Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics.

Romain Ragonnet,Emma S Mcbryde,Margaret Hellard,Nicholas L Geard,James M Trauer,Justin T Denholm

doi:10.1038/srep15468

Abstract

Vaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination, and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, ‘all or nothing’ vaccines are more effective than ‘leaky’ vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased, and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic.

Highlights

This variation in vaccine impact makes it difficult to predict the true population effect of a vaccination program
Some aspects of the complexity involved in assessment of the vaccine impact have been addressed previously, with prior work considering the impact of different study designs, as well as different indicators of vaccine effectiveness[20,21]
Our study highlights the challenges of assessing vaccine impact and reinforces that the potential effectiveness of vaccination programs is poorly characterized by efficacy alone

Summary

Introduction

This variation in vaccine impact makes it difficult to predict the true population effect of a vaccination program. Gomes et al have previously modelled the impact of the level of natural immunity acquired from infection on the reduction of the disease burden[27,28] Both are important issues in assessing the impact of vaccines, heterogeneity of vaccine efficacy across recipients and the potential for inaccurate estimates are often studied separately, despite their interdependence having been described in relation to acute epidemics of measles and influenza[24]. We present a general model of endemic infectious disease that is flexible to assumptions regarding vaccine leakiness, the presence and duration of latency and the degree of protection or increased susceptibility following a previous infection We use this model to study the impact of an imperfect vaccine, which may produce either partial or complete immunity in vaccinated subjects, to assess both direct and indirect vaccine effectiveness. This approach allows consideration of a broad range of vaccination outcomes, in terms of both observed and population effects, using a model that is applicable to a broad range of vaccines and infections

Methods

Results

Conclusion