THE "uNHOLY" CHIKUNGUNYA-DENGUE-ZIKA TRINITY: A THEORETICAL ANALYSIS

Aedes aegypti is the vector for numerous diseases in humans and other (reservoir) hosts, such as chikungunya, dengue fever and Zika virus. A new deterministic model is designed and used to assess the dynamics of the three diseases in a population where Aedes mosquitoes are abundant. The model to be designed incorporates the recently-released imperfect vaccine against dengue virus (Dengvaxia® vaccine by Sanofi Pasteur) as well as allow for sexual transmission of Zika. Further, the model allows for the assessment of the population-level impact of three biological hypotheses, namely a competitive dengue-chikungunya-Zika superinfection hierarchy, an antibody-dependent enhancement of dengue over Zika and that the Dengvaxia vaccine can induce reduced susceptibility to Zika infection in vaccinated individuals. After carrying out detailed theoretical analyses to gain insight into its qualitative features, the model is then fitted to the data recorded during the 2015-2016 outbreaks of the three diseases in Mexico. Simulations of the model show a reasonable fit to observed dynamics consistent with the competitive hierarchy assumed for the interactions of the viruses. Furthermore, Zika transmission dynamics is only mildly affected by changes in the parameter related to the infectiousness of Zika in relation to dengue, even in the region where antibody-dependent enhancement is assumed. The dengue vaccine has a very marginal impact on Zika transmission dynamics (and that the vaccine, no matter the coverage and efficacy levels, is unable to reduce the reproduction number for Zika transmission to a value less than unity). The model is extended to include the effect of seasonality and local weather variability (temperature and rainfall) on the dynamics of the three diseases. Simulations of the resulting non-autonomous model, using weather and demographic data for Mexico, show that for the current mean monthly rainfall value for Mexico, the burden of the three diseases increases with increasing mean monthly temperature in the range 16-29°C, and decreases with increasing mean monthly temperature thereafter. Additionally, for the current fixed mean monthly temperature and rainfall data for Mexico, simulations show maximum transmission activity of all three diseases if the temperature and rainfall values lie in the range 25-26.4°C and 90-128mm, respectively (these values are typically recorded in Mexico during the months of June, July and September). Simulations for two Mexican states (Oaxaca and Chiapas) where the three diseases are endemic show maximum transmission activity for all three diseases when temperature and rainfall lie in the ranges 20-25°C and 51-102mm for Oaxaca (these ranges are recorded during the months of May through September) and 19-21°C and 85-107mm for Chiapas (there ranges are recorded during the months of May, July, August and October), respectively. These simulations suggest suitable time when anti-mosquito control efforts should be intensified in Mexico (and the two selected states).