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.

Identifying the seasonal origins of human campylobacteriosis.

Human campylobacteriosis exhibits a distinctive seasonality in temperate regions. This paper aims to identify the origins of this seasonality. Clinical isolates [typed by multi-locus sequence typing (MLST)] and epidemiological data were collected from Scotland. Young rural children were found to have an increased burden of disease in the late spring due to strains of non-chicken origin (e.g. ruminant and wild bird strains from environmental sources). In contrast the adult population had an extended summer peak associated with chicken strains. Travel abroad and UK mainland travel were associated with up to 17% and 18% of cases, respectively. International strains were associated with chicken, had a higher diversity than indigenous strains and a different spectrum of MLST types representative of these countries. Integrating empirical epidemiology and molecular subtyping can successfully elucidate the seasonal components of human campylobacteriosis. The findings will enable public health officials to focus strategies to reduce the disease burden.

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.

Community incidence of pathogen-specific gastroenteritis: reconstructing the surveillance pyramid for seven pathogens in seven European Union member states.

By building reconstruction models for a case of gastroenteritis in the general population moving through different steps of the surveillance pyramid we estimated that millions of illnesses occur annually in the European population, leading to thousands of hospitalizations. We used data on the healthcare system in seven European Union member states in relation to pathogen characteristics that influence healthcare seeking. Data on healthcare usage were obtained by harmonized cross-sectional surveys. The degree of under-diagnosis and underreporting varied by pathogen and country. Overall, underreporting and under-diagnosis were estimated to be lowest for Germany and Sweden, followed by Denmark, The Netherlands, UK, Italy and Poland. Across all countries, the incidence rate was highest for Campylobacter spp. and Salmonella spp. Incidence estimates resulting from the pyramid reconstruction approach are adjusted for biases due to different surveillance systems and are therefore a better basis for international comparisons than reported data.

Molecular epidemiology of human Campylobacter jejuni shows association between seasonal and international patterns of disease.

We sought to explain seasonality and other aspects of Campylobacter jejuni epidemiology by integrating population genetic and epidemiological analysis in a large 3-year longitudinal, two-centre, population-based study. Epidemiological information was collected for 1505 isolates, which were multilocus sequence-typed. Analyses compared pathogen population structure between areas, over time, and between clinical presentations. Pooled analysis was performed with published international datasets. Subtype association with virulence was not observed. UK sites had nearly identical C. jejuni populations. A clade formed by ST45 and ST283 clonal complexes showed a summer peak. This clade was common in a Finnish dataset but not in New Zealand and Australian collections, countries with less marked seasonality. The UK, New Zealand and Australian collections were otherwise similar. These findings map to known in-vitro differences of this clade. This identifies a target for studies to elucidate the drivers of the summer peak in human C. jejuni infection.

The role of sunlight exposure in determining the vitamin D status of the U.K. white adult population.

BACKGROUND: Vitamin D is necessary for bone health and is potentially protective against a range of malignancies. Opinions are divided on whether the proposed optimal circulating 25-hydroxyvitamin D [25(OH)D] level (≥ 32 ng mL⁻¹) is an appropriate and feasible target at population level. OBJECTIVES: We examined whether personal sunlight exposure levels can provide vitamin D sufficient (≥ 20 ng mL⁻¹) and optimal status in the U.K. public. METHODS: This prospective cohort study measured circulating 25(OH)D monthly for 12 months in 125 white adults aged 20-60 years in Greater Manchester. Dietary vitamin D and personal ultraviolet radiation (UVR) exposure were assessed over 1-2 weeks in each season. The primary analysis determined the post-summer peak 25(OH)D required to maintain sufficiency in wintertime. RESULTS: Dietary vitamin D remained low in all seasons (median 3·27 µg daily, range 2·76-4·15) while personal UVR exposure levels were high in spring and summer, low in autumn and negligible in winter. Mean 25(OH)D levels were highest in September [28·4 ng mL⁻¹; 28% optimal, zero deficient (<5 ng mL⁻¹)], and lowest in February (18·3 ng mL⁻¹; 7% optimal, 5% deficient). A February 25(OH)D level of 20 ng mL⁻¹ was achieved following a mean (95% confidence interval) late summer level of 30·4 (25·6-35·2) and 34·9 (27·9-41·9) ng mL⁻¹ in women and men, respectively, with 62% of variance explained by gender and September levels. CONCLUSIONS: Late summer 25(OH)D levels approximating the optimal range are required to retain sufficiency throughout the U.K. winter. Currently the majority of the population fails to reach this post-summer level and becomes vitamin D insufficient during the winter.

Haplotype-dependent HLA susceptibility to nasopharyngeal carcinoma in a Southern Chinese population.

We have conducted a comprehensive case-control study of a nasopharyngeal carcinoma (NPC) population cohort from Guangxi Province of Southern China, a region with one of the highest NPC incidences on record. A total of 1407 individuals including NPC patients, healthy controls, and their adult children were examined for the human leukocyte antigen (HLA) association, which is so far the largest NPC cohort reported for such studies. Stratified analysis performed in this study clearly demonstrated that while NPC protection is associated with independent HLA alleles, most NPC susceptibility is strictly associated with HLA haplotypes. Our study also detected for the first time that A(*)0206, a unique A2 subtype to South and Southeast Asia is also associated with a high risk for NPC. HLA-A(*)0206, HLA-B(*)3802 alleles plus the A(*)0207-B(*)4601 and A(*)3303-B(*)5801 haplotypes conferred high risk for NPC showing a combined odds ratio (OR) of 2.6 (P<0.0001). HLA alleles that associate with low risk for NPC include HLA-A(*)1101, B(*)27, and B(*)55 with a combined OR of 0.42 (P<0.0001). The overall high frequency of NPC-susceptible HLA factors in the Guangxi population is likely to have contributed to the high-NPC incidence in this region.

Widespread retinal degenerative disease mutation (rdAc) discovered among a large number of popular cat breeds.

The recent discovery of a mutational variant in the CEP290 gene (CEP290: IVS50+9T>G), conferring recessive retinal degeneration in Abyssinian and Somali (long-haired Abyssinian) cats (rdAc) prompted a survey among 41 cat breeds (846 individuals) to assess the incidence, frequency and clinical consequence of rdAc. The rdAc allele displayed widespread distribution, observed in 16/43 (37%) breeds, exhibiting a high allele frequency (∼33%) in North American and European Siamese populations. Clinical evaluations demonstrated high concordance between rdAc pathology and the CEP290 (IVS50+9T>G) homozygous genotype (P=1.1E-6), with clinical disease similar to affected Abyssinians/Somalis. This retinal degeneration has not been reported in breeds other than the Abyssinian/Somali and poses a significant health risk particularly in the Siamese breed group. Alertness of the veterinary community and the present availability of commercial diagnostic testing could synergistically enable breeders to reduce the incidence of rdAc blindness in pure-bred cat populations.

Infection control measures for norovirus: a systematic review of outbreaks in semi-enclosed settings.

We carried out a review of published, peer-reviewed articles to assess the evidence for effectiveness of control measures during norovirus outbreaks in enclosed settings. There were 47 papers identified for review, some of which reported more than one outbreak, providing 72 outbreaks for analysis. We extracted the following data items: attack rates; the number of people affected and at risk, case or outbreak definition; whether outbreak control measures were implemented; and claims of effectiveness of interventions. We analysed the data to identify any differences in the outbreaks experienced in different settings and any differences experienced during outbreaks according to whether control measures were implemented or not. All of the reviewed papers described outbreaks occurring in industrialised countries. We found no evidence that implementing infection control measures affected the duration of outbreaks, or the attack rates either overall (all settings combined) or within particular settings. The median outbreak duration was 16 days (range: 1-44) compared with 14 (range: 2-92) where control measures were and were not utilized, respectively. Sound infection control procedures are key to controlling norovirus outbreaks but unfortunately, the present body of the published literature does not provide an evidence-base for the value of specific measures.

Is there a need to include HIV, HBV and HCV viruses in the Saudi premarital screening program on the basis of their prevalence and transmission risk factors?

BACKGROUND: In January 2008, the Saudi Arabian health authority included mandatory testing for HIV, HBV and HCV viruses in the premarital screening program. Epidemiologically, there were few justifications for their inclusion as disease prevalences and distributions are poorly understood in the population. This study aims to provide information about HBV, HCV and HIV prevalences and risk factors for disease transmission and so produce evidence for informed decision-making on the inclusion of these infectious diseases in the screening program. METHODS: This is a cross-sectional descriptive study embedded in the existing national premarital screening program for thalassaemia and sickle cell disease to estimate the prevalence of HIV, HBV and HCV infections (n=74,662 individuals), followed by a case-control study to identify risk factors responsible for infection transmission (n=540). RESULTS: The average HIV prevalence is 0.03%, 1.31% for HBV and 0.33% for HCV. Sharing personal belongings particularly razors, blood transfusions, cuts at barbershops and extramarital relationships showed the highest significant associations with the transmission of these viruses. CONCLUSION: The prevalences of HIV, HBV and HCV in Saudi Arabia are among the lowest worldwide. However, all the important risk factors associated with transmitting these viruses are significantly present in the Saudi community. Saudi Arabia is financially capable of screening for these infections in the mandatory premarital program and of providing medical care for the discovered cases, but focusing on the health education programs may offset the need to mandatory testing.

Extended IL10 haplotypes and their association with HIV progression to AIDS.

Interleukin-10 (IL-10) is a pleiotropic cytokine with both immunosuppressive and immunostimulatory functions. Its roles in infections and autoimmunity may have resulted in selective pressures on polymorphisms within the gene, leading to genomic coexistence of several semi-conserved haplotypes involved with diverse pathogen interactions during genomic evolution. Previous studies focused either exclusively on promoter haplotypes or on individual SNPs. We genotyped 21 single nucleotide polymorphisms in the human IL10 gene and examined this variation compared to other mammalian species sequences. Haplotype heterogeneity in human populations is centered around 'classic' 'proximal' promoter polymorphisms: -592, -819 and -1082. High-producing GCC haplotypes are by far the most numerous and diverse group, the intermediate IL-10 producing ACC-inclusive haplotypes seem to be related most closely to the ancestral haplotype, and the ATA-inclusive haplotypes cluster a separate branch with strong bootstrap support. We looked at associations of corresponding haplotypes with HIV progression. A haplotype trend regression confirmed that individuals carrying the low-producing ATA-inclusive haplotypes in European Americans progress to AIDS faster, and most likely explain the role of IL10. Our findings are consistent with the hypothesis that existing polymorphisms in this gene may reflect a balance of historic adaptive responses to autoimmune, infectious and other disease agents.

Chromosome painting shows that skunks (Mephitidae, Carnivora) have highly rearranged karyotypes.

The karyotypic relationships of skunks (Mephitidae) with other major clades of carnivores are not yet established. Here, multi-directional chromosome painting was used to reveal the karyological relationships among skunks and between Mephitidae (skunks) and Procyonidae (raccoons). Representative species from three genera of Mephitidae (Mephitis mephitis, 2n = 50; Mephitis macroura, 2n = 50; Conepatus leuconotus, 2n = 46; Spilogale gracilis, 2n = 60) and one species of Procyonidae (Procyon lotor, 2n = 38) were studied. Chromosomal homology was mapped by hybridization of five sets of whole-chromosome paints derived from stone marten (Martes foina, 2n = 38), cat, skunks (M. mephitis; M. macroura) and human. The karyotype of the raccoon is highly conserved and identical to the hypothetical ancestral musteloid karyotype, suggesting that procyonids have a particular importance for establishing the karyological evolution within the caniforms. Ten fission events and five fusion events are necessary to generate the ancestral skunk karyotype from the ancestral carnivore karyotype. Our results show that Mephitidae joins Canidae and Ursidae as the third family of carnivores that are characterized by a high rate of karyotype evolution. Shared derived chromosomal fusion of stone marten chromosomes 6 and 14 phylogenetically links the American hog-nosed skunk and eastern spotted skunk.