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.

Understanding norovirus reporting patterns in England: a mixed model approach.

BACKGROUND: Norovirus has a higher level of under-reporting in England compared to other intestinal infectious agents such as Campylobacter or Salmonella, despite being recognised as the most common cause of gastroenteritis globally. In England, this under-reporting is a consequence of the frequently mild/self-limiting nature of the disease, combined with the passive surveillance system for infectious diseases reporting. We investigated heterogeneity in passive surveillance system in order to improve understanding of differences in reporting and laboratory testing practices of norovirus in England. METHODS: The reporting patterns of norovirus relating to age and geographical region of England were investigated using a multivariate negative binomial model. Multiple model formulations were compared, and the best performing model was determined by proper scoring rules based on one-week-ahead predictions. The reporting patterns are represented by epidemic and endemic random intercepts; values close to one and less than one imply a lower number of reports than expected in the given region and age-group. RESULTS: The best performing model highlighted atypically large and small amounts of reporting by comparison with the average in England. Endemic random intercept varied from the lowest in East Midlands in those in the under 5 year age-group (0.36, CI 0.18-0.72) to the highest in the same age group in South West (3.00, CI 1.68-5.35) and Yorkshire & the Humber (2.93, CI 1.74-4.94). Reporting by age groups showed the highest variability in young children. CONCLUSION: We identified substantial variability in reporting patterns of norovirus by age and by region of England. Our findings highlight the importance of considering uncertainty in the design of forecasting tools for norovirus, and to inform the development of more targeted risk management approaches for norovirus disease.

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.

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.

Investigation of a national outbreak of STEC Escherichia coli O157 using online consumer panel control methods: Great Britain, October 2014.

In October 2014, Public Health England (PHE) identified cases of Shiga toxin-producing Escherichia coli (STEC) serogroup O157 sharing a multiple locus variable-number tandem repeat analysis (MLVA) profile. We conducted a case-control study using multivariable logistic regression to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) testing a range of exposures. Cases were defined as laboratory-confirmed STEC O157 with the implicated MLVA profile, were UK residents aged ⩾18 years with symptom onset between 25 September and 30 October 2014, and had no history of travel abroad within 5 days of symptom onset. One hundred and two cases were identified. Cases were mostly female (65%; median age 49, range 2-92 years). It was the second largest outbreak seen in England, to date, and a case-control study was conducted using market research panel controls and online survey methods. These methods were instrumental in the rapid data collection and analysis necessary to allow traceback investigations for short shelf-life products. This is a new method of control recruitment and this is the first in which it was a standalone recruitment method. The case-control study suggested a strong association between consumption of a ready-to-eat food and disease (aOR 28, 95% CI 5·0-157) from one retailer. No reactive microbiological testing of food items during the outbreak was possible due to the short shelf-life of the product. Collaboration with industrial bodies is needed to ensure timely traceback exercises to identify contamination events and initiate appropriate and focused microbiological testing and implement control measures.

Advanced biomaterial strategies to transplant preformed micro-tissue engineered neural networks into the brain.

OBJECTIVE: Connectome disruption is a hallmark of many neurological diseases and trauma with no current strategies to restore lost long-distance axonal pathways in the brain. We are creating transplantable micro-tissue engineered neural networks (micro-TENNs), which are preformed constructs consisting of embedded neurons and long axonal tracts to integrate with the nervous system to physically reconstitute lost axonal pathways. APPROACH: We advanced micro-tissue engineering techniques to generate micro-TENNs consisting of discrete populations of mature primary cerebral cortical neurons spanned by long axonal fascicles encased in miniature hydrogel micro-columns. Further, we improved the biomaterial encasement scheme by adding a thin layer of low viscosity carboxymethylcellulose (CMC) to enable needle-less insertion and rapid softening for mechanical similarity with brain tissue. MAIN RESULTS: The engineered architecture of cortical micro-TENNs facilitated robust neuronal viability and axonal cytoarchitecture to at least 22 days in vitro. Micro-TENNs displayed discrete neuronal populations spanned by long axonal fasciculation throughout the core, thus mimicking the general systems-level anatomy of gray matter-white matter in the brain. Additionally, micro-columns with thin CMC-coating upon mild dehydration were able to withstand a force of 893 ± 457 mN before buckling, whereas a solid agarose cylinder of similar dimensions was predicted to withstand less than 150 µN of force. This thin CMC coating increased the stiffness by three orders of magnitude, enabling needle-less insertion into brain while significantly reducing the footprint of previous needle-based delivery methods to minimize insertion trauma. SIGNIFICANCE: Our novel micro-TENNs are the first strategy designed for minimally invasive implantation to facilitate nervous system repair by simultaneously providing neuronal replacement and physical reconstruction of long-distance axon pathways in the brain. The micro-TENN approach may offer the ability to treat several disorders that disrupt the connectome, including Parkinson's disease, traumatic brain injury, stroke, and brain tumor excision.

Intratympanic Contrast in the Evaluation of Menière Disease: Understanding the Limits.

BACKGROUND AND PURPOSE: Studies describing endolymphatic hydrops in Menière disease after off-label intratympanic gadolinium-based contrast have been limited by long acquisition times. We aimed to demonstrate the feasibility of post-intratympanic imaging on a 3T MR imaging system within a clinically tolerable acquisition time and to address potential pitfalls in acquisition or interpretation. MATERIALS AND METHODS: FDA Investigational New Drug 115,342 and institutional review board approval were obtained for intratympanic injection of 8-fold diluted Gd-DTPA into the more symptomatic ear of 6 adults with Menière disease. 3T MR imaging was performed using a 3-inch surface coil before and up to 28 hours after injection using FLAIR to define the nonenhancing endolymphatic space within the enhancing perilymph. Variable FLAIR TI images were used to determine the impact of fluid-suppression on interpretation. Image quality was assessed for perilymphatic and extralabyrinthine contrast enhancement, definition of endolymphatic anatomy, and other anatomic variants or pathologic findings. RESULTS: The surface coil afforded 0.375 × 0.375 mm in-plane FLAIR resolution in <4 minutes 30 seconds, sufficient to perceive the nonenhancing spiral lamina, interscalar septa, and endolymphatic structures. Coronal views highlighted a potential interpretation pitfall of vestibular endolymphatic distention overestimation due to partial volume averaging. Varying FLAIR TI resulted in visible changes in the perception of the cochlear endolymphatic space. CSF enhancement was detectable at the internal auditory canal fundus on the injected side in half of the patients, which may confound interpretation. CONCLUSIONS: Using a surface coil preserves high resolution within a clinically acceptable acquisition time. Pitfalls remain regarding the interpretation of these images and optimizing protocols across platforms in the absence of a clear internal reference for standardization.

The development of Web-based surveillance provides new insights into the burden of norovirus outbreaks in hospitals in England.

A new surveillance system for outbreaks of norovirus in English hospitals, the hospital norovirus outbreak reporting system (HNORS), was launched in January 2009. On site investigators were enabled to enter data on outbreaks of norovirus directly onto a tailored system via an Internet-based front end. A standard dataset was designed to collect information describing the key epidemiological characteristics of each outbreak. In the period 1992-2008, 1817 suspected and confirmed outbreaks of norovirus in English hospitals were reported to national surveillance. After introduction of the new system there were 3980 reports of outbreaks of suspected and confirmed norovirus received in the years 2009-2011. Data from the new reporting system demonstrates that transmission of norovirus levies a heavy burden on English hospitals. On average, reported outbreaks are associated with 13,000 patients and 3400 staff becoming ill, 8900 days of ward closure and the loss of over 15,500 bed-days annually.

Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies.

The hypothesis is that the mechanical mismatch between brain tissue and microelectrodes influences the inflammatory response. Our unique, mechanically adaptive polymer nanocomposite enabled this study within the cerebral cortex of rats. The initial tensile storage modulus of 5 GPa decreases to 12 MPa within 15 min under physiological conditions. The response to the nanocomposite was compared to surface-matched, stiffer implants of traditional wires (411 GPa) coated with the identical polymer substrate and implanted on the contralateral side. Both implants were tethered. Fluorescent immunohistochemistry labeling examined neurons, intermediate filaments, macrophages, microglia and proteoglycans. We demonstrate, for the first time, a system that decouples the mechanical and surface chemistry components of the neural response. The neuronal nuclei density within 100 µm of the device at four weeks post-implantation was greater for the compliant nanocomposite compared to the stiff wire. At eight weeks post-implantation, the neuronal nuclei density around the nanocomposite was maintained, but the density around the wire recovered to match that of the nanocomposite. The glial scar response to the compliant nanocomposite was less vigorous than it was to the stiffer wire. The results suggest that mechanically associated factors such as proteoglycans and intermediate filaments are important modulators of the response of the compliant nanocomposite.

Motor asymmetry and estimation of body-scaled aperture width in Parkinson's disease.

The present study examined how asymmetrical motor symptomatology helps predict the pattern of perceptual judgements of body-scaled aperture width in lateralised Parkinson's disease (PD). Eleven patients with PD predominantly affecting the left side of their body (LPD), 16 patients with PD predominantly affecting their right side (RPD), and 16 healthy controls made forced-choice judgements about whether or not they would fit without turning their shoulders through a life-sized schematic doorway shown on a large screen. Whereas control and LPD groups made accurate estimations of body-scaled aperture width, RPD patients significantly underestimated aperture width relative to their body, perceiving doorways on average that were 12% narrower than their bodies as wide enough to allow them to pass through without rotation. Across all patients, estimates of body-scaled aperture width correlated with ratio of right-to-left symptom severity. These perceptual errors may indicate a mismatch between the neural representation of external space and that of body size in PD.

In vivo deployment of mechanically adaptive nanocomposites for intracortical microelectrodes.

We recently introduced a series of stimuli-responsive, mechanically adaptive polymer nanocomposites. Here, we report the first application of these bio-inspired materials as substrates for intracortical microelectrodes. Our hypothesis is that the ideal electrode should be initially stiff to facilitate minimal trauma during insertion into the cortex, yet become mechanically compliant to match the stiffness of the brain tissue and minimize forces exerted on the tissue, attenuating inflammation. Microprobes created from mechanically reinforced nanocomposites demonstrated a significant advantage compared to model microprobes composed of neat polymer only. The nanocomposite microprobes exhibit a higher storage modulus (E' = ~5 GPa) than the neat polymer microprobes (E' = ~2 GPa) and can sustain higher loads (~12 mN), facilitating penetration through the pia mater and insertion into the cerebral cortex of a rat. In contrast, the neat polymer microprobes mechanically failed under lower loads (~7 mN) before they were capable of insertion into cortical tissue. Further, we demonstrated the material's ability to morph while in the rat cortex to more closely match the mechanical properties of the cortical tissue. Nanocomposite microprobes that were implanted into the rat cortex for up to eight weeks demonstrated increased cell density at the microelectrode-tissue interface and a lack of tissue necrosis or excessive gliosis. This body of work introduces our nanocomposite-based microprobes as adaptive substrates for intracortical microelectrodes and potentially for other biomedical applications.

Carotid endarterectomy for symptomatic, but "haemodynamically insignificant" carotid stenosis.

OBJECTIVE: Carotid endarterectomy (CEA) guidelines in symptomatic carotid stenosis are based on NASCET and ECST criteria with 70% or greater carotid stenosis as estimated from a catheter angiogram the major indication. This has several problems: (1) lack of reliable correlation between non-invasive imaging and catheter angiography, which has been largely superseded by non-invasive imaging in investigating carotid stenosis; (2) errors inherent in estimating the degree of stenosis from catheter angiography; (3) disregard for the fact that stroke risk also depends on plaque stability, and number of ischaemic events. METHODS: A retrospective review of ischaemic events, imaging results, operative findings, surgical complications and stroke-free follow-up in 31 patients presenting over a 23 year period with TIA/stroke (symptoms lasting > 24 h and/or imaging evidence of infarction) who had 70% or less carotid stenosis (on non-invasive imaging), but nonetheless underwent CEA. RESULTS: Nineteen patients had small strokes, 7 had TIAs and 5 had ocular events; 28 patients had features of unstable plaque on imaging; 19 patients experienced multiple events before CEA. All had haemorrhagic, ruptured plaque at CEA. One patient suffered an intra-operative stroke, only 1 patient suffered a further stroke/TIA (mean follow-up 4.2 years). CONCLUSION: To predict the likelihood of major stroke in symptomatic carotid stenosis and the benefit of CEA, plaque stability and the number of ischaemic events might be as important as an estimate of the degree of stenosis.

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.

Improved outcomes with endovascular stent grafts for thoracic aorta transections.

OBJECTIVE: To retrospectively assess the outcome of endovascular stent-graft implantation for thoracic aortic transections (ETAT). DESIGN: Retrospective review. METHODS: 16 patients median age 30 years, treated between May 2000 and April 2007. Median injury severity score was 33 (range 29 to 66) in 14 acute patients; 2 patients had thoracic pseudoaneurysms. The Cook-Zenith endograft was used in eight patients, Medtronic-Talent (6) and Gore-Excluder (2). Average procedure time was 90 minutes, blood loss 100 (range 40 to 3000) mls, screening time 10.8 (range 5.9 to 22.6) minutes, and contrast dose was 195 (range 60 to 400) mls. RESULTS: Graft deployment was successful in all cases. There was one death within 30 days. The left subclavian artery was completely covered in one case, and partially in three. Two patients had Type I endoleak, and one delayed Type II endoleak. One patient had iatrogenic right coronary artery dissection. Two patients developed difficult to treat hypertension, and one acute renal failure. CONCLUSION: Endovascular intervention is a safe and effective treatment for aortic transection in multiple trauma patients. ETAT reduces the major morbidity and mortality associated with open repair in multiple trauma patients. The majority of these patients are young and long-term follow up is necessary to assess graft durability.

Evaluating rotavirus vaccination in England and Wales. Part I. Estimating the burden of disease.

Rotavirus is a major cause of gastroenteritis in young children. New vaccines for rotavirus are now available and countries need to establish the health and economic burden of rotavirus disease to assess whether vaccine introduction is advisable. This study assesses the fraction of acute gastroenteritis in children under 5 years that may be attributable to rotavirus using multiple linear regression. Results suggest around 45% of hospitalisations, 25% of GP consultations, 27% of NHS Direct calls and 20% of accident and emergency (A&E) attendances for acute gastroenteritis in this age group may be attributable to rotavirus. The annual incidence is estimated to be 4.5 hospitalisations, 9.3 A&E consultations, and 28-44 GP consultations per 1000 children under five years of age. The cost to the health service is estimated to be pound 14.2m per annum. Rotavirus vaccination has the potential to reduce this burden of disease. This study provides a sound basis on which to make this assessment and serves as a baseline against which any reductions that do occur if vaccination is introduced can be measured against.

Endovascular popliteal aneurysm repair: are the results comparable to open surgery?

INTRODUCTION: The aim of this study was to review our experience of popliteal aneurysms using endovascular techniques. METHODS: Thirty popliteal aneurysms in 25 patients were treated over an 11-year period. Median aneurysm diameter was 26 (16-48) mm. Five were symptomatic and 25 asymptomatic. Patients were treated with the Haemobahn/Viabahn stent-graft (26), Passager (two), Aneurx (one), and PTFE homemade device (one). Data were assessed using life table analysis, and expressed as cumulative patency rates and standard error (SE). RESULTS: Median follow-up was 24 (range 1-95) months. Primary patency was 92.9% (SE 4.5%), 84.7% (SE 6.8%), 80% (SE 8.2%), 74.5% (SE 9.4%) and 74.5% (11.3%) at 1, 6, 12, 24 and 36 months, respectively. Cumulative secondary patency was 96.5% (SE 3.3%), 88.7% (SE 6.0%), 88.7% (SE 8.6%), 83.2% (SE 8.0%) and 83.2% (SE 9.8%) at 1, 6, 12, 24 and 36 months, respectively. CONCLUSION: Endovascular treatment of popliteal aneurysms in this series achieved patency rates similar to open surgery. Aneurysm repair was performed without peroperative deaths and the risks associated with open surgery.

Complications of aortic endografting.

Endovascular repair of abdominal aortic aneurysm has been shown to have a significantly lower perioperative mortality rate compared with open repair. It has been a blessing for patients at high risk who were previously denied treatment for their aortic aneurysms. It does, however, have a substantial need for re-intervention for complications. Many of these complications including endoleak, endotension, migration, post implant syndrome and conversion to open repair are unique to endovascular aneurysm repair. Others including injury to the iliac arteries, graft limb thromboses and structural failure of prostheses occur with greater frequency in endovascular repair compared with open repair. It is important, therefore, for vascular surgeons to be aware of these complications including their prevention and appropriate that patients are informed of their incidence. This review discusses the local and vascular complications of endovascular repair of abdominal aortic aneurysm with an emphasis on newer aspects.