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An extensive multi-country outbreak of multidrug-resistant monophasic

An extensive multi-country outbreak of multidrug-resistant monophasic Salmonella Typhimurium infection in 10 countries with 150 reported cases, predominantly affecting young children, has been linked to chocolate products produced by a large multinational company. Extensive withdrawals and recalls of multiple product lines have been undertaken. With Easter approaching, widespread product distribution and the vulnerability of the affected population, early and effective real-time sharing of microbiological and epidemiological information has been of critical importance in effectively managing this serious food-borne incident.

BackgroundTo reduce the coronavirus disease burden in England, along with many other countries, the Government implemented a package of non-pharmaceutical interventions (NPIs) that have also impacted other transmissible infectious diseases such as norovirus. It is unclear what future norovirus disease incidence is likely to look like upon lifting these restrictions.MethodsHere we use a mathematical model of norovirus fitted to community incidence data in England to project forward expected incidence based on contact surveys that have been collected throughout 2020-2021.ResultsWe report that susceptibility to norovirus infection has likely increased between March 2020 to mid-2021. Depending upon assumptions of future contact patterns incidence of norovirus that is similar to pre-pandemic levels or an increase beyond what has been previously reported is likely to occur once restrictions are lifted. Should adult contact patterns return to 80% of pre-pandemic levels the incidence of norovirus will be similar to previous years. If contact patterns return to pre-pandemic levels there is a potential for the expected annual incidence to be up to 2-fold larger than in a typical year. The age-specific incidence is similar across all ages.ConclusionsContinued national surveillance for endemic diseases such as norovirus will be essential after NPIs are lifted to allow healthcare services to adequately prepare for a potential increase in cases and hospital pressures beyond what is typically experienced.

Summary Background Salmonella spp are a major cause of food-borne outbreaks in Europe. We investigated a large multi-country outbreak of Salmonella enterica serotype Enteritidis in the EU and European Economic Area (EEA). Methods A confirmed case was defined as a laboratory-confirmed infection with the outbreak strains of S Enteritidis based on whole-genome sequencing (WGS), occurring between May 1, 2015, and Oct 31, 2018. A probable case was defined as laboratory-confirmed infection with S Enteritidis with the multiple-locus variable-number tandem repeat analysis outbreak profile. Multi-country epidemiological, trace-back, trace-forward, and environmental investigations were done. We did a case-control study including confirmed and probable cases and controls randomly sampled from the population registry (frequency matched by age, sex, and postal code). Odds ratios (ORs) for exposure rates between cases and controls were calculated with unmatched univariable and multivariable logistic regression. Findings 18 EU and EEA countries reported 838 confirmed and 371 probable cases. 509 (42%) cases were reported in 2016, after which the number of cases steadily increased. The case-control study results showed that cases more often ate in food establishments than did controls (OR 3·4 [95% CI 1·6–7·3]), but no specific food item was identified. Recipe-based food trace-back investigations among cases who ate in food establishments identified eggs from Poland as the vehicle of infection in October, 2016. Phylogenetic analysis identified two strains of S Enteritidis in human cases that were subsequently identified in salmonella-positive eggs and primary production premises in Poland, confirming the source of the outbreak. After control measures were implemented, the number of cases decreased, but increased again in March, 2017, and the increase continued into 2018. Interpretation This outbreak highlights the public health value of multi-country sharing of epidemiological, trace-back, and microbiological data. The re-emergence of cases suggests that outbreak strains have continued to enter the food chain, although changes in strain population dynamics and fewer cases indicate that control measures had some effect. Routine use of WGS in salmonella surveillance and outbreak response promises to identify and stop outbreaks in the future. Funding European Centre for Disease Prevention and Control; Directorate General for Health and Food Safety, European Commission; and National Public Health and Food Safety Institutes of the authors' countries (see Acknowledgments for full list).

Fresh betel leaves (Piper betle L.), imported into the UK are a traditional ready-to-eat food consumed by Asian populations. We report here the consolidation of routinely collected data to model the public health risks from consumption of this food. Amongst 2110 samples collected at Border Inspection, wholesale, catering or retail, Salmonella was detected in 488 (23%) of samples tested between 2011 and 2017 and was the most commonly Salmonella-contaminated ready-to-eat food examined by Public Health England during this period. Using data from multiple samples (usually 5) tested per consignment sampled at Border Inspection, contamination levels were calculated by most probable number: seasonal, temporal and country specific differences were detected. Quantitative contamination data was used to estimate the levels present at retail, and a β-Poisson dose response model the probability of illness was calculated. Using data for products imported from India, the probability of acquiring infection following a single exposure (comprising of a single leaf) was estimated to be between 0.00003 (January-March) and 0.0001 (July-September). Using British Asian population data for individuals over 30 years of age in England in 2011, two estimates of consumption were modelled as 2.1 and 12.8 million servings per annum. Results from the model estimated 160 cases (range 102 to 242) and 960 cases (range 612 to 1456) per year in England for the two consumption estimates and equated to 34 (range 22 to 51) and 204 (range 130 to 310) salmonellosis cases per year reported to national surveillance. Salmonella from 475 of the contaminated samples were further characterised which showed a heterogeneous population structure with 46 S. enterica subsp. Enterica serovars, together with S. enterica subs diarizonae and salamae identified. Isolates from individual consignments were diverse and close genetic relationships between independent isolates were very rare except from within an individual consignment. There were no outbreaks detected as associated with betel leaf consumption. However analysis by whole genome sequencing of the 2014-17 data identified two cases where the clinical isolate had5 single nucleotide polymorphism differences to isolates from betel leaves which is indicative of a likely epidemiological link and common source of contamination. Due to the diversity of the Salmonella contaminating this product, associations between salmonellosis cases and betel leaf consumption will appear sporadic and unlikely to be detected by current surveillance strategies based on outbreak detection.

Background The COVID-19 pandemic has impacted surveillance activities for multiple pathogens. Since March 2020, there was a decline in the number of reports of norovirus and Campylobacter recorded by England’s national laboratory surveillance system. The aim is to estimate and compare the impact of the COVID-19 pandemic on norovirus and Campylobacter surveillance data in England. Methods We utilised two quasi-experimental approaches based on a generalised linear model for sequential count data. The first approach estimates overall impact and the second approach focuses on the impact of specific elements of the pandemic response (COVID-19 diagnostic testing and control measures). The following time series (27, 2015–43, 2020) were used: weekly laboratory-confirmed norovirus and Campylobacter reports, air temperature, conducted Sars-CoV-2 tests and Index of COVID-19 control measures stringency. Results The period of Sars-CoV-2 emergence and subsequent sustained transmission was associated with persistent reductions in norovirus laboratory reports (p = 0.001), whereas the reductions were more pronounced during pandemic emergence and later recovered for Campylobacter (p = 0.075). The total estimated reduction was 47% - 79% for norovirus (12–43, 2020). The total reduction varied by time for Campylobacter, e.g. 19% - 33% in April, 1% - 7% in August. Conclusion Laboratory reporting of norovirus was more adversely impacted than Campylobacter by the COVID-19 pandemic. This may be partially explained by a comparatively stronger effect of behavioural interventions on norovirus transmission and a relatively greater reduction in norovirus testing capacity. Our study underlines the differential impact a pandemic may have on surveillance of gastrointestinal infectious diseases.

Since the introduction of rotavirus vaccination in England in July 2013, norovirus has become the second-largest contributor of inpatient gastroenteritis, preventing 57800 patients from being admitted annually. Economic costs amount to £297.7 million, which translates into 6300 quality-adjusted life years., Background Norovirus places a substantial burden on healthcare systems, arising from infected patients, disease outbreaks, beds kept unoccupied for infection control, and staff absences due to infection. In settings with high rates of bed occupancy, opportunity costs arise from patients who cannot be admitted due to beds being unavailable. With several treatments and vaccines against norovirus in development, quantifying the expected economic burden is timely. Methods The number of inpatients with norovirus-associated gastroenteritis in England was modeled using infectious and noninfectious gastrointestinal Hospital Episode Statistics codes and laboratory reports of gastrointestinal pathogens collected at Public Health England. The excess length of stay from norovirus was estimated with a multistate model and local outbreak data. Unoccupied bed-days and staff absences were estimated from national outbreak surveillance. The burden was valued conventionally using accounting expenditures and wages, which we contrasted to the opportunity costs from forgone patients using a novel methodology. Results Between July 2013 and June 2016, 17.7% (95% confidence interval [CI], 15.6%‒21.6%) of primary and 23.8% (95% CI, 20.6%‒29.9%) of secondary gastrointestinal diagnoses were norovirus attributable. Annually, the estimated median 290000 (interquartile range, 282000‒297000) occupied and unoccupied bed-days used for norovirus displaced 57800 patients. Conventional costs for the National Health Service reached £107.6 million; the economic burden approximated to £297.7 million and a loss of 6300 quality-adjusted life-years annually. Conclusions In England, norovirus is now the second-largest contributor of the gastrointestinal hospital burden. With the projected impact being greater than previously estimated, improved capture of relevant opportunity costs seems imperative for diseases such as norovirus.

Background Salmonella enterica serovar Enteritidis is a cause of both poultry- and egg-associated enterocolitis globally and bloodstream-invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa (sSA). Distinct, multi-drug resistant genotypes associated with iNTS disease in sSA have recently been described, often requiring treatment with fluoroquinolone antibiotics. In industrialised countries, antimicrobial use in poultry production has led to frequent fluoroquinolone resistance amongst globally prevalent enterocolitis-associated lineages. Methodology/Principal findings Twenty seven S. Enteritidis isolates from patients with iNTS disease and two poultry isolates, collected between 2007 and 2015 in the Ashanti region of Ghana, were whole-genome sequenced. These isolates, notable for a high rate of diminished ciprofloxacin susceptibility (DCS), were placed in the phyletic context of 1,067 sequences from the Public Health England (PHE) S. Enteritidis genome database to understand whether DCS was associated with African or globally-circulating clades of S. Enteritidis. Analysis showed four of the major S. Enteritidis clades were represented, two global and two African. All thirteen DCS isolates, containing a single gyrA mutation at codon 87, belonged to a global PT4-like clade responsible for epidemics of poultry-associated enterocolitis. Apart from two DCS isolates, which clustered with PHE isolates associated with travel to Spain and Brazil, the remaining DCS isolates, including one poultry isolate, belonged to two monophyletic clusters in which gyrA 87 mutations appear to have developed within the region. Conclusions/Significance Extensive phylogenetic diversity is evident amongst iNTS disease-associated S. Enteritidis in Ghana. Antimicrobial resistance profiles differed by clade, highlighting the challenges of devising empirical sepsis guidelines. The detection of fluoroquinolone resistance in phyletically-related poultry and human isolates is of major concern and surveillance and control measures within the region’s burgeoning poultry industry are required to protect a human population at high risk of iNTS disease., Author summary Salmonella enterica serovar Enteritidis is both a prominent global cause of zoonotic gastroenteritis, in association with the industrial production of eggs and poultry, and of bloodstream-invasive infection in sub-Saharan Africa, a clinical syndrome referred to as invasive nontyphoidal Salmonella (iNTS) disease. African epidemic iNTS strains are frequently multi-drug resistant, leaving fluoroquinolone antibiotics as key agents in reducing iNTS-associated morbidity and mortality. We analysed the genomes of S. Enteritidis collected in Ghana from patients with iNTS disease to investigate the emergence of fluoroquinolone resistance in the region. Extensive phylogenetic diversity was present, however, fluoroquinolone resistance was confined to a single clade causing global epidemics of poultry-associated gastroenteritis. This resistance has predominantly emerged locally, rather than being imported. We found that antimicrobial resistance patterns differed by S. Enteritidis clade, highlighting the challenges of devising empirical sepsis treatment guidelines in the absence of diagnostic microbiology facilities to monitor changes in resistance profiles. Furthermore, we detected fluoroquinolone resistance in closely related poultry and human isolates, suggesting a role of antimicrobial use within the growing local poultry industry in driving the emergence of resistance and a need for surveillance measures within this industry to protect a human population at high risk of iNTS disease.

In 2017, an outbreak of gastroenteritis in England attributed to Salmonella Adjame was detected and investigated. With the introduction of whole genome sequencing (WGS) for microbial typing, methods for comparing international outbreak data require evaluation. A case was defined as a person resident in England with a clinical sample from 1 June 2017 to 27 July 2017 from whom S. Adjame was isolated. Cases were interviewed and exposures analysed. Backward tracing of food provenance was undertaken. WGS was performed on isolates from cases and historical isolates and compared using Public Health England’s SnapperDB high-quality SNP pipeline and Enterobase’s Salmonella core genome multi-locus sequence typing (cgMLST) scheme. In total, 14 cases were identified. The majority were vegetarian, probably of South Asian descent, with a median age of 66.5 years with no recent international travel reported. Cases consumed a range of fresh food products including herbs and spices bought from South Asian grocers. Backward tracing did not identify a common source. WGS typing showed sub-clustering and considerable genetic variation across human samples. cgMLST allele-based analysis was comparable to SNP-derived phylogenetic analysis and clusters were defined using each method. Imported herbs or spices were suspected vehicles. The cases were linked in time and place but WGS showed marked heterogeneity, atypical of a point source Salmonella outbreak. The application of incorporating SNP or allelic differences into the case definition may not always be appropriate. With further validation, cgMLST could be used for international outbreak alerts when WGS analysis is being undertaken to facilitate comparison.

A focus on eliminating phage type 4 in egg and poultry production has greatly reduced foodborne disease among humans., In England and Wales, the emergence of Salmonella enterica serovar Enteritidis resulted in the largest and most persistent epidemic of foodborne infection attributable to a single subtype of any pathogen since systematic national microbiological surveillance was established. We reviewed 67 years of surveillance data to examine the features, underlying causes, and overall effects of S. enterica ser. Enteritidis. The epidemic was associated with the consumption of contaminated chicken meat and eggs, and a decline in the number of infections began after the adoption of vaccination and other measures in production and distribution of chicken meat and eggs. We estimate that >525,000 persons became ill during the course of the epidemic, which caused a total of 6,750,000 days of illness, 27,000 hospitalizations, and 2,000 deaths. Measures undertaken to control the epidemic have resulted in a major reduction in foodborne disease in England and Wales.

Objectives In response to the first report of transmissible colistin resistance mediated by the mcr-1 gene in Escherichia coli and Klebsiella spp. from animals and humans in China, we sought to determine its presence in Enterobacteriaceae isolated in the UK. Methods The PHE archive of whole-genome sequences of isolates from surveillance collections, submissions to reference services and research projects was retrospectively analysed for the presence of mcr-1 using Genefinder. The genetic environment of the gene was also analysed. Results Rapid screening of the genomes of ∼24 000 Salmonella enterica, E. coli, Klebsiella spp., Enterobacter spp., Campylobacter spp. and Shigella spp. isolated from food or humans identified 15 mcr-1-positive isolates. These comprised: 10 human S. enterica isolates submitted between 2012 and 2015 (8 Salmonella Typhimurium, 1 Salmonella Paratyphi B var Java and 1 Salmonella Virchow) from 10 patients; 3 isolates of E. coli from 2 patients; and 2 isolates of Salmonella Paratyphi B var Java from poultry meat imported from the EU. The mcr-1 gene was located on diverse plasmids belonging to the IncHI2, IncI2 and IncX4 replicon types and its association with ISApl1 varied. Six mcr-1-positive S. enterica isolates were from patients who had recently travelled to Asia. Conclusions Analysis of WGS data allowed rapid confirmation of the presence of the plasmid-mediated colistin resistance gene mcr-1 in diverse genetic environments and plasmids. It has been present in E. coli and Salmonella spp. harboured by humans in England and Wales since at least 2012.

SUMMARYSalmonella entericaserovar Typhimurium definitive phage type (DT) 8 is uncommon in humans in the UK. In July 2010, the Health Protection Agency reported an excess isolation rate of pan-susceptibleS. Typhimurium DT8 in England and Northern Ireland. By the end of October, this amounted to 81 laboratory-confirmed human cases for all regions of England and Northern Ireland in 2010, an increase of 26% and 41% on 2009 and 2008, respectively. Descriptive epidemiological investigation found a strong association with infection and consumption of duck eggs. Duck eggs contaminated withS. Typhimurium DT8 were collected from a patient's home and also at farms in the duck-egg supply chain. Although duck eggs form a small part of total UK eggs sales, there has been significant growth in sales in recent years. This is the first known outbreak of salmonellosis linked to duck eggs in the UK since 1949 and highlighted the impact of a changing food source and market on the re-emergence of salmonellosis linked to duck eggs. Control measures by the duck-egg industry should be improved along with a continued need to remind the public and commercial caterers of the potential high risks of contracting salmonellosis from duck eggs.

The implementation of disease control programs on farms requires an act of behavioral change. This study presents a theoretical framework from behavioral science, combined with basic epidemiological principles to investigate and explain the control of zoonotic agents on cattle farms. A pathway to disease control model was adapted from existing models in behavioral science and human medicine. Field data was used to demonstrate the validity of the model to identify and explain motivational factors for implementation of disease control programs among English and Welsh cattle farmers. The field data consisted of interviews conducted with 43 farmers, which were analyzed to investigate the farmers' perception of responsibility for safe cattle produce as well as the intrinsic and extrinsic barriers that inhibited the implementation of a zoonotic control program on their farms. The model was used to illustrate barriers affecting the implementation process and to classify farmers according to their current level of zoonotic control at each stage within the model. Ordinal multivariable logistic regression was used to identify the motivators associated with different levels of implementation. Younger farmers and/or larger herds were more likely to place financial responsibility upon the industry rather than government and all but two farmers accepted a social responsibility for food safety within cattle production. In general, attitudes towards zoonotic control were positive, but approximately half the farmers showed no intent to control and were inhibited by non-supportive social norms and/or a lack of belief in self-efficacy. The remaining farmers showed intent to control, but had not implemented any structured control program due to external barriers including lack of knowledge and both cultural and economic pressure from society and industry. The farmers with no intent to adopt control measures identified their private veterinarian as the preferred motivator, whereas consumer-demand and financial rewards or penalties were significantly associated with farmers who intended to control.

SIR, — Earlier this year European bat lyssavirus (eblv) type 2 — a rabies-like virus that can cause rabies in humans — was confirmed in an injured bat. Six bat handlers who had been involved in the care of the bat, and the private veterinary surgeon who had operated to remove the bat's wing