The optimal age of vaccination against dengue with an age-dependent biting rate with application to Brazil

Maier, Sandra B. and Massad, Eduardo and Amaku, Marcos and Burattini, Marcelo N. and Greenhalgh, David (2020) The optimal age of vaccination against dengue with an age-dependent biting rate with application to Brazil. Bulletin of Mathematical Biology, 82. 12. ISSN 0092-8240 (

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In this paper we introduce a single-serotype transmission model, including an age-dependent mosquito biting rate, to nd the optimal vaccination age against dengue in Brazil with Dengvaxia. The optimal vaccination age and minimal lifetime expected risk of hospitalisation are found by adapting a method due to Hethcote [1]. Any number and combination of the four dengue serotypes DENv1-4 is considered. Successful vaccination against a serotype corresponds to a silent infection. The effects of antibody dependent enhancement (ADE) and permanent cross-immunity after two heterologous infections are studied. ADE is assumed to imply risk-free primary infections, while permanent cross-immunity implies risk-free tertiary and quaternary infections. Data from trials of Dengvaxia indicate vaccine efficacy to be age- and serostatus-dependent, and vaccination of seronegative individuals to induce an increased risk of hospitalisation. Some of the scenarios are therefore reconsidered taking these findings into account. The optimal vaccination age is compared to that achievable under the current age-restriction of the vaccine. If vaccination is not considered to induce risk optimal vaccination ages are very low. The assumption of ADE generally leads to a higher optimal vaccination age in this case. For a single stereotype vaccination is not recommended in the case of ADE. Permanent cross-immunity results in a slightly lower optimal vaccination age. If vaccination induces a risk the optimal vaccination ages are much higher, particularly for permanent cross-immunity. ADE has no effect on the optimal vaccination age when permanent cross-immunity is considered, otherwise it leads to a slight increase in optimal vaccination age.