Measles Infection Dose Responses: Insights from Mathematical Modeling

by Anet Anelone & Hannah Clapham 

The measles virus (MV) is highly contagious and affects the whole body, including the skin and the immune system. As MV infection dose increases above one infectious particle, the peak of infectious viral load occurs sooner, yet its magnitude remains constant. It is important to improve understanding of measles, in part due to the re-emergence of measles outbreak worldwide, and a lack of research. We investigated mechanisms determining the outcomes of measles infection doses. We evaluated relevant biological hypotheses, and their respective mathematical formulations, to describe and fit data on the time course of measles infectious viral load in the peripheral blood of monkeys, following experimental measles infection with different doses. When MV infection dose increases, the initial viral load, and the initial number of responding immune cells increase. This mechanism decreases the time it takes for immune cells to control and remove infectious viral load. This mechanism also underpins the dose-independent magnitudes for measles viral load, and the loss of immune cells. Together, these findings suggest that the outcome of measles depends on how the immune system responds to incoming MV right from the beginning. This work encourages prevention, vaccination, and early diagnosis of measles.

Caption: Measles infection dose responses: insights from mathematical modeling. Top: Model-data fits for acute viremia in response to changes in MV infection doses. using model parameterizations and assumptions in Table in the paper. 104, 103, 102, 10 and 1 TCID50 correspond to red diamonds, blue stars, orange triangles, magenta dots, and green squares respectively. The solid lines represent the trajectories generated by the proposed model parameterization. The shapes represent data. The dark grey dotted dashed line represents the limit of detection < 0.3. Bottom: Cartoon illustrating that the healthy body adjusts the response of the immune system to remove measles infectious particles sooner when the measles infection dose increases; however, the peak viral load remains constant