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

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.

Age-targeted tuberculosis vaccination in China and implications for vaccine development: a modelling study

“…The vaccine was assumed to provide all or nothing protection, but the alternative leaky assumption could reduce effect estimates. 31 Because of high treatment success and case detection during calibration years, these were assumed to plateau after the calibration period. Potential future policy changes are challenging to predict, but if improvements in care measures (eg, mass active case finding) were achieved, or better diagnostics or treatments introduced, the impact achieved by vaccines could potentially be reduced.…”

Modelling the effect of short-course multidrug-resistant tuberculosis treatment in Karakalpakstan, Uzbekistan

“…1 and the modelling approach is described in detail in Additional file 1, which lists compartment abbreivations (Additional file 1: Table S1) and parameter values (Additional file 1: Table S2). The model is based on our previous work [14] and incorporates a number of aspects that we consider important to modelling TB epidemiology in regions highly endemic for both TB and MDR-TB, including partial vaccine efficacy (leakiness) [15, 16], declining risk of active disease with time from infection, reinfection during latency, and acquisition of drug resistance through de novo amplification.…”

Vaccination: Epidemiological Review

“…The assessment of the impact of vaccination on an individual or population requires an analysis of both the direct and indirect effects of immunization [27]. The theoretical concept of vaccine efficacy describes the individual level benefit or how much less likely an individual is to acquire infection following a given exposure [1] [27].…”

“…The theoretical concept of vaccine efficacy describes the individual level benefit or how much less likely an individual is to acquire infection following a given exposure [1] [27]. Most clinical trials however assess vaccine effectiveness at the population level [1] [27] however the indirect effect of vaccination accounting for the reduction in transmission to unvaccinated subjects in the wider population may go unnoted [1] [27].…”

“…The theoretical concept of vaccine efficacy describes the individual level benefit or how much less likely an individual is to acquire infection following a given exposure [1] [27]. Most clinical trials however assess vaccine effectiveness at the population level [1] [27] however the indirect effect of vaccination accounting for the reduction in transmission to unvaccinated subjects in the wider population may go unnoted [1] [27]. It is the combination of direct and indirect effects that should interest public health experts in fully evaluating vaccination impact since there may be little known about the apparent or real vaccine impacts, as well as the risk of reinfection and mechanism of protection [1] [27].…”