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      Waning Immunity Is Associated with Periodic Large Outbreaks of Mumps: A Mathematical Modeling Study of Scottish Data

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          Abstract

          Vaccination programs for childhood diseases, such as measles, mumps and rubella have greatly contributed to decreasing the incidence and impact of those diseases. Nonetheless, despite long vaccination programmes across the world, mumps has not yet been eradicated in those countries: indeed, large outbreaks continue. For example, in Scotland large outbreaks occurred in 2004, 2005, and 2015, despite introducing the MMR (Measles-Mumps-Rubella) vaccine more than 20 years ago. There are indications that this vaccine-preventable disease is re-emerging in highly vaccinated populations. Here we investigate whether the resurgence of mumps is due to waning immunity, and further, could a booster dose be the solution to eradicate mumps or would it just extend the period of waning immunity? Using mathematical modeling we enhance a seasonally-structured disease model with four scenarios: no vaccination, vaccinated individuals protected for life, vaccinated individuals at risk of waning immunity, and introduction of measures to increase immunity (a third dose, or a better vaccine). The model is parameterised from observed clinical data in Scotland 2004–2015 and the literature. The results of the four scenarios are compared with observed clinical data 2004–2016. While the force of infection is relatively sensitive to the duration of immunity and the number of boosters undertaken, we conclude that periodic large outbreaks of mumps will be sustained for all except the second scenario. This suggests that the current protocol of two vaccinations is optimal in the sense that while there are periodic large outbreaks, the severity of cases in vaccinated individuals is less than in unvaccinated individuals, and the size of the outbreaks does not decrease sufficiently with a third booster to make economic sense. This recommendation relies on continuous efforts to maintain high levels of vaccination uptake.

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          The pre-vaccination epidemiology of measles, mumps and rubella in Europe: implications for modelling studies.

          Data on the pre-vaccination patterns of infection for measles, mumps and rubella are collated from a number of European countries in order to compare the epidemiology of the three viruses. Key epidemiological parameters, such as the age-specific force of infection and the basic reproduction number (R0) are estimated from case notification or serological data using standard techniques. A method is described to compare force of infection estimates derived from serological data. Analysis suggests that the pre-vaccination patterns of measles and mumps infection in the different countries were similar. In contrast, the epidemiology of rubella was highly variable between countries. This suggests that it may be acceptable to use parameter values estimated from other countries to model measles and mumps transmission, but that this approach to modelling rubella transmission requires more caution. Estimates of R0 depend on underlying mixing assumptions. Constraints were placed on R0 estimates by utilising knowledge of likely mixing patterns. The estimates for R0 were highest for measles, intermediate for mumps, and generally lowest for rubella. Analysis of within- and between-age-group transmission rates suggested that mumps transmission tends to be more concentrated within young children than the other two viruses. The implications for the design of immunization programmes are that mumps may be the easiest to control via infant immunization since it is predominantly transmitted between the very young and the variability in rubella epidemiology requires that careful consideration of the possible effects of vaccination options should be made using local data when planning rubella immunization programmes.
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            Bio-PEPA: A framework for the modelling and analysis of biological systems

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              Understanding the persistence of measles: reconciling theory, simulation and observation.

              Ever since the pattern of localized extinction associated with measles was discovered by Bartlett in 1957, many models have been developed in an attempt to reproduce this phenomenon. Recently, the use of constant infectious and incubation periods, rather than the more convenient exponential forms, has been presented as a simple means of obtaining realistic persistence levels. However, this result appears at odds with rigorous mathematical theory; here we reconcile these differences. Using a deterministic approach, we parameterize a variety of models to fit the observed biennial attractor, thus determining the level of seasonality by the choice of model. We can then compare fairly the persistence of the stochastic versions of these models, using the 'best-fit' parameters. Finally, we consider the differences between the observed fade-out pattern and the more theoretically appealing 'first passage time'.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                25 April 2017
                2017
                : 8
                : 233
                Affiliations
                [1] 1Department of Computing Science, University of Oran1 Ahmed BenBella Oran, Algeria
                [2] 2Health Protection Scotland Glasgow, UK
                [3] 3Department of Computing Science and Mathematics, University of Stirling Stirling, UK
                Author notes

                Edited by: Krasimira Tsaneva-Atanasova, University of Exeter, UK

                Reviewed by: Maria Vittoria Barbarossa, Heidelberg University, Germany; Mauricio Lima, Pontifical Catholic University of Chile, Chile

                This article was submitted to Computational Physiology and Medicine, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2017.00233
                5404202
                28487657
                a3bda8d5-0daf-4027-aea5-fd999408f42d
                Copyright © 2017 Hamami, Cameron, Pollock and Shankland.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 January 2017
                : 03 April 2017
                Page count
                Figures: 8, Tables: 0, Equations: 1, References: 49, Pages: 11, Words: 7348
                Categories
                Physiology
                Original Research

                Anatomy & Physiology
                mumps,vaccination,waning immunity,mathematical and computational modeling and simulation,bio-pepa

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