Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant.

BACKGROUND: A rapid increase in coronavirus disease 2019 (Covid-19) cases due to the omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 in highly vaccinated populations has aroused concerns about the effectiveness of current vaccines. METHODS: We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease caused by the omicron and delta (B.1.617.2) variants in England. Vaccine effectiveness was calculated after primary immunization with two doses of BNT162b2 (Pfizer-BioNTech), ChAdOx1 nCoV-19 (AstraZeneca), or mRNA-1273 (Moderna) vaccine and after a booster dose of BNT162b2, ChAdOx1 nCoV-19, or mRNA-1273. RESULTS: Between November 27, 2021, and January 12, 2022, a total of 886,774 eligible persons infected with the omicron variant, 204,154 eligible persons infected with the delta variant, and 1,572,621 eligible test-negative controls were identified. At all time points investigated and for all combinations of primary course and booster vaccines, vaccine effectiveness against symptomatic disease was higher for the delta variant than for the omicron variant. No effect against the omicron variant was noted from 20 weeks after two ChAdOx1 nCoV-19 doses, whereas vaccine effectiveness after two BNT162b2 doses was 65.5% (95% confidence interval [CI], 63.9 to 67.0) at 2 to 4 weeks, dropping to 8.8% (95% CI, 7.0 to 10.5) at 25 or more weeks. Among ChAdOx1 nCoV-19 primary course recipients, vaccine effectiveness increased to 62.4% (95% CI, 61.8 to 63.0) at 2 to 4 weeks after a BNT162b2 booster before decreasing to 39.6% (95% CI, 38.0 to 41.1) at 10 or more weeks. Among BNT162b2 primary course recipients, vaccine effectiveness increased to 67.2% (95% CI, 66.5 to 67.8) at 2 to 4 weeks after a BNT162b2 booster before declining to 45.7% (95% CI, 44.7 to 46.7) at 10 or more weeks. Vaccine effectiveness after a ChAdOx1 nCoV-19 primary course increased to 70.1% (95% CI, 69.5 to 70.7) at 2 to 4 weeks after an mRNA-1273 booster and decreased to 60.9% (95% CI, 59.7 to 62.1) at 5 to 9 weeks. After a BNT162b2 primary course, the mRNA-1273 booster increased vaccine effectiveness to 73.9% (95% CI, 73.1 to 74.6) at 2 to 4 weeks; vaccine effectiveness fell to 64.4% (95% CI, 62.6 to 66.1) at 5 to 9 weeks. CONCLUSIONS: Primary immunization with two doses of ChAdOx1 nCoV-19 or BNT162b2 vaccine provided limited protection against symptomatic disease caused by the omicron variant. A BNT162b2 or mRNA-1273 booster after either the ChAdOx1 nCoV-19 or BNT162b2 primary course substantially increased protection, but that protection waned over time. (Funded by the U.K. Health Security Agency.).

Preliminary investigation of a significant national Cryptosporidium exceedance in the United Kingdom, August 2023 and ongoing.

Routine laboratory surveillance has identified an unprecedented and ongoing exceedance of Cryptosporidium spp. across the United Kingdom, notably driven by C. hominis transmission, since 14 August 2023. Information from 477 reported cases in England and Wales, followed up with a standardised exposure questionnaire as of 25 September 2023, identified foreign travel in 250 (54%) of 463 respondents and swimming in 234 (66%) of 353 cases. A significant, common exposure has not yet been identified in first analyses.

Enhancing epidemiological surveillance of the emergence of the SARS-CoV-2 Omicron variant using spike gene target failure data, England, 15 November to 31 December 2021.

When SARS-CoV-2 Omicron emerged in 2021, S gene target failure enabled differentiation between Omicron and the dominant Delta variant. In England, where S gene target surveillance (SGTS) was already established, this led to rapid identification (within ca 3 days of sample collection) of possible Omicron cases, alongside real-time surveillance and modelling of Omicron growth. SGTS was key to public health action (including case identification and incident management), and we share applied insights on how and when to use SGTS.

The spatio-temporal distribution of COVID-19 infection in England between January and June 2020.

The spatio-temporal dynamics of an outbreak provide important insights to help direct public health resources intended to control transmission. They also provide a focus for detailed epidemiological studies and allow the timing and impact of interventions to be assessed.A common approach is to aggregate case data to administrative regions. Whilst providing a good visual impression of change over space, this method masks spatial variation and assumes that disease risk is constant across space. Risk factors for COVID-19 (e.g. population density, deprivation and ethnicity) vary from place to place across England so it follows that risk will also vary spatially. Kernel density estimation compares the spatial distribution of cases relative to the underlying population, unfettered by arbitrary geographical boundaries, to produce a continuous estimate of spatially varying risk.Using test results from healthcare settings in England (Pillar 1 of the UK Government testing strategy) and freely available methods and software, we estimated the spatial and spatio-temporal risk of COVID-19 infection across England for the first 6 months of 2020. Widespread transmission was underway when partial lockdown measures were introduced on 23 March 2020 and the greatest risk erred towards large urban areas. The rapid growth phase of the outbreak coincided with multiple introductions to England from the European mainland. The spatio-temporal risk was highly labile throughout.In terms of controlling transmission, the most important practical application of our results is the accurate identification of areas within regions that may require tailored intervention strategies. We recommend that this approach is absorbed into routine surveillance outputs in England. Further risk characterisation using widespread community testing (Pillar 2) data is needed as is the increased use of predictive spatial models at fine spatial scales.

Evidence of on-going transmission of Shiga toxin-producing Escherichia coli O157:H7 following a foodborne outbreak.

In August 2019, public health surveillance systems in Scotland and England identified seven, geographically dispersed cases infected with the same strain (defined as isolates that fell within the same five single nucleotide polymorphism single linage cluster) of Shiga toxin-producing Escherichia coli O157:H7. Epidemiological analysis of enhanced surveillance questionnaire data identified handling raw beef and shopping from the same national retailer (retailer A) as the common exposure. Concurrently, a microbiological survey of minced beef at retail identified the same strain in a sample of minced beef sold by retailer A, providing microbiological evidence of the link. Between September and November 2019, a further four primary and two secondary cases infected with the same strain were identified; two cases developed haemolytic uraemic syndrome. None of the four primary cases reported consumption of beef from retailer A and the transmission route of these subsequent cases was not identified, although all four primary cases visited the same petting farm. Generally, outbreaks of STEC O157:H7 in the UK appear to be distinct, short-lived events; however, on-going transmission linked to contaminated food, animals or environmental exposures and person-to-person contact do occur. Although outbreaks of STEC caused by contaminated fresh produce are increasingly common, undercooked meat products remain a risk of infection.

Utility of whole-genome sequencing during an investigation of multiple foodborne outbreaks of Shigella sonnei.

In April 2018, Public Health England was notified of cases of Shigella sonnei who had eaten food from three different catering outlets in England. The outbreaks were initially investigated as separate events, but whole-genome sequencing (WGS) showed they were caused by the same strain. The investigation included analyses of epidemiological data, the food chain and microbiological examination of food samples. WGS was used to determine the phylogenetic relatedness and antimicrobial resistance profile of the outbreak strain. Ultimately, 33 cases were linked to this outbreak; the majority had eaten food from seven outlets specialising in Indian or Middle Eastern cuisine. Five outlets were linked to two or more cases, all of which used fresh coriander although a shared supplier was not identified. An investigation at one of the venues recorded that 86% of cases reported eating dishes with coriander as an ingredient or garnish. Four cases were admitted to hospital and one had evidence of treatment failure with ciprofloxacin. Phylogenetic analysis showed that the outbreak strain was part of a wider multidrug-resistant clade associated with travel to Pakistan. Poor hygiene practices during cultivation, distribution or preparation of fresh produce are likely contributing factors.

Epidemiology of Hepatitis E in England and Wales: A 10-Year Retrospective Surveillance Study, 2008-2017.

Indigenous, foodborne transmission of hepatitis E virus genotype 3 (HEV G3) has become recognized as an emerging problem in industrialized countries. Although mostly asymptomatic, HEV G3 infection has a range of outcomes, including mild illness, severe acute hepatitis, and, of particular concern, chronic progressive hepatitis in immunocompromised patients. Public Health England has monitored cases of acute HEV infection in England and Wales since 2003. Between 2010 and 2017, enhanced surveillance using 2 linked laboratory databases and questionnaires on clinical features and risk factors was conducted. There was a year-on-year increase in the number of infections from 2008 (183) through 2016 (1243). Then, in 2017, the number of infections declined (to 912). As reported previously, HEV G3 group 2 (also known as "G3 abcdhij") is the predominant cause of acute infections, and older men are most at risk. Consumption of pork and pork products was significantly higher among patients than in the general population, but other previously reported associations, such as consumption of shellfish, were not observed. Ongoing surveillance is required to monitor future trends and changes in the epidemiology of the virus. The changing methods of animal husbandry and processing and distribution of animal products needs to be further investigated.

Seasonality and the effects of weather on Campylobacter infections.

BACKGROUND: Campylobacteriosis is a major public health concern. The weather factors that influence spatial and seasonal distributions are not fully understood. METHODS: To investigate the impacts of temperature and rainfall on Campylobacter infections in England and Wales, cases of Campylobacter were linked to local temperature and rainfall at laboratory postcodes in the 30 days before the specimen date. Methods for investigation included a comparative conditional incidence, wavelet, clustering, and time series analyses. RESULTS: The increase of Campylobacter infections in the late spring was significantly linked to temperature two weeks before, with an increase in conditional incidence of 0.175 cases per 100,000 per week for weeks 17 to 24; the relationship to temperature was not linear. Generalized structural time series model revealed that changes in temperature accounted for 33.3% of the expected cases of Campylobacteriosis, with an indication of the direction and relevant temperature range. Wavelet analysis showed a strong annual cycle with additional harmonics at four and six months. Cluster analysis showed three clusters of seasonality with geographic similarities representing metropolitan, rural, and other areas. CONCLUSIONS: The association of Campylobacteriosis with temperature is likely to be indirect. High-resolution spatial temporal linkage of weather parameters and cases is important in improving weather associations with infectious diseases. The primary driver of Campylobacter incidence remains to be determined; other avenues, such as insect contamination of chicken flocks through poor biosecurity should be explored.

A spatial and temporal analysis of risk factors associated with sporadic Shiga toxin-producing Escherichia coli O157 infection in England between 2009 and 2015.

Infection with STEC O157 is relatively rare but has potentially serious sequelae, particularly for children. Large outbreaks have prompted considerable efforts designed to reduce transmission primarily from food and direct animal contact. Despite these interventions, numbers of infections have remained constant for many years and the mechanisms leading to many sporadic infections remain unclear.Here, we show that two-thirds of all cases reported in England between 2009 and 2015 were sporadic. Crude rates of infection differed geographically and were highest in rural areas during the summer months. Living in rural areas with high densities of cattle, sheep or pigs and those served by private water supplies were associated with increased risk. Living in an area of lower deprivation contributed to increased risk but this appeared to be associated with reported travel abroad. Fresh water coverage and residential proximity to the coast were not risk factors.To reduce the overall burden of infection in England, interventions designed to reduce the number of sporadic infections with STEC should focus on the residents of rural areas with high densities of livestock and the effective management of non-municipal water supplies. The role of sheep as a reservoir and potential source of infection in humans should not be overlooked.

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.

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.

Antimicrobial resistance in Shiga toxin-producing Escherichia coli serogroups O157 and O26 isolated from human cases of diarrhoeal disease in England, 2015.

OBJECTIVES: Shiga toxin-producing Escherichia coli (STEC) are zoonotic and transmission to humans occurs via contaminated food or contact with infected animals. In this study, WGS data were used to predict antimicrobial resistance (AMR) in STEC from symptomatic human cases to assess the extent of transmission of antibiotic-resistant E. coli from animals to humans. METHODS: WGS data from 430 isolates of STEC were mapped to genes known to be associated with phenotypic AMR. Susceptibility testing was performed by a breakpoint method on all viable isolates exhibiting resistance to at least one antimicrobial. RESULTS: 327/396 (82.6%) of STEC O157 and 22/34 (64.7%) of STEC O26 lacked identifiable resistance genes and were predicted to be fully susceptible to 11 diverse classes of antimicrobials. For the remaining 81 isolates, 74 were phenotypically tested and there was concordance between WGS-predicted resistance and expression of phenotypic resistance. The most common resistance profile was ampicillin, streptomycin, trimethoprim/sulphonamide and tetracycline occurring in 25 (5.8%) isolates. Resistance to other antimicrobials, including resistance to chloramphenicol (2.1%), resistance to azithromycin (0.2%) and reduced susceptibility to ciprofloxacin (2.6%), was less frequent. Three isolates were identified as ESBL producers. CONCLUSIONS: ß-Lactams, trimethoprim/sulphonamides and tetracyclines account for the majority of therapeutic antimicrobials sold for veterinary use and this may be a risk factor for the presence of AMR in domestically acquired human clinical isolates of STEC. Isolates that were resistant to ampicillin, streptomycin, sulphonamide, tetracycline and azithromycin and had reduced susceptibility to ciprofloxacin were associated with cases who reported recent travel abroad.

Comparison of phenotypic and WGS-derived antimicrobial resistance profiles of Shigella sonnei isolated from cases of diarrhoeal disease in England and Wales, 2015.

Objectives: Phenotypic and genotypic methods for the detection of antimicrobial resistance (AMR) in Shigella sonnei in England and Wales were compared and evaluated. Methods: WGS data from 341 isolates of S. sonnei isolated between June 2015 and January 2016 were mapped to genes known to be associated with phenotypic AMR. Antimicrobial susceptibility testing was performed on all viable isolates (n = 335). Results: Fifteen of 335 isolates had a discrepancy between phenotypic and genotypic testing for 1 of the 10 antimicrobial classes tested, equating to 15 (0.45%) discordant results out of a possible 3350 isolate/antimicrobial combinations. All 15 mismatched results were genotypically resistant but phenotypically susceptible. Eleven of the 15 discrepancies were observed in streptomycin resistance profiles. The most common resistance profile was trimethoprim, sulphonamides, tetracyclines and streptomycin, occurring in 97 (28.4%) isolates. Resistances to ciprofloxacin and the third-generation cephalosporins, not detected in England and Wales prior to 2002, were identified in 18.2% and 12% of isolates, respectively. Three hundred and four (89.1%) isolates were MDR. There was no significant association between any of the AMR determinants tested and recent foreign travel in male or female cases. The number of isolates of S. sonnei harbouring blaTEM-1 and ermB/mphA was significantly higher in men who reported no recent travel outside the UK. Conclusions: The use of WGS for routine public health surveillance is a reliable method for rapid detection of emerging AMR in isolates of S. sonnei.

Cyclosporiasis in travellers returning to the United Kingdom from Mexico in 2017: lessons from the recent past to inform the future.

During the summers of 2015 and 2016, the United Kingdom experienced large outbreaks of cyclosporiasis in travellers returning from Mexico. As the source of the outbreaks was not identified, there is the potential for a similar outbreak to occur in 2017; indeed 78 cases had already been reported as at 27 July 2017. Early communication and international collaboration is essential to provide a better understanding of the source and extent of this recurring situation.

Shiga Toxin-Producing Escherichia coli O157, England and Wales, 1983-2012.

We evaluated clinical Shiga toxin-producing Escherichia coli O157 infections in England and Wales during 1983-2012 to describe changes in microbiological and surveillance methods. A strain replacement event was captured; phage type (PT) 2 decreased to account for just 3% of cases by 2012, whereas PT8 and PT21/28 strains concurrently emerged, constituting almost two thirds of cases by 2012. Despite interventions to control and reduce transmission, incidence remained constant. However, sources of infection changed over time; outbreaks caused by contaminated meat and milk declined, suggesting that interventions aimed at reducing meat cross-contamination were effective. Petting farm and school and nursery outbreaks increased, suggesting the emergence of other modes of transmission and potentially contributing to the sustained incidence over time. Studies assessing interventions and consideration of policies and guidance should be undertaken to reduce Shiga toxin-producing E. coli O157 infections in England and Wales in line with the latest epidemiologic findings.

ESBL-Producing and Macrolide-Resistant Shigella sonnei Infections among Men Who Have Sex with Men, England, 2015.

In England in 2015, Shigella sonnei isolates from men who have sex with men produced extended-spectrum ß-lactamases and exhibited macrolide resistance. Whole-genome sequencing showed a close relationship among the isolates, which harbored a plasmid that was previously identified in a shigellosis outbreak among this population but has acquired a mobile element.

Factors influencing the time between onset of illness and specimen collection in the diagnosis of non-pregnancy associated listeriosis in England and Wales.

BACKGROUND: Listeriosis is an opportunistic bacterial infection caused by Listeria monocytogenes and predominantly affects people who are immunocompromised. Due to its severity and the population at risk, prompt clinical diagnosis and treatment of listeriosis is essential. A major step to making a clinical diagnosis is the collection of the appropriate specimen(s) for testing. This study explores factors that may influence the time between onset of illness and collection of specimen in order to inform clinical policy and develop necessary interventions. METHODS: Enhanced surveillance data on non-pregnancy associated listeriosis in England and Wales between 2004 and 2013 were collected and analysed. The difference in days between onset of symptoms and collection of specimen was calculated and factors influencing the time difference were identified using a gamma regression model. RESULTS: The median number of days between onset of symptoms and collection of specimen was two days with 27.1 % of cases reporting one day between onset of symptoms and collection of specimen and 18.8 % of cases reporting more than seven days before collection of specimen. The median number of days between onset of symptoms and collection of specimen was shorter for cases infected with Listeria monocytogenes serogroup 1/2b (one day) and cases with an underlying condition (one day) compared with cases infected with serotype 4 (two days) and cases without underlying conditions (two days). CONCLUSIONS: Our study has shown that Listeria monocytogenes serotype and the presence of an underlying condition may influence the time between onset of symptoms and collection of specimen.

Whole-genome sequencing for national surveillance of Shiga toxin-producing Escherichia coli O157.

BACKGROUND: National surveillance of gastrointestinal pathogens, such as Shiga toxin-producing Escherichia coli O157 (STEC O157), is key to rapidly identifying linked cases in the distributed food network to facilitate public health interventions. In this study, we used whole-genome sequencing (WGS) as a tool to inform national surveillance of STEC O157 in terms of identifying linked cases and clusters and guiding epidemiological investigation. METHODS: We retrospectively analyzed 334 isolates randomly sampled from 1002 strains of STEC O157 received by the Gastrointestinal Bacteria Reference Unit at Public Health England, Colindale, in 2012. The genetic distance between each isolate, as estimated by WGS, was calculated and phylogenetic methods were used to place strains in an evolutionary context. RESULTS: Estimates of linked clusters representing STEC O157 outbreaks in England and Wales increased by 2-fold when WGS was used instead of traditional typing techniques. The previously unidentified clusters were often widely geographically distributed and small in size. Phylogenetic analysis facilitated identification of temporally distinct cases sharing common exposures and delineating those that shared epidemiological and temporal links. Comparison with multi locus variable number tandem repeat analysis (MLVA) showed that although MLVA is as sensitive as WGS, WGS provides a more timely resolution to outbreak clustering. CONCLUSIONS: WGS has come of age as a molecular typing tool to inform national surveillance of STEC O157; it can be used in real time to provide the highest strain-level resolution for outbreak investigation. WGS allows linked cases to be identified with unprecedented specificity and sensitivity that will facilitate targeted and appropriate public health investigations.

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.