Nanopore sequencing of influenza A and B in Oxfordshire and the United Kingdom, 2022-23.

OBJECTIVES: We evaluated Nanopore sequencing for influenza surveillance. METHODS: Influenza A and B PCR-positive samples from hospital patients in Oxfordshire, UK, and a UK-wide population survey from winter 2022-23 underwent Nanopore sequencing following targeted rt-PCR amplification. RESULTS: From 941 infections, successful sequencing was achieved in 292/388 (75 %) available Oxfordshire samples: 231 (79 %) A/H3N2, 53 (18 %) A/H1N1, and 8 (3 %) B/Victoria and in 53/113 (47 %) UK-wide samples. Sequencing was more successful at lower Ct values. Most same-sample replicate sequences had identical haemagglutinin segments (124/141, 88 %); 36/39 (92 %) Illumina vs. Nanopore comparisons were identical, and 3 (8 %) differed by 1 variant. Comparison of Oxfordshire and UK-wide sequences showed frequent inter-regional transmission. Infections were closely-related to 2022-23 vaccine strains. Only one sample had a neuraminidase inhibitor resistance mutation. 849/941 (90 %) Oxfordshire infections were community-acquired. 63/88 (72 %) potentially healthcare-associated cases shared a hospital ward with ≥ 1 known infectious case. 33 epidemiologically-plausible transmission links had sequencing data for both source and recipient: 8 were within ≤ 5 SNPs, of these, 5 (63 %) involved potential sources that were also hospital-acquired. CONCLUSIONS: Nanopore influenza sequencing was reproducible and antiviral resistance rare. Inter-regional transmission was common; most infections were genomically similar. Hospital-acquired infections are likely an important source of nosocomial transmission and should be prioritised for infection prevention and control.

SARS-CoV-2, influenza A/B and respiratory syncytial virus positivity and association with influenza-like illness and self-reported symptoms, over the 2022/23 winter season in the UK: a longitudinal surveillance cohort.

BACKGROUND: Syndromic surveillance often relies on patients presenting to healthcare. Community cohorts, although more challenging to recruit, could provide additional population-wide insights, particularly with SARS-CoV-2 co-circulating with other respiratory viruses. METHODS: We estimated the positivity and incidence of SARS-CoV-2, influenza A/B, and RSV, and trends in self-reported symptoms including influenza-like illness (ILI), over the 2022/23 winter season in a broadly representative UK community cohort (COVID-19 Infection Survey), using negative-binomial generalised additive models. We estimated associations between test positivity and each of the symptoms and influenza vaccination, using adjusted logistic and multinomial models. RESULTS: Swabs taken at 32,937/1,352,979 (2.4%) assessments tested positive for SARS-CoV-2, 181/14,939 (1.2%) for RSV and 130/14,939 (0.9%) for influenza A/B, varying by age over time. Positivity and incidence peaks were earliest for RSV, then influenza A/B, then SARS-CoV-2, and were highest for RSV in the youngest and for SARS-CoV-2 in the oldest age groups. Many test positives did not report key symptoms: middle-aged participants were generally more symptomatic than older or younger participants, but still, only ~ 25% reported ILI-WHO and ~ 60% ILI-ECDC. Most symptomatic participants did not test positive for any of the three viruses. Influenza A/B-positivity was lower in participants reporting influenza vaccination in the current and previous seasons (odds ratio = 0.55 (95% CI 0.32, 0.95)) versus neither season. CONCLUSIONS: Symptom profiles varied little by aetiology, making distinguishing SARS-CoV-2, influenza and RSV using symptoms challenging. Most symptoms were not explained by these viruses, indicating the importance of other pathogens in syndromic surveillance. Influenza vaccination was associated with lower rates of community influenza test positivity.

Intracolonic vancomycin for severe Clostridium difficile colitis.

BACKGROUND: Clostridium difficile colitis is associated with increased age, antibiotic usage, and hospitalization. Severe C. difficile colitis refractory to medical therapy may require surgical intervention including subtotal colectomy. We initiated an adjuvant intracolonic vancomycin (ICV) enema protocol for inpatients with severe C. difficile colitis and compared the response to this therapy in patients from the community and nursing homes. METHODS: A single-hospital, retrospective chart review was done on 47 consecutive patients with C. difficile colitis treated with ICV (1 g/500 mL normal saline q6h) from January 2007 through October 2009. The proportions of patients with the outcomes of response to the ICV protocol, need for subtotal colectomy, and death were described. Associations of patient characteristics with these outcomes were examined with bivariate tests and multivariable logistic models with adjustment for age, hypoalbuminemia, acidosis, and nursing-home status. RESULTS: Thirty-three of 47 patients (70%) with severe C. difficile colitis responded to adjunct ICV with complete resolution without surgery. Incomplete responders who had surgery were more likely to survive than those patients who did not undergo subtotal colectomy (p<0.01). Seven of nine patients who underwent surgery survived >90 d, and overall, 37 of 47 patients (79%) survived after ICV therapy. Nursing-home residence, acidosis, and hypoalbuminemia were significantly associated with the non-resolution of colitis in bivariate analyses (all p<0.01), whereas nursing-home residence and hypoalbuminemia showed non-significant trends toward association with death (p=0.07 and p=0.06, respectively). Multivariate logistic-regression models showed significant associations of acidosis with an incomplete response to ICV (p=0.02), of older age with death (p=0.04), and of hypoalbuminemia with both an incomplete response to ICV and death (both p=0.04). No complications were attributable to ICV. CONCLUSION: Complete resolution without surgery was achieved in 70% in this series of patients with severe C. difficile colitis who received adjunct ICV therapy. A clinical trial will be needed to determine whether ICV as compared with standard therapy alone can reduce the need for surgery with non-inferior or superior outcomes.