Abstract
In this paper we introduce a single serotype transmission model, including an age-dependent mosquito biting rate, to find 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 (Math Biosci 89:29–52). 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 serotype 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.
Highlights
Dengue is considered the most important mosquito-borne viral disease of humans with half of the world’s population living in endemic areas and over 2 million dengue cases reported each year to the World Health Organization (2009, 2012)
We want to find the optimal ages for vaccination against dengue with Dengvaxia for any combination of serotypes in an endemic region by numerically evaluating the lifetime expected risk derived in Sect
The vaccination ages Ai are such that the initial dose can be given at any age, while the second and third dose is given according to the licence of Dengvaxia, i.e. A2 = A1 + 6 months and A3 = A1 + 12 months
Summary
Dengue is considered the most important mosquito-borne viral disease of humans with half of the world’s population living in endemic areas and over 2 million dengue cases reported each year to the World Health Organization (2009, 2012). A consequence of the coexistence of several serotypes seems to be the enhancement of infection, during secondary infections and during primary infections in infancy when maternal antibodies fall to low levels This increase in infection severity is believed to be caused by a higher virulence which is in turn due to antibodies specific to the first serotype an individual was infected with or those passed on by the mother. These antibodies are cross-reactive with heterologous dengue types but non-neutralising and cause antibody-dependent enhancement (ADE) by binding on to the very similar dengue serotype and allowing the active virus entry into its target cells more (Halstead 2009; Jain and Chaturvedi 2010). Considering all of these complex interdependencies it is not surprising that instead of vaccines mainly vector control strategies were used to prevent the transmission of dengue in the past
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