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.

Evaluating the impact on health outcomes of an event that resulted in a delay in contact tracing of COVID-19 cases in England, September 2020: an observational study.

OBJECTIVE: In September 2020, 15 861 SARS-CoV-2 case records failed to upload from the Second Generation Surveillance System (SGSS) to the Contact Tracing Advisory Service (CTAS) tool, delaying the contact tracing of these cases. This study used CTAS data to determine the impact of this delay on population health outcomes: transmission events, hospitalisations and mortality. Previously, a modelling study suggested a substantial impact. DESIGN: Observational study. SETTING: England. POPULATION: Individuals testing positive for SARS-CoV-2 and their reported contacts. MAIN OUTCOME MEASURES: Secondary attack rates (SARs), hospitalisations and deaths among primary and secondary contacts were calculated, compared with all other concurrent, unaffected cases. Affected SGSS records were matched to CTAS records. Successive contacts and cases were identified and matched to hospital episode and mortality outcomes. RESULTS: Initiation of contact tracing was delayed by 3 days on average in the primary cases in the delay group (6 days) compared with the control group (3 days). This was associated with lower completion of contact tracing: 80% (95% CI: 79% to 81%) in delay group and 83% (95% CI: 83% to 84%) in control group. There was some evidence to suggest increased transmission to non-household contacts among those affected by the delay. The SAR for non-household contacts was higher among secondary contacts in the delay group than the control group (delay group: 7.9%, 95% CI: 6.5% to 9.2%; control group: 5.9%, 95% CI: 5.3% to 6.6%). There did not appear to be a significant difference between the delay and control groups in the odds of hospitalisation (crude OR: 1.1 (95% CI: 0.9 to 1.2)) or death (crude OR: 0.7 (95% CI: 0.1 to 4.0)) among secondary contacts. CONCLUSIONS: Our analysis suggests that the delay in contact tracing had a limited impact on population health outcomes; however, contact tracing was not completed for all individuals, so some transmission events might not be captured.

Local Salmonella Enteritidis restaurant outbreak investigation in England provides further evidence for eggs as source in widespread international cluster, March to April 2023.

We report a 5-single nucleotide polymorphism cluster of Salmonella Enteriditis in England, part of a global cluster of S. Enteritidis ST11. Forty-seven confirmed cases have been investigated of whom 25 were linked to a restaurant. In addition, there were 18 probable cases with restaurant exposure. Epidemiological investigations suggested eggs or chicken as the most likely cause of the outbreak but were unable to distinguish between those two food vehicles. Ongoing food chain investigations indicated links to imported eggs from Poland.

Diversity in new flagellum tip attachment in bloodstream form African trypanosomes.

The closely related parasites Trypanosoma brucei, T. congolense, and T. vivax cause neglected tropical diseases collectively known as African Trypanosomiasis. A characteristic feature of bloodstream form T. brucei is the flagellum that is laterally attached to the side of the cell body. During the cell cycle, the new flagellum is formed alongside the old flagellum, with the new flagellum tip embedded within a mobile transmembrane junction called the groove. The molecular composition of the groove is currently unknown, which limits the analysis of this junction and assessment of its conservation in related trypanosomatids. Here, we identified 13 proteins that localize to the flagellar groove through a small-scale tagging screen. Functional analysis of a subset of these proteins by RNAi and gene deletion revealed three proteins, FCP4/TbKin15, FCP7, and FAZ45, that are involved in new flagellum tip attachment to the groove. Despite possessing orthologues of all 13 groove proteins, T. congolense and T. vivax did not assemble a canonical groove around the new flagellum tip according to 3D electron microscopy. This diversity in new flagellum tip attachment points to the rapid evolution of membrane-cytoskeleton structures that can occur without large changes in gene complement and likely reflects the niche specialization of each species.

Association of Results of Four Lateral Flow Antibody Tests with Subsequent SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine coverage remains incomplete, being only 15% in low-income countries. Rapid point-of-care tests predicting SARS-CoV-2 infection susceptibility in the unvaccinated may assist in risk management and vaccine prioritization. We conducted a prospective cohort study in 2,826 participants working in hospitals and Fire and Police services in England, UK, during the pandemic (ISRCTN5660922). Plasma taken at recruitment in June 2020 was tested using four lateral flow immunoassay (LFIA) devices and two laboratory immunoassays detecting antibodies against SARS-CoV-2 (UK Rapid Test Consortium's AbC-19 rapid test, OrientGene COVID IgG/IgM rapid test cassette, SureScreen COVID-19 rapid test cassette, and Biomerica COVID-19 IgG/IgM rapid test; Roche N and Euroimmun S laboratory assays). We monitored participants for microbiologically confirmed SARS-CoV-2 infection for 200 days. We estimated associations between test results at baseline and subsequent infection, using Poisson regression models adjusted for baseline demographic risk factors for SARS-CoV-2 exposure. Positive IgG results on each of the four LFIAs were associated with lower rates of subsequent infection with adjusted incidence rate ratios (aIRRs) of 0.00 (95% confidence interval, 0.00 to 0.01), 0.03 (0.02 to 0.05), 0.07 (0.05 to 0.10), and 0.09 (0.07 to 0.12), respectively. The protective association was strongest for AbC-19 and SureScreen. The aIRR for the laboratory Roche N antibody assay at the manufacturer-recommended threshold was similar to those of the two best performing LFIAs at 0.03 (0.01 to 0.10). Lateral flow devices measuring SARS-CoV-2 IgG predicted disease risk in unvaccinated individuals over a 200-day follow-up. The association of some LFIAs with subsequent infection was similar to laboratory immunoassays. IMPORTANCE Previous research has demonstrated an association between the detection of antibodies to SARS-CoV-2 following natural infection and protection from subsequent symptomatic SARS-CoV-2 infection. Lateral flow immunoassays (LFIAs) detecting anti-SARS-CoV-2 IgG are a cheap, readily deployed technology that has been used on a large scale in population screening programs, yet no studies have investigated whether LFIA results are associated with subsequent SARS-CoV-2 infection. In a prospective cohort study of 2,826 United Kingdom key workers, we found positivity in lateral flow test results had a strong negative association with subsequent SARS-CoV-2 infection within 200 days in an unvaccinated population. Positivity on more-specific but less-sensitive tests was associated with a markedly decreased rate of disease; protection associated with testing positive using more sensitive devices detecting lower levels of anti-SARS-CoV-2 IgG was more modest. Lateral flow tests with high specificity may have a role in estimation of SARS-CoV-2 disease risk in unvaccinated populations.

Describing the indirect impact of COVID-19 on healthcare utilisation using syndromic surveillance systems.

BACKGROUND: Since the end of January 2020, the coronavirus (COVID-19) pandemic has been responsible for a global health crisis. In England a number of non-pharmaceutical interventions have been introduced throughout the pandemic, including guidelines on healthcare attendance (for example, promoting remote consultations), increased handwashing and social distancing. These interventions are likely to have impacted the incidence of non-COVID-19 conditions as well as healthcare seeking behaviour. Syndromic Surveillance Systems offer the ability to monitor trends in healthcare usage over time. METHODS: This study describes the indirect impact of COVID-19 on healthcare utilisation using a range of syndromic indicators including eye conditions, mumps, fractures, herpes zoster and cardiac conditions. Data from the syndromic surveillance systems monitored by Public Health England were used to describe the number of contacts with NHS 111, general practitioner (GP) In Hours (GPIH) and Out-of-Hours (GPOOH), Ambulance and Emergency Department (ED) services over comparable periods before and during the pandemic. RESULTS: The peak pandemic period in 2020 (weeks 13-20), compared to the same period in 2019, displayed on average a 12% increase in NHS 111 calls, an 11% decrease in GPOOH consultations, and a 49% decrease in ED attendances. In the GP In Hours system, conjunctivitis consultations decreased by 64% and mumps consultations by 31%. There was a 49% reduction in attendance at EDs for fractures, and there was no longer any weekend increase in ED fracture attendances, with similar attendance patterns observed across each day of the week. There was a decrease in the number of ED attendances with diagnoses of myocardial ischaemia. CONCLUSION: The COVID-19 pandemic drastically impacted healthcare utilisation for non-COVID-19 conditions, due to a combination of a probable decrease in incidence of certain conditions and changes in healthcare seeking behaviour. Syndromic surveillance has a valuable role in describing and understanding these trends.

Developing a model to predict individualised treatment for gonorrhoea: a modelling study.

OBJECTIVE: To develop a tool predicting individualised treatment for gonorrhoea, enabling treatment with previously recommended antibiotics, to reduce use of last-line treatment ceftriaxone. DESIGN: A modelling study. SETTING: England and Wales. PARTICIPANTS: Individuals accessing sentinel health services. INTERVENTION: Developing an Excel model which uses participants' demographic, behavioural and clinical characteristics to predict susceptibility to legacy antibiotics. Model parameters were calculated using data for 2015-2017 from the Gonococcal Resistance to Antimicrobials Surveillance Programme. MAIN OUTCOME MEASURES: Estimated number of doses of ceftriaxone saved, and number of people delayed effective treatment, by model use in clinical practice. Model outputs are the predicted risk of resistance to ciprofloxacin, azithromycin, penicillin and cefixime, in groups of individuals with different combinations of characteristics (gender, sexual orientation, number of recent sexual partners, age, ethnicity), and a treatment recommendation. RESULTS: Between 2015 and 2017, 8013 isolates were collected: 64% from men who have sex with men, 18% from heterosexual men and 18% from women. Across participant subgroups, stratified by all predictors, resistance prevalence was high for ciprofloxacin (range: 11%-51%) and penicillin (range: 6%-33%). Resistance prevalence for azithromycin and cefixime ranged from 0% to 13% and for ceftriaxone it was 0%. Simulating model use, 88% of individuals could be given cefixime and 10% azithromycin, saving 97% of ceftriaxone doses, with 1% of individuals delayed effective treatment. CONCLUSIONS: Using demographic and behavioural characteristics, we could not reliably identify a participant subset in which ciprofloxacin or penicillin would be effective. Cefixime resistance was almost universally low; however, substituting ceftriaxone for near-uniform treatment with cefixime risks re-emergence of resistance to cefixime and ceftriaxone. Several subgroups had low azithromycin resistance, but widespread azithromycin monotherapy risks resistance at population level. However, this dataset had limitations; further exploration of individual characteristics to predict resistance to a wider range of legacy antibiotics may still be appropriate.