Predicting Norovirus in England Using Existing and Emerging Syndromic Data: Infodemiology Study.

BACKGROUND: Norovirus is associated with approximately 18% of the global burden of gastroenteritis and affects all age groups. There is currently no licensed vaccine or available antiviral treatment. However, well-designed early warning systems and forecasting can guide nonpharmaceutical approaches to norovirus infection prevention and control. OBJECTIVE: This study evaluates the predictive power of existing syndromic surveillance data and emerging data sources, such as internet searches and Wikipedia page views, to predict norovirus activity across a range of age groups across England. METHODS: We used existing syndromic surveillance and emerging syndromic data to predict laboratory data indicating norovirus activity. Two methods are used to evaluate the predictive potential of syndromic variables. First, the Granger causality framework was used to assess whether individual variables precede changes in norovirus laboratory reports in a given region or an age group. Then, we used random forest modeling to estimate the importance of each variable in the context of others with two methods: (1) change in the mean square error and (2) node purity. Finally, these results were combined into a visualization indicating the most influential predictors for norovirus laboratory reports in a specific age group and region. RESULTS: Our results suggest that syndromic surveillance data include valuable predictors for norovirus laboratory reports in England. However, Wikipedia page views are less likely to provide prediction improvements on top of Google Trends and Existing Syndromic Data. Predictors displayed varying relevance across age groups and regions. For example, the random forest modeling based on selected existing and emerging syndromic variables explained 60% variance in the ≥65 years age group, 42% in the East of England, but only 13% in the South West region. Emerging data sets highlighted relative search volumes, including "flu symptoms," "norovirus in pregnancy," and norovirus activity in specific years, such as "norovirus 2016." Symptoms of vomiting and gastroenteritis in multiple age groups were identified as important predictors within existing data sources. CONCLUSIONS: Existing and emerging data sources can help predict norovirus activity in England in some age groups and geographic regions, particularly, predictors concerning vomiting, gastroenteritis, and norovirus in the vulnerable populations and historical terms such as stomach flu. However, syndromic predictors were less relevant in some age groups and regions likely due to contrasting public health practices between regions and health information-seeking behavior between age groups. Additionally, predictors relevant to one norovirus season may not contribute to other seasons. Data biases, such as low spatial granularity in Google Trends and especially in Wikipedia data, also play a role in the results. Moreover, internet searches can provide insight into mental models, that is, an individual's conceptual understanding of norovirus infection and transmission, which could be used in public health communication strategies.

Can cases and outbreaks of norovirus in children provide an early warning of seasonal norovirus infection: an analysis of nine seasons of surveillance data in England UK.

BACKGROUND: Children are important transmitters of norovirus infection and there is evidence that laboratory reports in children increase earlier in the norovirus season than in adults. This raises the question as to whether cases and outbreaks in children could provide an early warning of seasonal norovirus before cases start increasing in older, more vulnerable age groups. METHODS: This study uses weekly national surveillance data on reported outbreaks within schools, care homes and hospitals, general practice (GP) consultations for infectious intestinal disease (IID), telehealth calls for diarrhoea and/or vomiting and laboratory norovirus reports from across England, UK for nine norovirus seasons (2010/11-2018/19). Lagged correlation analysis was undertaken to identify lead or lag times between cases in children and those in adults for each surveillance dataset. A partial correlation analysis explored whether school outbreaks provided a lead time ahead of other surveillance indicators, controlling for breaks in the data due to school holidays. A breakpoint analysis was used to identify which surveillance indicator and age group provided the earliest warning of the norovirus season each year. RESULTS: School outbreaks occurred 3-weeks before care home and hospital outbreaks, norovirus laboratory reports and NHS 111 calls for diarrhoea, and provided a 2-week lead time ahead of NHS 111 calls for vomiting. Children provided a lead time ahead of adults for norovirus laboratory reports (+ 1-2 weeks), NHS 111 calls for vomiting (+ 1 week) and NHS 111 calls for diarrhoea (+ 1 week) but occurred concurrently with adults for GP consultations. Breakpoint analysis revealed an earlier seasonal increase in cases among children compared to adults for laboratory, GP and NHS 111 data, with school outbreaks increasing earlier than other surveillance indicators in five out of nine surveillance years. CONCLUSION: These findings suggest that monitoring cases and outbreaks of norovirus in children could provide an early warning of seasonal norovirus infection. However, both school outbreak data and syndromic surveillance data are not norovirus specific and will also capture other causes of IID. The use of school outbreak data as an early warning indicator may be improved by enhancing sampling in community outbreaks to confirm the causative organism.

pouC Regulates Expression of bmp4 During Atrioventricular Canal Formation in Zebrafish.

BACKGROUND: Many human gene mutations have been linked to congenital heart disease (CHD), yet CHD remains a major health issue worldwide due in part to an incomplete understanding of the molecular basis for cardiac malformation. RESULTS: Here we identify the orthologous mouse Pou6f1 and zebrafish pouC as POU homeodomain transcription factors enriched in the developing heart. We find that pouC is a multi-functional transcriptional regulator containing separable activation, repression, protein-protein interaction, and DNA binding domains. Using zebrafish heart development as a model system, we demonstrate that pouC knockdown impairs cardiac morphogenesis and affects cardiovascular function. We also find that levels of pouC expression must be fine-tuned to enable proper heart formation. At the cellular level, we demonstrate that pouC knockdown disrupts atrioventricular canal (AVC) cardiomyocyte maintenance, although chamber myocyte specification remains intact. Mechanistically, we show that pouC binds a bmp4 intronic regulatory element to mediate transcriptional activation. CONCLUSIONS: Taken together, our study establishes pouC as a novel transcriptional input into the regulatory hierarchy that drives AVC morphogenesis in zebrafish. We anticipate that these findings will inform future efforts to explore functional conservation in mammals and potential association with atrioventricular septal defects in humans. Developmental Dynamics 248:173-188, 2019. © 2018 Wiley Periodicals, Inc.

What proportion of care home outbreaks are caused by norovirus? An analysis of viral causes of gastroenteritis outbreaks in care homes, North East England, 2016-2018.

BACKGROUND: Outbreaks of infectious gastroenteritis are common in care homes for the elderly. Norovirus can cause these outbreaks, but diagnosis is frequently based solely on clinical characteristics. Our objective in this study was to describe the epidemiology of norovirus and other gastrointestinal pathogens in these settings. METHODS: We analysed surveillance data from gastroenteritis outbreaks reported in North East England between 04 July 2016 to 01 July 2018. Stool samples taken during these outbreaks were tested for a range of viral and bacterial pathogens. We described the epidemiology of these outbreaks and explored the characteristics of norovirus outbreaks versus from other viral causes using multivariable logistic regression. RESULTS: From the 566 care home gastroenteritis outbreaks in this study, we found that norovirus was the pathogen most frequently isolated. Norovirus was detected in 64% of outbreaks with a pathogen identified. Sapovirus was found in 13%; rotavirus in 11%. We found that norovirus outbreaks were associated with higher attack rates (aOR 1.03, 95% CI 1.01-1.05) and fewer cases sampled (aOR 0.74, 95% CI 0.60-0.91), compared to outbreaks caused by other viral pathogens. CONCLUSIONS: These results are important as they quantify the contribution of norovirus to gastroenteritis outbreaks in care homes. Given this evidence, we emphasize the importance of non-specific outbreak interventions that can affect the impact of all such outbreaks. We further recommend that these findings are used to inform the implementation strategies of any norovirus-specific interventions such as a norovirus vaccine.

Norovirus strain types found within the second infectious intestinal diseases (IID2) study an analysis of norovirus circulating in the community.

BACKGROUND: Norovirus 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. METHODS: Analysis 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. RESULTS: There 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 < 5 years 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). CONCLUSIONS: We found that there is a difference in disease severity by age group. Children aged < 5 years 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.

Estimating the burden of care home gastroenteritis outbreaks in England, 2014-2016.

BACKGROUND: Outbreaks of infectious gastroenteritis in care homes are common, with norovirus a frequent cause. In England there is no co-ordinated national surveillance system. We aimed to estimate the burden of these outbreaks. METHODS: Using a generalised linear mixed effects regression model we described the relationship between the observed number of care home outbreaks and covariates. Estimated model parameters were used to infer uplift in the number of outbreaks expected if all areas were subjected to enhanced surveillance. From this we then estimated the total burden of care home gastroenteritis outbreaks in this period. RESULTS: We estimated a total of 14,146 care home gastroenteritis outbreaks in England during 2014-2016; this is 47% higher than the reported total and a rate of 32.4 outbreaks per 100 care homes per year. The median number of outbreaks from the model estimates was 31 (IQR 20-46) compared to 19 (IQR 12-34) reported from routine surveillance. CONCLUSIONS: This estimated care home gastroenteritis burden in England indicates that current surveillance substantially underestimates the number of outbreaks, by almost half. Improving this surveillance could provide better epidemiological knowledge of the burden of norovirus to inform public health policy, particularly with the advent of norovirus vaccines.

Foodborne and Food-Handler Norovirus Outbreaks: A Systematic Review.

Norovirus (NoV) is the commonest cause of gastrointestinal disease in the United Kingdom and in many developed countries, causing diarrhea and vomiting in millions of cases worldwide annually. Transmission is most often mediated from person to person. NoV infection has, however, additionally been associated with the consumption of food, either through the consumption of food contaminated at source such as seafood, berries, and salad, or as a consequence of the foodstuff being contaminated in some way by a food handler during processing or serving. A systematic review of outbreaks attributed to NoV between January 2003 and July 2017 was conducted to assess the contribution of food handlers to the burden of NoV, and to identify foods commonly associated with NoV outbreaks. A total of 3021 articles were screened, of which 27 met the definition of confirmed foodborne outbreaks and 47 met the criteria for definite food-handler NoV outbreaks. Of all food types, shellfish were implicated in the greatest number of definite foodborne outbreaks. Food handlers contributed to definite food-handler outbreaks involving a diverse range of foodstuffs and in a wide variety of settings, including weddings and military establishments. More genotypes of NoV were found in people who were ill than in samples from food and food handlers. The potential for both food products and food handlers to contribute to the burden of NoV infection is demonstrated conclusively.

Understanding the impact of haemodialysis on UK National Health Service patients' well-being: A qualitative investigation.

AIMS AND OBJECTIVES: While haemodialysis is an effective treatment for end-stage renal disease, the requirements and restrictions it imposes on patients can be onerous. The aim of this study was to obtain UK National Health Service patients' perspectives on the challenges arising from haemodialysis with the intention of identifying potential improvements. BACKGROUND: Depression rates are particularly high in those with end-stage renal disease; however, there is limited insight into the range of stressors associated with haemodialysis treatment within the National Health Service contributing to such high rates, particularly those of a cognitive or psychological nature. DESIGN: A qualitative approach was used to obtain rich, patient-focused data; one-to-one semi-structured interviews were conducted with twenty end-stage renal disease at a UK National Health Service centre. METHODS: Patients were interviewed during a typical haemodialysis session. Thematic analysis was used to systematically interpret the data. Codes were created in an inductive and cyclical process using a constant comparative approach. RESULTS: Three themes emerged from the data: (i) fluctuations in cognitive/physical well-being across the haemodialysis cycle, (ii) restrictions arising from the haemodialysis treatment schedule, (iii) emotional impact of haemodialysis on the self and others. The findings are limited to predominantly white, older patients (median = 74 years) within a National Health Service setting. CONCLUSIONS: Several of the experiences reported by patients as challenging and distressing have so far been overlooked in the literature. A holistic-based approach to treatment, acknowledging all aspects of a patient's well-being, is essential if optimal quality of life is to be achieved by healthcare providers. RELEVANCE TO CLINICAL PRACTICE: The findings can be used to inform future interventions and guidelines aimed at improving patients' treatment adherence and outcomes, for example, improved reliable access to mental health specialists.

Norovirus Surveillance: An Epidemiological Perspective.

Surveillance for norovirus is challenging because the nature of illness due to norovirus is such that the majority of people who are infected will not have any contact with medical services and are highly unlikely to have a sample collected for diagnosis. Public health advice urges people to not visit hospitals or their family physicians, to prevent the risk further spread. The recognition of the importance of this pathogen was quickly established following the introduction of surveillance of outbreaks of gastrointestinal infection in England and Wales in 1992. This period saw >1800 outbreaks of norovirus infection reported in hospitals in England, affecting >45 000 patients and staff. A new system for reporting outbreaks of norovirus infection in hospitals, the Hospital Norovirus outbreak Reporting Scheme (HNORS), began in January 2009. Summary information on outbreaks is provided by infection control staff at hospitals and includes questions on the date the first and last person in the outbreak became symptomatic and whether closure of a bay or ward was needed. In the first 3 years (2009-2011) of the HNORS surveillance scheme, 4000 outbreaks were reported, affecting 40 000 patients and 10 000 staff. Over the last 3 years, these outbreaks have been associated with an average of 13 000 patients and 3400 staff becoming ill, with 15 000 lost bed-days annually. With the possible introduction of a vaccine on the horizon, targeted research with a more integrated approach to laboratory testing and outbreak reporting is essential to a greater understanding of the epidemiology of norovirus.

Shiga Toxin-Producing Escherichia coli O157, England and Wales, 1983-2012.

We evaluated clinical Shiga toxin-producing Escherichia coli O157 infections in England and Wales during 1983-2012 to describe changes in microbiological and surveillance methods. A strain replacement event was captured; phage type (PT) 2 decreased to account for just 3% of cases by 2012, whereas PT8 and PT21/28 strains concurrently emerged, constituting almost two thirds of cases by 2012. Despite interventions to control and reduce transmission, incidence remained constant. However, sources of infection changed over time; outbreaks caused by contaminated meat and milk declined, suggesting that interventions aimed at reducing meat cross-contamination were effective. Petting farm and school and nursery outbreaks increased, suggesting the emergence of other modes of transmission and potentially contributing to the sustained incidence over time. Studies assessing interventions and consideration of policies and guidance should be undertaken to reduce Shiga toxin-producing E. coli O157 infections in England and Wales in line with the latest epidemiologic findings.

Withaferin A suppresses the up-regulation of acetyl-coA carboxylase 1 and skin tumor formation in a skin carcinogenesis mouse model.

Withaferin A (WA), a natural product derived from Withania somnifera, has been used in traditional oriental medicines to treat neurological disorders. Recent studies have demonstrated that this compound may have a potential for cancer treatment and a clinical trial has been launched to test WA in treating melanoma. Herein, WA's chemopreventive potential was tested in a chemically-induced skin carcinogenesis mouse model. Pathological examinations revealed that WA significantly suppressed skin tumor formation. Morphological observations of the skin tissues suggest that WA suppressed cell proliferation rather than inducing apoptosis during skin carcinogenesis. Antibody Micro array analysis demonstrated that WA blocked carcinogen-induced up-regulation of acetyl-CoA carboxylase 1 (ACC1), which was further confirmed in a skin cell transformation model. Overexpression of ACC1 promoted whereas knockdown of ACC1 suppressed anchorage-independent growth and oncogene activation of transformable skin cells. Further studies demonstrated that WA inhibited tumor promotor-induced ACC1 gene transcription by suppressing the activation of activator protein 1. In melanoma cells, WA was also able to suppress the expression levels of ACC1. Finally, results using human skin cancer tissues confirmed the up-regulation of ACC1 in tumors than adjacent normal tissues. In summary, our results suggest that withaferin A may have a potential in chemoprevention and ACC1 may serve as a critical target of WA. © 2015 Wiley Periodicals, Inc.

Comparison of statistical approaches to predicting norovirus laboratory reports before and during COVID-19: insights to inform public health surveillance.

Social distancing interrupted transmission patterns of contact-driven infectious agents such as norovirus during the Covid-19 pandemic. Since routine surveillance of norovirus was additionally disrupted during the pandemic, traditional naïve forecasts that rely only on past public health surveillance data may not reliably represent norovirus activity. This study investigates the use of statistical modelling to predict the number of norovirus laboratory reports in England 4-weeks ahead of time before and during Covid-19 pandemic thus providing insights to inform existing practices in norovirus surveillance in England. We compare the predictive performance from three forecasting approaches that assume different underlying structure of the norovirus data and utilized various external data sources including mobility, air temperature and relative internet searches (Time Series and Regularized Generalized Linear Model, and Quantile Regression Forest). The performance of each approach was evaluated using multiple metrics, including a relative prediction error against the traditional naive forecast of a five-season mean. Our data suggest that all three forecasting approaches improve predictive performance over the naïve forecasts, especially in the 2020/21 season (30-45% relative improvement) when the number of norovirus reports reduced. The improvement ranged from 7 to 22% before the pandemic. However, performance varied: regularized regression incorporating internet searches showed the best forecasting score pre-pandemic and the time series approach achieved the best results post pandemic onset without external data. Overall, our results demonstrate that there is a significant value for public health in considering the adoption of more sophisticated forecasting tools, moving beyond traditional naïve methods, and utilizing available software to enhance the precision and timeliness of norovirus surveillance in England.

Use of Internet search data to monitor impact of rotavirus vaccination in the United States.

Google-based Internet query share (IQS) for rotavirus search terms correlated well with US rotavirus laboratory detections from 2004 to 2010 (r = 0.88; P < .001), capturing the reduction observed during postvaccine years (2008-2010). IQS analysis could become an inexpensive and reliable supplement for monitoring the impact of rotavirus vaccination in the United States.

Early diagnosis and resection of an asymptomatic leiomyosarcoma of the inferior vena cava prior to caval obstruction.

Leiomyosarcoma of the inferior vena cava is a rare and aggressive tumor, characterized by a slow growth and usually late diagnosis. The mainstay of therapy is surgical resection with limited role for chemotherapy or radiotherapy; resection modalities and the need for caval reconstruction are still matters of debate. In this case report, we describe an asymptomatic intraluminal leiomyosarcoma of the inferior vena cava diagnosed incidentally prior to caval occlusion during a routine ultrasound examination of the upper abdomen.

Symptom profiling for infectious intestinal disease (IID): Do symptom profiles alter with age?

Symptom profiles have previously been identified for infectious intestinal disease (IID) which distinguish bacterial from viral organisms. However, there is evidence that the seasonality, severity, and duration of IID may differ between children, adults and elderly. A secondary data analysis was undertaken to explore whether symptom profiles for bacterial and viral IID vary across different age groups. Data from 844 cases of IID were divided into three age categories: <16 years, 16-65 years and >65 years. Multivariable logistic regression modelling was used to compare the significance of different symptoms across the three age groups. The odds of bacterial IID in children were increased by onset in the summer, diarrhoea in the absence of vomiting and fever. These symptoms were also associated with lower odds of a viral pathogen. In adults, diarrhoea but no vomiting, bloody diarrhoea and diarrhoea lasting more than 3 days were associated with increased odds of a bacterial organism, whilst onset in the winter or spring and a loss of appetite were associated with viral IID. In the elderly, diarrhoea in the absence of vomiting and diarrhoea lasting more than 3 days were associated with higher odds of bacterial IID and lower odds of a viral cause. Only diarrhoea in the absence of vomiting emerged as a key symptom across all three age groups. Variation in symptom profiles by age has implications for clinicians, public health specialists and epidemiologists who use symptoms to guide presumptive diagnoses in the absence of microbiological confirmation.

School Attendance Registers for the Syndromic Surveillance of Infectious Intestinal Disease in UK Children: Protocol for a Retrospective Analysis.

BACKGROUND: Infectious intestinal disease (IID) is common, and children are more likely than adults both to have IID and to transmit infection onto others. Before the introduction of the vaccine, rotavirus was the leading cause of severe childhood diarrhea, with norovirus and Campylobacter predominate pathogens. Public health surveillance of IID is primarily based on health care data, and as such, illness that is managed within the community will often go undetected. School attendance registers offer a novel data set that has the potential to identify community cases and outbreaks of IID that would otherwise be missed by current health surveillance systems. Although studies have explored the role of school attendance registers in the monitoring of influenza among children, no studies have been identified that consider this approach in the surveillance of IID. OBJECTIVE: The aim of this study is to explore the role and utility of school attendance registers in the detection and surveillance of IID in children. The secondary aims are to estimate the burden of IID on school absenteeism and to assess the impact of the rotavirus vaccine on illness absence among school-aged children. METHODS: This study is a retrospective analysis of school attendance registers to investigate whether school absences due to illness can be used to capture seasonal trends and outbreaks of infectious intestinal disease among school-aged children. School absences in Merseyside, United Kingdom will be compared and combined with routine health surveillance data from primary care, laboratories, and telehealth services. These data will be used to model spatial and temporal variations in the incidence of IID and to apportion likely causes to changes in school absenteeism trends. This will be used to assess the potential utility of school attendance data in the surveillance of IID and to estimate the burden of IID absenteeism in schools. It will also inform an analysis of the impact of the rotavirus vaccine on disease within this age group. RESULTS: This study has received ethical approval from the University of Liverpool Research Ethics Committee (reference number 1819). Use of general practice data has been approved for the evaluation of rotavirus vaccination in Merseyside by NHS Research Ethics Committee, South Central-Berkshire REC Reference 14/SC/1140. CONCLUSIONS: This study is unique in considering whether school attendance registers could be used to enhance the surveillance of IID. Such data have multiple potential applications and could improve the identification of outbreaks within schools, allowing early intervention to reduce transmission both within and outside of school settings. These data have the potential to act as an early warning system, identifying infections circulating within the community before they enter health care settings. School attendance data could also inform the evaluation of vaccination programs, such as rotavirus and, in time, norovirus. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30078.

Use of routine death and illness surveillance data to provide insight for UK pandemic planning: lessons from COVID-19.

OBJECTIVES: Reporting of COVID-19 cases, deaths and testing has often lacked context for appropriate assessment of disease burden within risk groups. The research considers how routine surveillance data might provide initial insights and identify risk factors, setting COVID-19 deaths early in the pandemic into context. This will facilitate the understanding of wider consequences of a pandemic from the earliest stage, reducing fear, aiding in accurately assessing disease burden and ensuring appropriate disease mitigation. SETTING: UK, 2020. PARTICIPANTS: The study is a secondary analysis of routine, public domain, surveillance data and information from Office for National Statistics (ONS), National Health Service (NHS) 111 and Public Health England (PHE) on deaths and disease. PRIMARY AND SECONDARY OUTCOME MEASURES: Our principal focus is ONS data on deaths mentioning COVID-19 on the death certificate. We also consider information provided in NHS 111 and PHE data summaries. RESULTS: Deaths with COVID-19 significantly contributed to, yet do not entirely explain, abnormally elevated all-cause mortality in the UK from weeks 12-18 of 2020. Early in the UK epidemic, COVID-19 was the greatest threat to those with underlying illness, rarely endangering people aged under 40 years. COVID-19-related death rates differed by region, possibly reflecting underlying population structure. Risk of COVID-19-related death was greater for healthcare and social care staff and black, Asian and minority ethnic individuals, having allowed for documented risk factors. CONCLUSION: Early contextualisation of public health data is critical to recognising who gets sick, when and why. Understanding at-risk groups facilitates a targeted response considering indirect consequences of society's reaction to a pandemic alongside disease-related impacts. COVID-19-related deaths mainly mirror historical patterns, and excess non-COVID-19-related deaths partly reflect reduced access to and uptake of healthcare during lockdown. Future outbreak response will improve through better understanding of connectivity between disease monitoring systems to aid interpretation of disease risk patterns, facilitating nuanced mitigation measures.

Differential impact of the COVID-19 pandemic on laboratory reporting of norovirus and Campylobacter in England: A modelling approach.

BACKGROUND: The COVID-19 pandemic has impacted surveillance activities for multiple pathogens. Since March 2020, there was a decline in the number of reports of norovirus and Campylobacter recorded by England's national laboratory surveillance system. The aim is to estimate and compare the impact of the COVID-19 pandemic on norovirus and Campylobacter surveillance data in England. METHODS: We utilised two quasi-experimental approaches based on a generalised linear model for sequential count data. The first approach estimates overall impact and the second approach focuses on the impact of specific elements of the pandemic response (COVID-19 diagnostic testing and control measures). The following time series (27, 2015-43, 2020) were used: weekly laboratory-confirmed norovirus and Campylobacter reports, air temperature, conducted Sars-CoV-2 tests and Index of COVID-19 control measures stringency. RESULTS: The period of Sars-CoV-2 emergence and subsequent sustained transmission was associated with persistent reductions in norovirus laboratory reports (p = 0.001), whereas the reductions were more pronounced during pandemic emergence and later recovered for Campylobacter (p = 0.075). The total estimated reduction was 47% - 79% for norovirus (12-43, 2020). The total reduction varied by time for Campylobacter, e.g. 19% - 33% in April, 1% - 7% in August. CONCLUSION: Laboratory reporting of norovirus was more adversely impacted than Campylobacter by the COVID-19 pandemic. This may be partially explained by a comparatively stronger effect of behavioural interventions on norovirus transmission and a relatively greater reduction in norovirus testing capacity. Our study underlines the differential impact a pandemic may have on surveillance of gastrointestinal infectious diseases.

A potential barrier to adherence? Memory for future intentions is impaired in hemodialysis patients.

INTRODUCTION: End-stage renal disease (ESRD) has been associated with a range of cognitive deficits, including impaired retrospective memory and attention. Prospective memory (PM) is memory for future intentions, such as remembering to take medication on time. Prospective memory has not been examined in any ESRD patients; yet, the implications upon diet and medication management could potentially have detrimental effects on patient welfare. This is the first study to examine PM in ESRD patients being treated with hemodialysis (HD). METHODS: Hemodialysis patients (n = 18) were compared with age-matched and education-matched controls (n = 18) on a boardgame task that emulates a typical week of activities (i.e., grocery shopping, meetings with friends), requiring the participant to remember a series of upcoming tasks. Other measures were also examined, including general cognitive decline, measures of independent living, IQ, and mood. FINDINGS: Patients recalled significantly fewer upcoming events than the control group, suggesting an impairment of PM. No significant relationship was found between PM performance and any other measures, suggesting the difference between groups is likely due to the effects of ESRD, HD treatment, or some associated comorbidity. DISCUSSION: This is the first study to demonstrate a PM deficit in patients undergoing HD treatment. This finding contributes to the current knowledge of the cognitive profile of patients undergoing HD while also highlighting the implications that a PM deficit may have on patient quality of life. The finding may go some way to explaining variances in patients' ability to monitor and adhere to medication and dietary regimes and, ultimately, to live independently. The study also highlights the necessity of viewing treatment for ESRD as a holistic process to maximize patient well-being.

Epidemiology and genotype diversity of norovirus infections among children aged <5 years following rotavirus vaccine introduction in Blantyre, Malawi.

BACKGROUND: Following rotavirus vaccine introduction, norovirus has emerged as a significant pathogen associated with acute gastroenteritis among children in some high- and middle-income countries. In a case-control study following rotavirus vaccination in Malawi, we used PCR to test for multiple enteric pathogens in fecal samples from children aged <5 years hospitalized with diarrhea, and from asymptomatic community controls (Iturriza-Gómara et al. 2019). OBJECTIVES: To describe the epidemiology and genotype diversity of norovirus infections among infants and young children in Blantyre, Malawi, following rotavirus vaccine introduction in 2012. STUDY DESIGN: We analysed data from the case-control study to assess annual and agespecific norovirus prevalence and the presence of co-infection. Norovirus-containing specimens were amplified by PCR and sequenced to determined genotype. RESULTS: Norovirus prevalence in cases was similar for each complete year of study (11.4% in 2013, 9.3% in 2014 and 11.2% in 2015). Prevalence of norovirus among children aged <6 months, 6-11 months, 12-23 months and 24+ months was 15.3% (11/72), 13.3% (44/331), 11.0% (24/219) and 6.6% (4/61) respectively in cases and 6.7% (2/30), 13.1% (30/229), 4.2% (8/192) and 7.1 (5/70) in controls. Co-pathogens were commonly detected in norovirus positive cases (77/83) and controls (44/45). Norovirus GII.4 was the most commonly identified genotype, comprising 48% and 41% of genotyped strains among cases and controls, respectively. CONCLUSIONS: Norovirus disease prevalence was unchanged during the study period, and was greatest amongst infants. Frequent co-infection and asymptomatic shedding suggests intense community transmission of norovirus and other enteric pathogens in this low-income, African setting.