RT-PCR genotyping assays to identify SARS-CoV-2 variants in England in 2021: a design and retrospective evaluation study.

BACKGROUND: Whole-genome sequencing (WGS) is the gold standard diagnostic tool to identify and genetically characterise emerging pathogen mutations (variants), but cost, capacity, and timeliness limit its use when large populations need rapidly assessing. We assessed the potential of genotyping assays to provide accurate and timely variant information at scale by retrospectively examining surveillance for SARS-CoV-2 variants in England between March and September, 2021, when genotyping assays were used widely for variant detection. METHODS: We chose a panel of four RT-PCR genotyping assays to detect circulating variants of SARS-COV-2 in England and developed a decision algorithm to assign a probable SARS-CoV-2 variant to samples using the assay results. We extracted surveillance data from the UK Health Security Agency databases for 115 934 SARS-CoV-2-positive samples (March 1-Sept 6, 2021) when variant information was available from both genotyping and WGS. By comparing the genotyping and WGS variant result, we calculated accuracy metrics (ie, sensitivity, specificity, and positive predictive value [PPV]) and the time difference between the sample collection date and the availability of variant information. We assessed the number of samples with a variant assigned from genotyping or WGS, or both, over time. FINDINGS: Genotyping and an initial decision algorithm (April 10-May 11, 2021 data) were accurate for key variant assignment: sensitivities and PPVs were 0·99 (95% CI 0·99-0·99) for the alpha, 1·00 (1·00-1·00) for the beta, and 0·91 (0·80-1·00) for the gamma variants; specificities were 0·97 (0·96-0·98), 1·00 (1·00-1·00), and 1·00 (1·00-1·00), respectively. A subsequent decision algorithm over a longer time period (May 27-Sept 6, 2021 data) remained accurate for key variant assignment: sensitivities were 0·91 (95% CI 0·74-1·00) for the beta, 0·98 (0·98-0·99) for the delta, and 0·93 (0·81-1·00) for the gamma variants; specificities were 1·00 (1·00-1·00), 0·96 (0·96-0·97), and 1·00 (1·00-1·00), respectively; and PPVs were 0·83 (0·62-1·00), 1·00 (1·00-1·00), and 0·78 (0·59-0·97), respectively. Genotyping produced variant information a median of 3 days (IQR 2-4) after the sample collection date, which was faster than with WGS (9 days [8-11]). The flexibility of genotyping enabled a nine-times increase in the quantity of samples tested for variants by this method (from 5000 to 45 000). INTERPRETATION: RT-PCR genotyping assays are suitable for high-throughput variant surveillance and could complement WGS, enabling larger scale testing for known variants and timelier results, with important implications for effective public health responses and disease control globally, especially in settings with low WGS capacity. However, the choice of panels of RT-PCR assays is highly dependent on database information on circulating variants generated by WGS, which could limit the use of genotyping assays when new variants are emerging and spreading rapidly. FUNDING: UK Health Security Agency and National Institute for Health Research Health Protection Research Unit in Emergency Preparedness and Response.

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.

Did anonymity in self-administered questionnaires improve disclosure of sensitive information during the 2022 mpox outbreak in England? An observational study.

BACKGROUND: Between May 6, 2022, and Jan 16, 2023, 3555 mpox cases were reported in England, predominantly in gay, bisexual, and other men who have sex with men. Initially, the UK Health Security agency administered questionnaires to laboratory-detected cases via telephone calls. From June, 2022, cases were requested by text or email to complete the questionnaire online, with optional anonymous completion. To inform future approaches, we assess whether anonymity improved disclosure of sensitive information. METHODS: In this observational study we analysed questionnaire data completed by people with a laboratory-detected case of mpox. We included questionnaires that were completed from May 25, 2022, to Jan 16, 2023, and restricted them to anonymous or identifiable self-completed responses. Questionnaires with forename, surname, and birth date, or an ID emailed to participants, which therefore could link to laboratory data, were considered identifiable. Questionnaires without any personal identifiable information were considered anonymous. We compared the responses to seven sensitive risk factor or exposure questions using Pearson's χ2. FINDINGS: All 3555 people diagnosed with mpox infection in England were invited to complete the questionnaire through either phone call or web link.We obtained 1075 (30%) completed questionnaires, with a response rate decreasing from 45% in May to 20% in July 2022. We included 531 self-completed questionnaires in this analysis, of which 259 (49%) were anonymous and 272 (51%) were identifiable. The median age of participants was 39 years, with 514 (97%) men, 12 (2%) women, and five (1%) other. The largest ethnic groups were white (79%; n=422) and mixed or multiple ethnic groups (9%; n=47). Results of all seven questions were similar: 98% (n=254/259) of anonymous and 97% (n=265/272) of identifiable cases answered all seven questions, 49% (n=127) and 54% (n=147) reported a sexually transmitted infection diagnosis in the past 12 months (p=0·2), 24% (n=63) and 27% (n=73) reported ten or more sexual partners in the past 3 months (p=0·8), and 15% (n=38) and 18% (n=50) reported knowing another person with mpox infection (p=0·5), respectively. INTERPRETATION: Transitioning to self-completed questionnaires resulted in reduced uptake, although optional anonymity possibly prevented a steeper drop. Anonymity did not appear to affect reporting of sensitive information, specifically of sexual behaviours or history associated with mpox risk, which reinforces results of previous literature. Our interpretation is limited, however, by relatively low questionnaire uptake, and by only analysing reported rather than true risk. The decision to implement anonymous questionnaires should therefore weigh the potential benefits of increased uptake against the disadvantage of restricted data linkage. FUNDING: None.

Application of a new multi-locus variable number tandem repeat analysis (MLVA) scheme for the seasonal investigation of Cryptosporidium parvum cases in Wales and the northwest of England, spring 2022.

The protozoan Cryptosporidium parvum is an important cause of gastroenteritis in humans and livestock, and cryptosporidiosis outbreaks are common. However, a multi-locus genotyping scheme is not widely adopted. We describe the further development and application of a seven-locus multi-locus variable number of tandem repeats analysis (MLVA) scheme. From 28th March to 31st July 2022, confirmed C. parvum stools (n = 213) from cryptosporidiosis patients (cases) in Wales (n = 95) and the north west of England (n = 118) were tested by MLVA. Typability (defined as alleles identified at all seven loci in a sample) was 81.2% and discriminatory power estimated by Hunter Gaston Discriminatory Index was 0.99. A MLVA profile was constructed from the alleles, expressed in chromosomal order. Profiles were defined as simple (single allele at each locus) or mixed (more than one allele at any locus). A total of 161 MLVA profiles were identified; 13 were mixed, an additional 38 simple profiles contained null records, and 110 were complete simple profiles. A minimum spanning tree was constructed of simple MLVA profiles and those identical at all seven loci defined genetic clusters of cases (here, null records were considered as an allele); 77 cases formed 25 clusters, ranging from two to nine (mode = two) cases. The largest cluster, following epidemiological investigation, signalled a newly-identified outbreak. Two other cases with mixed profiles that contained the outbreak alleles were included in the outbreak investigation. In another epidemiologically-identified outbreak of six initial cases, MLVA detected two additional cases. In a third, small outbreak of three cases, identical MLVA profiles strengthened the microbiological evidence. Review of the performance characteristics of the individual loci and of the seven-locus scheme suggested that two loci might be candidates for review, but a larger dataset over a wider geographical area and longer timeframe will help inform decision-making about the scheme by user laboratories and stakeholders (such as public health agencies). This MLVA scheme is straightforward in use, fast and cheap compared to sequence-based methods, identifies mixed infections, provides an important tool for C. parvum surveillance, and can enhance outbreak investigations and public health action.

Preliminary investigation of a significant national Cryptosporidium exceedance in the United Kingdom, August 2023 and ongoing.

Routine laboratory surveillance has identified an unprecedented and ongoing exceedance of Cryptosporidium spp. across the United Kingdom, notably driven by C. hominis transmission, since 14 August 2023. Information from 477 reported cases in England and Wales, followed up with a standardised exposure questionnaire as of 25 September 2023, identified foreign travel in 250 (54%) of 463 respondents and swimming in 234 (66%) of 353 cases. A significant, common exposure has not yet been identified in first analyses.

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.

Influence of SARS-CoV-2 surveillance outputs produced by the UK health security agency (UKHSA) outbreak surveillance team on decision-making by local stakeholders.

BACKGROUND: The UK Health Security Agency (UKHSA) COVID-19 Outbreak Surveillance Team (OST) was established in June 2020 to provide Local Authorities (LAs) in England with surveillance intelligence to aid their response to the SARS-CoV-2 epidemic. Reports were produced using standardised metrics in an automated format. Here we evaluate how the SARS-CoV-2 surveillance reports influenced decision making, how resources evolved and how they could be refined to meet the requirements of stakeholders in the future. METHODS: Public health professionals (n = 2,400) involved in the COVID-19 response from the 316 English LAs were invited to take part in an online survey. The questionnaire covered five themes: (i) report use; (ii) influence of surveillance outputs on local intervention strategies; (iii) timeliness; (iv) current and future data requirements; and (v) content development. RESULTS: Of the 366 respondents to the survey, most worked in public health, data science, epidemiology, or business intelligence. Over 70% of respondents used the LA Report and Regional Situational Awareness Report daily or weekly. The information had been used by 88% to inform decision making within their organisations and 68% considered that intervention strategies had been instituted as a result of these decisions. Examples of changes instigated included targeted communications, pharmaceutical and non-pharmaceutical interventions, and the timing of interventions. Most responders considered that the surveillance content had reacted well to evolving demands. The majority (89%) said that their information requirements would be met if the surveillance reports were incorporated into the COVID-19 Situational Awareness Explorer Portal. Additional information suggested by stakeholders included vaccination and hospitalisation data as well as information on underlying health conditions, infection during pregnancy, school absence and wastewater testing. CONCLUSIONS: The OST surveillance reports were a valuable information resource used by local stakeholders in their response to the SARS-CoV-2 epidemic. Control measures that affect disease epidemiology and monitoring requirements need to be considered in the continuous maintenance of surveillance outputs. We identified areas for further development and, since the evaluation, information on repeat infections and vaccination data have been included in the surveillance reports. Furthermore, timeliness of publications has been improved by updating the data flow pathways.

Animal and environmental risk factors for sporadic Shiga toxin-producing Escherichia coli (STEC) infection in England: a case control study for O157, O26 and other STEC serotypes.

Most Shiga toxin-producing E. coli (STEC) infections are sporadic. Routine enhanced surveillance questionnaires of confirmed STEC cases in England contained promising data to conduct a case-control study to identify non-food exposures linked to the risk of becoming infected with different STEC serotypes, including O157, O26 and all others; this study pulled eligible cases from the recorded enhanced surveillance data. Controls were recruited from the general population and answered a comparable postal questionnaire. Logistic regression was performed to identify risk factors associated with STEC infection for O157, O26 and other serotype cases. In adjusted models, travel outside of the U.K. and childcare occupations raised the risk of infection for all serotypes. Day trips within the UK, exposure to dogs and contact with soil were linked to lower infection risk. Resident region within England was often linked to decreased risk. Summer season was linked to O157 and O26, but not other STEC. Swimming in the sea was linked to increased risk of infection by O157, but not other types of STEC. Correlations between exposures and infection were similar when the analysis was repeated excluding participants with a history of foreign travel. As the first case-control study in England to include sporadic non-O157 STEC, the varying risk factors between O157 and non-O157 cases suggest there are potentially unique reservoirs for different serotypes.

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.

Community transmission of monkeypox in the United Kingdom, April to May 2022.

Between 7 and 25 May, 86 monkeypox cases were confirmed in the United Kingdom (UK). Only one case is known to have travelled to a monkeypox virus (MPXV) endemic country. Seventy-nine cases with information were male and 66 reported being gay, bisexual, or other men who have sex with men. This is the first reported sustained MPXV transmission in the UK, with human-to-human transmission through close contacts, including in sexual networks. Improving case ascertainment and onward-transmission preventive measures are ongoing.

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.

Public acceptability of a technology-mediated stool sample collection platform to inform community-based surveillance of infectious intestinal disease: a pilot study.

BACKGROUND: In the UK approximately a quarter of the population experience infectious intestinal disease (IID) each year. However, only 2% present to primary care, preventing a true determination of community burden and pathogen aetiology. The aim of this pilot study was to gauge public acceptability of a technology-mediated platform for reporting episodes of IID and for providing stool samples. METHODS: This study employed a cross-sectional online survey design, targeting individuals 16 + years old within Liverpool City Region, UK. Information sought included demographics, comfortability of reporting illness and IID symptoms, willingness to provide stool, and favoured stool-provision method. Univariable logistic regression was used to examine associations between demographic variables and providing a stool sample. Odds ratios (OR) and associated 95% confidence intervals (CIs) were produced. RESULTS: A total of 174 eligible participants completed the survey, with 69% female. The sample was skewed towards younger populations, with 2.9% aged 65 + years. Nearly a third (29%) had a household income of less than £30,000 per annum and 70% had attained a degree or higher. The majority identified as White British (81%) and 11% identified as ethnicities typically grouped Black, Asian and minority ethnic (BAME). Three quarters of participants were either 'Comfortable' or 'Very Comfortable' with reporting illness (75%) and with answering symptom-related questions (79%); 78% reported that they would provide a stool sample. Upon univariable analysis, increasing age - being 55 + (OR 6.28, 95% CI 1.15-117.48), and lower income (OR 2.5, 95% CI 1.02-6.60), was associated with willingness to provide a stool sample. Additionally, respondents identifying as BAME ethnicities and men may be less inclined to provide a stool sample. CONCLUSIONS: This pilot study assessed the acceptability of technology-mediated platforms for reporting IID and provision of stool samples in the community. Respondents were biased towards younger, technologically inclined, more affluent and educated populations. Acceptability for reporting illness and providing a stool sample through technology-mediated platforms was high. While older populations were under-represented, they were more likely to agree to provide a stool sample. Qualitative research is required to better reach older and more deprived populations, and to understand potential age, gender and ethnic differences in compliance with stool sampling.

Transmission dynamics of COVID-19 in household and community settings in the United Kingdom, January to March 2020.

BackgroundHouseholds appear to be the highest risk setting for COVID-19 transmission. Large household transmission studies in the early stages of the pandemic in Asia reported secondary attack rates ranging from 5 to 30%.AimWe aimed to investigate the transmission dynamics of COVID-19 in household and community settings in the UK.MethodsA prospective case-ascertained study design based on the World Health Organization FFX protocol was undertaken in the UK following the detection of the first case in late January 2020. Household contacts of cases were followed using enhanced surveillance forms to establish whether they developed symptoms of COVID-19, became confirmed cases and their outcomes. We estimated household secondary attack rates (SAR), serial intervals and individual and household basic reproduction numbers. The incubation period was estimated using known point source exposures that resulted in secondary cases.ResultsWe included 233 households with two or more people with 472 contacts. The overall household SAR was 37% (95% CI: 31-43%) with a mean serial interval of 4.67 days, an R0 of 1.85 and a household reproduction number of 2.33. SAR were lower in larger households and highest when the primary case was younger than 18 years. We estimated a mean incubation period of around 4.5 days.ConclusionsRates of COVID-19 household transmission were high in the UK for ages above and under 18 years, emphasising the need for preventative measures in this setting. This study highlights the importance of the FFX protocol in providing early insights on transmission dynamics.

Enhancing epidemiological surveillance of the emergence of the SARS-CoV-2 Omicron variant using spike gene target failure data, England, 15 November to 31 December 2021.

When SARS-CoV-2 Omicron emerged in 2021, S gene target failure enabled differentiation between Omicron and the dominant Delta variant. In England, where S gene target surveillance (SGTS) was already established, this led to rapid identification (within ca 3 days of sample collection) of possible Omicron cases, alongside real-time surveillance and modelling of Omicron growth. SGTS was key to public health action (including case identification and incident management), and we share applied insights on how and when to use SGTS.

Impact of the COVID-19 pandemic on gastrointestinal infection trends in England, February-July 2020.

OBJECTIVE: To establish the impact of the first 6 months of the COVID-19 outbreak response on gastrointestinal (GI) infection trends in England. DESIGN: Retrospective ecological study using routinely collected national and regional surveillance data from seven UK Health Security Agency coordinated laboratory, outbreak and syndromic surveillance systems using key dates of UK governmental policy change to assign phases for comparison between 2020 and historic data. RESULTS: Decreases in GI illness activity were observed across all surveillance indicators as COVID-19 cases began to peak. Compared with the 5-year average (2015-2019), during the first 6 months of the COVID-19 response, there was a 52% decrease in GI outbreaks reported (1544 vs 3208 (95% CI 2938 to 3478)) and a 34% decrease in laboratory confirmed cases (27 859 vs 42 495 (95% CI 40 068 to 44 922)). GI indicators began to rise during the first lockdown and lockdown easing, although all remained substantially lower than historic figures. Reductions in laboratory confirmed cases were observed across all age groups and both sexes, with geographical heterogeneity observed in diagnosis trends. Health seeking behaviour changed substantially, with attendances decreasing prior to lockdown across all indicators. CONCLUSIONS: There has been a marked change in trends of GI infections in the context of the COVID-19 pandemic. The drivers of this change are likely to be multifactorial; while changes in health seeking behaviour, pressure on diagnostic services and surveillance system ascertainment have undoubtably played a role, there has likely been a true decrease in the incidence for some pathogens resulting from the control measures and restrictions implemented. This suggests that if some of these changes in behaviour such as improved hand hygiene were maintained, then we could potentially see sustained reductions in the burden of GI illness.

Cross-sectional household transmission study of Cryptosporidium shows that C. hominis infections are a key risk factor for spread.

BACKGROUND: Infection with the Cryptosporidium parasite causes over 4000 cases of diagnosed illness (cryptosporidiosis) in England and Wales each year. The incidence of sporadic disease has not been sufficiently established, and how frequently this arises from contact with other infected people is not well documented. This project aimed to explore potential transmission in the home and attempt to identify asymptomatic infections, which might play a role in transmission. Risk factors and characteristics associated with spread of infection in the home were described including any differences between Cryptosporidium species. METHODS: The study identified cryptosporidiosis cases from North West England and Wales over a year and invited them and their household to take part. Each household was sent a study pack containing study information and a questionnaire, and stool sample kits to provide samples from consenting household members. Cryptosporidium-positive stool samples, identified by immunofluorescence microscopy, were characterised using molecular methods to help describe any patterns of transmission. Characteristics of households with and without additional cases were described, and compared using odds ratios (OR) and a multivariable logistic regression identified independent risk factors for household transmission. Data collection ran for one year, beginning in September 2018 with an initial pilot phase. RESULTS: We enrolled 128 index cases and their households. Additional illness occurred in over a quarter of homes, each reporting an average of two additional cases. The majority of these were undiagnosed and unreported to surveillance. This burden was even greater in households where the index case was infected with C. hominis versus C. parvum, or the index case was under five years old, with mums and siblings most at risk of secondary infection. Only having an index case of C. hominis was independently associated with transmission in the multivariable model (OR 4.46; p = 0.01). CONCLUSIONS: Cryptosporidium was a considerable burden in the home. At-risk homes were those where the index was less than five years old and/or infected with C. hominis. Of particular risk were female caregivers and siblings. Hygiene advice should be specifically directed here. This work provides evidence for humans as sources of C. hominis infection and that person-person is a key pathway. We recommend that all stools submitted for the investigation of gastrointestinal pathogens are tested for Cryptosporidium to better capture cases, inclusion of speciation data in routine surveillance, and the consideration of specific clinical advice on prevention for high-risk homes.

Estimating the potential for global dissemination of pandemic pathogens using the global airline network and healthcare development indices.

Pandemics have the potential to incur significant health and economic impacts, and can reach a large number of countries from their origin within weeks. Early identification and containment of a newly emerged pandemic within the source country is key for minimising global impact. To identify a country's potential to control and contain a pathogen with pandemic potential, we compared the quality of a country's healthcare system against its global airline connectivity. Healthcare development was determined using three multi-factorial indices, while detailed airline passenger data was used to identify the global connectivity of all countries. Proximities of countries to a putative 'Worst Case Scenario' (extreme high-connectivity and low-healthcare development) were calculated. We found a positive relationship between a country's connectivity and healthcare metrics. We also identified countries that potentially pose the greatest risk for pandemic dissemination, notably Dominican Republic, India and Pakistan. China and Mexico, both sources of recent influenza and coronavirus pandemics were also identified as among the highest risk countries. Collectively, lower-middle and upper-middle income countries represented the greatest risk, while high income countries represented the lowest risk. Our analysis represents an alternative approach to identify countries where increased within-country disease surveillance and pandemic preparedness may benefit global health.

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.

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.

Epidemiological and clinical characteristics of early COVID-19 cases, United Kingdom of Great Britain and Northern Ireland.

OBJECTIVE: To describe the clinical presentation, course of disease and health-care seeking behaviour of the first few hundred cases of coronavirus disease 2019 (COVID-19) in the United Kingdom of Great Britain and Northern Ireland. METHODS: We implemented the World Health Organization's First Few X cases and contacts investigation protocol for COVID-19. Trained public health professionals collected information on 381 virologically confirmed COVID-19 cases from 31 January 2020 to 9 April 2020. We actively followed up cases to identify exposure to infection, symptoms and outcomes. We also collected limited data on 752 symptomatic people testing negative for COVID-19, as a control group for analyses of the sensitivity, specificity and predictive value of symptoms. FINDINGS: Approximately half of the COVID-19 cases were imported (196 cases; 51.4%), of whom the majority had recent travel to Italy (140 cases; 71.4%). Of the 94 (24.7%) secondary cases, almost all reported close contact with a confirmed case (93 cases; 98.9%), many through household contact (37 cases; 39.8%). By age, a lower proportion of children had COVID-19. Most cases presented with cough, fever and fatigue. The sensitivity and specificity of symptoms varied by age, with nonlinear relationships with age. Although the proportion of COVID-19 cases with fever increased with age, for those with other respiratory infections the occurrence of fever decreased with age. The occurrence of shortness of breath also increased with age in a greater proportion of COVID-19 cases. CONCLUSION: The study has provided useful evidence for generating case definitions and has informed modelling studies of the likely burden of COVID-19.