School-based surveillance of acute infectious disease in children: a systematic review.

BACKGROUND: Syndromic surveillance systems are an essential component of public health surveillance and can provide timely detection of infectious disease cases and outbreaks. Whilst surveillance systems are generally embedded within healthcare, there is increasing interest in novel data sources for monitoring trends in illness, such as over-the-counter purchases, internet-based health searches and worker absenteeism. This systematic review considers the utility of school attendance registers in the surveillance of infectious disease outbreaks and occurrences amongst children. METHODS: We searched eight databases using key words related to school absence, infectious disease and syndromic surveillance. Studies were limited to those published after 1st January 1995. Studies based in nursery schools or higher education settings were excluded. Article screening was undertaken by two independent reviewers using agreed eligibility criteria. Data extraction was performed using a standardised data extraction form. Outcomes included estimates of absenteeism, correlation with existing surveillance systems and associated lead or lag times. RESULTS: Fifteen studies met the inclusion criteria, all of which were concerned with the surveillance of influenza. The specificity of absence data varied between all-cause absence, illness absence and syndrome-specific absence. Systems differed in terms of the frequency of data submissions from schools and the level of aggregation of the data. Baseline rates of illness absence varied between 2.3-3.7%, with peak absences ranging between 4.1-9.8%. Syndrome-specific absenteeism had the strongest correlation with other surveillance systems (r = 0.92), with illness absenteeism generating mixed results and all-cause absenteeism performing the least well. A similar pattern of results emerged in terms of lead and lag times, with influenza-like illness (ILI)-specific absence providing a 1-2 week lead time, compared to lag times reported for all-cause absence data and inconsistent results for illness absence data. CONCLUSION: Syndrome-specific school absences have potential utility in the syndromic surveillance of influenza, demonstrating good correlation with healthcare surveillance data and a lead time of 1-2 weeks ahead of existing surveillance measures. Further research should consider the utility of school attendance registers for conditions other than influenza, to broaden our understanding of the potential application of this data for infectious disease surveillance in children. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2019 CRD42019119737.

Risk factors associated with outbreaks of seasonal infectious disease in school settings, England, UK.

Children are important transmitters of infection. Within schools they encounter large numbers of contacts and infections can spread easily causing outbreaks. However, not all schools are affected equally. We conducted a retrospective analysis of school outbreaks to identify factors associated with the risk of gastroenteritis, influenza, rash or other outbreaks. Data on reported school outbreaks in England were obtained from Public Health England and linked with data from the Department for Education and the Office for Standards in Education, Children's Services and Skills (Ofsted). Primary and all-through schools were found to be at increased risk of outbreaks, compared with secondary schools (odds ratio (OR) 5.82, 95% confidence interval (CI) 4.50-7.58 and OR 4.66, 95% CI 3.27-6.61, respectively). School size was also significantly associated with the risk of outbreaks, with higher odds associated with larger schools. Attack rates were higher in gastroenteritis and influenza outbreaks, with lower attack rates associated with rashes (relative risk 0.17, 95% CI 0.15-0.20). Deprivation and Ofsted rating were not associated with either outbreak occurrence or the subsequent attack rate. This study identifies primary and all-through schools as key settings for health protection interventions. Public health teams need to work closely with these schools to encourage early identification and reporting of outbreaks.

Regional differences in presence of Shiga toxin-producing Escherichia coli virulence-associated genes in the environment in the North West and East Anglian regions of England.

Shiga toxin-producing Escherichia coli is carried in the intestine of ruminant animals, and outbreaks have occurred after contact with ruminant animals or their environment. The presence of STEC virulence genes in the environment was investigated along recreational walking paths in the North West and East Anglia regions of England. In all, 720 boot sock samples from walkers' shoes were collected between April 2013 and July 2014. Multiplex PCR was used to detect E. coli based on the amplification of the uidA gene and investigate STEC-associated virulence genes eaeA, stx1 and stx2. The eaeA virulence gene was detected in 45·5% of the samples, where stx1 and/or stx2 was detected in 12·4% of samples. There was a difference between the two regions sampled, with the North West exhibiting a higher proportion of positive boot socks for stx compared to East Anglia. In univariate analysis, ground conditions, river flow and temperature were associated with positive boot socks. The detection of stx genes in the soil samples suggests that STEC is present in the English countryside and individuals may be at risk for infection after outdoor activities even if there is no direct contact with animals. SIGNIFICANCE AND IMPACT OF THE STUDY: Several outbreaks within the UK have highlighted the danger of contracting Shiga toxin-producing Escherichia coli from contact with areas recently vacated by livestock. This is more likely to occur for STEC infections compared to other zoonotic bacteria given the low infectious dose required. While studies have determined the prevalence of STEC within farms and petting zoos, determining the risk to individuals enjoying recreational outdoor activities that occur near where livestock may be present is less researched. This study describes the prevalence with which stx genes, indicative of STEC bacteria, were found in the environment in the English countryside.

Influence of socio-economic status on Shiga toxin-producing Escherichia coli (STEC) infection incidence, risk factors and clinical features.

Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010-2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19-2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10-1.75) and hospitalisation (OR 1.71, 95% CI 1.36-2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16-2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40-2.27; OR 1.85, 95% CI 1.35-2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22-2.70; soil contact, OR 1.52, 95% CI 2.13-1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.

Symptom profiling for infectious intestinal disease (IID): a secondary data analysis of the IID2 study.

Less than half of stool samples from people symptomatic with infectious intestinal disease (IID) will identify a causative organism. A secondary data analysis was undertaken to explore whether symptomology alone could be used to make inferences about causative organisms. Data were utilised from the Second Study of Infectious Intestinal Disease in the Community. A total of 844 cases were analysed. Few symptoms differentiated individual pathogens, but grouping pathogens together showed that viral IID was more likely when symptom onset was in winter (odds ratio (OR) 2.08, 95% confidence interval (CI) 1.16-3.75) or spring (OR 1.92, 95% CI 1.11-3.33), the patient was aged under 5 years (OR 3.63, 95% CI 2.24-6.03) and there was loss of appetite (OR 2.19, 95% CI 1.29-3.72). The odds of bacterial IID were higher with diarrhoea in the absence of vomiting (OR 3.54, 95% CI 2.37-5.32), diarrhoea which persisted for >3 days (OR 2.69, 95% CI 1.82-3.99), bloody diarrhoea (OR 4.17, 95% CI 1.63-11.83) and fever (OR 1.67, 95% CI 1.11-2.53). Symptom profiles could be of value to help guide clinicians and public health professionals in the management of IID, in the absence of microbiological confirmation.

The use of capture-recapture methods to provide better estimates of the burden of norovirus outbreaks from seafood in England, 2004-2011.

Norovirus (NoV) is the greatest cause of infectious intestinal disease in the UK. The burden associated with foodborne outbreaks is underestimated in part because data are dispersed across different organisations. Each looks at outbreaks through a different lens. To estimate the burden of NoV from seafood including shellfish we used a capture-recapture technique using datasets from three different organisations currently involved in collecting information on outbreaks. The number of outbreaks of NoV related to seafood including shellfish in England was estimated for the period of 2004-2011. The combined estimates were more than three times as high (N = 360 using Chao's sample coverage approach) as the individual count from organisation three (N = 115), which captured more outbreaks than the other two organisations. The estimates were calculated for both independence and dependence between the datasets. There was evidence of under-reporting of NoV outbreaks and inconsistency of reporting between organisations, which means that, currently, more than one data source needs to be used to estimate as accurately as possible the total number of NoV outbreaks and associated cases. Furthermore, either the integration of reporting mechanisms or simplifying the process of reporting outbreaks to organisations is essential for understanding and, hence, controlling disease burden.

Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs in chronic HBV infection.

The underlying mechanism of coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antigen antibody (anti-HBs) is still controversial. To identify the host genetic factors related to this unusual clinical phenomenon, a two-stage study was conducted in the Chinese Han population. In the first stage, we performed a case-control (1:1) age- and gender-matched study of 101 cases with concurrent HBsAg and anti-HBs and 102 controls with negative HBsAg and positive anti-HBs using whole exome sequencing. In the second validation stage, we directly sequence the 16 exons on the OAS3 gene in two dependent cohorts of 48 cases and 200 controls. Although, in the first stage, a genome-wide association study of 58,563 polymorphism variants in 101 cases and 102 controls found no significant loci (P-value ≤ .05/58563), and neither locus achieved a conservative genome-wide significance threshold (P-value ≤ 5e-08), gene-based burden analysis showed that OAS3 gene rare variants were associated with the coexistence of HBsAg and anti-HBs. (P-value = 4.127e-06 ≤ 0.05/6994). A total of 16 rare variants were screened out from 21 cases and 3 controls. In the second validation stage, one case with a stop-gained rare variant was identified. Fisher's exact test of all 149 cases and 302 controls showed that the rare coding sequence mutations were more frequent in cases vs controls (P-value = 7.299e-09, OR = 17.27, 95% CI [5.01-58.72]). Protein-coding rare variations on the OAS3 gene are associated with the coexistence of HBsAg and anti-HBs in patients with chronic HBV infection in Chinese Han population.

Towards an integrated food safety surveillance system: a simulation study to explore the potential of combining genomic and epidemiological metadata.

Foodborne infection is a result of exposure to complex, dynamic food systems. The efficiency of foodborne infection is driven by ongoing shifts in genetic machinery. Next-generation sequencing technologies can provide high-fidelity data about the genetics of a pathogen. However, food safety surveillance systems do not currently provide similar high-fidelity epidemiological metadata to associate with genetic data. As a consequence, it is rarely possible to transform genetic data into actionable knowledge that can be used to genuinely inform risk assessment or prevent outbreaks. Big data approaches are touted as a revolution in decision support, and pose a potentially attractive method for closing the gap between the fidelity of genetic and epidemiological metadata for food safety surveillance. We therefore developed a simple food chain model to investigate the potential benefits of combining 'big' data sources, including both genetic and high-fidelity epidemiological metadata. Our results suggest that, as for any surveillance system, the collected data must be relevant and characterize the important dynamics of a system if we are to properly understand risk: this suggests the need to carefully consider data curation, rather than the more ambitious claims of big data proponents that unstructured and unrelated data sources can be combined to generate consistent insight. Of interest is that the biggest influencers of foodborne infection risk were contamination load and processing temperature, not genotype. This suggests that understanding food chain dynamics would probably more effectively generate insight into foodborne risk than prescribing the hazard in ever more detail in terms of genotype.

Existing medications among non-pregnancy-related listeriosis patients in England, 2007-2009.

To identify which medications were most commonly taken by non-pregnancy-related listeriosis patients prior to illness, we compared the medications reported by 512 cases identified via national surveillance in England between 2007 and 2009 with national prescription data, using British National Formulary (BNF) coding. Relative risks and corresponding confidence intervals were calculated, as appropriate, for BNF chapters and sections. Among listeriosis cases, the rates for cytotoxic drugs, drugs affecting the immune response and corticosteroids were significantly higher than for other medications. However, interactions between medications and how medications might confound or be confounded by concurrent medical conditions need to be investigated further. Nevertheless our findings suggest that targeting food-safety advice to prevent this foodborne disease in certain treatment groups is warranted.