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.

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.

A qualitative process analysis of daily contact testing as an alternative to self-isolation following close contact with a confirmed carrier of SARS-CoV-2.

BACKGROUND: In July 2021, a randomised controlled trial was conducted to compare the effect on SARS-CoV-2 transmission of seven days of Daily Contact Testing (DCT) using Lateral Flow Test (LFT) and two Polymerase Chain Reaction (PCR) tests as an alternative to 10 days of standard self-isolation with one PCR, following close contact with a SARS-CoV-2 carrier. In this qualitative study, we used a nested process evaluation to aid interpretation of the trial and provide insight into factors influencing use of tests, understanding of test results, and how tests were used to inform behavioural decisions. METHODS: Interviews were conducted with 60 participants (42 randomised to DCT and 18 randomised to self-isolation) who had been in close contact with a confirmed SARS-CoV-2 carrier and had consented to take part in the trial. RESULTS: Data were organised into three overarching themes: (1) assessing the risks and benefits of DCT (2) use of testing during the study period and (3) future use of testing. Attitudes toward DCT as an alternative to self-isolation and behaviour during the testing period appeared to be informed by an assessment of the associated risks and benefits. Participants reported how important it was for them to avoid isolation, how necessary self-isolation was considered to be, and the ability of LFTs to detect infection. Behaviour during the testing period was modified to reduce risks and harms as much as possible. Testing was considered a potential compromise, reducing both risk of transmission and the negative impact of self-isolation, and was regarded as a way to return to normal. CONCLUSION: Participants in this study viewed DCT as a sensible, feasible, and welcome means of avoiding unnecessary self-isolation. Although negative LFTs provided reassurance, most people still restricted their activity as recommended. DCT was also highly valued by those in vulnerable households as a means of providing reassurance of the absence of infection and as an important means of detecting infection and prompting self-isolation when necessary.

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.

Engagement with daily testing instead of self-isolating in contacts of confirmed cases of SARS-CoV-2.

BACKGROUND: In December 2020, Public Health England with NHS Test and Trace initiated a pilot study in which close contacts of people with confirmed COVID-19 were given the option to carryout lateral flow device antigen tests at home, as an alternative to self-isolation for 10-14 days. In this study, we evaluated engagement with daily testing, and assessed levels of adherence to the rules relating to behaviour following positive or negative test results. METHODS: We conducted a service evaluation of the pilot study, examining survey responses from a subset of those who responded to an evaluation questionnaire. We used an online cross-sectional survey offered to adult contacts of confirmed COVID-19 cases who consented to daily testing. We used a comparison group of contacts who were not offered testing and instead self-isolated. RESULTS: Acceptability of daily testing was lower among survey respondents who were not offered the option of testing and among people from ethnic minority groups. Overall, 52% of respondents reported being more likely to share details of people that they had been in contact with following a positive test result, if they knew that their contacts would be offered the option of daily testing. Only 2% reported that they would be less likely to provide details of their contacts. On the days that they were trying to self-isolate, 19% of participants reported that they left the house, with no significant group differences. Following a negative test, 13% of respondents reported that they increased their contacts, but most (58%) reported having fewer risky contacts. CONCLUSIONS: Our data suggest that daily testing is potentially acceptable, may facilitate sharing contact details of close contacts among those who test positive for COVID-19, and promote adherence to self-isolation. A better understanding is needed of how to make this option more acceptable for all households. The impact of receiving a negative test on behaviour remains a risk that needs to be monitored and mitigated by appropriate messaging. Future research should examine attitudes and behaviour in a context where infection levels are lower, testing is more familiar, and restrictions on activity have been reduced.

Increased Risk for Invasive Group A Streptococcus Disease for Household Contacts of Scarlet Fever Cases, England, 2011-2016.

The incidence of scarlet fever in England and Wales is at its highest in 50 years. We estimated secondary household risk for invasive group A Streptococcus (iGAS) disease within 60 days after onset of scarlet fever. Reports of scarlet fever in England during 2011-2016 were matched by residential address to persons with laboratory-confirmed iGAS infections. We identified 11 iGAS cases in ≈189,684 household contacts and a 60-day incidence rate of 35.3 cases/100,000 person-years, which was 12.2-fold higher than the background rate (2.89). Infants and contacts >75 years of age were at highest risk. Three cases were fatal; sepsis and cellulitis were the most common manifestations. Typing for 6 iGAS cases identified emm 1.0 (n = 4), emm 4.0 (n = 1), and emm 12.0 (n = 1). Although absolute risk in household contacts was low, clinicians assessing household contacts should be aware of the risk to expedite diagnosis and initiate life-saving treatment.

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.

Role of the Hospital Environment in Norovirus Containment.

Norovirus is an important cause of gastroenteritis in healthcare settings; these infections occur frequently, are highly contagious, and can be difficult to control. Norovirus outbreaks were investigated during a 3-month enhanced surveillance period from 1 February to 30 April 2015 in 6 London, United Kingdom, hospitals (coded A-E). During this surveillance period, 1379 stool samples were tested for the presence of norovirus. Of these, 129 (9.4%) demonstrated the presence of norovirus RNA. Two of these hospitals (A and D) reported 0 outbreaks, 2 (hospitals C and F) reported 1 outbreak, 1 hospital (B) reported 2 outbreaks, and hospital E reported 16 norovirus outbreaks during this period. The hospital with a newer infrastructure (B), which reported 2 norovirus outbreaks, demonstrated that 7 bed-days had been lost over the 3-month period, compared with 512 bed-days lost by the hospital with an older, Nightingale-style infrastructure (E). Control measures included isolation, hand hygiene, environmental cleaning, and rapid diagnostic testing. Our data suggest that outbreak control is more difficult to achieve in a hospital with Nightingale-style wards and limited isolation facilities.

Two Linked Enteroinvasive Escherichia coli Outbreaks, Nottingham, UK, June 2014.

Enteroinvasive Escherichia coli (EIEC) outbreaks are uncommon in Europe. In June 2014, two EIEC outbreaks occurred in Nottingham, UK, within 2 days; outbreak A was linked to a takeaway restaurant and outbreak B to a wedding party. We conducted 2 analytical studies: a case-control study for outbreak A and a cohort study for outbreak B. We tested microbiological and environmental samples, including by using whole-genome sequencing. For both outbreaks combined, we identified 157 probable case-patients; 27 were laboratory-confirmed as EIEC O96:H19-positive. Combined epidemiologic, microbiological, and environmental findings implicated lettuce as the vehicle of infection in outbreak A, but the source of the organism remained unknown. Whole-genome sequencing identified the same organism in cases from both outbreaks, but no epidemiologic link was confirmed. These outbreaks highlight that EIEC has the capacity to cause large and severe gastrointestinal disease outbreaks and should be considered as a potential pathogen in foodborne outbreaks in Europe.

Evaluation of the Biofire FilmArray BioThreat-E Test (v2.5) for Rapid Identification of Ebola Virus Disease in Heat-Treated Blood Samples Obtained in Sierra Leone and the United Kingdom.

Rapid Ebola virus (EBOV) detection is crucial for appropriate patient management and care. The performance of the FilmArray BioThreat-E test (v2.5) using whole-blood samples was evaluated in Sierra Leone and the United Kingdom and was compared with results generated by a real-time Ebola Zaire PCR reference method. Samples were tested in diagnostic laboratories upon availability, included successive samples from individual patients, and were heat treated to facilitate EBOV inactivation prior to PCR. The BioThreat-E test had a sensitivity of 84% (confidence interval [CI], 64% to 95%) and a specificity of 89% (CI, 73% to 97%) in Sierra Leone (n = 60; 44 patients) and a sensitivity of 75% (CI, 19% to 99%) and a specificity of 100% (CI, 97% to 100%) in the United Kingdom (n = 108; 70 patients) compared to the reference real-time PCR. Statistical analysis (Fisher's exact test) indicated there was no significant difference between the methods at the 99% confidence level in either country. In 9 discrepant results (5 real-time PCR positives and BioThreat-E test negatives and 4 real-time PCR negatives and BioThreat-E test positives), the majority (n = 8) were obtained from samples with an observed or probable low viral load. The FilmArray BioThreat-E test (v2.5) therefore provides an attractive option for laboratories (either in austere field settings or in countries with an advanced technological infrastructure) which do not routinely offer an EBOV diagnostic capability.

Impact of baseline microbiological status on clinical outcomes in generalized aggressive periodontitis patients treated with or without adjunctive amoxicillin and metronidazole: an exploratory analysis from a randomized controlled clinical trial.

AIM: To explore whether subjects harbouring A. actinomycetemcomitans, P. gingivalis or T. forsythia at baseline showed increased clinical benefits with the adjunctive use of systemic amoxicillin and metronidazole (AMX-MET) during non-surgical treatment of generalized aggressive periodontitis (GAgP). MATERIAL AND METHODS: Forty one subjects were included in this 6-month randomized placebo-controlled clinical trial using a 7-day course of systemic AMX-MET or placebo as adjuncts to non-surgical periodontal therapy. Clinical and microbiological parameters were collected at baseline, 2 and 6 months after treatment. Microbiological cultures were processed for pooled subgingival samples and identities of isolates were determined by PCR for A. actinomycetemcomitans, P. gingivalis and T. forsythia RESULTS: At 6 months, the test treatment resulted in significant additional improvements in the primary outcome variable compared to placebo, and the effect of the adjunctive antimicrobials was not modified by the baseline microbiological status in the primary analysis. However, secondary exploratory subgroup analyses showed improved clinical outcomes in subjects harbouring A. actinomycetemcomitans at baseline compared to subjects who did not harbour this pathogen. CONCLUSIONS: All subjects benefited from the tested adjunctive antimicrobial regimen, although subjects who harboured A. actinomycetemcomitans at baseline may show greater clinical benefits. Larger appropriately powered studies are needed to confirm whether adjunctive AMX-MET is more beneficial for GAgP patients who harbour A. actinomycetemcomitans, along with other key periodontal pathogens.

An assessment of the effectiveness of mechanical and chemical cleaning of Essix orthodontic retainer.

OBJECTIVES: To determine the effectiveness of mechanical and chemical cleaning on the removal of microorganisms from Essix orthodontic retainers. DESIGN: In vitro laboratory study. SETTING: Department of Orthodontics and Microbiology, Eastman Dental Institute, University College London, UK. METHODS: Study 1: 120 Essix retainers were divided into four cleaning groups. The effectiveness of each cleaning method to remove a single species biofilm of Streptococcus mutans from the retainer was assessed. Study 2: 140 Essix retainers were divided into four study groups (brushing with fluoride toothpaste, chlorhexidine gel, immersion in chlorhexidine solution only and a control) to investigate the chemical and mechanical cleaning of the multispecies biolfilm of (Streptococcus sanguis, Actinomyces naeslundii, methicillin-resistant Staphylococcus aureus and Candida albicans). RELEVANT RESULTS: In study 1, brushing with toothpaste resulted in 99% reduction of Streptococcus mutans. In study 2, all three cleaning methods recorded similarly statistically significant reductions in colony forming units per millilitre compared to the control. There were no statistically significant differences between any of the cleaning groups for any of the microorganisms except MRSA-16. For MRSA-16, chlorhexidine mouthwash and gel were significantly more potent in eliminating the microorganism than the fluoride toothpaste. CONCLUSIONS: All three cleaning methods effectively removed 99% of microorganisms from the Essix retainers. Brushing with fluoride toothpaste can therefore be confirmed as an effective method for cleaning retainers in most circumstances. The use of chlorhexidine gel or mouthwash is recommended in patients where bacterial infection has to be avoided due to immunosuppression or other reasons.

A pragmatic cluster randomised controlled trial of air filtration to prevent symptomatic winter respiratory infections (including COVID-19) in care homes (AFRI-c) in England: Trial protocol.

BACKGROUND: Respiratory tract infections are readily transmitted in care homes. Airborne transmission of pathogens causing respiratory tract illness is largely unmitigated. Portable high-efficiency-particulate-air (HEPA) filtration units capture microbial particles from the air, but it is unclear whether this is sufficient to reduce infections in care home residents. The Air Filtration to prevent symptomatic winter Respiratory Infections (including COVID-19) in care homes (AFRI-c) randomized controlled trial will determine whether using HEPA filtration units reduces respiratory infection episodes in care home residents. METHODS: AFRI-c is a cluster randomized controlled trial that will be delivered in residential care homes for older people in England. Ninety-one care homes will be randomised to take part for one winter period. The intervention care homes will receive HEPA filtration units for use in communal areas and private bedrooms. Normal infection control measures will continue in all care homes. Anonymised daily data on symptoms will be collected for up to 30 residents. Ten to 12 of these residents will be invited to consent to a primary care medical notes review and (in intervention homes) to having an air filter switched on in their private room. The primary outcome will be number of symptomatic winter respiratory infection episodes. Secondary outcomes include specific clinical measures of infection, number of falls / near falls, number of laboratory confirmed infections, hospitalisations, staff sickness and cost-effectiveness. A mixed methods process evaluation will assess intervention acceptability and implementation. DISCUSSION: The results of AFRI-c will provide vital information about whether portable HEPA filtration units reduce symptomatic winter respiratory infections in older care home residents. Findings about effectiveness, fidelity, acceptability and cost-effectiveness will support stakeholders to determine the use of HEPA filtration units as part of infection control policies.

Changes in dental plaque following hospitalisation in a critical care unit: an observational study.

INTRODUCTION: Previous research has suggested that deterioration in oral health can occur following hospitalisation. The impact of such deterioration could increase the risk of oral disease, reduce quality of life and increase the potential for healthcare-associated infections (HCAI) such as healthcare-associated pneumonia (HAP). However, the strength of the evidence is limited by, amongst other factors, the few observational studies published that assess oral health longitudinally. In view of the microbiological component of oral diseases and HCAIs, the objective of this study was to investigate the microbiological changes in dental plaque following hospitalisation in a Critical Care Unit (CCU): (1) total number of cultivable bacteria and (2) presence and changes in specific HAP pathogens. METHODS: We conducted a prospective, longitudinal observational study in the CCU of University College Hospital, London. Study participants were recruited within 24 hours of admission. Dental plaque samples were collected from up to six sites per patient. The primary outcome was microbiological change from baseline to seven days with additional analysis for participants still present at day 14. RESULTS: 50 patients were recruited with 36 available for review at one week, with early discharge accounting for much of the loss to follow-up. The median total viable count of the plaque microbiota at baseline was 4.40 × 105 cfu/ml and increased at week one to 3.44 × 106 cfu/ml. The total viable microbe counts increased by a median of 2.26 × 106 cfu/ml from baseline to week one (95% CI: 3.19 × 106, 1.24 × 107) and this was statistically significant (P < 0.01). Specific HAP bacteria were detected in 26% of participants sampled, although accounted for a relatively low proportion of the total viable bacteria. CONCLUSION: Total bacterial count of dental plaque increases during hospitalisation in CCU. This finding, together with the colonisation of dental plaque by HAP bacteria strengthens the evidence for a deterioration in oral health in CCU and a risk factor for negative health and quality of life outcomes.

Staphylococcus capitis: Review of Its Role in Infections and Outbreaks.

In June 2021, a national incident team was formed due to an increased detection of Staphylococcus capitis in samples from hospitalised infants. Staphylococcus capitis has been known to cause outbreaks in neonatal units across the globe, but the extent of the UK spread was unclear. A literature review was undertaken to support case identification, clinical management and environmental infection control. A literature search was undertaken on multiple databases from inception to 24 May 2021, using keywords such as "Staphylococcus capitis", "NRCS-A", "S. capitis", "neonate", "newborn" and "neonatal intensive care unit" (NICU). After screening, 223 articles of relevance were included. Results show incidences of S. capitis outbreaks have frequently been associated with the outbreak clone (NRCS-A) and environmental sources. The NRCS-A harbours a multidrug resistance profile that includes resistance to beta-lactam antibiotics and aminoglycosides, with several papers noting resistance or heteroresistance to vancomycin. The NRCS-A clone also harbours a novel SCCmec-SCCcad/ars/cop composite island and increased vancomycin resistance. The S. capitis NRCS-A clone has been detected for decades, but the reasons for the potentially increased frequency are unclear, as are the most effective interventions to manage outbreaks associated with this clone. This supports the need for improvements in environmental control and decontamination strategies to prevent transmission.

Whole-genome sequencing reveals widespread presence of Staphylococcus capitis NRCS-A clone in neonatal units across the United Kingdom.

OBJECTIVE: Increased incidence of neonatal Staphylococcus capitis bacteraemia in summer 2020, London, raised suspicion of widespread multidrug-resistant clone NRCS-A. We set out to investigate the molecular epidemiology of this clone in neonatal units (NNUs) across the UK. METHODS: We conducted whole-genome sequencing (WGS) on presumptive S. capitis NRCS-A isolates collected from infants admitted to nationwide NNUs and from environmental sampling in two distinct NNUs in 2021. Previously published S. capitis genomes were added for comparison. Genetic clusters of NRCS-A isolates were defined based on core-genome single-nucleotide polymorphisms. RESULTS: We analysed WGS data of 838 S. capitis isolates and identified 750 NRCS-A isolates. We discovered a possible UK-specific NRCS-A lineage consisting of 611 isolates collected between 2005 and 2021. We determined 28 genetic clusters of NRCS-A isolates, which covered all geographical regions in the UK, and isolates of 19 genetic clusters were found in ≥2 regions, suggesting inter-regional spread. Within the NRCS-A clone, strong genetic relatedness was identified between contemporary clinical and incubator-associated fomite isolates and between clinical isolates associated with inter-hospital infant transfer. CONCLUSIONS: This WGS-based study confirms the dispersion of S. capitis NRCS-A clone amongst NNUs across the UK and urges research on improving clinical management of neonatal S. capitis infection.

The acceptability of testing contacts of confirmed COVID-19 cases using serial, self-administered lateral flow devices as an alternative to self-isolation.

Introduction. Evidence suggests that although people modify their behaviours, full adherence to self-isolation guidance in England may be suboptimal, which may have a detrimental impact on COVID-19 transmission rates.Hypothesis. Testing asymptomatic contacts of confirmed COVID-19 cases for the presence of SARS-CoV-2 could reduce onward transmission by improving case ascertainment and lessen the impact of self-isolation on un-infected individuals.Aim. This study investigated the feasibility and acceptability of implementing a 'test to enable approach' as part of England's tracing strategy.Methodology. Contacts of confirmed COVID-19 cases were offered serial testing as an alternative to self-isolation using daily self-performed lateral flow device (LFD) tests for the first 7 days post-exposure. Asymptomatic participants with a negative LFD result were given 24 h of freedom from self-isolation between each test. A self-collected confirmatory PCR test was performed on testing positive or at the end of the LFD testing period.Results. Of 1760 contacts, 882 consented to daily testing, of whom 812 individuals were within 48 h of exposure and were sent LFD testing packs. Of those who declined to participate, 39.1% stated they had already accessed PCR testing. Of the 812 who were sent LFD packs, 570 (70.2%) reported one or more LFD results; 102 (17.9%) tested positive. Concordance between reported LFD result and a supplied LFD image was 97.1%. In total, 82.8% of PCR-positive samples and 99.6% of PCR-negative samples were correctly detected by LFD. The proportion of secondary cases from contacts of those who participated in the study and tested positive (6.3%; 95% CI: 3.4-11.1%) was comparable to a comparator group who self-isolated (7.6%; 95% CI: 7.3-7.8%).Conclusion. This study shows a high acceptability, compliance and positivity rates when using self-administered LFDs among contacts of confirmed COVID-19 cases. Offering routine testing as a structured part of the contact tracing process is likely to be an effective method of case ascertainment.

Daily use of lateral flow devices by contacts of confirmed COVID-19 cases to enable exemption from isolation compared with standard self-isolation to reduce onward transmission of SARS-CoV-2 in England: a randomised, controlled, non-inferiority trial.

BACKGROUND: In the UK, during the study period (April to July, 2021), all contacts of people with COVID-19 were required to self-isolate for 10 days, which had adverse impacts on individuals and society. Avoiding the need to self-isolate for those who remain uninfected would be beneficial. We investigated whether daily use of lateral flow devices (LFDs) to test for SARS-CoV-2, with removal of self-isolation for 24 h if negative, could be a safe alternative to self-isolation as a means to minimise onward transmission of the virus. METHODS: We conducted a randomised, controlled, non-inferiority trial in adult contacts identified by COVID-19 contact tracing in England. Consenting participants were randomly assigned to self-isolation (single PCR test, 10-day isolation) or daily contact testing (DCT; seven LFD tests, two PCR tests, no isolation if negative on LFD); participants from a single household were assigned to the same group. Participants were prospectively followed up, with the effect of each intervention on onward transmission established from routinely collected NHS Test and Trace contact tracing data for participants who tested PCR-positive for SARS-CoV-2 during the study period and tertiary cases arising from their contacts (ie, secondary contacts). The primary outcome of the study was the attack rate, the percentage of secondary contacts (close contacts of SARS-CoV-2-positive study participants) who became COVID-19 cases (tertiary cases) in each group. Attack rates were derived from Bernoulli regression models using Huber-White (robust) sandwich estimator clustered standard errors. Attack rates were adjusted for household exposure, vaccination status, and ability to work from home. The non-inferiority margin was 1·9%. The primary analysis was a modified intention-to-treat analysis excluding those who actively withdrew from the study as data from these participants were no longer held. This study is registered with the Research Registry (number 6809). Data collection is complete; analysis is ongoing. FINDINGS: Between April 29 and July 28, 2021, 54 923 eligible individuals were enrolled in the study, with final group allocations (following withdrawals) of 26 123 (52·6%) participants in the DCT group and 23 500 (47·4%) in the self-isolation group. Overall, 4694 participants tested positive for SARS-CoV-2 by PCR (secondary cases), 2364 (10·1%) in the self-isolation group and 2330 (8·9%) in the DCT group. Adjusted attack rates (among secondary contacts) were 7·5% in the self-isolation group and 6·3% in the DCT group (difference of -1·2% [95% CI -2·3 to -0·2]; significantly lower than the non-inferiority margin of 1·9%). INTERPRETATION: DCT with 24 h exemption from self-isolation for essential activities appears to be non-inferior to self-isolation. This study, which provided evidence for the UK Government's daily lateral flow testing policy for vaccinated contacts of COVID-19 cases, indicated that daily testing with LFDs could allow individuals to reduce the risk of onward transmission while minimising the adverse effects of self-isolation. Although contacts in England are no longer required to isolate, the findings will be relevant for future policy decisions around COVID-19 or other communicable infections. FUNDING: UK Government Department of Health and Social Care.

Frequency of transmission, asymptomatic shedding, and airborne spread of Streptococcus pyogenes in schoolchildren exposed to scarlet fever: a prospective, longitudinal, multicohort, molecular epidemiological, contact-tracing study in England, UK.

BACKGROUND: Despite recommendations regarding prompt treatment of cases and enhanced hygiene measures, scarlet fever outbreaks increased in England between 2014 and 2018. We aimed to assess the effects of standard interventions on transmission of Streptococcus pyogenes to classroom contacts, households, and classroom environments to inform future guidance. METHODS: We did a prospective, longitudinal, multicohort, molecular epidemiological, contact-tracing study in six settings across five schools in Greater London, UK. Schools and nurseries were eligible to participate if they had reported two cases of scarlet fever within 10 days of each other among children aged 2-8 years from the same class, with the most recent case arising in the preceding 48 h. We cultured throat swabs from children with scarlet fever, classroom contacts, and household contacts at four timepoints. We also cultured hand swabs and cough plates from all cases in years 1 and 2 of the study, and from classroom contacts in year 2. Surface swabs from toys and other fomites in classrooms were cultured in year 1, and settle plates from classrooms were collected in year 2. Any sample with S pyogenes detected was recorded as positive and underwent emm genotyping and genome sequencing to compare with the outbreak strain. FINDINGS: Six classes, comprising 12 cases of scarlet fever, 17 household contacts, and 278 classroom contacts were recruited between March 1 and May 31, 2018 (year 1), and between March 1 and May 31, 2019 (year 2). Asymptomatic throat carriage of the outbreak strains increased from 11 (10%) of 115 swabbed children in week 1, to 34 (27%) of 126 in week 2, to 26 (24%) of 108 in week 3, and then five (14%) of 35 in week 4. Compared with carriage of outbreak S pyogenes strains, colonisation with non-outbreak and non-genotyped S pyogenes strains occurred in two (2%) of 115 swabbed children in week 1, five (4%) of 126 in week 2, six (6%) of 108 in week 3, and in none of the 35 children in week 4 (median carriage for entire study 2·8% [IQR 0·0-6·6]). Genome sequencing showed clonality of outbreak isolates within each of six classes, confirming that recent transmission accounted for high carriage. When transmissibility was tested, one (9%) of 11 asymptomatic carriers of emm4 and five (36%) of 14 asymptomatic carriers of emm3.93 had a positive cough plate. The outbreak strain was identified in only one (2%) of 60 surface swabs taken from three classrooms; however, in the two classrooms with settle plates placed in elevated locations, two (17%) of 12 and six (50%) of 12 settle plates yielded the outbreak strain. INTERPRETATION: Transmission of S pyogenes in schools is intense and might occur before or despite reported treatment of cases, underlining a need for rapid case management. Despite guideline adherence, heavy shedding of S pyogenes by few classroom contacts might perpetuate outbreaks, and airborne transmission has a plausible role in its spread. These findings highlight the need for research to improve understanding and to assess effectiveness of interventions to reduce airborne transmission of S pyogenes. FUNDING: Action Medical Research, UK Research Innovation, and National Institute for Health Research.

Randomized controlled trial of toothbrushing to reduce ventilator-associated pneumonia pathogens and dental plaque in a critical care unit.

AIM: To investigate the effect of a powered toothbrush on colonization of dental plaque by ventilator-associated pneumonia (VAP)-associated organisms and dental plaque removal. MATERIALS AND METHODS: Parallel-arm, single-centre, examiner- and analyst-masked randomized controlled trial. Forty-six adults were recruited within 48 h of admission. Test intervention: powered toothbrush, control intervention: sponge toothette, both used four times per day for 2 min. Groups received 20 ml, 0.2% chlorhexidine mouthwash at each time point. RESULTS: The results showed a low prevalence of respiratory pathogens throughout with no statistically significant differences between groups. A highly statistically significantly greater reduction in dental plaque was produced by the powered toothbrush compared with the control treatment; mean plaque index at day 5, powered toothbrush 0.75 [95% confidence interval (CI) 0.53, 1.00], sponge toothette 1.35 (95% CI 0.95, 1.74), p=0.006. Total bacterial viable count was also highly statistically significantly lower in the test group at day 5; Log(10) mean total bacterial counts: powered toothbrush 5.12 (95% CI 4.60, 5.63), sponge toothette 6.61 (95% CI 5.93, 7.28), p=0.002. CONCLUSIONS: Powered toothbrushes are highly effective for plaque removal in intubated patients in a critical unit and should be tested for their potential to reduce VAP incidence and health complications.