Analytic Methods for Infectious Disease Lecture 3 M. Elizabeth - PowerPoint PPT Presentation

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Analytic Methods for Infectious Disease Lecture 3 M. Elizabeth Halloran Hutchinson Research Center and University of Washington Seattle, WA, USA January 13, 2009

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Herd Immunity Definition Manifestations Examples VE Overview General VE S VE S : Exposure data available VE S :Time-of-event VE S :Final value data Conditional VE Estimating VE S , VE I , VE T Population Effects Study Designs for Dependent Happenings

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Herd Immunity Definition Manifestations Examples VE Overview General VE S VE S : Exposure data available VE S :Time-of-event VE S :Final value data Conditional VE Estimating VE S , VE I , VE T Population Effects Study Designs for Dependent Happenings

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Herd Immunity ❼ the collective immunological status of a population of hosts, as opposed to an individual organism, with respect to a given infectious agent. ❼ can be low or high ❼ can be from previous natural infection or immunization

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Herd Immunity ❼ a higher herd immunity will reduce R ❼ herd immunity is a biological condition that can be measured in various ways ❼ herd immunity due to vaccination can produce population-level effects

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Figure: Anti-HAV and Anti-HEV: 97% vs 16% prevalence

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Threshold Herd Immunity ❼ What level of herd immunity is necessary for elimination of transmission? ❼ Related to R 0 and R ❼ Elimination versus eradication ❼ Smallpox versus measles

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Results of increased herd immunity ❼ Reduced incidence of infection ❼ Increased age of first infection ❼ Population- level effects

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Danger of increased age of first infection ❼ Rubella: danger of congenital rubella syndrome ❼ Vaccinate young teenage girls only ❼ Vaccinate boys and girls in first year of life ❼ Mumps in the US ❼ Mid-levels of vaccination produced age-shift with high incidence of post-pubertal mumps

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Recent examples: Conjugate vaccines ❼ Hemophilus influenzae (Hib) vaccination ❼ Pneumococcal vaccines ❼ Meningococcal vaccines

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Vaccine efficacy and effectiveness ❼ generally estimated as one minus some measure of relative risk, RR , in the vaccinated group compared to the unvaccinated group: VE = 1 − RR . ❼ The groups being compared could be composed of individuals or of populations or communities.

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Table: Some Vaccine Effects of Interest Symbol Definition VE S vaccine efficacy for susceptibility VE SP vaccine efficacy for susceptibility to disease VEcol vaccine efficacy for colonization VE P vaccine efficacy for progression, pathogenicity VE I vaccine efficacy for infectiousness VE T total vaccine efficacy VE indirect indirect effects of vaccination in those not vaccinated VE total total effects of vaccination in those vaccinated VE overall overall population-level effects

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Dependent Happenings and Vaccine Effects ❼ Due to the dependent happenings in infectious diseases (Ross 1916), vaccination can produce several different kinds of effects ❼ At the individual level ❼ And at the population level.

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Vaccine Efficacy and Effectiveness ❼ Vaccine efficacy for susceptibility, VE S : ❼ direct protective effects ❼ sometimes outcome is infection, VE S ❼ sometimes outcome disease, VE SP ❼ carriage, VEcol ❼ Vaccine efficacy for progression, VE P ❼ after being infected, the effect on probability of developing symptoms (pathogenicity) ❼ or after developing symptoms, probability of severe disease ❼ other post-infection outcomes, such as viral load

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Vaccine Efficacy and Effectiveness ❼ Vaccine efficacy for infectiousness, VE I ❼ the effect in reducing transmission from a vaccinated compared to an unvaccinated infected person. ❼ Vaccine efficacy if both are vaccinated, VE T ❼ the effect in reducing transmission if both infected and susceptible are vaccinated compared to if neither are vaccinated.

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Population-level Vaccine Effectiveness ❼ Indirect effects, VE IIa ❼ effects of widespread vaccination on someone who is not vaccinated ❼ Total Effects, VE IIb ❼ possibly synergistic effect of being vaccinated and widespread vaccination on someone who is vaccinated ❼ Overall effects, VE III ❼ overall population effect, say, reduction in incidence, (change of average of of first infection, R 0 ) of widespread vaccination.

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Vaccine efficacy and effectiveness ❼ Prevented risk in the exposed (vaccinated) VE = 1 − RR . ❼ Extension in two directions of family of parameters of attributable or prevented risk in the exposed (Greenland and Robins 1988, 1989)

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Table: Parameters used for measuring various effects of vaccination ∗ Comparison groups and effect Level Parameter Susceptibility Infectiousness Combined change in choice susceptibility and infectiousness Conditional on exposure: VE S , p † = 1 − p · 1 VE I , p = 1 − p 1 · VE T , p = 1 − p 11 I Transmission p · 1 p 0 · p 00 probability Study design I IIA IIB III direct indirect total overall Unconditional: VE S , IR = 1 − IR A 1 VE IIA , IR = 1 − IR A 0 VE IIB , IR = 1 − IR A 1 VE III , IR = 1 − IR A · II Incidence IR A 0 IR B 0 IR B 0 IR B · or hazard VE S ,λ = 1 − λ A 1 VE IIA ,λ = 1 − λ A 0 VE IIB ,λ = 1 − λ A 1 VE III ,λ = 1 − λ A · rate, IR, λ λ A 0 λ B 0 λ B 0 λ B · VE S , PH = 1 − e β 1 III Proport. NA NA NA hazards, PH VE S , CI = 1 − CI A 1 VE IIA , CI = 1 − CI A 0 VE IIB , CI = 1 − CI A 1 VE III , CI = 1 − CI A · IV Cumulative CI A 0 CI B 0 CI B 0 CI B · incidence ∗ From Halloran, Struchiner, Longini, Am. J. Epidemiol 1997; 146;789–803.

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Vaccine efficacy for susceptibility, VE S (VE SP ) ❼ Under the assumption of equal exposure to the infectious agent in the vaccinated and unvaccinated groups (Greenwood and Yule 1915), R(vaccinated people) VE S = 1 − R(unvaccinated people) , where R denotes one of the measures of risk. ❼ VE SP

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Vaccine efficacy for susceptibility, VE S The measure of risk can be ❼ a form of the transmission probability, such as the secondary attack rate (SAR) which conditions on exposure to infection, or ❼ the incidence rate, hazard rate, or cumulative incidence (attack rate), which do not condition on exposure to infection.

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Greenwood and Yule (1915) ❼ The Statistics of Anti-typhoid and Anti-cholera Inoculations, and the Interpretation of such Statistics in general ❼ Proc R Soc Med (1915) 8(part 2):113-94

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Conditions Necessary for Valid Inference 1. The persons must be, in all material respects, alike. 2. The effective exposure to the disease must be identical in the case of inoculated and uninoculated persons. 3. The criteria of the fact of inoculation and of the fact of the disease having occurred must be independent.

Outline Herd Immunity VE Overview VE S Conditional VE Population Effects Table: Parameters used for measuring various effects of vaccination ∗ Comparison groups and effect Level Parameter Susceptibility Infectiousness Combined change in choice susceptibility and infectiousness Conditional on exposure: VE S , p † = 1 − p · 1 VE I , p = 1 − p 1 · VE T , p = 1 − p 11 I Transmission p · 1 p 0 · p 00 probability Study design I IIA IIB III direct indirect total overall Unconditional: VE S , IR = 1 − IR A 1 VE IIA , IR = 1 − IR A 0 VE IIB , IR = 1 − IR A 1 VE III , IR = 1 − IR A · II Incidence IR A 0 IR B 0 IR B 0 IR B · or hazard VE S ,λ = 1 − λ A 1 VE IIA ,λ = 1 − λ A 0 VE IIB ,λ = 1 − λ A 1 VE III ,λ = 1 − λ A · rate, IR, λ λ A 0 λ B 0 λ B 0 λ B · VE S , PH = 1 − e β 1 III Proport. NA NA NA hazards, PH VE S , CI = 1 − CI A 1 VE IIA , CI = 1 − CI A 0 VE IIB , CI = 1 − CI A 1 VE III , CI = 1 − CI A · IV Cumulative CI A 0 CI B 0 CI B 0 CI B · incidence ∗ From Halloran, Struchiner, Longini, Am. J. Epidemiol 1997; 146;789–803.