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Marc Lipsitch

Publications and source records attributed to Marc Lipsitch.

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Vaccine effects on heterogeneity in susceptibility and implications for population health management

Heterogeneity in host susceptibility is a key determinant of infectious disease dynamics but is rarely accounted for in assessment of disease control measures. Understanding how susceptibility is distributed in populations, and how control measures change this distribution, is integral to predicting the course of epidemics with and without interventions. Using multiple experimental and modeling approaches, we show that rainbow trout have relatively homogeneous susceptibility to infection with infectious hematopoietic necrosis virus and that vaccination increases heterogeneity in susceptibility in a nearly all-or-nothing fashion. In a simple transmission model with an R 0 of 2, the highly heterogeneous vaccine protection would cause a 35 percentage-point reduction in outbreak size over an intervention inducing homogenous protection at the same mean level. More broadly, these findings provide validation of methodology that can help to reduce biases in predictions of vaccine impact in natural settings and provide insight into how vaccination shapes population susceptibility.

mBio

A missing dimension in measures of vaccination impacts

Immunological protection, acquired from either natural infection or vaccination, varies among hosts, reflecting underlying biological variation and affecting population-level protection. Owing to the nature of resistance mechanisms, distributions of susceptibility and protection entangle with pathogen dose in a way that can be decoupled by adequately representing the dose dimension. Any infectious processes must depend in some fashion on dose, and empirical evidence exists for an effect of exposure dose on the probability of transmission to mumps-vaccinated hosts [1] , the case-fatality ratio of measles [2] , and the probability of infection and, given infection, of symptoms in cholera [3] . Extreme distributions of vaccine protection have been termed leaky (partially protects all hosts) and all-or-nothing (totally protects a proportion of hosts) [4] . These distributions can be distinguished in vaccine field trials from the time dependence of infections [5] . Frailty mixing models have also been proposed to estimate the distribution of protection from time to event data [6] , [7] , although the results are not comparable across regions unless there is explicit control for baseline transmission [8] . Distributions of host susceptibility and acquired protection can be estimated from dose-response data generated under controlled experimental conditions [9] – [11] and natural settings [12] , [13] . These distributions can guide research on mechanisms of protection, as well as enable model validity across the entire range of transmission intensities. We argue for a shift to a dose-dimension paradigm in infectious disease science and community health.

PLoS Pathogens