Early Detection of Epidemic GII-4 Norovirus Strains in UK and Malawi: Role of Surveillance of Sporadic Acute Gastroenteritis in Anticipating Global Epidemics

Abstract

Noroviruses are endemic in the human population, and are recognised as a leading cause of acute gastroenteritis worldwide. Although they are a highly diverse group of viruses, genogroup-II genotype-4 (GII-4) noroviruses are the most frequently identified strains worldwide. The predominance of GII-4 norovirus strains is driven by the periodic emergence of antigenic variants capable of evading herd protection. The global molecular epidemiology of emerging GII-4 strains is largely based on data from outbreak surveillance programmes, but the epidemiology of GII-4 strains among sporadic or community cases is far less well studied. To understand the distribution of GII-4 norovirus strains associated with gastroenteritis in the wider population, we characterised the GII-4 norovirus strains detected during studies of sporadic cases of infectious gastroenteritis collected in the UK and Malawi between 1993 and 2009. Our data shows that GII-4 norovirus strains that have emerged as strains of global epidemic importance have circulated in the community up to 18 years before their recognition as pandemic strains associated with increases in outbreaks. These data may suggest that more comprehensive surveillance programmes that incorporate strains associated with sporadic cases may provide a way for early detection of emerging strains with pandemic potential. This may be of particular relevance as vaccines become available.

A norovirus intervariant GII.4 recombinant in Victoria, Australia, June 2016: the next epidemic variant?

“…A key observation in this report is the delay between the first appearance of an epidemic norovirus strain and the subsequent epidemic involving that strain. This observation accords well with the recent findings of Allen et al [ 16 ], who suggest that pandemic strains may circulate at low levels in the community up to several years before their global spread. The concept of delay in norovirus epidemic variant circulation is still poorly understood and clearly requires further investigation.…”

The Vast and Varied Global Burden of Norovirus: Prospects for Prevention and Control

“…In addition to their evolutionary dynamics, there are public health reasons that a successful norovirus vaccine must provide protection against GII.4 viruses: they are the predominant cause of pediatric infections worldwide [ 36 ], they predominate overwhelmingly as a cause of disease amongst the elderly in health care–associated outbreaks, and they result in more severe illness and death [ 37 ]. Studies published in this Collection are consistent with the view that GII.4 viruses predominate globally [ 17 , 25 , 26 ], with rare exception in the last 20 years [ 38 ].…”

“…Most of our understanding of the molecular epidemiology of norovirus comes from outbreak samples. However, Allen et al examined samples from sporadic cases in diverse settings: the UK and Malawi [ 25 ]. Certain GII.4 strains that caused global increases in outbreak activity could be found in sporadic samples in both of these settings many years before becoming globally predominant.…”

GII.4 norovirus recombinant causes gastroenteritis epidemic in Eastern Australia, winter 2017

“…While intermediate or early forms of a new variant may circulate up to 18 years prior to their emergence as an epidemic strain, once present in its epidemic form, a recent study determined that a variant will typically show a delay of 2‐7 months between the first detection of a new GII.4 epidemic variant and the subsequent norovirus epidemic linked to that variant. The study also noted that a newly detected GII.4 recombinant form (GII.P4_NewOrleans_2009/GII.4_Sydney_2012) was first detected in Victoria, Australia, in August 2015 at low frequency and then re‐emerged in June 2016, having undergone genetic change in the capsid region.…”