Minimizing Severity of Dengue Serotype 1 Infection By Transmissible Interfering Particles

Abstract

Inhibition of dengue wild{type virus (DENV) by transmissible interfering dengue particles (DENV{TIPs) is seen in some in vitro studies, and it is hypothesized that DENV{TIPs may be used as a therapeutic agent. However, the efficiency of DENV{TIPs in limiting DENV infection in patients is yet to be explored at an epidemiological scale. Using data collected from dengue serotype 1 infected patients from Vietnam, we model how DENV replicates in an infected patient and show how effective DENV{TIPs are in controlling that replication. Our analyses are based on Bayesian statistical modeling approach. Our results determine that the initial DENV viral load is sufficient to recreate the observed variation between patients. We do not find a significant difference between primary and secondary types of infection. We conclude that, when the effectiveness of DENV{TIPs in inhibiting DENV from coinfected cells is at least 80%, a dose as high as 10^12 copies per milliliter of blood is required to reduce duration of infection and peak virus level at any time point of infection. Our results are of use in the evaluation of DENV{TIPs as a potential antiviral agent.

Keywords: Dengue, transmissible interfering particles, Bayesian hierarchical modeling, within-host dynamics, anti-viral