The emergence of severe acute respiratory syndrome 2 (SARS-CoV-2) variants of concern (VOCs), with mutations linked to increased transmissibility, vaccine escape and virulence, has necessitated the widespread genomic surveillance of SARS-CoV-2. This has placed a strain on global sequencing capacity, especially in areas lacking the resources for large scale sequencing activities. Here we have developed three separate multiplex high-resolution melting assays to enable the identification of Alpha, Beta, Delta and Omicron VOCs. The assays were evaluated against whole genome sequencing on upper-respiratory swab samples collected during the Alpha, Delta and Omicron [BA.1] waves of the UK pandemic. The sensitivities of the eight individual primer sets were all 100%, and specificity ranged from 94.6 to 100%. The multiplex HRM assays have potential as a tool for high throughput surveillance of SARS-CoV-2 VOCs, particularly in areas with limited genomics facilities.

Human norovirus is the leading cause of acute gastroenteritis. Young children and the elderly bear the great-est burden of disease, representing more than 200,000 deaths annually. Infection prevalence peaks at younger than 2 years and is driven by novel GII.4 variants that emerge and spread globally. Using a surrogate neutralization assay, we characterize the evolution of the serological neutralizing antibody (nAb) landscape in young children as they transition between sequential GII.4 pandemic variants. Following upsurge of the replacement variant, antigenic cartography illustrates remodeling of the nAb landscape to the new variant accompanied by improved nAb titer. However, nAb relative avidity remains focused on the preceding variant. These data support immune imprinting as a mechanism of immune evasion and GII.4 virus persistence across a population. Understanding the complexities of immunity to rapidly evolving and co-circulating viral variants, like those of norovirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), and dengue viruses, will fundamentally inform vaccine design for emerging pathogens.

Acute gastroenteritis (AGE) is a disease of global public health importance. Recent studies show that children with AGE have an altered gut microbiota relative to non-AGE controls. Yet, how the gut microbiota differs in Ghanaian children with and without AGE remains unclear. Here, we explore the 16S rRNA gene-based faecal microbiota profiles of Ghanaian children five years of age and younger, comprising 57 AGE cases and 50 healthy controls. We found that AGE cases were associated with lower microbial diversity and altered microbial sequence profiles relative to the controls. The faecal microbiota of AGE cases was enriched for disease-associated bacterial genera, including Enterococcus, Streptococcus, and Staphylococcus. In contrast, the faecal microbiota of controls was enriched for potentially beneficial genera, including Faecalibacterium, Prevotella, Ruminococcus, and Bacteroides. Lastly, distinct microbial correlation network characteristics were observed between AGE cases and controls, thereby supporting broad differences in faecal microbiota structure. Altogether, we show that the faecal microbiota of Ghanaian children with AGE differ from controls and are enriched for bacterial genera increasingly associated with diseases.

In our model, preepidemic human norovirus variants harbor genetic diversification that translates into novel antigenic features without compromising viral fitness. Through surveillance, we identified two viruses fitting this profile, forming long branches on a phylogenetic tree.

AIMS:Norovirus remains the most significant virological risk that is transmitted via food and the environment to cause acute gastroenteritis. This study aimed to investigate the hypothesis that the contamination of the commercial food production environment with norovirus will be higher in premises that have recently reported a foodborne norovirus outbreak than those that have not.METHODS:Sampling of commercial food production environments was carried out across a 16-month period between January 2015 and April 2016 in the South East and the North West of England by local authority environmental health departments as part of routine surveillance visits to premises. A total of 2982 samples, 2038 virological and 944 bacteriological, were collected from 256 premises. Sixteen of these premises, six from South East and ten from North West England, were sampled as part of a public health outbreak investigation.RESULTS & CONCLUSIONS:Overall, 2038 swabs were submitted for norovirus testing, with an average of eight swabs per premises (range 4 to 23) and a median of seven. Of the premises sampled, 11.7% (30/256) yielded at least one norovirus-positive sample (environmental, and/or food handler hand swab), and 2.5% of the swabs were positive for norovirus. A peak in the positivity rate was seen in the South East in April 2016. No associations were found between norovirus positivity and bacteriology indicators, or between bacteriology indicators and hygiene ratings.SIGNIFICANCE AND IMPACT OF STUDY:This study demonstrates that food premises and food handlers remain a potential source of norovirus transmission and outbreaks.

Human norovirus is a leading cause of acute gastroenteritis, driven by antigenic variants within the GII.4 genotype. Antibody responses to GII.4 vaccination in adults are shaped by immune memory. How children without extensive immune memory will respond to GII.4 vaccination has not been reported. Here, we characterized the GII.4 neutralizing antibody (nAb) landscape following natural infection using a surrogate assay and antigenic site chimera virus-like particles. We demonstrate that the nAb landscape changes with age and virus exposure. Among sites A, C, and G, nAbs from first infections are focused on sites A and C. As immunity develops with age/exposure, site A is supplemented with antibodies that bridge site A to sites C and G. Cross-site nAbs continue to develop into adulthood, accompanied by an increase in nAb to site G. Continued exposure to GII.4 2012 Sydney correlated with a shift to co-dominance of sites A and G. Furthermore, site G nAbs correlated with the broadening of nAb titer across antigenically divergent variants. These data describe fundamental steps in the development of immunity to GII.4 over a lifetime, and illustrate how the antigenicity of one pandemic variant could influence the pandemic potential of another variant through the redirection of immunodominant epitopes.

Standardised molecular methods are available for the detection of norovirus from water and specific food items. Detection of norovirus from stool samples also relies on molecular methods, but differences exist between nucleic acid extraction, reverse transcription, and amplification strategies recommended by the ISO 15216-1:2017, and those employed in clinical laboratories. Here, we conduct a direct comparison of two methods for the detection and quantitation of norovirus from a stool sample and from artificially contaminated swabs. We also compare use of linear dsDNA standards as recommended in ISO 15216:2017 against an in vitro-transcribed single-stranded RNA (ssRNA) for estimation of norovirus genome copy number. Our results show that the two methods have comparable sensitivity for the detection of norovirus RNA from a clinical sample or swab. The use of a ssRNA standard revealed that quantitation performed against a linear dsDNA standard consistently underestimated the genome copy numbers by 1.5 to 2 log due to the relative inefficiency of the reverse transcription step. This has important implications for the estimation of the sensitivity of norovirus detection methods, comparability of results across sites, and assessment of viral loads that may be clinically significant or estimated to constitute infectious doses.

Crimean-Congo hemorrhagic fever virus (CCHFV) is the most geographically widespread of the tick-borne viruses. However, African strains of CCHFV are poorly represented in sequence databases. In addition, almost all sequence data collected to date have been obtained from cases of human disease, while information regarding the circulation of the virus in tick and animal reservoirs is severely lacking. Here, we characterize the complete coding region of a novel CCHFV strain, detected in African blue ticks (Rhipicephalus (Boophilus) decoloratus) feeding on cattle in an abattoir in Kampala, Uganda. These cattle originated from a farm in Mbarara, a major cattle-trading hub for much of Uganda. Phylogenetic analysis indicates that the newly sequenced strain belongs to the African genotype II clade, which predominantly contains the sequences of strains isolated from West Africa in the 1950s, and South Africa in the 1980s. Whilst the viral S (nucleoprotein) and L (RNA polymerase) genome segments shared >90% nucleotide similarity with previously reported genotype II strains, the glycoprotein-coding M segment shared only 80% nucleotide similarity with the next most closely related strains, which were derived from ticks in Western India and Northern China. This genome segment also displayed a large number of non-synonymous mutations previously unreported in the genotype II strains. Characterization of this novel strain adds to our limited understanding of the natural diversity of CCHFV circulating in both ticks and in Africa. Such data can be used to inform the design of vaccines and diagnostics, as well as studies exploring the epidemiology and evolution of the virus for the establishment of future CCHFV control strategies.

Human noroviruses (HuNoVs) circulate globally, affect all age groups and place a substantial burden upon health services. High genetic diversity leading to antigenic variation plays a significant role in HuNoV epidemiology, driving periodic global emergence of epidemic variants. Studies have suggested that immunocompromised individuals may be a reservoir for such epidemic variants, but studies investigating the diversity and emergence of HuNoV variants in immunocompetent individuals are underrepresented. To address this, we sequenced the genomes of HuNoVs present in samples collected longitudinally from one immunocompetent (acute infection) and one immunocompromised (chronic infection) patient. A broadly reactive HuNoV capture-based method was used to concentrate the virus present in these specimens prior to massively parallel sequencing to recover near complete viral genomes. Using a novel bioinformatics pipeline, we demonstrated that persistent minor alleles were present in both acute and chronic infections, and that minor allele frequencies represented a larger proportion of the population during chronic infection. In acute infection, minor alleles were more evenly spread across the genome, although present at much lower frequencies, and therefore difficult to discern from error. By contrast, in the chronic infection, more minor alleles were present in the minor structural protein. No non-synonymous minor alleles were detected in the major structural protein over the short sampling period of the HuNoV chronic infection, suggesting where immune pressure is variable or non-existent, epidemic variants could emerge over longer periods of infection by random chance.

Foodborne outbreaks associated with transmission of norovirus are increasingly becoming a public health concern. Foods can be contaminated with faecal material at the point of production or during food preparation, in both the home and in commercial premises. Transmission of norovirus occurs through the faecal-oral route, either via person-to-person contact or through faecal-contamination of food, water, or environmental surfaces. Understanding the role and pathways of norovirus transmission – either via food handlers' hands, contaminated foods or the environment – remains a key public health priority to reduce the burden of norovirus-associated gastroenteritis. However the proportion of norovirus that is typically transferred remains unknown. Understanding this is necessary to estimate the risk of infection and the burden of gastroenteritis caused by norovirus.In this paper we present a novel method of capture, concentration and molecular detection of norovirus from a wider range of complex food matrices than those demonstrated in existing published methods. We demonstrate that this method can be used as a tool to detect and quantify norovirus from naturally contaminated food, and for monitoring norovirus transfer between food handlers' gloved hands, food or the environment. We measure the effect of introducing contamination at different food production process stages, to the final food product, to determine whether this could cause infection and disease. Between 5.9 and 6.3 Log10 cDNA copies/μl of norovirus GII were inoculated onto food handlers' gloved hands, food or the environment and 1.1–7.4% of norovirus contamination was recovered from all samples tested. When interpreted quantitatively, this percentage equates to levels predicted to be sufficient to cause infection and disease through consumption of the final food product, demonstrating a public health risk. Overall detection and quantification of norovirus from foods, food handlers' gloved hands and the environment, when suspected to be implicated in foodborne transmissions, is paramount for appropriate outbreak investigation.

Since the emergence and spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused the COVID-19 pandemic, many countries have rapidly expanded their viral surveillance systems. Wastewater sampling has been increasingly implemented, as substantial quantities of SARS-CoV-2 are shed in the stool of infected individuals.1Xu Y Li X Zhu B et al.Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding.Nat Med. 2020; 26: 502-505Crossref PubMed Scopus (1024) Google Scholar So far, wastewater sampling has retrospectively shown that virus is present in cities several months before large COVID-19 outbreaks,2Kelland K Italy sewage study suggests COVID-19 was there in December 2019. Reuters, June 19, 2020https://uk.reuters.com/article/us-health-coronavirus-italy-sewage-idUKKBN23Q1J9Date accessed: June 22, 2020Google Scholar that there is a correlation between quantitative RT-PCR data and the reported incidence of cases,3Wu F Xiao A Zhang J et al.SARS-CoV-2 titers in wastewater are higher than expected from clinically confirmed cases.medRxiv. 2020; (published online April 7.) (preprint)https://doi.org/10.1101/2020.04.05.20051540Google Scholar and that the presence of SARS-CoV-2 in wastewater is ubiquitous.4Medema G Heijnen L Elsinga G Italiaander R Brouwer A Presence of SARS-Coronavirus-2 in sewage.medRxiv. 2020; (published online March 30.) (preprint)https://doi.org/10.1101/2020.03.29.20045880Google Scholar There are numerous benefits of wastewater sampling, but the collection and interpretation of data is an emerging field. Within the Global Polio Eradication Initiative, wastewater sampling has successfully been used to detect polioviruses and inform eradication for several decades.5Asghar H Diop OM Weldegebriel G et al.Environmental surveillance for polioviruses in the global polio eradication initiative.J Infect Dis. 2014; 210: S294-S303Crossref PubMed Scopus (230) Google Scholar This virological analysis and investigation of wastewater has been done by the Global Polio Laboratory Network and independent laboratories. Here, we highlight several challenges of wastewater sampling for SARS-CoV-2 and outline lessons that can be learnt from polio eradication. Interpretation of a single positive wastewater sample is difficult; longitudinal sampling alongside clinical surveillance is more informative. One positive sample merely suggests that at least one individual has shed virus upstream from the sampling site, and does little to inform epidemiology. Quantitative data (eg, quantitative PCR, metagenomics), and longitudinal sampling from the same site can provide more context. In the COVID-19 pandemic, the interpretation of positive samples will vary according to local assessment of the epidemiology: from an importation event to continued infection in the community. Development of protocols for interpreting and responding to positive SARS-CoV-2 samples are essential even in the early stages of use. RNA from the virus has been detected in stool (via RT-PCR amplification), but there is little evidence for infectious virus in stool,1Xu Y Li X Zhu B et al.Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding.Nat Med. 2020; 26: 502-505Crossref PubMed Scopus (1024) Google Scholar, 6Xiao F Sun J Xu Y et al.Infectious SARS-CoV-2 in feces of patient with severe COVID-19.Emerg Infect Dis. 2020; (published online May 18.)https://doi.org/10.3201/eid2608.200681Crossref Scopus (356) Google Scholar meaning that whether stool is a source of new infections is unclear. Sample site characteristics affect virus detection and require further study. Locations include the entrances of sewage treatment works, upstream pumping stations, or direct collection at rivers or latrines. Industry effluence, runoff from excess rain, and the pH of the sample7Hamisu AW Blake IM Sume G et al.Characterizing environmental surveillance sites in Nigeria and their sensitivity to detect poliovirus and other enteroviruses.J Infect Dis. 2020; (published online April 9.)https://doi.org/10.1093/infdis/jiaa175Crossref PubMed Scopus (10) Google Scholar can all affect sample quality, which might influence the ability to detect and isolate virus. The method of sampling (eg, 24-h composite samples vs periodic grab samples), population demographics of the catchment area, and local epidemiological factors are important for planning environmental surveillance. The method and volume of sample is also important: several approaches (eg, bag filtration and composite sampling) are used to increase the volume of a sample.8Manor Y Handsher R Halmut T et al.Detection of poliovirus circulation by environmental surveillance in the absence of clinical cases in Israel and the Palestinian authority.J Clin Microbiol. 1999; 37: 1670-1675Crossref PubMed Google Scholar Although large sample volumes might increase identification of virus in wastewater, this can make samples increasingly intractable to handle and process in laboratories. Wastewater sampling in cities requires good maps of sewer networks to understand what population is being represented. In very mobile populations (exemplified in Pakistan) sampling might indicate the presence of virus but not the affected population. Outside of dense populations there are fewer converging sewer networks that enable informative wastewater sampling; alternative sampling strategies for remote settings are a recognised need. Laboratory methods should be validated, and for the assays that are used, analytical specificity and limits of detection should be reported.9Lodder WJ Buisman AM Rutjes SA Heijne JC Teunis PF de Roda Husman AM Feasibility of quantitative environmental surveillance in poliovirus eradication strategies.Appl Environ Microbiol. 2012; 78: 3800-3805Crossref PubMed Scopus (53) Google Scholar Suitable process controls should be defined to validate results, identify false negatives, and minimise cross-contamination. In polio surveillance, isolation of the related non-polio enteroviruses (a group of ubiquitous enteric viruses) has been a useful quality indicator for field samples and testing performance. WHO protocols suggest that at least 10–30% of samples should reveal non-polio enteroviruses, and sites can be rejected if isolation is not possible. A clear separation in sample handling and processing is needed to reduce the risk of cross-contamination. Generally, samples are processed within biosafety level two laboratory conditions, separate from clinical samples, where the standard process involves a two-phase separation procedure (for virus concentration), followed by virus culture and isolation, as well as molecular methods that offer genome detection. Increasingly, specialist laboratories are also adopting modern sequence-based methods for wastewater surveillance, such as metagenomics or nanopore sequencing,10Shaw AG Majumdar M Troman C et al.Rapid and sensitive direct detection and identification of poliovirus from stool and environmental surveillance samples using nanopore sequencing.bioRxiv. 2020; (published online April 28.) (preprint)https://doi.org/10.1101/2020.04.27.053421Google Scholar which generates high-resolution genomic information that offers detailed insights into possible virus origins. Despite the challenges, wastewater sampling has long been an important supplement to clinical surveillance in polio eradication and has the potential to inform the epidemiology of COVID-19. Wastewater sampling can act as an early warning system for local infection, and support clinical surveillance to confirm local elimination through negative samples. To be an informative mode of surveillance, it will be essential to set minimum criteria for surveillance sites, develop a consistent sampling strategy, establish laboratory testing protocols to enhance sensitivity and minimise the risks of cross-contamination, and to collaborate internationally. We declare no competing interests.

Background: The monovalent oral rotavirus vaccine Rotarix (R) was introduced into the UK infant immunisation programme in 2013. We estimated vaccine effectiveness (VE) in the first two years of the programme. Methods: We used a test-negative case-control design and enhanced national surveillance data for 1869 vaccine-eligible children tested for rotavirus infection to obtain adjusted odds ratios and VE against laboratory-confirmed rotavirus infections. Linked anonymised UK primary care and hospitalisation data from the Clinical Practice Research Datalink (40,723 children) and random-effects Poisson regression were used in a cohort study to estimate VE against all-cause acute gastroenteritis (AGE) and AGE hospitalisations. Results: VE against laboratory-confirmed infection was 69% (95% Confidence Interval: 40-84%) for one dose and 77% (95%CI: 66-85%) for two doses. Two-dose VE in children aged <12 months and >= 12 months was 85% (95%CI: 74-91%) and 54% (95%CI: 15-75%), respectively. In contrast, we found no evidence that the vaccine was effective against all-cause AGE (VE = -20%, 95%CI: -36% to -5%), or against AGE hospitalisations (VE = 35%, 95% CI: -86% to 77%). Conclusions: In this first detailed assessment of VE of the Rotarix (R) vaccine in the English national programme, we show that Rotarix (R) was highly effective in preventing laboratory-confirmed rotavirus infection in young children. This provides reassurance about the vaccine's performance in real-life settings and gives key information for future cost-effectiveness analyses. The high VE against rotavirus-specific AGE, and the exceptionally successful implementation of the national rotavirus vaccine programme (with >90% vaccine coverage), explains the lack of VE against all-cause AGE because most AGE in the post-vaccine era would not have been due to rotavirus, although some underestimation of VE could also have occurred due to differential healthcare utilisation by vaccinated and unvaccinated infants. This highlights the importance of using specific vaccine-preventable endpoints for these scenarios. (C) 2019 Published by Elsevier Ltd.

BackgroundNorovirus is the commonest cause of infectious intestinal disease (IID) worldwide. In the UK community incidence of norovirus has been estimated at 59/1000 population, equating to four million cases a year. Whilst norovirus infects people of all ages, a substantial burden occurs in infants and young children. The population of viruses found in sporadic cases among infants has been observed to be more diverse than that associated with outbreaks. In this study, we analysed norovirus-positive specimens collected during the second study of infectious intestinal diseases (IID2 Study) a national community cohort study conducted between April 2008 and August 2009 We examined the data for differences in circulating norovirus strains between two arms of a community cohort, and differences between genotypes and disease outcomes such as illness duration and symptom profiles.MethodsAnalysis was conducted to assess genetic diversity of noroviruses in the community. We also assessed differences in the cycle threshold (Ct) value, as a proxy for viral load, between norovirus genogroups and genotypes, and differences in reported symptoms or length of illness in relation to genogroup and genotype.ResultsThere were 477 samples where norovirus was detected. Whilst 85% of people recovered within two days for vomiting; diarrhoea symptoms were reported to day 4 for 83% of the cases, and 10% of people reported symptoms of diarrhoea lasting between five and six days. Both diarrhoea and vomiting symptoms lasted longer in children aged <5years compared to adults. There was a significantly higher proportion of GII.4 in samples obtained from the GP arm of the study (chi-square=17.8, p<0.001) compared to samples received via post in the self-reporting arm. In the latter group, the prevalence of GII.6 was significantly higher (chi-square=7.5, p<0.001).ConclusionsWe found that there is a difference in disease severity by age group. Children aged <5years had longer duration of illness, with 10% still having diarrhoea at seven days, and vomiting of between four and five days. The duration of illness reported is higher overall than one might expect for cases in the community in otherwise healthy individuals which has implications for infection control. No differences were observed in relation to duration of vomiting and or diarrhoea by genotype.

Background: Healthcare-associated infections represent a major threat to patient, staff and visitor safety. Identification of episodes that are likely to have resulted from nosocomial transmission has important implications for infection control. Routinely collected data on ward admissions and sample dates, combined with pathogen genomic information could provide useful insights. We describe a novel, open-source, application for visualising these data, and demonstrate its utility for investigating nosocomial transmission using a case study of a large outbreak of norovirus infection. Methods: We developed the application using Shiny, a web application framework for R. For the norovirus case study, cases were defined as patients who had a faecal sample collected at the hospital in a winter season that tested positive for norovirus. Patient demographics and ward admission dates were extracted from hospital systems. Detected norovirus strains were genotyped and further characterised through sequencing of the hypervariable P2 domain. The most commonly detected sub-strain was visualised using the interactive application. Results: There were 156 norovirus-positive specimens collected from 107 patients. The most commonly detected sub-strain affected 30 patients in five wards. We used the interactive application to produce three visualisations: a bar chart, a timeline, and a schematic ward plan highlighting plausible transmission links. Visualisations showed credible links between cases on the elderly care ward. Conclusions: Use of the interactive application provided insights into transmission in this large nosocomial outbreak of norovirus, highlighting where infection control practices worked well or could be improved. This is a flexible tool that could be used for investigation of any infection in any hospital by interactively changing parameters. Challenges include integration with hospital systems for extracting data. Prospective use of this application could inform better infection control in real time.

Introduction Rotavirus vaccination with the live-attenuated monovalent (a G1P[8] human rotavirus strain) two-dose Rotarix vaccine was introduced in England in July 2013. Since then, there have been significant reductions in rotavirus gastroenteritis incidence. Aim We assessed the vaccine’s impact on rotavirus genotype distribution and diversity 3 years post-vaccine introduction. Methods Epidemiological and microbiological data on genotyped rotavirus-positive samples between September 2006 and August 2016 were supplied by EuroRotaNet and Public Health England. Multinomial multivariable logistic regression adjusting for year, season and age was used to quantify changes in genotype prevalence in the vaccine period. Genotype diversity was measured using the Shannon’s index (H′) and Simpson’s index of diversity (D). Results We analysed genotypes from 8,044 faecal samples. In the pre-vaccine era, G1P[8] was most prevalent, ranging from 39% (411/1,057) to 74% (527/709) per year. In the vaccine era, G1P[8] prevalence declined each season (35%, 231/654; 12%, 154/1,257; 5%, 34/726) and genotype diversity increased significantly in 6–59 months old children (H’ p < 0.001: D p < 0.001). In multinomial analysis, G2P[4] (adjusted multinomial odds ratio (aMOR): 9.51; 95% confidence interval (CI): 7.02–12.90), G3P[8] (aMOR: 2.83; 95% CI: 2.17–3.81), G12P[8] (aMOR: 2.46; 95% CI: 1.62–3.73) and G4P[8] (aMOR: 1.42; 95% CI: 1.02–1.96) significantly increased relative to G1P[8]. Conclusions In the context of reduced rotavirus disease incidence, genotype diversity has increased, with a relative change in the dominant genotype from G1P[8] to G2P[4] after vaccine introduction. These changes will need continued surveillance as the number and age of vaccinated birth cohorts increase in the future.

Objectives This study aimed to prospectively collect detailed clinical information for all enterovirus (EV) and human parechovirus (HPeV) meningitis cases in infants aged <90 days in the UK and Ireland. Participants, design and setting Prospective, active national surveillance during July 2014 to July 2015 through the British Paediatric Surveillance Unit. Reporting paediatricians completed questionnaires requesting information on clinical presentation, investigations, management and outcomes at hospital discharge and after 12 months. Main outcome measures To describe the clinical burden of EV and HPeV meningitis in infants aged <90 days. Results During the 13-month surveillance period, 703 cases (668 EV, incidence0.79/1,000 live-births; 35 HPeV, 0.04/1,000 live-births) were identified. The most common clinical presentations were fever (EV: 570/668(85%); HPeV: 28/35(80%)), irritability (EV: 441/668(66%); HPeV: 23/35(66%)) and reduced feeding (EV: 363/668(54%); HPeV 23/35(66%)). Features of circulatory shock were present in 27% (182/668) of EV and 43% (15/35) of HPeV cases. Overall, 11% (76/668) of EV and 23% (8/35) of HPeV cases required intensive care support. Nearly all cases (678/703, 96%) were confirmed by cerebrospinal fluid (CSF) PCR, with 52% (309/600) having normal CSF white cell count for age. Two infants with EV meningitis died (2/668, 0.3%) and four survivors (4/666, 0.6%) had long-term complications at 12 months' follow-up. Infants with HPeV meningitis survived without sequelae. Overall 189 infants had a formal hearing test and none had sensorineural hearing loss. Conclusion The incidence of laboratory-confirmed EV/HPeV meningitis in young infants is more than twice that for bacterial meningitis. Less than 1% will develop severe neurological complications or die of their infection. Further studies are required to formally assess long-term neurodevelopmental sequelae.

Since the introduction of rotavirus vaccination in England in July 2013, norovirus has become the second-largest contributor of inpatient gastroenteritis, preventing 57800 patients from being admitted annually. Economic costs amount to £297.7 million, which translates into 6300 quality-adjusted life years.

Comparison of children hospitalized with enterovirus or human parechovirus (HPeV) detected in their cerebrospinal fluid revealed that HPeV infections presented with more persistent fever, irritability and feeding problems, more frequent leukopenia and lymphopenia and higher admission rates to high dependency or intensive care units. Few HPeV cases were followed up, further studies on long-term outcomes are needed.

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.

We note with interest the high background seropositivity of EVD68 in infants and children in some parts of China (Jiangsu). 1 Sun SY Gao F Hu YL Bian LL Mao QY Wu X et al. Seroepidemiology of enterovirus D68 infection in infants and children in Jiangsu, China. J Infect. 2018; 76: 563-569 Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar Similarly, in our study below, we only found one acute case of EVD68 in our patient cohort, suggesting that most paediatric and adult EVD68 infections cause asymptomatic or mild disease.