Fitting varicella zoster virus dynamics
Varicella zoster virus (VZV) is a herpesvirus that causes chickenpox and shingles. The biological mechanisms underpinning the multi-decadal latency of VZV in the body and subsequent viral reactivation---which occurs in approximately 30% of individuals---are largely unknown. Because chickenpox and shingles are endemic worldwide, understanding the relationship between VZV transmission and reactivation is important for informing disease treatment and control. While chickenpox is a vaccine-preventable childhood disease with a rich legacy of research, shingles is not a notifiable disease in most countries. To date, population-level studies of shingles have had to rely on small-scale hospital or community-level datasets. Here, we examined chickenpox and shingles notifications from Thailand and found strong seasonal incidence in both diseases, with a 3-month lag between peak chickenpox transmission season and peak shingles reactivation. We tested and fit 14 mathematical models examining the biological drivers of chickenpox and shingles over an 8-year period to estimate rates of VZV transmission, reactivation, and immunity boosting, wherein re-exposure to VZV boosts VZV-specific immunity to reinforce protection against shingles. The models suggested the seasonal cycles of chickenpox and shingles have different underlying mechanisms, with ultraviolet radiation (UV) being correlated with shingles reactivation.
This work was recently accepted in the American Journal of Epidemiology
This work was recently accepted in the American Journal of Epidemiology
Above: Chickenpox and shingles cases in Thailand with complementary UV covariates. (A) Monthly log-detrended cases of chickenpox (blue) and shingles (red). UV radiation shown in orange for the corresponding time period. Vertical dotted lines represent the end of the year. (B) Boxplot of monthly log-detrended chickenpox cases in Thailand. (C) Boxplot of monthly log-detrended shingles cases in Thailand. (D) Correlation between monthly log-detrended shingles cases and monthly UV.
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Above: (top) Biological structure of the fourteen model variants fit to the chickenpox and shingles data from Thailand. Model schematic, model variants differed in the (i) and (ii) parameters which can be seen in the bottom panels. A single seasonal driver was fit for each chickenpox and shingles (e.g. Model 11: Term-Time forcing - children in or out of school for chickenpox and a B-Spline for shingles, without immunity boosting).
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Results
Right: Comparison of simulated cases of chickenpox and shingles from the best fit model with monthly log-detrended clinical cases in Thailand 2003-2010. (a) Reported log-detrended cases of chickenpox (black) with 2500 fitted simulations (blue) shown through 2010. (b) Maximum likelihood (B-spline) estimate of the monthly seasonal forcing for chickenpox from the best fit model (black), and school terms for Thailand (green). (c) Reported log-detrended cases of shingles (black) with the 2500 fitted simulations (red) through 2010. (d) Maximum likelihood (B-spline) estimate of the monthly seasonal forcing for shingles from the best fit model (red), and mean monthly UV values for Thailand (orange).
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