National outbreak of Shiga toxin-producing Escherichia coli O157:H7 linked to mixed salad leaves, United Kingdom, 2016.

We investigated a large outbreak of Escherichia coli O157 in the United Kingdom (UK) with 165 cases between 31 May and 29 July 2016. No linked cases were reported in other countries. Cases were predominately female (n = 128) and adult (n = 150), 66 attended hospital and nine had features of haemorrhagic uraemic syndrome. A series of epidemiological studies (case-control, case-case, ingredients-based and venue-based studies) and supply chain investigations implicated mixed salad leaves from Supplier A as the likely outbreak vehicle. Whole genome sequencing (WGS) indicated a link with strains from the Mediterranean and informed the outbreak control team to request that Supplier A cease distributing salad leaves imported from Italy. Microbiological tests of samples of salad leaves from Supplier A were negative. We were unable to confirm the source of contamination or the contaminated constituent leaf although our evidence pointed to red batavia received from Italy as the most likely vehicle. Variations in Shiga toxin-producing E.coli surveillance and diagnosis may have prevented detection of cases outside the UK and highlights a need for greater standardisation. WGS was useful in targeting investigations, but greater coverage across Europe is needed to maximise its potential.

Transmission of toxigenic Corynebacterium diphtheriae by a fully immunised resident returning from a visit to West Africa, United Kingdom, 2017.

In early 2017, a United Kingdom (UK)-born person in their 20s presented with a skin ulcer on the foot 3 weeks after returning from Ghana. The patient had last received a diphtheria-containing vaccine in 2013, completing the recommended course. MALDI-TOF of a cutaneous swab identified Corynebacterium diphtheriae. Real-time PCR ascertained the species and presence of the diphtheria toxin gene. An Elek test confirmed toxigenicity. The isolate was macrolide sensitive and penicillin resistant. The local Public Health England (PHE) Health Protection Team obtained the patient's clinical history and traced contacts to inform appropriate public health action. One close contact (in their early 80s with uncertain immunisation status who had not recently travelled) had a positive throat swab for toxigenic C. diphtheriae and reported a history of mild coryzal symptoms. Multilocus sequence typing revealed that strains from the index case and contact had Sequence Type 463. Diphtheria is extremely rare in the UK due to high vaccine coverage and this is the first documented transmission in 30 years. Clinicians and laboratory staff should remain highly suspicious of lesions in overseas travellers, even when patients are fully vaccinated. Older individuals who might not have completed a full immunisation course may have higher diphtheria susceptibility.

Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study.

BACKGROUND: Increasing numbers of individuals with cystic fibrosis are becoming infected with the multidrug-resistant non-tuberculous mycobacterium (NTM) Mycobacterium abscessus, which causes progressive lung damage and is extremely challenging to treat. How this organism is acquired is not currently known, but there is growing concern that person-to-person transmission could occur. We aimed to define the mechanisms of acquisition of M abscessus in individuals with cystic fibrosis. METHOD: Whole genome sequencing and antimicrobial susceptibility testing were done on 168 consecutive isolates of M abscessus from 31 patients attending an adult cystic fibrosis centre in the UK between 2007 and 2011. In parallel, we undertook detailed environmental testing for NTM and defined potential opportunities for transmission between patients both in and out of hospital using epidemiological data and social network analysis. FINDINGS: Phylogenetic analysis revealed two clustered outbreaks of near-identical isolates of the M abscessus subspecies massiliense (from 11 patients), differing by less than ten base pairs. This variation represents less diversity than that seen within isolates from a single individual, strongly indicating between-patient transmission. All patients within these clusters had numerous opportunities for within-hospital transmission from other individuals, while comprehensive environmental sampling, initiated during the outbreak, failed to detect any potential point source of NTM infection. The clusters of M abscessus subspecies massiliense showed evidence of transmission of mutations acquired during infection of an individual to other patients. Thus, isolates with constitutive resistance to amikacin and clarithromycin were isolated from several individuals never previously exposed to long-term macrolides or aminoglycosides, further indicating cross-infection. INTERPRETATION: Whole genome sequencing has revealed frequent transmission of multidrug resistant NTM between patients with cystic fibrosis despite conventional cross-infection measures. Although the exact transmission route is yet to be established, our epidemiological analysis suggests that it could be indirect. FUNDING: The Wellcome Trust, Papworth Hospital, NIHR Cambridge Biomedical Research Centre, UK Health Protection Agency, Medical Research Council, and the UKCRC Translational Infection Research Initiative.

Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study.

BACKGROUND: The burden and influence of health-care associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unknown. We aimed to examine the use of rapid SARS-CoV-2 sequencing combined with detailed epidemiological analysis to investigate health-care associated SARS-CoV-2 infections and inform infection control measures. METHODS: In this prospective surveillance study, we set up rapid SARS-CoV-2 nanopore sequencing from PCR-positive diagnostic samples collected from our hospital (Cambridge, UK) and a random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h. We established a weekly review and reporting system with integration of genomic and epidemiological data to investigate suspected health-care associated COVID-19 cases. FINDINGS: Between March 13 and April 24, 2020, we collected clinical data and samples from 5613 patients with COVID-19 from across the East of England. We sequenced 1000 samples producing 747 high-quality genomes. We combined epidemiological and genomic analysis of the 299 patients from our hospital and identified 35 clusters of identical viruses involving 159 patients. 92 (58%) of 159 patients had strong epidemiological links and 32 (20%) patients had plausible epidemiological links. These results were fed back to clinical, infection control, and hospital management teams, leading to infection-control interventions and informing patient safety reporting. INTERPRETATION: We established real-time genomic surveillance of SARS-CoV-2 in a UK hospital and showed the benefit of combined genomic and epidemiological analysis for the investigation of health-care associated COVID-19. This approach enabled us to detect cryptic transmission events and identify opportunities to target infection-control interventions to further reduce health-care associated infections. Our findings have important implications for national public health policy as they enable rapid tracking and investigation of infections in hospital and community settings. FUNDING: COVID-19 Genomics UK funded by the Department of Health and Social Care, UK Research and Innovation, and the Wellcome Sanger Institute.

Unrecognised Outbreak: Human parainfluenza virus infections in a pediatric oncology unit. A new diagnostic PCR and virus monitoring system may allow early detection of future outbreaks.

Background: Human parainfluenza viruses (HPIVs) are significant causes of both upper and lower respiratory tract infections with type 3 (HPIV3) causing the most severe disease in the immunocompromised cohorts.  The objective of this study was to analyse the epidemiological nature of a cluster of cases of HPIV3 in a pediatric oncology unit of a major teaching hospital. Methods: In order to determine whether the activity observed represented a deviation from the norm, seasonal trends of HPIV3 in the surrounding geographical area as well as on the ward in question were analysed.  The genetic link between cases was established by the phylogenetic analysis of the non-coding hypervariable region between the M (Matrix) and F (fusion) genes of HPIV3. The 15 cases involved and 15 unrelated cases were sequenced.  Transmission routes were subsequently inferred and visualized using Konstanz Information Miner (KNIME) 3.3.2. Results: Of the 15 cases identified, 14 were attributed to a point source outbreak. Two out of 14 outbreak cases were found to differ by a single mutation A182C. The outbreak strain was also seen in 1 out of 15 unrelated cases, indicating that it was introduced from the community. Transmission modeling was not able to link all the cases and establish a conclusive chain of transmission. No staff were tested during the outbreak period. No deaths occurred as a result of the outbreak. Conclusion: A point source outbreak of HPIV3 was recognized post factum on an oncology pediatric unit in a major teaching hospital. This raised concern about the possibility of a future more serious outbreak. Weaknesses in existing systems were identified and a new dedicated respiratory virus monitoring system introduced.  Pediatric oncology units require sophisticated systems for early identification of potentially life-threatening viral outbreaks.

Excess Mortality Attributable to Clostridium difficile and Risk Factors for Infection in an Historic Cohort of Hospitalised Patients Followed Up in the United Kingdom Death Register.

METHODS: We compared time from hospital admission to death in a probability sample of 100 Clostridium difficile infected cases and a probability sample of 98 non-cases admitted to an English teaching hospital between 2005 and 2007 with follow up in the UK national death register using survival analysis. RESULTS: Clostridium difficile infection was associated with a 50% increased risk of death (Hazard Ratio 1.51 (95% CI: 1.05-2.19 p = 0.03) at between five to eight years in Cox Regression analysis adjusting for age, sex, Charlson comorbidity index, diagnosis of a malignant condition and insertion of a nasogastric tube during admission. Acquisition of Clostridium difficile infection was independently associated with an almost six fold higher odds of being admitted with a diagnosis of infection of any other type (OR 5.79 (2.19, 15.25) p<0.001). CONCLUSIONS: Our results strongly support continued priority being given to improve prevention and treatment of Clostridium difficile infection in the English National Health Service particularly in patients admitted with an infection. Our results may be applicable to other health systems.