
• lt 5 236(18.4) 489(24.3) 248(24.5)
• 5-19 687(53.6) 741(36.8) 356(35.2)
• gt 20 359(28.0) 785(39.0) 407(40.3)
• Total 1,282 2,015 1,011

8
After School Holiday
Years
Percentage
Epidemic Period
Interrupted by School Holiday
Percentage
Epidemic Period
9
Influenza vaccines generate optimal immune
responses in healthy schoolchildrenand working
adults.

• Immunization of these groups has the potential
  for establishing indirect protection of the
  vulnerable HERD IMMUNITY or HERD PROTECTION
  efficient use of influenza vaccine.

10
Examples of Herd Protection byCurrently Used
Vaccines

• Rubella vaccine infant immunization protects
  pregnant women

• Hemophilus influenzae type b (Hib) vaccines in
  The Gambia (Adegbola et al. Lancet 2005366144)

• Pneumococcal conjugate vaccine (7-valent) in
  infants (Poehling et al. JAMA 20062951668 in
  adults (Metlay et al. Vaccine 2006 24468
  Hammitt et al. JID 2006193 1487 Flannery et
  al. Ann Int Med 2006144 1-9.)

• Hepatitis A vaccine in US adults (Wasley et
  al. JAMA 2005294194 in Israel (Dagan et al
  2005294202.).

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Herd Protection by Influenza Vaccines

• Tecumseh MI study (Monto et al. Bull WHO
  196941537) 67 reduction in adult illness
  rates by single dose of TIV in school children.
• Northern Territory, Australia (Warburton et al.
  Med J Aust 1972267) reduction in attack rate
  in communities with variable vaccine coverage
  compared to those with no vaccine.
• Novgorod, Russia schoolchildren study (Rudenko
  et al. J Infect Dis 1993168881) reduction in
  attack rate in staff where LAIV given to
  students.
• San Diego (Hurwitz et al. JAMA 20002841677)
  TIV for daycare toddlers reduced ILI in older
  siblings and parents.
• Moscow, Russia (Ghendon et al. Epidemiol Infect
  200613471) TIV in 57 of preschool and 72 of
  school children reduced illness and
  complications in unvaccinated, non- institutionali
  zed adults.

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Herd Protection Proof of Concept

• Japanese School Children Program (Reichert et al.
  N Engl J Med 2001344889)
• In the decade, 1977-1987, influenza vaccine was
  mandatory for school attendance. Two doses of
  inactivated vaccine were recommended each year.

Influenza was not recommended for elderly or high
risk patients.
The Japanese policy makers were unaware of the
indirect effectiveness until Reichert analyzed
wintertime excess mortality from 1959-1998.
Coincident with the school program, he found that
influenza- related excess mortality was reduced
by 35,000 to 47,000 lives per year. When the
program was discontinued, excess mortality rose
to pre-program levels.
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Herd Protection Proof of ConceptContinued

• Reichert also showed that the summertime
  baseline mortality trends for Japan were very
  different than the wintertime excess mortality,
  separating the school influenza program from the
  economic recovery of Japan after WWII. (Reichert
  TA. Seminars Pediatr Infect Dis 200213104).

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Control of Epidemic InfluenzaStudy Design

• An open-label, non-randomized, community-based
  trial of annual influenza immunization of
  school-age children to effect herd immunity

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MAARI Rates in the Intervention and Comparison
Sitesduring Influenza Outbreaks for SWHP Members
gt 35 years old
Piedra et al Vaccine 2005231540-8
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CAIV-T FIELD TRIAL Summary

• Safe-side effects do not increase direct medical
  costs.
• Direct Effectiveness
• Protection inversely related to age (VEadj
  0.70-0.91)
• Persists through two seasons
• Heterovariant
• Single dose is sufficient
• Indirect Effectiveness (Herd Immunity) For
  proportion vaccinated compatible with Longini
  Model.