Immunological serotype interactions and their effect on the epidemiological pattern of dengue
Proceedings of the Royal Society B: Biological Sciences
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Long-term epidemiological data reveal multi-annual fluctuations in the incidence of dengue fever and dengue haemorrhagic fever, as well as complex cyclical behaviour in the dynamics of the four serotypes of the dengue virus. It has previously been proposed that these patterns are due to the phenomenon of the so-called antibody-dependent enhancement (ADE) among dengue serotypes, whereby viral replication is increased during secondary infection with a heterologous serotype; however, recent studies have implied that this positive reinforcement cannot account for the temporal patterns of dengue and that some form of cross-immunity or external forcing is necessary. Here, we show that ADE alone can produce the observed periodicities and desynchronized oscillations of individual serotypes if its effects are decomposed into its two possible manifestations: enhancement of susceptibility to secondary infections and increased transmissibility from individuals suffering from secondary infections. This decomposition not only lowers the level of enhancement necessary for realistic disease patterns but also reduces the risk of stochastic extinction. Furthermore, our analyses reveal a time-lagged correlation between serotype dynamics and disease incidence rates, which could have important implications for understanding the irregular pattern of dengue epidemics.
We would like to thank Hang Vu Thi Ti and Thui Nguyen Thi Van from OUCRU for their help with the data. M.R. and K.B.B. were funded by the Institute for Emerging Infections, James Martin 21st Century School. We would also like to acknowledge the Royal Society and the Wellcome Trust for their financial support.
This is the final version of the article. Available from the Royal Society via the DOI in this record.
Vol. 276 (1667), pp. 2541 - 2548
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