What is the duration of immunity to norovirus? A mathematical modeling study Open Access

Simmons, Kirsten Anne (2012)

Permanent URL: https://etd.library.emory.edu/concern/etds/dj52w4980?locale=en%5D
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Abstract

What is the duration of immunity to natural norovirus infection?
A mathematical modeling study
Background

The duration of immunity to norovirus (NoV) is traditionally believed to be on the order of 2-6 months.
However, at any point in time, approximately 30% of the population has acquired immunity. Since
community incidence rates in the general population are approximately 5% per year, we hypothesize
that duration of immunity may be substantially longer.
Methods
We developed a compartmental mathematical model of community NoV transmission based on the
natural history of the disease. Parameter values were obtained from a literature review. The model was
fit to incidence data from England and Wales and seasonality data from the United States using
maximum likelihood. Since there are a range of unknowns regarding NoV transmission, we developed
several scenarios to determine the effect of unknown factors on our estimate of the duration of
immunity.
Results
Our baseline model estimates the duration of immunity to NoV to be 5.1 (95% CI: 2.9 - 9.6) years. In
other scenarios, the duration of immunity ranges from 5.1 to 6.5 years.
Conclusion
Our analysis suggests that the duration of immunity to NoV is significantly longer than previously
thought. This finding argues for the continued development of vaccines for NoV, since a short duration
of immunity has been considered a major obstacle.
Keywords: norovirus, duration of immunity, mathematical model, vaccine development

Table of Contents


Table of Contents
Introduction ..................................................................................................................................... 1

Disease Burden ......................................................................................................................................... 1
Virus and Host ........................................................................................................................................... 3
Figure 1: Norovirus Genetic Tree ............................................................................................................ 3
Immunity ................................................................................................................................................... 4
Methods ........................................................................................................................................... 7
Model Design ............................................................................................................................................ 7
Figure 2: Model Schematic without Genetic Resistance ......................................................................... 7
Figure 3: Model Schematic with Genetic Resistance ............................................................................... 8
Model Equations ..................................................................................................................................... 8
Seasonality ................................................................................................................................................ 9
Alternate Model Structures Considered ................................................................................................. 10
Fitting Data .............................................................................................................................................. 10
Table 1: Literature Review for Proportion of Population Immune ........................................................ 11
Contact Rates .......................................................................................................................................... 11
Table 2: Contact Rates Used in Model .................................................................................................. 11
Model Scenarios ...................................................................................................................................... 12
Table 3: Static Model Inputs and Their Sources .................................................................................. 13
Upper and Lower Limits .......................................................................................................................... 13
Results ............................................................................................................................................ 15
Table 4: Fitted Parameter Output for All Scenarios ............................................................................ 17
Table 5: Proportions Aysmptomatic, Recovered and Annual Incidence by Age Group ....................... 18
Figure 4: Baseline and Scenario Fits to Available Data ....................................................................... 19
Figure 5: Duration of Immunity by Scenario with Upper and Lower Bounds ...................................... 10
Discussion ...................................................................................................................................... 21
Works Cited .............................................................................................................................................. 25

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