A genetically related cluster of Salmonella Typhimurium cases in humans associated with ruminant livestock and related food chains, United Kingdom, August 2021-December 2022.

Following an outbreak of Salmonella Typhimurium in Wales in July 2021 associated with sheep meat and offal, further genetically related cases were detected across the UK. Cases were UK residents with laboratory-confirmed Salmonella Typhimurium in the same 5-single-nucleotide polymorphism (SNP) single-linkage cluster with specimen date between 01/08/2021-2031/12/2022. We described cases using routine (UK) and enhanced (Wales only) surveillance data. Exposures in cases in Wales were compared with non-Typhimurium Salmonella case-controls. Environmental Health Practitioners and the Food Standards Agency investigated supply chains of food premises reported by ≥2 cases. Animal, carcass, and environmental samples taken for diagnostic or monitoring purposes for gastrointestinal pathogens were included in microbiological investigations. We identified 142 cases: 75% in England, 23% in Wales and 3% in Scotland. Median age was 32 years, and 59% were male. Direct contact with sheep was associated with becoming a case (aOR: 14, 95%CI: 1.4-145) but reported by few (6/32 cases). No single food item, premises, or supplier linked all cases. Multi-agency collaboration enabled the identification of isolates in the same 5-SNP single-linkage cluster from a sheep carcass at an English abattoir and in ruminant, wildlife, poultry, and environmental samples, suggesting multiple vehicles and pathways of infection.

A large outbreak of COVID-19 in a UK prison, October 2020 to April 2021.

Prisons are susceptible to outbreaks. Control measures focusing on isolation and cohorting negatively affect wellbeing. We present an outbreak of coronavirus disease 2019 (COVID-19) in a large male prison in Wales, UK, October 2020 to April 2021, and discuss control measures.We gathered case-information, including demographics, staff-residence postcode, resident cell number, work areas/dates, test results, staff interview dates/notes and resident prison-transfer dates. Epidemiological curves were mapped by prison location. Control measures included isolation (exclusion from work or cell-isolation), cohorting (new admissions and work-area groups), asymptomatic testing (case-finding), removal of communal dining and movement restrictions. Facemask use and enhanced hygiene were already in place. Whole-genome sequencing (WGS) and interviews determined the genetic relationship between cases plausibility of transmission.Of 453 cases, 53% (n = 242) were staff, most aged 25-34 years (11.5% females, 27.15% males) and symptomatic (64%). Crude attack-rate was higher in staff (29%, 95% CI 26-64%) than in residents (12%, 95% CI 9-15%).Whole-genome sequencing can help differentiate multiple introductions from person-to-person transmission in prisons. It should be introduced alongside asymptomatic testing as soon as possible to control prison outbreaks. Timely epidemiological investigation, including data visualisation, allowed dynamic risk assessment and proportionate control measures, minimising the reduction in resident welfare.

Epidemiological analysis of Salmonella clusters identified by whole genome sequencing, England and Wales 2014.

The unprecedented level of bacterial strain discrimination provided by whole genome sequencing (WGS) presents new challenges with respect to the utility and interpretation of the data. Whole genome sequences from 1445 isolates of Salmonella belonging to the most commonly identified serotypes in England and Wales isolated between April and August 2014 were analysed. Single linkage single nucleotide polymorphism thresholds at the 10, 5 and 0 level were explored for evidence of epidemiological links between clustered cases. Analysis of the WGS data organised 566 of the 1445 isolates into 32 clusters of five or more. A statistically significant epidemiological link was identified for 17 clusters. The clusters were associated with foreign travel (n = 8), consumption of Chinese takeaways (n = 4), chicken eaten at home (n = 2), and one each of the following; eating out, contact with another case in the home and contact with reptiles. In the same time frame, one cluster was detected using traditional outbreak detection methods. WGS can be used for the highly specific and highly sensitive detection of biologically related isolates when epidemiological links are obscured. Improvements in the collection of detailed, standardised exposure information would enhance cluster investigations.

Whole genome sequencing reveals an outbreak of Salmonella Enteritidis associated with reptile feeder mice in the United Kingdom, 2012-2015.

Analysis of whole genome sequencing data uncovered a previously undetected outbreak of Salmonella Enteritidis that had been on-going for four years. Cases were resident in all countries of the United Kingdom and 40% of the cases were aged less than 11 years old. Initial investigations revealed that 30% of cases reported exposure to pet snakes. A case-control study was designed to test the hypothesis that exposure to reptiles or their feed were risk factors. A robust case-definition, based on the single nucleotide polymorphism (SNP) profile, increased the power of the analytical study. Following univariable and multivariable analysis, exposure to snakes was the only variable independently associated with infection (Odds ratio 810 95% CI (85-7715) p < 0.001). Isolates of S. Enteritidis belonging to the outbreak profile were recovered from reptile feeder mice sampled at the retail and wholesale level. Control measures included improved public health messaging at point of sale, press releases and engagement with public health and veterinary counterparts across Europe. Mice destined to be fed to reptiles are not regarded as pet food and are not routinely tested for pathogenic bacteria. Routine microbiological testing to ensure feeder mice are free from Salmonella is recommended.

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.

Prevalence of Giardia infection in households of Giardia cases and risk factors for household transmission.

BACKGROUND: Giardia is a leading but neglected cause of infectious gastroenteritis worldwide and is treatable. There is a substantial burden of undetected Giardia in the UK and for every one case of Giardia reported to national surveillance there are 14 cases in the community. We aimed to ascertain the prevalence of, and risk factors associated with secondary household Giardia infections to assess the burden of infection and inform control measures. METHODS: We identified all giardiasis cases notified in nine local authorities in Lancashire between June 2014 and June 2015, and invited their household contacts to submit faecal specimens for Giardia testing and complete a risk factor questionnaire. We estimated the proportion of households with additional Giardia infection. We compared household risk factors between households with and without additional Giardia using Fisher's exact test. We used multivariable logistic regression to identify independent risk factors for additional Giardia infections. RESULTS: We identified additional Giardia infections in 30% (27/91) of included households. A total of 41 infections were found from 212 household members, of which 37 were asymptomatic. The majority of infections were assemblage B (57%) but there were also a high number of mixed infections (20%). Risk factors significantly associated with additional household infections were; having children under 5 years in the household (odds ratio 42; 95% confidence intervals 10-178) and the presence of gastrointestinal illness in the household before the onset of the index case (odds ratio 9; 95% confidence intervals 1.5-48). CONCLUSIONS: Our finding of a high household prevalence of asymptomatic infection has raised the public health question of whether treatment of asymptomatic household contacts may be justified in preventing Giardia re-infection of the index case or in preventing secondary cases and household clusters. We recommend the communication of this risk in household contacts of Giardia and reinforcement of standard hygiene controls.

Control selection methods in recent case-control studies conducted as part of infectious disease outbreaks.

Successful investigation of national outbreaks of communicable disease relies on rapid identification of the source. Case-control methodologies are commonly used to achieve this. We assessed control selection methods used in recently published case-control studies for methodological and resource issues to determine if a standard approach could be identified. Neighbourhood controls were the most frequently used method in 53 studies of a range of different sizes, infections and settings. The most commonly used method of data collection was face to face interview. Control selection issues were identified in four areas: method of identification of controls, appropriateness of controls, ease of recruitment of controls, and resource requirements. Potential biases arising from the method of control selection were identified in half of the studies assessed. There is a need to develop new ways of selecting controls in a rapid, random and representative manner to improve the accuracy and timeliness of epidemiological investigations and maximise the effectiveness of public health interventions. Innovative methods such as prior recruitment of controls could improve timeliness and representativeness of control selection.

Whole-genome sequencing to determine transmission of Neisseria gonorrhoeae: an observational study.

BACKGROUND: New approaches are urgently required to address increasing rates of gonorrhoea and the emergence and global spread of antibiotic-resistant Neisseria gonorrhoeae. We used whole-genome sequencing to study transmission and track resistance in N gonorrhoeae isolates. METHODS: We did whole-genome sequencing of isolates obtained from samples collected from patients attending sexual health services in Brighton, UK, between Jan 1, 2011, and March 9, 2015. We also included isolates from other UK locations, historical isolates from Brighton, and previous data from a US study. Samples from symptomatic patients and asymptomatic sexual health screening underwent nucleic acid amplification testing; positive samples and all samples from symptomatic patients were cultured for N gonorrhoeae, and resulting isolates were whole-genome sequenced. Cefixime susceptibility testing was done in selected isolates by agar incorporation, and we used sequence data to determine multi-antigen sequence types and penA genotypes. We derived a transmission nomogram to determine the plausibility of direct or indirect transmission between any two cases depending on the time between samples: estimated mutation rates, plus diversity noted within patients across anatomical sites and probable transmission pairs, were used to fit a coalescent model to determine the number of single nucleotide polymorphisms expected. FINDINGS: 1407 (98%) of 1437 Brighton isolates between Jan 1, 2011, and March 9, 2015 were successfully sequenced. We identified 1061 infections from 907 patients. 281 (26%) of these infections were indistinguishable (ie, differed by zero single nucleotide polymorphisms) from one or more previous cases, and 786 (74%) had evidence of a sampled direct or indirect Brighton source. We observed multiple related samples across geographical locations. Of 1273 infections in Brighton (including historical data), 225 (18%) were linked to another case elsewhere in the UK, and 115 (9%) to a case in the USA. Four lineages initially identified in Brighton could be linked to 70 USA sequences, including 61 from a lineage carrying the mosaic penA XXXIV allele, which is associated with reduced cefixime susceptibility. INTERPRETATION: We present a whole-genome-sequencing-based tool for genomic contact tracing of N gonorrhoeae and demonstrate local, national, and international transmission. Whole-genome sequencing can be applied across geographical boundaries to investigate gonorrhoea transmission and to track antimicrobial resistance. FUNDING: Oxford National Institute for Health Research Health Protection Research Unit and Biomedical Research Centre.

Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents.

Covariation in the structural composition of the gut microbiome and the spectroscopically derived metabolic phenotype (metabotype) of a rodent model for obesity were investigated using a range of multivariate statistical tools. Urine and plasma samples from three strains of 10-week-old male Zucker rats (obese (fa/fa, n=8), lean (fa/-, n=8) and lean (-/-, n=8)) were characterized via high-resolution 1H NMR spectroscopy, and in parallel, the fecal microbial composition was investigated using fluorescence in situ hydridization (FISH) and denaturing gradient gel electrophoresis (DGGE) methods. All three Zucker strains had different relative abundances of the dominant members of their intestinal microbiota (FISH), with the novel observation of a Halomonas and a Sphingomonas species being present in the (fa/fa) obese strain on the basis of DGGE data. The two functionally and phenotypically normal Zucker strains (fa/- and -/-) were readily distinguished from the (fa/fa) obese rats on the basis of their metabotypes with relatively lower urinary hippurate and creatinine, relatively higher levels of urinary isoleucine, leucine and acetate and higher plasma LDL and VLDL levels typifying the (fa/fa) obese strain. Collectively, these data suggest a conditional host genetic involvement in selection of the microbial species in each host strain, and that both lean and obese animals could have specific metabolic phenotypes that are linked to their individual microbiomes.

Kinetics of the reactions between [S(2)MoS(2)Cu(SC(6)H(4)R-4)](2-)(R = MeO, H, Cl or NO(2)) and CN(-): substitution mechanism at a 3-coordinate Cu(I) site.

The kinetics of the reaction between [S(2)MoS(2)Cu(SC(6)H(4)R-4)](2-)(R = MeO, H, Cl or NO(2)) and CN(-) to form [S(2)MoS(2)CuCN](2-) have been studied in MeCN using stopped-flow spectrophotometry. In all cases, the rate law is of the form, Rate ={k+k(2)(R)[CN(-)]}[S(2)MoS(2)Cu(SC(6)H(4)R-4)(2-)]. It is proposed that both k and k correspond to associative substitution mechanisms. The k pathway involves attack by CN(-) at the copper site followed by dissociation of the thiolate. The k pathway involves attack of the solvent (MeCN) at the copper site, followed by dissociation of the thiolate to form [S(2)MoS(2)Cu(NCMe)](-). Subsequent rapid substitution of the coordinated solvent by cyanide produces [S(2)MoS(2)CuCN](2-). The evidence that both the k and k pathways involve associative mechanisms are: (i) the 4-R-substituent on the thiolate ligand has a similar effect on both k and k, with electron-withdrawing 4-R-substituents facilitating substitution; (ii) both the k and k pathways are associated with similar activation parameters (for k(1)(H): DeltaH++ = 5.5 +/- 0.5 kcal mol(-1), DeltaS++ = -23.9 +/- 2.0 cal deg(-1) mol(-1); for k(2)(H): DeltaH++ = 2.3 +/- 0.5 kcal mol(-1), DeltaS++ = - 23.9 +/- 2.0 cal deg(-1) mol(-1)) and (iii) addition of C(6)H(5)S(-) results in a similar increase in both k and k.