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The effects of tertiary and quaternary infections on the epidemiology of dengue.

Wikramaratna PS, Simmons CP, Gupta S, Recker M - PLoS ONE (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.

ABSTRACT
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.

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Related in: MedlinePlus

General model dynamics under parameter changes.Here we observe the fluctuations in the total proportion of the population that has been infected by each serotype against time for different levels of transmissibility enhancement  (from left to right: , , , ; no enhancement is represented by ; increasing  corresponds to augmented levels of enhancement). The top panel is for the model with the assumption of total immunity after two infections only (model (i)) whilst the bottom is for the model which allows for infection with all four serotypes (model (ii)). The individual serotype dynamics seem to become ever more desynchronised as  increases in both models, though this effect appears stronger in model (ii).
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pone-0012347-g002: General model dynamics under parameter changes.Here we observe the fluctuations in the total proportion of the population that has been infected by each serotype against time for different levels of transmissibility enhancement (from left to right: , , , ; no enhancement is represented by ; increasing corresponds to augmented levels of enhancement). The top panel is for the model with the assumption of total immunity after two infections only (model (i)) whilst the bottom is for the model which allows for infection with all four serotypes (model (ii)). The individual serotype dynamics seem to become ever more desynchronised as increases in both models, though this effect appears stronger in model (ii).

Mentions: Figure 2 shows the general model output for fixed as a selection of time series (after removing the transients) and characterises the wide range of dynamical behaviours observed in both models under increased levels of enhancement . In line with previous studies [5], [6], [9], the following pattern of behaviour emerges. For low levels of enhancement we observe a steady-state equilibrium with all serotypes persisting at equal frequencies. As the degree of enhancement, , is increased, the equilibrium is replaced by synchronized oscillations. Further augmentation of desynchronises these oscillations, leading to the emergence of a more ‘chaotic’ strain structure where individual serotypes are sequentially replaced. Finally, we approach a state where we detect periods of low disease prevalence interspersed with semi-regular epidemic outbreaks. In both models this stage appears to be further characterised by the sequential replacement of the dominant serotype.


The effects of tertiary and quaternary infections on the epidemiology of dengue.

Wikramaratna PS, Simmons CP, Gupta S, Recker M - PLoS ONE (2010)

General model dynamics under parameter changes.Here we observe the fluctuations in the total proportion of the population that has been infected by each serotype against time for different levels of transmissibility enhancement  (from left to right: , , , ; no enhancement is represented by ; increasing  corresponds to augmented levels of enhancement). The top panel is for the model with the assumption of total immunity after two infections only (model (i)) whilst the bottom is for the model which allows for infection with all four serotypes (model (ii)). The individual serotype dynamics seem to become ever more desynchronised as  increases in both models, though this effect appears stronger in model (ii).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2925950&req=5

pone-0012347-g002: General model dynamics under parameter changes.Here we observe the fluctuations in the total proportion of the population that has been infected by each serotype against time for different levels of transmissibility enhancement (from left to right: , , , ; no enhancement is represented by ; increasing corresponds to augmented levels of enhancement). The top panel is for the model with the assumption of total immunity after two infections only (model (i)) whilst the bottom is for the model which allows for infection with all four serotypes (model (ii)). The individual serotype dynamics seem to become ever more desynchronised as increases in both models, though this effect appears stronger in model (ii).
Mentions: Figure 2 shows the general model output for fixed as a selection of time series (after removing the transients) and characterises the wide range of dynamical behaviours observed in both models under increased levels of enhancement . In line with previous studies [5], [6], [9], the following pattern of behaviour emerges. For low levels of enhancement we observe a steady-state equilibrium with all serotypes persisting at equal frequencies. As the degree of enhancement, , is increased, the equilibrium is replaced by synchronized oscillations. Further augmentation of desynchronises these oscillations, leading to the emergence of a more ‘chaotic’ strain structure where individual serotypes are sequentially replaced. Finally, we approach a state where we detect periods of low disease prevalence interspersed with semi-regular epidemic outbreaks. In both models this stage appears to be further characterised by the sequential replacement of the dominant serotype.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Oxford, Oxford, United Kingdom.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus