The effects of tertiary and quaternary infections on the epidemiology of dengue.
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The epidemiology of dengue is characterised by irregular epidemic outbreaks and desynchronised dynamics of its four co-circulating virus serotypes.Here we investigate the effect of third and subsequent infections on the transmission dynamics of dengue and show that although the qualitative patterns are largely equivalent, the system more readily exhibits the desynchronised serotype oscillations and multi-annual epidemic outbreaks upon their inclusion.Realistic age-prevalent patterns and seroconversion rates are therefore easier reconciled with a low value of dengue's transmission potential if allowing for more than two infections; this should have important consequences for dengue control and intervention measures.
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PubMed Central - PubMed
Affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.
ABSTRACT
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The epidemiology of dengue is characterised by irregular epidemic outbreaks and desynchronised dynamics of its four co-circulating virus serotypes. Whilst infection by one serotype appears to convey life-long protection to homologous infection, it is believed to be a risk factor for severe disease manifestations upon secondary, heterologous infection due to the phenomenon of Antibody-Dependent Enhancement (ADE). Subsequent clinical infections are rarely reported and, since the majority of dengue infections are generally asymptomatic, it is not clear if and to what degree tertiary or quaternary infections contribute to dengue epidemiology. Here we investigate the effect of third and subsequent infections on the transmission dynamics of dengue and show that although the qualitative patterns are largely equivalent, the system more readily exhibits the desynchronised serotype oscillations and multi-annual epidemic outbreaks upon their inclusion. More importantly, permitting third and fourth infections significantly increases the force of infection without resorting to high basic reproductive numbers. Realistic age-prevalent patterns and seroconversion rates are therefore easier reconciled with a low value of dengue's transmission potential if allowing for more than two infections; this should have important consequences for dengue control and intervention measures. Related in: MedlinePlus |
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Mentions: The only notable effect of third and fourth infections, so far, has been an overall higher propensity for desynchronised, large amplitude oscillations. This, however, can be directly attributed to an overall higher level of transmission that is achieved and maintained by a larger proportion of the population susceptible to infection and onward transmission. We therefore also expect an effect on age-structured prevalence and incidence rates. To explicitly compare the age structure of prevalence within each model we adapted the methods of [21]. We consider in both models the distinct (unstable) equilibrium solutions where all strains have equal forces of infection in the case of medium levels of enhancement (). This equilibrium serves as an approximation of the mean prevalence of each serotype over a long period of time. In this case, the proportion of the population that has experienced exactly āiā different strains is given by . The probability of acquiring a new infection is then proportionate to the number of yet un-encountered strains. In this case with four co-circulating dengue serotypes individuals enter from at a rate , where is the average per capita force of infection per strain. The dynamics of this system with respect to time, , and age, , may then be described by the following set of partial differential equations for :where the proportion of individuals yet unexposed is given by . We can then solve these equations (noting, in this instance, that the time derivative is zero) to approximate how the number of infections varies with age in each model. In Figure 5a we have then plotted this data for each model in order to compare and contrast age structures. In Figure 5b we have made a minor adaptation to the models in that we consider the case of just 2 or 3 co-circulating serotypes of dengue. To generate this figure we repeated the above and show how the age of first infection, average age of disease and total force of infection changes for each scenario in both models. Finally, Figure 5c shows how the average age of first infection changes with increasing in both of our models. |
View Article: PubMed Central - PubMed
Affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.