Shedding and exclusion from childcare in children with Shiga toxin-producing Escherichia coli, 2018-2022.

Excluding children with Shiga toxin-producing Escherichia coli (STEC) from childcare until microbiologically clear of the pathogen, disrupts families, education, and earnings. Since PCR introduction, non-O157 STEC serotype detections in England have increased. We examined shedding duration by serotype and transmission risk, to guide exclusion advice. We investigated STEC cases aged <6 years, residing in England and attending childcare, with diarrhoea onset or sample date from 31 March 2018 to 30 March 2022. Duration of shedding was the interval between date of onset or date first positive specimen and earliest available negative specimen date. Transmission risk was estimated from proportions with secondary cases in settings attended by infectious cases. There were 367 cases (STEC O157 n = 243, 66.2%; STEC non-O157 n = 124, 33.8%). Median shedding duration was 32 days (IQR 20-44) with no significant difference between O157 and non-O157; 2% (n = 6) of cases shed for ≥100 days. Duration of shedding was reduced by 17% (95% CI 4-29) among cases reporting bloody diarrhoea. Sixteen settings underwent screening; four had secondary cases (close contacts' secondary transmission rate = 13%). Shedding duration estimates were consistent with previous studies (median 31 days, IQR 17-41). Findings do not warrant guidance changes regarding exclusion and supervised return of prolonged shedders, despite serotype changes.

Cluster detection with random neighbourhood covering: Application to invasive Group A Streptococcal disease.

The rapid detection of outbreaks is a key step in the effective control and containment of infectious diseases. In particular, the identification of cases which might be epidemiologically linked is crucial in directing outbreak-containment efforts and shaping the intervention of public health authorities. Often this requires the detection of clusters of cases whose numbers exceed those expected by a background of sporadic cases. Quantifying exceedances rapidly is particularly challenging when only few cases are typically reported in a precise location and time. To address such important public health concerns, we present a general method which can detect spatio-temporal deviations from a Poisson point process and estimate the odds of an isolate being part of a cluster. This method can be applied to diseases where detailed geographical information is available. In addition, we propose an approach to explicitly take account of delays in microbial typing. As a case study, we considered invasive group A Streptococcus infection events as recorded and typed by Public Health England from 2015 to 2020.

The risk of all-cause mortality associated with anxiety: a retrospective cohort study using 'The Health Improvement Network' database.

BACKGROUND: Anxiety is a prevalent condition with a substantial associated burden of morbidity. Previous literature investigating effects of anxiety on mortality rates has found conflicting results. This is in part due to inadequate consideration of comorbid depression as a confounder and analysing sub-types of anxiety together. The objective of this study was to compare mortality risks in people diagnosed with anxiety. METHODS: We undertook a retrospective cohort study using the 'The Health Improvement Network' database (a UK primary care dataset) between 1st January 2005 to 1st January 2018. 345 903 patients with anxiety (exposed group) were matched to 691 449 unexposed patients. Cox regression analyses were used to adjusted hazard ratios (HRs) for mortality risk. RESULTS: During the study period 18 962 patients (5·5%) died in the exposed group compared to 32 288 (4·7%) in the unexposed group. This translated into a crude HR for all of 1·14 (95% CI 1·12 - 1·16), which remained significant after adjustment for key co-variates (including depression) giving a final HR of 1·05 (95% CI 1·03 - 1·07). When broken down by sub-type of anxiety (10·3% (35, 581) had phobias, 82·7% (385,882) has 'other' types, and 7·0% (24,262) had stress related anxiety) there were markedly different effect sizes. The adjusted model for the stress-related anxiety sub-type demonstrated a HR of 0·88 (95% CI 0·80 - 0·97). Conversely, the HR was increased in 'other' sub-types to 1·07 (95% CI 1·05 - 1·09) and non-significant in phobia types of anxiety. CONCLUSION: A complex relationship is found between anxiety and mortality. The presence of anxiety slightly increased the risk of death, but this risk varies depending on the type of anxiety diagnosed.

Forgotten but not gone: Yersinia infections in England, 1975 to 2020.

BackgroundYersiniosis is one of the most common food-borne zoonoses in Europe, but there are large variations in the reported incidence between different countries.AimWe aimed to describe the trends and epidemiology of laboratory-confirmed Yersinia infections in England and estimate the average annual number of undiagnosed Yersinia enterocolitica cases, accounting for under-ascertainment.MethodsWe analysed national surveillance data on Yersinia cases reported by laboratories in England between 1975 and 2020 and enhanced surveillance questionnaires from patients diagnosed in a laboratory that has implemented routine Yersinia testing of diarrhoeic samples since 2016.ResultsThe highest incidence of Yersinia infections in England (1.4 cases per 100,000 population) was recorded in 1988 and 1989, with Y. enterocolitica being the predominant species. The reported incidence of Yersinia infections declined during the 1990s and remained low until 2016. Following introduction of commercial PCR at a single laboratory in the South East, the annual incidence increased markedly (13.6 cases per 100,000 population in the catchment area between 2017 and 2020). There were notable changes in age and seasonal distribution of cases over time. The majority of infections were not linked to foreign travel and one in five patients was admitted to hospital. We estimate that around 7,500 Y. enterocolitica infections may be undiagnosed in England annually.ConclusionsFindings suggest a considerable number of undiagnosed yersiniosis cases in England, with possibly important changes in the epidemiology. The apparently low incidence of yersiniosis in England is probably due to limited laboratory testing.

Contrasting factors associated with COVID-19-related ICU admission and death outcomes in hospitalised patients by means of Shapley values.

Identification of those at greatest risk of death due to the substantial threat of COVID-19 can benefit from novel approaches to epidemiology that leverage large datasets and complex machine-learning models, provide data-driven intelligence, and guide decisions such as intensive-care unit admission (ICUA). The objective of this study is two-fold, one substantive and one methodological: substantively to evaluate the association of demographic and health records with two related, yet different, outcomes of severe COVID-19 (viz., death and ICUA); methodologically to compare interpretations based on logistic regression and on gradient-boosted decision tree (GBDT) predictions interpreted by means of the Shapley impacts of covariates. Very different association of some factors, e.g., obesity and chronic respiratory diseases, with death and ICUA may guide review of practice. Shapley explanation of GBDTs identified varying effects of some factors among patients, thus emphasising the importance of individual patient assessment. The results of this study are also relevant for the evaluation of complex automated clinical decision systems, which should optimise prediction scores whilst remaining interpretable to clinicians and mitigating potential biases.

Rheological and Solubility Properties of Soy Protein Isolate.

Soy protein isolate (SPI) powders often have poor water solubility, particularly at pH values close to neutral, which is an attribute that is an issue for its incorporation into complex nutritional systems. Therefore, the objective of this study was to improve SPI solubility while maintaining low viscosity. Thus, the intention was to examine the solubility and rheological properties of a commercial SPI powder at pH values of 2.0, 6.9, and 9.0, and determine if heat treatment at acidic or alkaline conditions might positively influence protein solubility, once re-adjusted back to pH 6.9. Adjusting the pH of SPI dispersions from pH 6.9 to 2.0 or 9.0 led to an increase in protein solubility with a concomitant increase in viscosity at 20 °C. Meanwhile, heat treatment at 90 °C significantly improved the solubility at all pH values and resulted in a decrease in viscosity in samples heated at pH 9.0. All SPI dispersions measured under low-amplitude rheological conditions showed elastic-like behaviour (i.e., G' > G″), indicating a weak "gel-like" structure at frequencies less than 10 Hz. In summary, the physical properties of SPI can be manipulated through heat treatment under acidic or alkaline conditions when the protein subunits are dissociated, before re-adjusting to pH 6.9.

Compositional and functional properties of milk and dairy products derived from cows fed pasture or concentrate-based diets.

Worldwide milk production is predominantly founded on indoor, high-concentrate feeding systems, whereas pasture-based feeding systems are most common in New Zealand and Ireland but have received greater attention recently in countries utilizing conventional systems. Consumer interest in 'pasture-fed' dairy products has also increased, arising from environmental, ethical, and nutritional concerns. A substantial body of research exists describing the effect of different feeding strategies on the composition of milk, with several recent studies focusing on the comparison of pasture- and concentrate-based feeding regimes. Significant variation is typically observed in the gross composition of milk produced from different supplemental feeds, but various changes in the discrete composition of macromolecular components in milk have also been associated with dietary influence, particularly in relation to the fatty acid profile. Changes in milk composition have also been shown to have implications for milk and dairy product processability, functionality and sensory properties. Methods to determine the traceability of dairy products or verify marketing claims such as 'pasture-fed' have also been established, based on compositional variation due to diet. This review explores the effects of feed types on milk composition and quality, along with the ultimate effect of diet-induced changes on milk and dairy product functionality, with particular emphasis placed on pasture- and concentrate-based feeding systems.

Comparison of statistical algorithms for daily syndromic surveillance aberration detection.

MOTIVATION: Public health authorities can provide more effective and timely interventions to protect populations during health events if they have effective multi-purpose surveillance systems. These systems rely on aberration detection algorithms to identify potential threats within large datasets. Ensuring the algorithms are sensitive, specific and timely is crucial for protecting public health. Here, we evaluate the performance of three detection algorithms extensively used for syndromic surveillance: the 'rising activity, multilevel mixed effects, indicator emphasis' (RAMMIE) method and the improved quasi-Poisson regression-based method known as 'Farrington Flexible' both currently used at Public Health England, and the 'Early Aberration Reporting System' (EARS) method used at the US Centre for Disease Control and Prevention. We model the wide range of data structures encountered within the daily syndromic surveillance systems used by PHE. We undertake extensive simulations to identify which algorithms work best across different types of syndromes and different outbreak sizes. We evaluate RAMMIE for the first time since its introduction. Performance metrics were computed and compared in the presence of a range of simulated outbreak types that were added to baseline data. RESULTS: We conclude that amongst the algorithm variants that have a high specificity (i.e. >90%), Farrington Flexible has the highest sensitivity and specificity, whereas RAMMIE has the highest probability of outbreak detection and is the most timely, typically detecting outbreaks 2-3 days earlier. AVAILABILITY AND IMPLEMENTATION: R codes developed for this project are available through https://github.com/FelipeJColon/AlgorithmComparison. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Incubation Period of Shiga Toxin-Producing Escherichia coli.

Shiga toxin-producing Escherichia coli are pathogenic bacteria found in the gastrointestinal tract of humans. Severe infections could lead to life-threatening complications, especially in young children and the elderly. Understanding the distribution of the incubation period, which is currently inconsistent and ambiguous, can help in controlling the burden of disease. We conducted a systematic review of outbreak investigation reports, extracted individual incubation data and summary estimates, tested for heterogeneity, classified studies into subgroups with limited heterogeneity, and undertook a meta-analysis to identify factors that may contribute to the distribution of the pathogen's incubation period. Twenty-eight studies were identified for inclusion in the review (1 of which included information on 2 outbreaks), and the resulting I2 value was 77%, indicating high heterogeneity. Studies were classified into 5 subgroups, with the mean incubation period ranging from 3.5 to 8.1 days. The length of the incubation period increased with patient age and decreased by 7.2 hours with every 10% increase in attack rate.

Pneumococcal Disease: A Systematic Review of Health Utilities, Resource Use, Costs, and Economic Evaluations of Interventions.

BACKGROUND: Pneumococcal diseases cause substantial mortality, morbidity, and economic burden. Evidence on data inputs for economic evaluations of interventions targeting pneumococcal disease is critical. OBJECTIVES: To summarize evidence on resource use, costs, health utilities, and cost-effectiveness for pneumococcal disease and associated interventions to inform future economic analyses. METHODS: We searched MEDLINE, Embase, Web of Science, CINAHL, PsycINFO, EconLit, and Cochrane databases for peer-reviewed studies in English on pneumococcal disease that reported health utilities using direct or indirect valuation methods, resource use, costs, or cost-effectiveness of intervention programs, and summarized the evidence descriptively. RESULTS: We included 383 studies: 9 reporting health utilities, 131 resource use, 160 economic costs of pneumococcal disease, 95 both resource use and costs, and 178 economic evaluations of pneumococcal intervention programs. Health state utility values ranged from 0 to 1 for both meningitis and otitis media and from 0.3 to 0.7 for both pneumonia and sepsis. Hospitalization was shortest for otitis media (range: 0.1-5 days) and longest for sepsis/septicemia (6-48). The main categories of costs reported were drugs, hospitalization, and household or employer costs. Resource use was reported in hospital length of stay and number of contacts with general practitioners. Costs and resource use significantly varied among population ages, disease conditions, and settings. Current vaccination programs for both adults and children, antibiotic use and outreach programs to promote vaccination, early disease detection, and educational programs are cost-effective in most countries. CONCLUSION: This study has generated a comprehensive repository of health economic evidence on pneumococcal disease that can be used to inform future economic evaluations of pneumococcal disease intervention programs.

The impact of childhood pneumococcal vaccination on hospital admissions in England: a whole population observational study.

BACKGROUND: Pneumococcal infections are major causes of morbidity and mortality worldwide. We use routine hospital admissions data and time-series modelling analysis to estimate the impact of the seven and thirteen valent pneumococcal conjugate vaccines (PCV7 and PCV13) on hospital admissions due to pneumococcal disease in England. METHODS: Hospital admissions for pneumococcal meningitis, bacteraemia and pneumonia between January 1, 2003 and December 31, 2015 were identified from the national Hospital Episode Statistics database for all age groups in England. We model the impact of pneumococcal vaccination using interrupted time series analysis. Hospital admissions prior to vaccine introduction were extrapolated to predict the expected number of admissions in the absence of pneumococcal vaccines. Admissions avoided over time were estimated by comparing the fitted interrupted time series and the expected model for no vaccination in a Bayesian framework. RESULTS: Overall, there were 43,531 (95% credible interval (CrI): 36486-51,346) fewer hospital admissions due to bacteraemia, meningitis and pneumonia in England during the period from 2006 to 2015 than would have been expected if pneumococcal vaccines had not been implemented, with the majority of hospital admissions avoided due to pneumonia. Among young children reductions in meningitis were more common, while among adults reductions in pneumonia admissions were relatively more important, with no evidence for reduced bacteraemia and meningitis among older adults. We estimated that 981 (95% CrI: 391-2018), 749 (95% CrI: 295-1442) and 1464 (95% CrI: 793-2522) bacteraemia, meningitis and pneumonia related hospital admissions, respectively, were averted in children < 2 years of age. CONCLUSIONS: Substantial reductions in hospital admissions for bacteraemia, meningitis and pneumonia in England were estimated after the introduction of childhood vaccination, with indirect effects being responsible for most of the hospital admissions avoided.

Physicochemical properties of whole milk powder derived from cows fed pasture or total mixed ration diets.

This study examined the effect of dietary factors on compositional and functional properties of whole milk powder (WMP) produced from bovine milk. Raw milk samples were obtained from 3 groups of 18 Holstein Friesian spring-calving cows randomly assigned to diets based on perennial ryegrass (GRS), perennial ryegrass/white clover sward (CLV), and total mixed ration (TMR). Raw milks obtained in late lactation were subsequently standardized for fat, heat-treated (90°C for 30 s), evaporated, and homogenized before spray drying. The WMP produced from each diet were analyzed to determine differences in color, particle size distribution, heat coagulation time, yogurt gelation, texture profile, and protein profile due to each diet. Significant differences in heat coagulation time were observed between the CLV and TMR samples, whereas color values were significantly different between GRS and TMR samples. No significant differences in gross composition, protein profile, or whey protein nitrogen index were found between the 3 WMP samples. Average D90 values (the particle size at which 90% of the particles were smaller than the specified size) for fat globules were significantly lower in the TMR sample compared with the GRS and CLV samples. Yogurts produced from GRS- and CLV-derived WMP had significantly higher elastic moduli (G') than those produced from TMR-derived WMP. Similarly, texture profile analysis revealed significantly higher firmness values in yogurt samples derived from CLV compared with TMR samples. Our data characterize the effect of these diets on the composition and functional properties of fat-standardized WMP, suggesting better yogurt functionality and thermal stability in WMP derived from pasture-based bovine diets.

A systematic review of source attribution of human campylobacteriosis using multilocus sequence typing.

BackgroundCampylobacter is a leading global cause of bacterial gastroenteritis, motivating research to identify sources of human infection. Population genetic studies have been increasingly applied to this end, mainly using multilocus sequence typing (MLST) data.ObjectivesThis review aimed to summarise approaches and findings of these studies and identify best practice lessons for this form of genomic epidemiology.MethodsWe systematically reviewed publications using MLST data to attribute human disease isolates to source. Publications were from January 2001, when this type of approach began. Searched databases included Scopus, Web of Science and PubMed. Information on samples and isolate datasets used, as well as MLST schemes and attribution algorithms employed, was obtained. Main findings were extracted, as well as any results' validation with subsequent correction for identified biases. Meta-analysis is not reported given high levels of heterogeneity.ResultsOf 2,109 studies retrieved worldwide, 25 were included, and poultry, specifically chickens, were identified as principal source of human infection. Ruminants (cattle or sheep) were consistently implicated in a substantial proportion of cases. Data sampling and analytical approaches varied, with five different attribution algorithms used. Validation such as self-attribution of isolates from known sources was reported in five publications. No publication reported adjustment for biases identified by validation.ConclusionsCommon gaps in validation and adjustment highlight opportunities to generate improved estimates in future genomic attribution studies. The consistency of chicken as the main source of human infection, across high income countries, and despite methodological variations, highlights the public health importance of this source.

Highly Pathogenic Clone of Shiga Toxin-Producing Escherichia coli O157:H7, England and Wales.

We used whole-genome sequencing to investigate the evolutionary context of an emerging highly pathogenic strain of Shiga toxin-producing Escherichia coli (STEC) O157:H7 in England and Wales. A timed phylogeny of sublineage IIb revealed that the emerging clone evolved from a STEC O157:H7 stx-negative ancestor ≈10 years ago after acquisition of a bacteriophage encoding Shiga toxin (stx) 2a, which in turn had evolved from a stx2c progenitor ≈20 years ago. Infection with the stx2a clone was a significant risk factor for bloody diarrhea (OR 4.61, 95% CI 2.24-9.48; p<0.001), compared with infection with other strains within sublineage IIb. Clinical symptoms of cases infected with sublineage IIb stx2c and stx-negative clones were comparable, despite the loss of stx2c. Our analysis highlighted the highly dynamic nature of STEC O157:H7 Stx-encoding bacteriophages and revealed the evolutionary history of a highly pathogenic clone emerging within sublineage IIb, a sublineage not previously associated with severe clinical symptoms.

Comparative efficacy of drugs for treating giardiasis: a systematic update of the literature and network meta-analysis of randomized clinical trials.

Background: Giardiasis is the commonest intestinal protozoal infection worldwide. The current first-choice therapy is metronidazole. Recently, other drugs with potentially higher efficacy or with fewer and milder side effects have increased in popularity, but evidence is limited by a scarcity of randomized controlled trials (RCTs) comparing the many treatment options available. Network meta-analysis (NMA) is a useful tool to compare multiple treatments when there is limited or no direct evidence available. Objectives: To compare the efficacy and side effects of all available drugs for the treatment of giardiasis. Methods: We selected all RCTs included in systematic reviews and expert reviews of all treatments for giardiasis published until 2014, extended the systematic literature search until 2016, and identified new studies by scanning reference lists for relevant studies. We then conducted an NMA of all available treatments for giardiasis by comparing parasitological cure (efficacy) and side effects. Results: We identified 60 RCTs from 58 reports (46 from published systematic reviews, 8 from reference lists and 4 from the updated systematic search). Data from 6714 patients, 18 treatments and 42 treatment comparisons were available. Tinidazole was associated with higher parasitological cure than metronidazole [relative risk (RR) 1.23, 95% CI 1.12-1.35] and albendazole (RR 1.35, 95% CI 1.21-1.50). Taking into consideration clinical efficacy, side effects and amount of the evidence, tinidazole was found to be the most effective drug. Conclusions: We provide additional evidence that single-dose tinidazole is the best available treatment for giardiasis in symptomatic and asymptomatic children and adults.

Incubation period of typhoidal salmonellosis: a systematic review and meta-analysis of outbreaks and experimental studies occurring over the last century.

BACKGROUND: Salmonella Typhi is a human pathogen that causes typhoid fever. It is a major cause of morbidity and mortality in developing countries and is responsible for several outbreaks in developed countries. Studying certain parameters of the pathogen, such as the incubation period, provides a better understanding of its pathophysiology and its characteristics within a population. Outbreak investigations and human experimental studies provide an avenue to study these relevant parameters. METHODS: In this study, the authors have undertaken a systematic review of outbreak investigation reports and experimental studies, extracted reported data, tested for heterogeneity, identified subgroups of studies with limited evidence of heterogeneity between them and identified factors that may contribute to the distribution of incubation period. Following identification of relevant studies, we extracted both raw and summary incubation data. We tested for heterogeneity by deriving the value of I2 and conducting a KS-test to compare the distribution between studies. We performed a linear regression analysis to identify the factors associated with incubation period and using the resulting p-values from the KS-test, we conducted a hierarchical cluster analysis to classify studies with limited evidence of heterogeneity into subgroups. RESULTS: We identified thirteen studies to be included in the review and extracted raw incubation period data from eleven. The value of I2 was 84% and the proportion of KS test p-values that were less than 0.05 was 63.6% indicating high heterogeneity not due to chance. We identified vaccine history and attack rates as factors that may be associated with incubation period, although these were not significant in the multivariable analysis (p-value: 0.1). From the hierarchical clustering analysis, we classified the studies into five subgroups. The mean incubation period of the subgroups ranged from 9.7 days to 21.2 days. Outbreaks reporting cases with previous vaccination history were clustered in a single subgroup and reported the longest incubation period. CONCLUSIONS: We identified attack rate and previous vaccination as possible associating factors, however further work involving analyses of individual patient data and developing mathematical models is needed to confirm these as well as examine additional factors that have not been included in our study.

Short communication: Multi-component interactions causing solidification during industrial-scale manufacture of pre-crystallized acid whey powders.

Acid whey (AW) is the liquid co-product arising from acid-induced precipitation of casein from skim milk. Further processing of AW is often challenging due to its high mineral content, which can promote aggregation of whey proteins, which contributes to high viscosity of the liquid concentrate during subsequent lactose crystallization and drying steps. This study focuses on mineral precipitation, protein aggregation, and lactose crystallization in liquid AW concentrates (∼55% total solids), and on the microstructure of the final powders from 2 independent industrial-scale trials. These AW concentrates were observed to solidify either during processing or during storage (24 h) of pre-crystallized concentrate. The more rapid solidification in the former was associated with a greater extent of lactose crystallization and a higher ash-to-protein ratio in that concentrate. Confocal laser scanning microscopy analysis indicated the presence of a loose network of protein aggregates (≤10 µm) and lactose crystals (100-300 µm) distributed throughout the solidified AW concentrate. Mineral-based precipitate was also evident, using scanning electron microscopy, at the surface of AW powder particles, indicating the formation of insoluble calcium phosphate during processing. These results provide new information on the composition- and process-dependent physicochemical changes that are useful in designing and optimizing processes for AW.

Novel application of the matched case-control design to compare food supply chains during an Escherichia coli O157 outbreak, United Kingdom, 2016.

There is a need for innovative methods to investigate outbreaks of food-borne infection linked to produce with a complex distribution network. The investigation of a large outbreak of Escherichia coli O157 PT34 infection in the United Kingdom in 2016 indicated that catering venues associated with multiple cases had used salad leaves sourced from one supplier. Our aim was to investigate whether catering venues linked to cases were more likely to have used salad leaves from this supplier. We conducted a matched case-control study, with catering venues as the units of analysis. We compared venues linked to cases to those without known linked cases. We included 43 study pairs and obtained information on salad leaf products received by each venue. The odds of a case venue being supplied with salad leaves by Supplier A were 7.67 times (95% confidence interval: 2.30-25.53) those of control venues. This association provided statistical evidence to support the findings of the other epidemiological investigations undertaken for this outbreak. This is a novel approach which is labour-intensive but which addresses the challenge of investigating exposures to food across a complex distribution network.

Lack of Secondary Transmission of Ebola Virus from Healthcare Worker to 238 Contacts, United Kingdom, December 2014.

In December 2014, Ebola virus disease (EVD) was diagnosed in a healthcare worker in the United Kingdom after the worker returned from an Ebola treatment center in Sierra Leone. The worker flew on 2 flights during the early stages of disease. Follow-up of 238 contacts showed no evidence of secondary transmission of Ebola virus.