Abstract
Four distinct serotypes of dengue virus co-circulate in many parts of the world. Antibodies to one serotype prevent infection with the homologous serotype, but may enhance infections with heterologous serotypes. Enhanced secondary infections have been implicated in the majority of severe cases, termed dengue hemorrhagic fever. Conventionally, mathematical models assume that all heterologous secondary infections are subject to enhanced susceptibility or transmissibility. However, empirical data show that only a minority of secondary infections lead to severe disease, which suggests that only a minority of secondary infections are subject to enhancement. We present a new modelling framework in which the population susceptible to secondary infection is split into a group prone to enhanced infection and a group with some degree of cross-protection. We use this framework to re-evaluate the role of enhanced infections in several well known dengue models that exhibit multi-annual epidemiological oscillations. We show that enhancement is unlikely to be driving such oscillations but may be modifying the effects of other drivers.
Highlights
1952; Reich et al, 2013)
We investigate how the new framework for antibody-dependent enhancement (ADE) affects the behaviour of long period oscillations in a model with stochastic seasonality (Adams et al, 2006) and a model with temporary heterologous cross-immunity (Wearing and Rohani, 2006; Aguiar et al, 2011)
We have chosen these models as representative examples of the main approaches to modelling epidemiological oscillations induced by immune cross-reaction, and our purpose is to assess the impact of refining the model framework for cross-enhancement in each of these contexts
Summary
1952; Reich et al, 2013). As this heterologous immunity wanes, antibody-dependent enhancement (ADE) may occur when nonneutralising antibodies bind to infecting viruses and facilitate cell entry. Complete but temporary heterologous cross-protection can lead to ‘immunity-induced’ oscillatory dynamics in systems where secondary infections are enhanced or neutral (Wearing and Rohani, 2006), or even have reduced transmissibility if severe disease associated with enhanced infection results in rapid hospitalisation (Aguiar et al, 2008, 2011) These conventional frameworks assume that all secondary infections are enhanced. Given that accelerated viral replication underlies the enhancement of susceptibility, transmission and disease severity, the prevalence of DHF is likely to be a reasonable estimate for the prevalence of ADE These empirical observations lead us to propose a new framework for modelling antibody-dependent enhancement of dengue. Breaking down the components of this average in our modified framework shows that enhancement is unlikely to be driving these cycles but is likely to be influencing the effects of other drivers
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