Estimating per-infection cost and burden for dengue and Zika as a function of antibody-dependent enhancement

The complex immune interactions produced by the tetravalent dengue vaccine Dengvaxia have foregrounded the important role of antibody-dependent enhancement (ADE) in dengue infection. Some evidence exists that ADE may extend beyond the four dengue serotypes to Zika, a closely related flavivirus transmitted by the same mosquito species as dengue, and may also account for the increased severity of some cases. Estimates of the public health impact of dengue vaccination may then need to include its effects on the transmission of Zika in addition to dengue. This study gathers primary references to build estimates of per-case economic cost and disease burden for dengue and Zika infection with and without ADE in the ten countries where clinical trials were held for Dengvaxia, under the hypothesis that severe outcomes are associated with ADE of disease. From these estimates, per-infection weighted averages are developed (without assumptions on transmission dynamics or case totals) which will facilitate population-level estimates of the potential impact of dengue vaccination on a dual outbreak using mathematical modeling. Results estimate that ADE amplifies the per-case toll of dengue by a factor of 2-16 but increases that of a Zika case by more than two orders of magnitude due to the greater risk of severe consequences. As expected, dengue vaccination affects per-infection dengue toll much more when high prior dengue seropositivity involves a different serotype than the one(s) circulating, but that same high dengue seropositivity makes vaccination exacerbate Zika toll less.