Within-vector viral dynamics challenges how to model the extrinsic incubation period for major arboviruses: dengue, Zika, and chikungunya

Abstract

Arboviruses represent a significant threat to human, animal, and plant health worldwide. To elucidate transmission, anticipate their spread and efficiently control them, mechanistic modelling has proven its usefulness. However, most models rely on assumptions about how the extrinsic incubation period (EIP) is represented: the intra-vector viral dynamics (IVD), occurring during the EIP, is approximated by a single state. After an average duration, all exposed vectors become infectious. Behind this are hidden two strong hypotheses: (i) EIP is exponentially distributed in the vector population; (ii) viruses successfully cross the infection, dissemination, and transmission barriers in all exposed vectors. To assess these hypotheses, we developed a stochastic compartmental model which represents successive IVD stages, associated to the crossing or not of these three barriers. We calibrated the model using an ABC-SMC (Approximate Bayesian Computation - Sequential Monte Carlo) method with model selection. We systematically searched for literature data on experimental infections of Aedes mosquitoes infected by either dengue, chikungunya, or Zika viruses. We demonstrated the discrepancy between the exponential hypothesis and observed EIP distributions for dengue and Zika viruses and identified more relevant EIP distributions . We also quantified the fraction of infected mosquitoes eventually becoming infectious, highlighting that often only a small fraction crosses the three barriers. This work provides a generic modelling framework applicable to other arboviruses for which similar data are available. Our model can also be coupled to population-scale models to aid future arbovirus control.