A population of bang-bang switches of defective interfering particles makes within-host dynamics of dengue virus controllable

Abstract

The titre of virus in a dengue patient and the duration of this viraemia has a profound effect on whether or not a mosquito will become infected when it feeds on the patient and this, in turn is a key driver of the magnitude of a dengue outbreak. As mosquitoes require 100-1000 times more virus to become infected than a patient, the transmission of dengue virus from a patient to a mosquito is a vulnerability that may be able to be targeted to improve disease control. The intrinsic variability in the within-host dynamics of viraemias is explored for a population of patients using the method of population of models (POMs). A dataset from 207 patients is used to calibrate 20,000 models for the infection kinetics for each of the four dengue virus serotypes. The effect of adding defective dengue virus interfering particles to patients as a therapeutic is evaluated using the calibrated POMs in a bang-bang optimal control setting.\n\nAuthor summaryDengue virions with deletions or defects in their genomes can be recovered from dengue patients. These defective viruses can only replicate with the assistance of fully functional viruses and they reduce the yield of the fully functional viruses. They are known as defective interfering (DI) particles. By administering additional, defined, DI particles to patients it may be possible to reduce the titre and duration of their viraemia. This, in turn may reduce the severity of the disease and the likelihood that dengue virus will be passed from the patient to a mosquito vector. This study estimates the number of DI particles that would need to be administered, and over what period, to have a significant effect on patient viraemia and subsequent dengue fever severity.