Janet Mans

Emergence of a novel GII.17 norovirus – end of the GII.4 era?

In the winter of 2014/15 a novel GII.P17-GII.17 norovirus strain (GII.17 Kawasaki 2014) emerged, as a major cause of gastroenteritis outbreaks in China and Japan. Since their emergence these novel GII.P17-GII.17 viruses have replaced the previously dominant GII.4 genotype Sydney 2012 variant in some areas in Asia but were only detected in a limited number of cases on other continents. This perspective provides an overview of the available information on GII.17 viruses in order to gain insight in the viral and host characteristics of this norovirus genotype. We further discuss the emergence of this novel GII.P17-GII.17 norovirus in context of current knowledge on the epidemiology of noroviruses. It remains to be seen if the currently dominant norovirus strain GII.4 Sydney 2012 will be replaced in other parts of the world. Nevertheless, the public health community and surveillance systems need to be prepared in case of a potential increase of norovirus activity in the next seasons caused by this novel GII.P17-GII.17 norovirus.

Diverse norovirus genotypes identified in sewage-polluted river water in South Africa

This study aimed to assess norovirus (NoV) contamination and genotype diversity in surface water in Gauteng, South Africa. Between January 2008 and December 2010, three rivers, namely Klip, Suikerbosrant, and Rietspruit were monitored for NoV genogroup (G)I and GII. Viruses were recovered using the glass wool adsorption-elution technique and detected by real-time reverse transcription-polymerase chain reaction. From 2008 to 2010, NoVs were detected in 66% (70/106) of Klip river samples. The Rietspruit and Suikerbosrant rivers were contaminated with NoV in 95% (20/21) and 21% (5/24) of samples, respectively. NoV-positive samples comprised of 33% GI, 29% GII and 38% of both GI and GII strains. Based on partial capsid gene analysis (region C), 16 NoV genotypes (6 GI, 10 GII) were identified. The major genotypes detected were GI.4, GI.5 and GII.4. These rivers could be a potential source of NoV infection for communities using the water for domestic or recreational purposes.

Novel norovirus recombinants detected in South Africa

BackgroundNoroviruses (NoV) are the leading cause of viral gastroenteritis worldwide. Recombination frequently occurs within and between NoV genotypes and recombinants have been implicated in sporadic cases, outbreaks and pandemics of NoV. There is a lack of data on NoV recombinants in Africa and therefore their presence and diversity was investigated in South Africa (SA).ResultsBetween 2010 and 2013, eleven types of NoV recombinants were identified in SA. Amplification of the polymerase/capsid region spanning the ORF1/2 junction and phylogenetic analysis confirmed each of the recombinant types. SimPlot and maximum x2 analysis indicated that all recombinants had a breakpoint in the region of the ORF1/2 junction (P < 0.05). The majority (9/11) were intergenotype recombinants, but two intragenotype GII.4 recombinants were characterised. Three combinations represent novel recombinants namely GII.P not assigned (NA)/GII.3, GII.P4 New Orleans 2009/GII.4 NA and GII.P16/GII.17. Several widely reported recombinants were identified and included GII.P21/GII.2, GII.P21/GII.3, GII.Pe/GII.4 Sydney 2012, and GII.Pg/GII.12. Other recombinants that were identified were GII.Pg/GII.1, GII.Pe/GII.4 Osaka 2007, GII.P4 New Orleans 2009/GII.4 Sydney 2012, GII.P7/GII.6. To date these recombinant types all have a reportedly restricted geographic distribution. This is the first report of the GII.P4 New Orleans 2009/GII.4 Sydney 2012 recombinant in Africa.ConclusionsOver the past four years, remarkably diverse NoV recombinants have been circulating in SA. Pandemic strains such as the GII.Pe/GII.4 Sydney 2012 recombinant co-circulated with novel and emerging recombinant strains. Combined polymerase- and capsid-based NoV genotyping is essential to determine the true diversity and global prevalence of these viruses.

Human calicivirus diversity in wastewater in South Africa

To investigate the diversity of human caliciviruses (HuCVs) in wastewater from small‐ to medium‐sized communities in five provinces of South Africa (SA).

Norovirus Epidemiology in Africa: A Review

Norovirus (NoV) is recognised as a leading cause of gastroenteritis worldwide across all age groups. The prevalence and diversity of NoVs in many African countries is still unknown, although early sero-prevalence studies indicated widespread early infection. Reports on NoVs in Africa vary widely in terms of study duration, population groups and size, inclusion of asymptomatic controls, as well as genotyping information. This review provides an estimate of NoV prevalence and distribution of genotypes of NoVs in Africa. Inclusion criteria for the review were study duration of at least 6 months, population size of >50 and diagnosis by RT-PCR. As regions used for genotyping varied, or genotyping was not always performed, this was not considered as an inclusion criteria. A literature search containing the terms norovirus+Africa yielded 74 publications. Of these 19 studies from 14 out of the 54 countries in Africa met the inclusion criteria. Data from studies not meeting the inclusion criteria, based on sample size or short duration, were included as discussion points. The majority of studies published focused on children, under five years of age, hospitalised with acute gastroenteritis. The mean overall prevalence was 13.5% (range 0.8–25.5%) in children with gastroenteritis and 9.7% (range 7–31%) in asymptomatic controls, where tested. NoV GII.4 was the predominant genotype identified in most of the studies that presented genotyping data. Other prevalent genotypes detected included GII.3 and GII.6. In conclusion, NoV is a common pathogen in children with diarrhoea in Africa, with considerable carriage in asymptomatic children. There is however, a paucity of data on NoV infection in adults.

Norovirus diversity in children with gastroenteritis in South Africa from 2009 to 2013: GII.4 variants and recombinant strains predominate

From 2009 to 2013 the diversity of noroviruses (NoVs) in children (⩽5 years) hospitalized with gastroenteritis in South Africa was investigated. NoVs were genotyped based on nucleotide sequence analyses of partial RNA-dependent RNA polymerase (RdRp) and capsid genes. Seventeen RdRp genotypes (GI.P2, GI.P3, GI.P6, GI.P7, GI.P not assigned (NA), GI.Pb, GI.Pf, GII.P2, GII.P4, GII.P7, GII.P13, GII.P16, GII.P21, GII.Pc, GII.Pe, GII.Pg, GII.PNA) and 20 capsid genotypes (GI.1, GI.2, GI.3, GI.5, GI.6, GI.7, GI.NA, GII.1, GII.2, GII.3, GII.4, GII.6, GII.7, GII.10, GII.12, GII.13, GII.14, GII.16, GII.17, GII.21) were identified. The combined RdRp/capsid genotype was determined for 275 GII strains. Fifteen confirmed recombinant NoV strains circulated during the study period. NoV GII.P4/GII.4 (47%) and GII.Pe/GII.4 (18%) predominated, followed by GII.PNA/GII.3 (10%) and GII.P21/GII.3 (7%). Other prevalent strains included GII.Pg/GII.12 (6%) and GII.Pg/GII.1 (3%). Two novel recombinants, GII.Pg/GII.2 and GII.Pg/GII.10 were identified. In 2013 the replacement of GII.4 New Orleans 2009 and GII.P21/GII.3, which predominated during the early part of the study, with GII.4 Sydney 2012 and GII.PNA/GII.3 was observed. This study presents the most comprehensive recent data on NoV diversity in Africa.

Human caliciviruses detected in HIV-seropositive children in Kenya.

The human caliciviruses (HuCVs) are important causes of gastroenteritis worldwide. Norovirus (NoV) and sapovirus (SaV) have been detected in HIV‐seropositive children but the genetic diversity of HuCVs circulating in these individuals is largely unknown. In this study the prevalence and genotype diversity of HuCVs circulating in Kenyan HIV‐positive children, with or without diarrhea, from the year 1999 to 2000 was investigated. The overall prevalence of HuCVs was 19% with NoV predominating at 17% (18/105) and SaV present in 5.7% (6/105) of specimens. Human CVs were detected in both symptomatic (24%) and asymptomatic (16%) children. Co‐infections with other enteric viruses were detected in 21.6% of children with diarrhea but only in 4.4% of children without diarrhea. Remarkable genetic diversity was observed with 12 genotypes (7 NoV, 5 SaV) being identified in 20 HuCV‐infected children. NoV genogroup II (GII) strains predominated with GII.2 and GII.4 each representing 27% of the NoV‐positive strains. The GII.4 strain was most closely related to the nonepidemic GII.4 Kaiso 2003 variant. Other NoV genotypes detected were GI.3, GII.6, GII.12, GII.14, and GII.17. Five different SaV genotypes (GI.2, GI.6, GII.1, GII.2, and GII.4) were characterized from six specimens. Diarrheal symptoms were not associated with any specific HuCV genotype. Overall the HuCV genotype distribution detected in this study reflects those in other studies worldwide. The strains detected are closely related to genotypes that have circulated on several continents since the year 2000. J. Med. Virol. 86:75–81, 2014.

Global spread of norovirus GII.17 Kawasaki 308, 2014–2016

Analysis of complete capsid sequences of the emerging norovirus GII.17 Kawasaki 308 from 13 countries demonstrated that they originated from a single haplotype since the initial emergence in China in late 2014. Global spread of a sublineage SL2 was identified. A new sublineage SL3 emerged in China in 2016.

Molecular surveillance of norovirus, 2005-16: an epidemiological analysis of data collected from the NoroNet network

BACKGROUND The development of a vaccine for norovirus requires a detailed understanding of global genetic diversity of noroviruses. We analysed their epidemiology and diversity using surveillance data from the NoroNet network. METHODS We included genetic sequences of norovirus specimens obtained from outbreak investigations and sporadic gastroenteritis cases between 2005 and 2016 in Europe, Asia, Oceania, and Africa. We genotyped norovirus sequences and analysed sequences that overlapped at open reading frame (ORF) 1 and ORF2. Additionally, we assessed the sampling date and country of origin of the first reported sequence to assess when and where novel drift variants originated. FINDINGS We analysed 16 635 norovirus sequences submitted between Jan 1, 2005, to Nov 17, 2016, of which 1372 (8·2%) sequences belonged to genotype GI, 15 256 (91·7%) to GII, and seven (<0·1%) to GIV.1. During this period, 26 different norovirus capsid genotypes circulated and 22 different recombinant genomes were found. GII.4 drift variants emerged with 2-3-year periodicity up to 2012, but not afterwards. Instead, the GII.4 Sydney capsid seems to persist through recombination, with a novel recombinant of GII.P16-GII.4 Sydney 2012 variant detected in 2014 in Germany (n=1) and the Netherlands (n=1), and again in 2016 in Japan (n=2), China (n=8), and the Netherlands (n=3). The novel GII.P17-GII.17, first reported in Asia in 2014, has circulated widely in Europe in 2015-16 (GII.P17 made up a highly variable proportion of all sequences in each country [median 11·3%, range 4·2-53·9], as did GII.17 [median 6·3%, range 0-44·5]). GII.4 viruses were more common in outbreaks in health-care settings (2239 [37·2%] of 6022 entries) compared with other genotypes (101 [12·5%] of 809 entries for GI and 263 [13·5%] of 1941 entries for GII non-GII.Pe-GII.4 or GII.P4-GII.4). INTERPRETATION Continuous changes in the global norovirus genetic diversity highlight the need for sustained global norovirus surveillance, including assessment of possible immune escape and evolution by recombination, to provide a full overview of norovirus epidemiology for future vaccine policy decisions. FUNDING European Unions Horizon 2020 grant COMPARE, ZonMw TOP grant, the Virgo Consortium funded by the Dutch Government, and the Hungarian Scientific Research Fund.

Comparative analysis of South African norovirus GII.4 strains identifies minor recombinant variants.

Recombination within the norovirus (NoV) GII.4 genotype is well documented as a mechanism by which novel variants evolve. Norovirus GII.4 has been the predominant NoV genotype detected in South Africa (SA) in recent years and putative NoV recombinants were previously identified in SA based on partial regions of the viral genome. The objective of this study was to determine the complete genome sequence of representative NoV GII.4 variants that have circulated in SA between 2009 and 2013 and to compare major and minor GII.4 variants based on nucleotide sequence. The complete genomes of 11/27 GII.4 strains could be amplified in three or five overlapping segments, these included major variants New_Orleans_2009 and Sydney_2012 as well as three types of minor GII.4 variants. Phylogenetic and recombination analysis identified GII.4 recombinants with breakpoints located at or near the ORF1/2 junction. Apart from recombinants already recognised as major variants (GII.P4 New_Orleans_2009/GII.4 Sydney_2012 (n=2) and GII.Pe/GII.4 Sydney_2012 (n=2)) four further recombinant strains were detected (GII.P4 New_Orleans_2009/GII.4 Hunter_2004 (n=1) and GII.P4 Yerseke_2006a/GII.4 Apeldoorn_2007 (n=3)) that were attributed to three distinct minor variants. The encoded proteins with the highest diversity were p48 (Nterm), p22, VP1 and VP2. Analysis of antigenic sites in VP1 revealed mutations at epitopes A, B, C, D and E, with epitopes A and D being most variable. The high variation at epitope D was reflected in structural differences in models of GII.4 variants in the epitope D loop region (aa 393-395). Major and minor variants could not be distinguished based on specific sequence differences. HBGA-binding studies will be necessary to assess the effect of the observed amino acid differences in the P2 domain of these GII.4 strains.