Global Trends in Norovirus Genotype Distribution Among Children With Acute Gastroenteritis

Jennifer L. Cannon; Joseph Bonifacio; Filemon Bucardo; Javier Buesa; Leesa Bruggink; Martin Chi-Wai Chan; Tulio M. Fumian; Sidhartha Giri; Mark D. Gonzalez; Joanne Hewitt; Jih-Hui Lin; Janet Mans; Christian Muñoz; Chao-Yang Pan; Xiao-Li Pang; Corinna Pietsch; Mustafiz Rahman; Naomi Sakon; Rangaraj Selvarangan; Hannah Browne; Leslie Barclay; Jan Vinjé

Disclosures

Emerging Infectious Diseases. 2021;27(5):1438-1445. 

In This Article

Abstract and Introduction

Abstract

Noroviruses are a leading cause of acute gastroenteritis (AGE) among adults and children worldwide. NoroSurv is a global network for norovirus strain surveillance among children <5 years of age with AGE. Participants in 16 countries across 6 continents used standardized protocols for dual typing (genotype and polymerase type) and uploaded 1,325 dual-typed sequences to the NoroSurv web portal during 2016–2020. More than 50% of submitted sequences were GII.4 Sydney[P16] or GII.4 Sydney[P31] strains. Other common strains included GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses. In total, 22 genotypes and 36 dual types, including GII.3 and GII.20 viruses with rarely reported polymerase types, were detected, reflecting high strain diversity. Surveillance data captured in NoroSurv enables the monitoring of trends in norovirus strains associated childhood AGE throughout the world on a near real-time basis.

Introduction

Globally, noroviruses are associated with ≈20% of acute gastroenteritis (AGE) cases, causing an estimated 685 million episodes and 210,000 deaths each year.[1,2] By 2 years of age, children have probably had ≥1 norovirus infection.[3–5] Children in this age group are at risk for severe illness, prolonged symptoms, and infection by multiple strains.[3–5] Sporadic illnesses among children might contribute to community transmission and outbreaks among all age groups.[6] In countries with successful rotavirus vaccination campaigns, norovirus is now the most common cause of pediatric AGE requiring medical attention.[7–9] As of January 2021, vaccines for norovirus are in clinical trials (phase I and II) and developmental stages.[10] However, their design is challenging because of the high genetic diversity of noroviruses and incomplete understanding of cross-protective immunity.[11] If candidate vaccines are successful at blocking onward transmission events, norovirus vaccination will benefit children and unvaccinated persons across all age groups.[12]

Norovirus classification is based on amino acid diversity of the major capsid protein (encoded by open reading frame [ORF] 2), which is also the primary neutralization site for antibodies produced after norovirus infection or vaccination.[13–15] Noroviruses are classified into 10 genogroups, GI–GX, and ≥48 genotypes: 9 genotypes in the GI genogroup, 26 in GII, 3 in GIII, 2 in GIV, 2 in GV, 2 in GVI, 1 in GVII, 1 in GVIII, 1 in GIX, and 1 in GX.[16] ORF1 encodes the viral nonstructural proteins including the polymerase, which is classified into ≥60 polymerase types (P-types).[16] Much about the evolutionary role of recombination among noroviruses, which occurs primarily at the ORF1/ORF2 junction, remains unknown.[17–19] Norovirus classification was recently updated to include typing of the polymerase region.[16] This dual typing strategy considers the genotype encoding the major capsid protein and the P-type encoding the polymerase region.[16] A short genomic region spanning the 3′ end of the polymerase gene through the 5′ end of the capsid gene is the basis for sequence-based dual typing.[20]

Genogroup II genotype 4 (GII.4) viruses have been the most frequently detected noroviruses globally since the mid-1990s, before which GII.3 viruses were dominant.[13,21,22] New GII.4 variants regularly emerge and spread across the globe and often contribute to increased illness and death, especially in healthcare settings.[23–25] During 2002–2012, new GII.4 variants with antigenically distinct capsid epitopes, which enable the viruses to escape neutralizing antibodies, emerged and replaced previous variants every 2–3 years.[15] These changes indicate that norovirus vaccines might need to be updated regularly. Despite recent recombination events resulting in the global spread of GII.4 Sydney viruses with a novel P16 polymerase, no new variant causing widespread infections has emerged since 2012.[20,26,27] Although GII.4 strains are the most common strains detected among all age groups, non-GII.4 strains, such as GII.2, GII.3, and GII.6 viruses, are common causes of sporadic cases and illness in young children.[6,28–32] Rare strains[4] and GII.4 variants can circulate, especially among children, for years before spreading globally among all age groups.[33,34] Consequently, children might be an important reservoir for emerging norovirus strains against which little or no population immunity exists.

NoroSurv (https://www.norosurv.org), which is maintained by the Centers for Disease Control and Prevention (Atlanta, Georgia, USA), is a global pediatric norovirus strain surveillance network for children <5 years of age with medically attended AGE and can only be accessed by registered NoroSurv laboratories. Surveillance of norovirus strains infecting children is crucial for monitoring the emergence of new or rare strains and for developing vaccines that protect against the most common strains.

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