Systematic Review and Meta-Analysis of the Global Distribution and Diversity of Norovirus GII.4 Variants Open Access

Ellis, Karen (Summer 2018)

Permanent URL: https://etd.library.emory.edu/concern/etds/4x51hj091?locale=en
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Abstract

 

Noroviruses are the leading cause of outbreaks and cases of non-bacterial acute gastroenteritis (AGE) worldwide. They pose an increasing threat to morbidity and mortality globally, causing 200,000 deaths annually, and contribute a significant burden on health systems in both high- and low-income countries. Noroviruses can be divided into seven genogroups, three of which are associated with human disease and can be further broken down into over 30 genotypes. The vast majority of outbreaks (including all pandemic outbreaks) and sporadic cases of norovirus, however, can be attributed to a single, rapidly-evolving genotype- GII.4, and its many variants. This goal of this study was to describe the global distribution and diversity of GII.4 variants over the time period that they have predominated human norovirus infection (early 1990s-present), and to quantify the effects of these variables on GII.4 diversity. To do this, we conducted a systematic review and meta-analysis of genotyping studies spanning the years of 1995-2016. 41 studies from 26 countries together provided data on 59 GII.4 variants, which were classified into eight pandemic-causing variant types in this study. Simpson’s and Shannon’s diversity indices were used as metrics for GII.4 variant diversity quantification. Linear regression techniques were performed on these indices to model any association between geographic, demographic, and temporal data (collected in the systematic review), and GII.4 diversity. The results of our descriptive analyses corroborated previous observations of the 2-3-year emergence of novel pandemic-causing GII.4 variants and demonstrated a varied pattern of their global distribution. Linear regression analyses indicated a weak positive relationship between GII.4 diversity and age, and a strong positive relationship between GII.4 diversity and time. The results of this review have strong implications for the future of norovirus vaccine development and implementation, specifically indicating possible benefits of targeting certain age groups and the importance of monitoring evolving pandemic variants. Additionally, they highlight the need for systematic norovirus genotype reporting, particularly in low-income environments.

Table of Contents

DISTRIBUTION AGREEMENT…………………………………………………………I

 

APPROVAL SHEET…………………………………………………………………..…II

 

ABSTRACT COVER PAGE……………………………………………………………III

 

ABSTRACT……………………………………………………………………………..IV

 

COVER PAGE……………………………………………………………………………V

 

ACKNOWLEDGEMENTS……………………………………………………………...VI

 

CHAPTER 1: LITERATURE REVIEW………………………………………………….1

 

CHAPTER 2:

a)     TITLE, AUTHOR(S), ABSTRACT……………………………………………..10

b)    INTRODUCTION……………………………………………………………….11

c)     METHODS…………………………………………………………………...….15

d)    RESULTS………………………………………………………………………..20

e)     DISCUSSION……………………………………………………………………25

f)     REFERENCES…………………………………………………………………..31

g)    TABLES…………………………………………………………………………35

h)    FIGURES………………………………………………………………………..40

 

CHAPTER 3: PUBLIC HEALTH IMPLICATIONS……………………………………49

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