Modelling Vaccine Strategies for Norovirus Gastroenteritis Open Access
Steele, Molly (2015)
Abstract
Background: Noroviruses are the leading cause of acute gastroenteritis and foodborne diarrheal disease in the United States. Norovirus vaccine development has progressed rapidly in recent years, but critical questions, including which age groups should be vaccinated to maximize population impact, remain to be addressed.
Methods: A deterministic, age-structured compartmental model was developed that tracks norovirus transmission and immunity in the U.S. population. Three age specific transmission parameters (q1-3) were estimated using maximum likelihood and fitting the model to age-specific monthly US hospitalizations between 1996 and 2007. Four vaccine strategies were simulated under the assumption that immunization provides the same duration of protection as natural infection: routine immunization around the time of birth and individuals turning 65 years old, followed by re-vaccination every five years. In initial simulations, vaccine efficacy is assumed to be 50% and vaccine coverage for 0-4 year-olds is assumed to be 90% while vaccine coverage for the 65 year and older age group is assumed to be 65%.
Results: Model outputs achieved good fit to the U.S. hospitalization data, and results indicated that the youngest age group, 0-4 year olds, have the highest susceptibility to norovirus with approximately 3.38 infections resulting from an infection from any age group. The older age groups are less susceptible to infection, as 1.86 and 0.33 infections occur in 5-64 year olds and 65 year and older, respectively, from an infection from any age group. Routine immunization of infants with 90% coverage at equilibrium was predicted to avert 6,318 (a 33% reduction) hospitalizations in 0-4 year olds and 8,974 (15%) hospitalizations in all other age groups annually. Routine immunization of 65 year-olds was estimated to avert 4,480 (16%) hospitalizations in the 65+ age group and 147 (0.4%) hospitalizations in all other age groups annually. In considering total population effects, vaccinating 0-4 and 65+ years was estimated to avert 395 and 72 hospitalizations, respectively, per 100,000 doses administered, with much greater indirect benefits accrued from the infant immunization program.
Conclusion: The modelling analysis demonstrated that population-level impacts of norovirus vaccination may be maximized by vaccinating young children, due to their importance in transmission.
Table of Contents
INTRODUCTION. 1
IMPACT OF NOROVIRUS. 1
CLASSIFICATION. 2
EPIDEMIOLOGY. 2
VACCINE DEVELOPMENT. 4
EPIDEMIOLOGICAL MODELS. 5
MATERIALS & METHODS. 8
COMPARTMENTAL MODEL. 8
MODEL PARAMETERS. 12
MODEL FITTING. 13
VACCINE SCENARIOS. 14
PARAMETER UNCERTAINTY ANALYSIS. 16
RESULTS. 17
MODEL FITTING. 17
VACCINE SCENARIOS. 18
DISCUSSION. 23
WORKS CITED. 31
FIGURES. 40
TABLES. 47
APPENDECES. 53
APPENDIX A. 53
APPENDIX B. 55
APPENDIX C. 56
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