Pros and Cons of Universal Vaccination of the Children, including Potential Herd Immunity

1. Pros and Cons of Universal Vaccination of the Children, including Potential Herd Immunity Most Critical Information Gaps that Need to be Filled before Moving to Universal Vaccination of Children Lone Simonsen, NIAID, NIH, Bethesda, MD, USA Emory/CDC/NVPO Workshop, Atlanta, October 24-25, 2005

2. A bit of History • ~1960: Prioritize “high risk” for vaccination • 1960-1994: concern – was it working? • 1994- : New generation cohort studies argued benefits were huge • ~50% reduction in ALL winter deaths • 1996: CDC workshop addressed why no reduction in excess mortality had occurred as vaccine coverage soared • Healthy People Year 2000 efforts

3. Excess P&I Mortality Rates – age adjustedYounger Elderly 65-74 years of age Red squares=H3N2Blue triangles=H1N1/B

4. Emerging evidence that VE was greatly overestimated in cohort studies of elderly • 2004: Mangtani et al, JID • residual bias identified using seasonality • After adjustment, VE=~0% for all-cause mortality • 2005: Simonsen et al, Arch Int Med • no reduction in excess mortality since 1980 • Only ~5% of ALL winter deaths are attributable to influenza • 2005: Falsey et al, NEJM • Observational study of lab-confirmed influenza hospitalizations in the elderly (RSV control) • Found that VE= ~30% for influenza-hospitalization • 2005: Cochrane review, Jefferson et al, Lancet • Concluded problems with VE for elderly mortality • 2005: Jackson et al (2 papers in review) • Demonstration of residual self-selection bias • max “VE” for mortality obtain before influenza circulates

5. A Placebo-controlled RCT set in 911 “younger” Dutch Elderly ** p<0.05 Gowaert 1994

6. Cannot separate discussion of universal vaccination from knowing: 1.How successful is current influenza control efforts of vaccinating “high risk” groups • Elderly? High-risk? Children<23mo? • Can unchanging mortality rates be explained by immune senescence? By failure to reach those at highest risk? • If we believe cohort studies – then there is no reason for seeking novel vaccination strategies that provide herd immunity • Need for consideration of residual bias • Need for studies of VE in elderly >75 years • Need for randomized clinical trials in elderly, perhaps head-to-head if not placebo-controlled

7. Cannot separate discussion of universal vaccination from considering: 2. How to prioritize “indirect” versus “direct” protection in seasons when there is vaccine shortage? • in pandemics preparedness planning? • for epidemic seasons? • How can universal vaccination program demonstrate that “indirect” benefits took place? • …. a common curse for public health….

8. Cannot separate discussion of universal vaccination from: • The need to “modernize” health metrics used for measuring influenza preventable disease burden and to define priority groups • A 99-year old death counts as much as a child • Consider Years of Life Lost (YLL) and DALYs like other disases? • Consider using new prioritization approach: Influenza risk x VE

9. Gaps • Reach agreement on effectiveness of current control efforts • Discuss universal immunization in context of vaccine shortage issues • Align with pandemic planning ? • Discuss use of live vaccine or “flushot” for children • LAIV seems the better choice - broader and longer-lasting protection; no vaccine shortage in LAIV so far • “Modern” health metrics for setting vaccine priorities • Counting YLL (and not deaths) tend to favour younger pop • How to demonstrate “indirect” protection success • lives saved by herd immunity are not tangible or visible – and difficult to measure