RT-PCR genotyping assays to identify SARS-CoV-2 variants in England in 2021: a design and retrospective evaluation study.

BACKGROUND: Whole-genome sequencing (WGS) is the gold standard diagnostic tool to identify and genetically characterise emerging pathogen mutations (variants), but cost, capacity, and timeliness limit its use when large populations need rapidly assessing. We assessed the potential of genotyping assays to provide accurate and timely variant information at scale by retrospectively examining surveillance for SARS-CoV-2 variants in England between March and September, 2021, when genotyping assays were used widely for variant detection. METHODS: We chose a panel of four RT-PCR genotyping assays to detect circulating variants of SARS-COV-2 in England and developed a decision algorithm to assign a probable SARS-CoV-2 variant to samples using the assay results. We extracted surveillance data from the UK Health Security Agency databases for 115 934 SARS-CoV-2-positive samples (March 1-Sept 6, 2021) when variant information was available from both genotyping and WGS. By comparing the genotyping and WGS variant result, we calculated accuracy metrics (ie, sensitivity, specificity, and positive predictive value [PPV]) and the time difference between the sample collection date and the availability of variant information. We assessed the number of samples with a variant assigned from genotyping or WGS, or both, over time. FINDINGS: Genotyping and an initial decision algorithm (April 10-May 11, 2021 data) were accurate for key variant assignment: sensitivities and PPVs were 0·99 (95% CI 0·99-0·99) for the alpha, 1·00 (1·00-1·00) for the beta, and 0·91 (0·80-1·00) for the gamma variants; specificities were 0·97 (0·96-0·98), 1·00 (1·00-1·00), and 1·00 (1·00-1·00), respectively. A subsequent decision algorithm over a longer time period (May 27-Sept 6, 2021 data) remained accurate for key variant assignment: sensitivities were 0·91 (95% CI 0·74-1·00) for the beta, 0·98 (0·98-0·99) for the delta, and 0·93 (0·81-1·00) for the gamma variants; specificities were 1·00 (1·00-1·00), 0·96 (0·96-0·97), and 1·00 (1·00-1·00), respectively; and PPVs were 0·83 (0·62-1·00), 1·00 (1·00-1·00), and 0·78 (0·59-0·97), respectively. Genotyping produced variant information a median of 3 days (IQR 2-4) after the sample collection date, which was faster than with WGS (9 days [8-11]). The flexibility of genotyping enabled a nine-times increase in the quantity of samples tested for variants by this method (from 5000 to 45 000). INTERPRETATION: RT-PCR genotyping assays are suitable for high-throughput variant surveillance and could complement WGS, enabling larger scale testing for known variants and timelier results, with important implications for effective public health responses and disease control globally, especially in settings with low WGS capacity. However, the choice of panels of RT-PCR assays is highly dependent on database information on circulating variants generated by WGS, which could limit the use of genotyping assays when new variants are emerging and spreading rapidly. FUNDING: UK Health Security Agency and National Institute for Health Research Health Protection Research Unit in Emergency Preparedness and Response.

Foodborne Outbreak of Extended Spectrum Beta-lactamase Producing Shigella sonnei Associated with Contaminated Spring Onions in the United Kingdom.

Globalization of the food supply chain has created conditions favorable for emergence and spread of multidrug-resistant (MDR) foodborne pathogens. In November 2021, the UK Health Security Agency detected an outbreak of 17 cases infected with the same strain of MDR extended spectrum beta-lactamase (ESBL)-producing Shigella sonnei. Phylogenetic analysis of whole-genome sequencing data revealed the outbreak was closely related to strains of S. sonnei isolated from travelers returning to the UK from Egypt. None of the outbreak cases reported travel and all 17 cases reported eating food from a restaurant/food outlet in the week prior to symptom onset, of which 11/17 (64.7%) ate at branches of the same national restaurant franchise. All 17 cases were adults and 14/17 (82.4%) were female. Ingredient-level analyses of the meals consumed by the cases identified spring onions as the common ingredient. Food chain investigations revealed that the spring onions served at the implicated restaurants could be traced back to a single Egyptian producer. The foodborne transmission of ESBL-producing bacteria is an emerging global health concern, and concerted action from all stakeholders is required to ensure an effective response to mitigate the risks to public health.

Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have been used since December 2020 in the United Kingdom. Real-world data have shown the vaccines to be highly effective against Covid-19 and related severe disease and death. Vaccine effectiveness may wane over time since the receipt of the second dose of the ChAdOx1-S (ChAdOx1 nCoV-19) and BNT162b2 vaccines. METHODS: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic Covid-19 and related hospitalization and death in England. Effectiveness of the ChAdOx1-S and BNT162b2 vaccines was assessed according to participant age and status with regard to coexisting conditions and over time since receipt of the second vaccine dose to investigate waning of effectiveness separately for the B.1.1.7 (alpha) and B.1.617.2 (delta) variants. RESULTS: Vaccine effectiveness against symptomatic Covid-19 with the delta variant peaked in the early weeks after receipt of the second dose and then decreased by 20 weeks to 44.3% (95% confidence interval [CI], 43.2 to 45.4) with the ChAdOx1-S vaccine and to 66.3% (95% CI, 65.7 to 66.9) with the BNT162b2 vaccine. Waning of vaccine effectiveness was greater in persons 65 years of age or older than in those 40 to 64 years of age. At 20 weeks or more after vaccination, vaccine effectiveness decreased less against both hospitalization, to 80.0% (95% CI, 76.8 to 82.7) with the ChAdOx1-S vaccine and 91.7% (95% CI, 90.2 to 93.0) with the BNT162b2 vaccine, and death, to 84.8% (95% CI, 76.2 to 90.3) and 91.9% (95% CI, 88.5 to 94.3), respectively. Greater waning in vaccine effectiveness against hospitalization was observed in persons 65 years of age or older in a clinically extremely vulnerable group and in persons 40 to 64 years of age with underlying medical conditions than in healthy adults. CONCLUSIONS: We observed limited waning in vaccine effectiveness against Covid-19-related hospitalization and death at 20 weeks or more after vaccination with two doses of the ChAdOx1-S or BNT162b2 vaccine. Waning was greater in older adults and in those in a clinical risk group.

Barriers and enablers to implementing tuberculosis control strategies in EU and European Economic Area countries: a systematic review.

Meeting the 2035 WHO targets of reducing tuberculosis incidence by 90% from 2015 levels requires the implementation of country-specific tuberculosis control strategies. This systematic review aims to identify factors that facilitate or impede the implementation of such strategies in EU and European Economic Area (EEA) settings. Focusing on providers of care, health system constraints, and social and political factors, this Review complements available evidence on the accessibility of tuberculosis services to recipients of care. Databases were searched for EU and EEA articles published between Jan 1, 1997, and Nov 6, 2020, that presented empirical data on tuberculosis policies, strategies, guidelines, or interventions. 2061 articles were screened and 65 were included. The most common barrier to tuberculosis control strategies described the divergence of health-care practices from guidelines, often related to inadequate knowledge or perceived usefulness of the guidelines by clinicians. The most commonly identified enabler to tuberculosis control strategies was the documented positive attitudes of health-care workers towards tuberculosis programmes. Divergence between clinical practice and guidelines was described in most EU and EEA settings, indicating the need for a focused review of guideline adherence. Strengths of this study involve its broad inclusion criteria and wide range of tuberculosis control strategies analysed.

Retrospective cohort study investigating extent of pertussis transmission during a boarding school outbreak, England, December 2017 to June 2018.

On 1 May 2018, a pertussis outbreak was declared and widespread vaccination recommended at an all-female secondary boarding school in southern England. We conducted a retrospective cohort study to determine the extent of pertussis transmission and identify risk factors in this semi-closed population. Of 504 students and staff assessed before post-exposure vaccination, 48% (n = 240) had evidence of pertussis. A sub-analysis of 409 students found that both residential dormitory (p = 0.05) and school year (p = 0.03) were associated with pertussis, with odds decreasing by 11% for each increase in school year (95% confidence interval: 0.7-20.2). Odds of pertussis were 1.7 times higher in those assumed to have received acellular vaccines for their primary course compared with those assumed to have received whole-cell vaccines (based on date of birth), although this difference was not significant (p = 0.12). Our findings support the need for timely, widespread vaccination following identification of cases among adolescents in a semi-closed United Kingdom (UK) setting and to review the evidence for the introduction of an adolescent pertussis booster to the UK routine vaccination programme.

Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant.

BACKGROUND: The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear. METHODS: We used a test-negative case-control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike (S) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients' vaccination status. RESULTS: Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. CONCLUSIONS: Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.).