Surge of lower respiratory tract group A streptococcal infections in England in winter 2022: epidemiology and clinical profile.

BACKGROUND: Following low incidence of invasive group A streptococcal (iGAS) infections during the COVID-19 pandemic, marked increases were noted in many countries during 2022, particularly in children. In November 2022, severe presentations of lower respiratory tract infections (LRTIs), including empyema, were notified by clinicians across the UK. UKHSA investigated this rise with the aim of informing clinical management and public health response. METHODS: We undertook a case-series analysis using multiple routine data sources, exempted from ethics approval or patient consent. We identified iGAS cases in England in children younger than 15 years with an LRTI reported between Oct 1 and Dec 21, 2022, using UKHSA laboratory surveillance data (GAS detected in LRT specimens) and notifications by clinicians and Health Protection Teams (HPTs). Symptoms, diagnoses, health-care interactions, and outcome (death or recovery) data were obtained from HPT case management notes, the National Child Mortality Database, and the NHS Digital Emergency Care Dataset. FINDINGS: We identified 147 cases of LRTI iGAS in children across England (77 [52%] male, 70 [48%] female; median age 4 years [IQR 2-6]). Predominant ethnicities were White (74 [65%] of 113 with known ethnicity) and Asian (18 [16%] of 113). Most reported symptoms were fever (90 [75%] of 120 children with ≥1 symptom) and cough (60 [50%] of 120), and 71 (48%) of all 147 children had a diagnosed respiratory viral coinfection (most commonly hMPV and RSV). 127 (86%) of children attended an emergency department, 31% (n=36/114 with onset date) at least twice within 21 days after symptom onset. 37 (25%) of 147 children died, with a median time from symptom onset to death of 4 days (IQR 3-7). Of 32 children with sample dates, 16 (84%) were tested for GAS on or after the day they died. Over half of deaths (21 [57%] of 37 deaths) occurred in the community after rapid deterioration, of whom 18 had previous contact with health-care services documented. INTERPRETATION: The UK saw an unusual rise in iGAS LRTIs in children in late 2022. One in four cases died, over half in the community. Non-specific symptoms, viral symptoms, or positive virology might have lowered suspicion of bacterial infection. Although the use of multiple available data sources expedited the analysis, varying data completeness limited interpretation. Our study highlights the need for earlier detection and identification of effective measures to prevent death. FUNDING: None.

Emerging Invasive Group A Streptococcus M1UK Lineage Detected by Allele-Specific PCR, England, 20201.

Increasing reports of invasive Streptococcus pyogenes infections mandate surveillance for toxigenic lineage M1UK. An allele-specific PCR was developed to distinguish M1UK from other emm1 strains. The M1UK lineage represented 91% of invasive emm1 isolates in England in 2020. Allele-specific PCR will permit surveillance for M1UK without need for genome sequencing.

Cluster detection with random neighbourhood covering: Application to invasive Group A Streptococcal disease.

The rapid detection of outbreaks is a key step in the effective control and containment of infectious diseases. In particular, the identification of cases which might be epidemiologically linked is crucial in directing outbreak-containment efforts and shaping the intervention of public health authorities. Often this requires the detection of clusters of cases whose numbers exceed those expected by a background of sporadic cases. Quantifying exceedances rapidly is particularly challenging when only few cases are typically reported in a precise location and time. To address such important public health concerns, we present a general method which can detect spatio-temporal deviations from a Poisson point process and estimate the odds of an isolate being part of a cluster. This method can be applied to diseases where detailed geographical information is available. In addition, we propose an approach to explicitly take account of delays in microbial typing. As a case study, we considered invasive group A Streptococcus infection events as recorded and typed by Public Health England from 2015 to 2020.

Making the invisible visible: using national surveillance data to identify people experiencing homelessness in England with COVID-19.

Persons experiencing homelessness (PEH) or rough sleeping are a vulnerable population, likely to be disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic. The impact of COVID-19 infection on this population is yet to be fully described in England. We present a novel method to identify COVID-19 cases in this population and describe its findings. A phenotype was developed and validated to identify PEH or rough sleeping in a national surveillance system. Confirmed COVID-19 cases in England from March 2020 to March 2022 were address-matched to known homelessness accommodations and shelters. Further cases were identified using address-based indicators, such as NHS pseudo postcodes. In total, 1835 cases were identified by the phenotype. Most were <39 years of age (66.8%) and male (62.8%). The proportion of cases was highest in London (29.8%). The proportion of cases of a minority ethnic background and deaths were disproportionality greater in this population, compared to all COVID-19 cases in England. This methodology provides an approach to track the impact of COVID-19 on a subset of this population and will be relevant to policy making. Future surveillance systems and studies may benefit from this approach to further investigate the impact of COVID-19 and other diseases on select populations.

Attribution of nosocomial seeding to long-term care facility COVID-19 outbreaks.

Residents of long-term care facilities (LTCFs) were disproportionately affected by the COVID-19 pandemic. We assessed the extent to which hospital-associated infections contributed to COVID-19 LTCF outbreaks in England. We matched addresses of cases between March 2020 and June 2021 to reference databases to identify LTCF residents. Linkage to health service records identified hospital-associated infections, with the number of days spent in hospital before positive specimen date used to classify these as definite or probable. Of 149,129 cases in LTCF residents during the study period, 3,748 (2.5%) were definite or probable hospital-associated and discharged to an LTCF. Overall, 431 (0.3%) were identified as index cases of potentially nosocomial-seeded outbreaks (2.7% (431/15,797) of all identified LTCF outbreaks). These outbreaks involved 4,521 resident cases and 1,335 deaths, representing 3.0% and 3.6% of all cases and deaths in LTCF residents, respectively. The proportion of outbreaks that were potentially nosocomial-seeded peaked in late June 2020, early December 2020, mid-January 2021, and mid-April 2021. Nosocomial seeding contributed to COVID-19 LTCF outbreaks but is unlikely to have accounted for a substantial proportion. The continued identification of such outbreaks after the implementation of preventative policies highlights the challenges of preventing their occurrence.

Comparative transmission of SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants and the impact of vaccination: national cohort study, England.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) rapidly replaced Delta (B.1.617.2) to become dominant in England. Our study assessed differences in transmission between Omicron and Delta using two independent data sources and methods. Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for named contacts were calculated in household and non-household settings using contact tracing data, while household clustering was identified using national surveillance data. Logistic regression models were applied to control for factors associated with transmission for both methods. For contact tracing data, higher secondary attack rates for Omicron vs. Delta were identified in households (15.0% vs. 10.8%) and non-households (8.2% vs. 3.7%). For both variants, in household settings, onward transmission was reduced from cases and named contacts who had three doses of vaccine compared to two, but this effect was less pronounced for Omicron (adjusted risk ratio, aRR 0.78 and 0.88) than Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed only in contacts who had three doses vs. two doses for both Delta (aRR 0.51) and Omicron (aRR 0.76). For national surveillance data, the risk of household clustering, was increased 3.5-fold for Omicron compared to Delta (aRR 3.54 (3.29-3.81)). Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.

Time to negative throat culture following initiation of antibiotics for pharyngeal group A Streptococcus: a systematic review and meta-analysis up to October 2021 to inform public health control measures.

BackgroundPublic health guidance recommending isolation of individuals with group A streptococcal (GAS) infection or carriage for 12-24 h from antibiotic initiation to prevent onward transmission requires a strong evidence base.AimTo estimate the pooled proportion of individuals who remain GAS culture-positive at set intervals after initiation of antibiotics through a systematic literature review (PROSPERO CRD42021290364) and meta-analysis.MethodsWe searched Ovid MEDLINE (1946-), EMBASE (1974-) and Cochrane library. We included interventional or observational studies with ≥ 10 participants reporting rates of GAS throat culture positivity during antibiotic treatment for culture-confirmed GAS pharyngitis, scarlet fever and asymptomatic pharyngeal GAS carriage. We did not apply age, language or geographical restrictions.ResultsOf 5,058 unique records, 43 were included (37 randomised controlled studies, three non-randomised controlled trials and three before-and-after studies). The proportion of individuals remaining culture-positive on day 1, day 2 and days 3-9 were 6.9% (95% CI: 2.7-16.8%), 5.4% (95% CI: 2.1-13.3%) and 2.6% (95% CI: 1.6-4.2%). For penicillins and cephalosporins, day 1 positivity was 6.5% (95% CI: 2.5-16.1%) and 1.6% (95% CI: 0.04-42.9%), respectively. Overall, for 9.1% (95% CI: 7.3-11.3), throat swabs collected after completion of therapy were GAS culture-positive. Only six studies had low risk of bias.ConclusionsOur review provides evidence that antibiotics for pharyngeal GAS achieve a high rate of culture conversion within 24 h but highlights the need for further research given methodological limitations of published studies and imprecision of pooled estimates. Further evidence is needed for non-beta-lactam antibiotics and asymptomatic individuals.

Increase in invasive group A streptococcal infection notifications, England, 2022.

Increases in invasive group A streptococcal (iGAS) infection and associated deaths, particularly in children, above seasonally expected levels are being seen this season (772 notifications reported in weeks 37 to 48 in 2022) across England. Diagnoses of iGAS infection from lower respiratory tract specimens in children under 15 years increased to 28% in November 2022. Medical practitioners have been alerted to the exceptional increase in incidence, including unusual numbers of children presenting with pulmonary empyema.

A Systematic Framework for Prioritizing Burden of Disease Data Required for Vaccine Development and Implementation: The Case for Group A Streptococcal Diseases.

Vaccine development and implementation decisions need to be guided by accurate and robust burden of disease data. We developed an innovative systematic framework outlining the properties of such data that are needed to advance vaccine development and evaluation, and prioritize research and surveillance activities. We focus on 4 objectives-advocacy, regulatory oversight and licensure, policy and post-licensure evaluation, and post-licensure financing-and identify key stakeholders and specific requirements for burden of disease data aligned with each objective. We apply this framework to group A Streptococcus, a pathogen with an underrecognized global burden, and give specific examples pertinent to 8 clinical endpoints. This dynamic framework can be adapted for any disease with a vaccine in development and can be updated as vaccine candidates progress through clinical trials. This framework will also help with research and innovation priority setting of the Immunization Agenda 2030 (IA2030) and accelerate development of future vaccines.

Effect of Returning University Students on COVID-19 Infections in England, 2020.

Each September in England, ≈1 million students relocate to study at universities. To determine COVID-19 cases and outbreaks among university students after their return to university during the COVID pandemic in September 2020, we identified students with COVID-19 (student case-patients) by reviewing contact tracing records identifying attendance at university and residence in student accommodations identified by matching case-patients' residential addresses with national property databases. We determined COVID-19 rates in towns/cities with and without a university campus. We identified 53,430 student case-patients during September 1-December 31, 2020, which accounted for 2.7% of all cases during this period. Student case-patients increased rapidly after the start of the term, driven initially by cases and outbreaks in student accommodations. Case rates among students 18-23 years of age doubled at the start of term in towns with universities. Our findings highlight the need for face-to-face and control measures to reduce virus transmission.

Invasive Group A Streptococcus Outbreaks Associated with Home Healthcare, England, 2018-2019.

Healthcare-associated invasive group A Streptococcus (iGAS) outbreaks are common worldwide, but only England has reported outbreaks associated with home healthcare (HHC). We describe 10 outbreaks during 2018-2019 in England. A total of 96 iGAS cases (range 2-39 per outbreak) and 28 deaths (case-fatality rate 29%) occurred. Outbreak duration ranged from 3-517 days; median time between sequential cases was 20.5 days (range 1-225 days). Outbreak identification was difficult, but emm typing and whole-genome sequencing improved detection. Network analyses indicated multiple potential transmission routes. Screening of 366 HHC workers from 9 outbreaks identified group A Streptococcus carriage in just 1 worker. Outbreak control required multiple interventions, including improved infection control, equipment decontamination, and antimicrobial prophylaxis for staff. Transmission routes and effective interventions are not yet clear, and iGAS outbreaks likely are underrecognized. To improve patient safety and reduce deaths, public health agencies should be aware of HHC-associated iGAS.

Increased Residential Clustering of COVID-19 Cases Associated With SARS-CoV-2 Variant of Concern B.1.1.7.

BACKGROUND: The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 variant in England in 2020 and subsequent global spread emphasized the need to understand epidemiologic characteristics of SARS-CoV-2 variants. A diagnostic proxy for this variant, referred to as S-gene target failure, provided a rich dataset to assess transmissibility of the variant in an analysis of clustering in residential settings. METHODS: We used a pair-matched case-control study design to estimate odds of onward transmission within households with S-gene target failure index cases versus nontarget failure index cases. We defined cases as the index in a household cluster (clustered case) and controls as a case with no subsequent household cluster (sporadic). We matched clustered and sporadic cases one-to-one on specimen week, geography, and property type. We used conditional logistic regression, adjusting for age, sex, ethnicity, and symptom status, to assess odds of residential clustering. RESULTS: Our study population comprised 57,244 individuals with specimen dates from 23 November 2020 to 4 January 2021. Crude analysis yielded 54% increased odds (odds ratio [OR] = 1.5; 95% confidence interval [CI] = 1.5, 1.6) of residential clustering associated with S-gene target failure; the association remained in the fully adjusted model (OR = 1.6, 95% CI = 1.5, 1.6). Stratified analyses by region showed increased odds of residential clustering associated with target failure in all regions apart from the Southwest, where we observed lower precision. Similar adjusted odds ratios with precise confidence intervals remained in stratified analyses by property category. CONCLUSION: We observed increased odds in all property types, consistent with greater transmissibility of the B.1.1.7 variant in this high-risk setting.

Differential impact of quarantine policies for recovered COVID-19 cases in England: a case cohort study of surveillance data, June to December 2020.

BACKGROUND: From 12th March 2020, individuals in England were advised to quarantine in their home if a household member tested positive for SARS-CoV-2. A mandatory isolation period of 10 days was introduced on 28th September 2020 and applied to all individuals with COVID-19. We assessed the frequency, timing, and characteristics of recovered COVID-19 cases requiring subsequent quarantine episodes due to household re-exposure. METHODS: In this case cohort study, all laboratory-confirmed COVID-19 cases notified in England (29th June to 28th December 2020) were analysed to identify consecutive household case(s). Multivariable logistic regression was used to determine associations between case characteristics and need to quarantine following recent infection (within 28 days of diagnosis). RESULTS: Among 1,651,550 cases resident in private dwellings and Houses of Multiple Occupancy (HMOs), 744,548 (45.1%) were the only case in their home and 56,179 (3.4%) were succeeded by further household cases diagnosed within 11-28 days of their diagnosis. Of 1,641,412 cases arising in private homes, the likelihood of further household cases was highest for Bangladeshi (aOR = 2.20, 95% CI = 2.10-2.31) and Pakistani (aOR = 2.15, 95% CI = 2.08-2.22) individuals compared to White British, as well as among young people (17-24y vs. 25-64y; aOR = 1.19, 95% CI = 1.16-1.22), men (vs. women; aOR = 1.06, 95% CI = 1.04-1.08), London residents (vs. Yorkshire and Humber; aOR = 1.57, 95% CI = 1.52-1.63) and areas of high deprivation (IMD 1 vs. 10; aOR = 1.13, 95% CI = 1.09-1.19). CONCLUSION: Policies requiring quarantine on re-exposure differentially impact some of the most disadvantaged populations. Quarantine exemption for recently recovered individuals could mitigate the socioeconomic impact of responses to COVID-19 or similar infectious disease outbreaks.

Assessment of mortality and hospital admissions associated with confirmed infection with SARS-CoV-2 Alpha variant: a matched cohort and time-to-event analysis, England, October to December 2020.

BackgroundThe emergence of the SARS-CoV-2 Alpha variant in England coincided with a rapid increase in the number of PCR-confirmed COVID-19 cases in areas where the variant was concentrated.AimOur aim was to assess whether infection with Alpha was associated with more severe clinical outcomes than the wild type.MethodsLaboratory-confirmed infections with genomically sequenced SARS-CoV-2 Alpha and wild type between October and December 2020 were linked to routine healthcare and surveillance datasets. We conducted two statistical analyses to compare the risk of hospital admission and death within 28 days of testing between Alpha and wild-type infections: a matched cohort study and an adjusted Cox proportional hazards model. We assessed differences in disease severity by comparing hospital admission and mortality, including length of hospitalisation and time to death.ResultsOf 63,609 COVID-19 cases sequenced in England between October and December 2020, 6,038 had the Alpha variant. In the matched cohort analysis, we matched 2,821 cases with Alpha to 2,821 to cases with wild type. In the time-to-event analysis, we observed a 34% increased risk in hospitalisation associated with Alpha compared with wild type, but no significant difference in the risk of mortality.ConclusionWe found evidence of increased risk of hospitalisation after adjusting for key confounders, suggesting increased infection severity associated with the Alpha variant. Rapid assessments of the relative morbidity in terms of clinical outcomes and mortality associated with emerging SARS-CoV-2 variants compared with dominant variants are required to assess overall impact of SARS-CoV-2 mutations.

Impact of SARS-CoV-2 Alpha variant (B.1.1.7) on prisons, England.

OBJECTIVES: Prisons are high-risk settings for infectious disease outbreaks because of their highly dynamic and crowded nature. During late 2020, prisons in England observed a surge in COVID-19 infection. This study describes the emergence of the Alpha variant in prisons during this period. METHODS: Alpha and non-Alpha variant COVID-19 cases were identified in prisoners in England using address-matched laboratory notifications and genomic information from COG-UK. RESULTS: Of 14,094 COVID-19-positive prisoner cases between 1 October 2020 and 28 March 2021, 11.5% (n = 1621) had sequencing results. Of these, 1082 (66.7%) were identified as the Alpha variant. Twenty-nine (2.7%) Alpha cases required hospitalisation compared with only five (1.0%; P = 0.02) non-Alpha cases. A total of 14 outbreaks were identified with the median attack rate higher for Alpha (17.9%, interquartile range [IQR] 3.2%-32.2%; P = 0.11) than non-Alpha outbreaks (3.5%, IQR 2.0%-10.2%). CONCLUSION: Higher attack rates and increased likelihood of hospitalisations were observed for Alpha cases compared with non-Alpha. This suggests a key contribution to the rise in cases, hospitalisations and outbreaks in prisons in the second wave. With prisons prone to COVID-19 outbreaks and the potential to act as reservoirs for variants of concern, sequencing of prison-associated cases alongside whole-institution vaccination should be prioritised.

Uncovering Infant Group B Streptococcal (GBS) Disease Clusters in the United Kingdom and Ireland Through Genomic Analysis: A Population-based Epidemiological Study.

BACKGROUND: The true frequency of hospital outbreaks of invasive group B streptococcal (iGBS; Streptococcus agalactiae) disease in infants is unknown. We used whole genome sequencing (WGS) of iGBS isolates collected during a period of enhanced surveillance of infant iGBS disease in the UK and Ireland to determine the number of clustered cases. METHODS: Potentially linked iGBS cases from infants with early (<7 days of life) or late-onset (7-89 days) disease were identified from WGS data (HiSeq 2500 platform, Illumina) from clinical sterile site isolates collected between 04/2014 and 04/2015. We assessed time and place of cases to determine a single-nucleotide polymorphism (SNP) difference threshold for clustered cases. Case details were augmented through linkage to national hospital admission data and hospital record review by local microbiologists. RESULTS: Analysis of sequences indicated a cutoff of ≤5 SNP differences to define iGBS clusters. Among 410 infant iGBS isolates, we identified 7 clusters (4 genetically identical pairs with 0 SNP differences, 1 pair with 3 SNP differences, 1 cluster of 4 cases with ≤1 SNP differences) of which 4 clusters were uncovered for the first time. The clusters comprised 16 cases, of which 15 were late-onset (of 192 late-onset cases with sequenced isolates) and 1 an early-onset index case. Serial intervals between cases ranged from 0 to 59 (median 12) days. CONCLUSIONS: Approximately 1 in 12 late-onset infant iGBS cases were part of a hospital cluster. Over half of the clusters were previously undetected, emphasizing the importance of routine submission of iGBS isolates to reference laboratories for cluster identification and genomic confirmation.

Epidemiology of COVID-19 in Prisons, England, 2020.

Using laboratory data and a novel address matching methodology, we identified 734 cases of coronavirus disease in 88 prisons in England during March 16-October 12, 2020. An additional 412 cases were identified in prison staff and household members. We identified 84 prison outbreaks involving 86% of all prison-associated cases.

Epidemiology of Confirmed COVID-19 Deaths in Adults, England, March-December 2020.

Of the 58,186 coronavirus deaths among adults in England during March-December 2020, 77% occurred in hospitals, 93% were in patients >60 years, and 91% occurred within 28 days of positive specimen. Cumulative mortality rates were highest among persons of Black, Asian, other, or mixed ethnicities and in socioeconomically deprived areas.

Surge in SARS-CoV-2 transmission in school-aged children and household contacts, England, August to October 2021.

Easing of COVID-19 restrictions in England in the summer of 2021 was followed by a sharp rise in cases among school-aged children. Weekly rates of SARS-CoV-2 infection in primary and secondary school children reached 733.3 and 1,664.7/100,000 population, respectively, by week 39 2021. A surge in household clusters with school-aged index cases was noted at the start of the school term, with secondary cases predominantly in children aged 5-15 years and adults aged 30-49 years.

Elevated risk of invasive group A streptococcal disease and host genetic variation in the human leucocyte antigen locus.

Invasive group A streptococcal (GAS) disease is uncommon but carries a high case-fatality rate relative to other infectious diseases. Given the ubiquity of mild GAS infections, it remains unclear why healthy individuals will occasionally develop life-threatening infections, raising the possibility of host genetic predisposition. Here, we present the results of a case-control study including 43 invasive GAS cases and 1540 controls. Using HLA imputation and linear mixed models, we find each copy of the HLA-DQA1*01:03 allele associates with a twofold increased risk of disease (odds ratio 2.3, 95% confidence interval 1.3-4.4, P = 0.009), an association which persists with classical HLA typing of a subset of cases and analysis with an alternative large control dataset with validated HLA data. Moreover, we propose the association is driven by the allele itself rather than the background haplotype. Overall this finding provides impetus for further investigation of the immunogenetic basis of this devastating bacterial disease.