Determining the acceptability of testing contacts of confirmed COVID-19 cases to improve secondary case ascertainment.

BACKGROUND: UK asymptomatic contacts of confirmed COVID-19 cases are not routinely tested for SARS-CoV-2. Testing contacts may improve case ascertainment and reduce onward transmission. This study investigated the acceptability of SARS-CoV-2 testing among contacts of confirmed cases as an integral part of the contact-tracing process. METHODS: A cross-sectional descriptive survey of case contacts was conducted in the UK. All contacts who completed a telephone call with the NHS Test and Trace Agile Lighthouse team were eligible for inclusion and were offered a molecular test. Consenting participants were sent a self-swab kit. RESULTS: Of the 1523 individuals contacted, 602 (39.5%) accepted the test offer. Of the 240 (39.9%) samples returned for testing, 16.3% tested polymerase chain reaction-positive for SARS-CoV-2.Most individuals who declined with a reason (638/905; 70.5%) reported they had already taken or booked a SARS-CoV-2 test, or were part of a testing programme. Matched laboratory records confirmed 73.1% of those who declined were tested by another route. CONCLUSIONS: Most case contacts were tested, either through arranging a test by themselves or by accepting the study offer. Results demonstrate high acceptability, with substantial test positivity, indicating that there is public health benefit in offering tests to contacts as a routine part of the contact-tracing process.

Disruption and bactericidal indices depicted in polygonal graphs to show multiple outcome effects of root canal irrigant supplements on single- and dual-species biofilms.

OBJECTIVES: The aims of this study were to (1) investigate the relative time-dependent disruption and bactericidal effects of detergent-type surfactants on single- or dual-species biofilms of root canal isolates and (2) to examine the utility of polygonal graphs for depiction of biofilm disruption and cell killing. MATERIALS AND METHODS: Single-species biofilms of Streptococcus sanguinis, Enterococcus faecalis, Fusobacterium nucleatum and Porphyromonas gingivalis were grown on nitro-cellulose membranes for 72 h and immersed in Tween®80, cetyltrimethylammoniumbromide (CTAB), and sodium dodecyl sulphate (SDS) for 1-, 5- or 10-min (n = 3 per test). The number of viable and non-viable bacteria "disrupted" from the biofilm and those "remaining-attached" was determined using a viability stain in conjunction with fluorescence microscopy. The data were analysed using non-parametric Kruskal-Wallis test with 5% significance level. RESULTS: Gram-negative obligate anaerobes were more susceptible to cell removal than gram-positive facultative anaerobes. The majority of cells were disrupted after 1-min of exposure; however, the extent varied according to the agent and species. CTAB and SDS were more effective than Tween 80™ at disrupting biofilms and killing cells but all agents failed to achieve 100% disruption/kill. CONCLUSIONS: Biofilm disruption and cell viability were influenced by the species, the test agent and the duration of exposure. CTAB and SDS were more effective in biofilm disruption than Tween 80™. Graphical depiction of biofilm disruption- and viability-outcomes provides an alternative means of simultaneously visualising and analysing relative efficacy in different domains. CLINICAL RELEVANCE: Surfactants were not as effective at biofilm disruption as NaOCl but may be added to other non-disruptive antibacterial agents to enhance this property.

Antibiotic susceptibility of Legionella pneumophila strains isolated in England and Wales 2007-17.

Objectives: Antibiotic susceptibility of Legionella pneumophila is poorly understood, with treatment of Legionnaires' disease often based on empirical choice. The aim of this study was to determine the antibiotic susceptibility of L. pneumophila strains. Methods: Antibiotic susceptibility of 92 L. pneumophila strains isolated in England and Wales between 2007 and 2017 was determined using a microbroth dilution methodology for each agent tested. MICs and MBCs were determined and compared with published intracellular concentrations of each agent tested. Results: The MIC range of erythromycin was 0.06-1 mg/L, the MIC range of rifampicin was 0.0001 mg/L, the MIC range of ciprofloxacin was 0.004-0.25 mg/L and the MIC range of levofloxacin and moxifloxacin was 0.03-0.25 mg/L. The MBC range of erythromycin was 1-32 mg/L, but the MBC range of ciprofloxacin was the same as the MIC range. For levofloxacin and moxifloxacin the MBC range was elevated by one dilution and two dilutions, respectively. Typically, intracellular bronchial secretion concentrations of erythromycin might be expected to reach a suitable level to exceed the MIC range; however, 91 of 92 (98.9%) isolates had an MBC below the expected intracellular concentrations, which indicated erythromycin may have variable efficacy. MIC and MBC values of ciprofloxacin, levofloxacin and moxifloxacin were below achievable intracellular levels within bronchial secretions. Comparison of the MIC/MBC correlation showed very little clustering for erythromycin, but strong clustering for levofloxacin and to a lesser extent ciprofloxacin. Conclusions: Use of the MIC/MBC linkage analysis seems an appropriate way forward for antimicrobial susceptibility testing and supports current guidance recommending levofloxacin for the treatment of Legionnaires' disease.

Large outbreak of multiple gastrointestinal pathogens associated with fresh curry leaves in North East England, 2013.

A total of 592 people reported gastrointestinal illness following attendance at Street Spice, a food festival held in Newcastle-upon-Tyne, North East England in February/March 2013. Epidemiological, microbiological and environmental investigations were undertaken to identify the source and prevent further cases. Several epidemiological analyses were conducted; a cohort study; a follow-up survey of cases and capture re-capture to estimate the true burden of cases. Indistinguishable isolates of Salmonella Agona phage type 40 were identified in cases and on fresh curry leaves used in one of the accompaniments served at the event. Molecular testing indicated entero-aggregative Escherichia coli and Shigella also contributed to the burden of illness. Analytical studies found strong associations between illness and eating food from a particular stall and with food items including coconut chutney which contained fresh curry leaves. Further investigation of the food supply chain and food preparation techniques identified a lack of clear instruction on the use of fresh uncooked curry leaves in finished dishes and uncertainty about their status as a ready-to-eat product. We describe the investigation of one of the largest outbreaks of food poisoning in England, involving several gastrointestinal pathogens including a strain of Salmonella Agona not previously seen in the UK.

Colonisation of dentures by Staphylococcus aureus and MRSA in out-patient and in-patient populations.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen, and colonisation with this organism can result in localised or systemic infections which may be fatal. One hundred in-patients admitted to a London teaching hospital and 100 out-patients attending prosthetic dentistry clinics were recruited into this study. Of the 100 out-patients, 27 % harboured S. aureus on their dentures, compared to 33 % of in-patients. Only one out-patient had MRSA colonising their dentures whereas 12 % of the in-patients harboured MRSA. The median total bacterial count of the denture plaque samples was 6.2 × 10(7) cfu/sample and 6.9 × 10(7) cfu/sample for the out-patient and in-patient populations, respectively. In most instances, where present, S. aureus comprised less than 1 % of the total viable denture microbiota. Phage typing demonstrated that EMRSA-15 and non-typeable strains were harboured on dentures. The results of this study have revealed that dentures are a potential reservoir of MRSA and so account should be taken of these findings when planning decontamination procedures for elimination of this pathogen.

Investigating an outbreak of Clostridium perfringens gastroenteritis in a school using smartphone technology, London, March 2013.

On 22 March 2013, 150 of 1,255 students (13­17 years) and staff at a school in London reported gastrointestinal symptoms; onset peaked 8 to 12 hours after a lunch served in the school on 21 March. We performed a retrospective cohort study of all students and staff. We defined cases as school attenders on 20 and 21 March with onset of gastrointestinal symptoms between 20 and 23 March. We tested food, environmental and stool samples of cases for common pathogens and bacterial toxins. We administered an online questionnaire via email, encouraging the use of smartphones to respond, to measure risk of illness for food items eaten at school on 20 and 21 March. Survey response was 45%. Adjusted risk ratios were generated in a multivariable analysis. Those who ate chicken balti on 21 March were 19.3 times more likely to become ill (95% confidence interval: 7.3­50.9). Clostridium perfringens was detected in all 19 stool samples collected. Within eight school hours of its launch, 412 of 561 (73%) responders had completed the survey. Hygienic standards in the kitchen were satisfactory. The investigation was done rapidly due to smartphone technology and we recommend considering this technology in future outbreaks.

Influence of IL-6 haplotypes on clinical and inflammatory response in aggressive periodontitis.

OBJECTIVES: The aim of this study was to investigate the inflammatory response in aggressive periodontitis (AgP) patients after periodontal therapy and associate these changes to subjects' interleukin-6 (IL-6) genetic variants. MATERIALS AND METHODS: Twelve non-smoking UK Caucasian patients with AgP were selected based on their IL6 haplotypes (six haplotype positive and six haplotype negative based on polymorphisms rs 2069827 and rs 2069825) and underwent full mouth non-surgical periodontal therapy, followed by open flap surgery. Gingival crevicular fluid (GCF) and peripheral blood samples were taken at baseline and at six different time points after treatment. Gingival biopsy samples were harvested during surgery and underwent immunohistochemical analysis for identification of IL-6. RESULTS: An overall improvement in clinical periodontal parameters was observed following periodontal therapy. Haplotype status was associated with clinical presentation, Aggregatibacter actinomycetemcomitans counts in subgingival plaque samples, white cell count, neutrophils, red cell count and haemoglobin. GCF IL-6 concentrations increased dramatically 1 day after surgery and IL-6 haplotype-positive subjects exhibited a higher magnitude in this increase. CONCLUSIONS: IL6 haplotypes may have an effect on clinical presentation and magnitude and kinetics of local and systemic inflammatory responses following non-surgical and surgical periodontal therapy in aggressive periodontitis. CLINICAL RELEVANCE: Detecting IL-6 haplotype-positive periodontitis patients might become helpful in identifying subjects prone to excessive inflammatory response and increased periodontal breakdown.

Detection, survival, and persistence of Staphylococcus capitis NRCS-A in neonatal units in England.

BACKGROUND: The multidrug-resistant Staphylococcus capitis clone, NRCS-A, is increasingly associated with late-onset sepsis in low birthweight newborns in neonatal intensive care units (NICUs) in England and globally. Understanding where this bacterium survives and persists within the NICU environment is key to developing and implementing effective control measures. AIM: To investigate the potential for S. capitis to colonize surfaces within NICUs. METHODS: Surface swabs were collected from four NICUs with and without known NRCS-A colonizations/infections present at the time of sampling. Samples were cultured and S. capitis isolates analysed via whole-genome sequencing. Survival of NRCS-A on plastic surfaces was assessed over time and compared to that of non-NRCS-A isolates. The bactericidal activity of commonly used chemical disinfectants against S. capitis was assessed. FINDINGS: Of 173 surfaces sampled, 40 (21.1%) harboured S. capitis with 30 isolates (75%) being NRCS-A. Whereas S. capitis was recovered from surfaces across the NICU, the NRCS-A clone was rarely recovered from outside the immediate neonatal bedspace. Incubators and other bedside equipment were contaminated with NRCS-A regardless of clinical case detection. In the absence of cleaning, S. capitis was able to survive for three days with minimal losses in viability (<0.5 log10 reduction). Sodium troclosene and a QAC-based detergent/disinfectant reduced S. capitis to below detectable levels. CONCLUSION: S. capitis NRCS-A can be readily recovered from the NICU environment, even in units with no recent reported clinical cases of S. capitis infection, highlighting a need for appropriate national guidance on cleaning within the neonatal care environment.

The prevalence of opportunistic pathogens associated with intraoral implants.

AIMS: The aim of this study was to determine the prevalence and proportions of opportunistic pathogens harboured on orthodontic retainers. METHODS AND RESULTS: First, Staphylococcus spp. and Candida spp. were isolated from the retainer's inner surface and from other mucosal surfaces of the subject's mouth by routine bacterial culture. The prevalence and proportions of these micro-organisms on retainers was compared in different areas of the mouth within a group of retainer wearers, and mucosal carriage was compared to a group of nonretainer wearers. Staphylococcus spp. were isolated from 50% of the retainers and comprised on average 8·4% of the viable microbiota. Candida spp. comprised 0·13% of the viable microbiota and were recovered from 66·7% of the retainers. Neither genus was isolated from nonretainer wearers. Second, the two most commonly worn retainers manufactured from different materials were sampled; again Staphylococcus spp. and Candida spp. were recovered; however, no statistical differences were observed between the devices. CONCLUSIONS: Opportunistic, nonoral, pathogenic micro-organisms were recovered from orthodontic retainers. SIGNIFICANCE AND IMPACT OF THE STUDY: It is possible that an orthodontic retainer could be a reservoir for opportunistic pathogens and act as a source of cross-, self- and re-infection.

Sevenless: a cell-specific homeotic mutation of the Drosophila eye.

Each ommatidium in the compound eye of the Drosophila mutant sevenless lacks photoreceptor number seven (R7) from the normal ommatidial complement of eight photoreceptors. A comparison of mutant and normal development reveals that this deficit is caused by the cell-specific transformation of the cell normally fated to produce R7 into a lens-secreting accessory cell, a cone cell.

Rescue of photoreceptor degeneration in rhodopsin-null Drosophila mutants by activated Rac1.

Rhodopsin is essential for photoreceptor morphogenesis; photoreceptors lacking rhodopsin degenerate in humans, mice, and Drosophila. Here we report that transgenic expression of a dominant-active Drosophila Rho guanosine triphosphatase, Drac1, rescued photoreceptor morphogenesis in rhodopsin-null mutants; expression of dominant-negative Drac1 resulted in a phenotype similar to that seen in rhodopsin-null mutants. Drac1 was localized in a specialization of the photoreceptor cortical actin cytoskeleton, which was lost in rhodopsin-null mutants. Thus, rhodopsin appears to organize the actin cytoskeleton through Drac1, contributing a structural support essential for photoreceptor morphogenesis.

Real-time whole genome sequencing to control a Streptococcus pyogenes outbreak at a national orthopaedic hospital.

BACKGROUND: Whole genome sequencing (WGS) of Streptococcus pyogenes linked to invasive disease has been used to identify and investigate outbreaks. The clinical application of WGS in real-time for outbreak control is seldom employed. AIMS: A fatal case of bacteraemia at a national orthopaedic hospital prompted an outbreak investigation to identify carriers and halt transmission using real-time WGS. METHODS: Retrospective surveillance was conducted to identify patients with Streptococcus pyogenes infections in the last year. Upon contact tracing, four patients and 179 staff were screened for Streptococcus pyogenes carriage. All isolates identified were emm-typed. WGS was performed in real-time on a subset of isolates. FINDINGS: Twelve isolates of Streptococcus pyogenes from the index case, two patients and eight staff were identified. Six isolates were emm 1.0, including the index case and five staff isolates. The remaining isolates belonged to distinct emm types. WGS analysis was undertaken on the six emm 1.0 isolates. Five were indistinguishable by single nucleotide polymorphism (SNP) analysis, with 0 SNP distance, and one had one SNP difference, supporting the hypothesis of recent local transmission. All screen-positive healthcare workers were offered treatment with penicillin or clindamycin. No further cases were identified. CONCLUSION: The increased molecular discrimination of WGS confirmed the clustering of these cases and the outbreak was contained. This demonstrates the clinical utility of WGS in managing outbreaks of invasive Streptococcus pyogenes in real-time and we recommend its implementation as a routine clinical service.

Disease severity associated with presence in subgingival plaque of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Tannerella forsythia, singly or in combination, as detected by nested multiplex PCR.

This study used a nested multiplex PCR method to detect three periodontal pathogens in subgingival plaque collected before treatment and at 2 and 6 months posttreatment from 107 patients with severe, generalized periodontitis. The proportions of the patients who harbored these bacteria before periodontal treatment were as follows: Tannerella forsythia, 81%; Porphyromonas gingivalis, 78%; and Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans, 47%. At 2 months posttreatment there was a significant reduction in the numbers of patients harboring P. gingivalis (46%; P < 0.001) or T. forsythia (63%; P = 0.043) but not A. actinomycetemcomitans (50%) compared to pretreatment data. At 6 months posttreatment, significantly fewer patients harbored P. gingivalis (43%; P < 0.001); A. actinomycetemcomitans, (31%; P = 0.025), or T. forsythia (63%; P = 0.030). Interestingly, at baseline and at 2 months posttherapy, subjects who harbored only a single pathogen had a greater level of periodontal disease than subjects who harbored two, or all three, of these periodontal pathogens. These data suggest that a reduction in the number of species present may be associated with an increase in the severity of periodontal diseases.

Gene polymorphisms and the prevalence of key periodontal pathogens.

Growing evidence suggests that individual genetic susceptibility may influence the host's response to infections. The aim of this project was to study whether gene polymorphisms of inflammatory markers are associated with the presence of viable periodontopathogenic bacteria. We extracted genomic DNA from 45 young adults diagnosed with generalized aggressive periodontitis to study Fc receptors, formyl peptide receptor, Interleukin-6, tumor necrosis factor-alpha, and vitamin D receptor polymorphisms. The presence and viable numbers of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythensis were determined by culture, and their identities confirmed by PCR. Multiple logistic regressions revealed that both Fcgamma receptor and IL-6 -174 polymorphisms were associated with increased odds of detecting A. actinomycetemcomitans, P. gingivalis, and T. forsythensis after adjustment for age, ethnicity, smoking, and periodontitis extent. These findings support the hypothesis that complex interactions between the microbiota and host genome may be at the basis of susceptibility to aggressive periodontitis.

Role of Food Handlers in Norovirus Outbreaks in London and South East England, 2013 to 2015.

Outbreaks caused by norovirus infection are common and occur throughout the year. Outbreaks can be related to food outlets either through a contaminated food source or an infected food handler. Both asymptomatic and symptomatic food handlers are potentially implicated in outbreaks, but evidence of transmission is limited. To understand potential food handler transmission in outbreak scenarios, epidemiological and microbiological data on possible and confirmed norovirus outbreaks reported in London and South East England in a 2-year period were reviewed. One hundred eighty-six outbreaks were associated with a food outlet or registered caterer in this period. These occurred throughout the year with peaks in quarter 1 of study years. A case series of 17 outbreaks investigated by the local field epidemiological service were evaluated further, representing more than 606 cases. In five outbreaks, symptomatic food handlers were tested and found positive for norovirus. In four outbreaks, symptomatic food handlers were not tested. Asymptomatic food handlers were tested in three outbreaks but positive for norovirus in one only. Environmental sampling did not identify the causative agent conclusively in any of the outbreaks included in this analysis. Food sampling identified norovirus in one outbreak. Recommendations from this study include for outbreak investigations to encourage testing of symptomatic food handlers and for food and environmental samples to be taken as soon as possible. In addition, sampling of asymptomatic food handlers should be considered when possible. However, in light of the complexity in conclusively identifying a source of infection, general measures to improve hand hygiene are recommended, with specific education among food handlers about the potential for foodborne pathogen transmission during asymptomatic infection, as well as reinforcing the importance of self-exclusion from food handling activities when symptomatic.

Evidence summary: the relationship between oral and cardiovascular disease.

Aim This paper reports on one review of four rapid reviews undertaken to explore the relationships between oral health and general medical conditions, in order to support teams within Public Health England, health practitioners and policy makers. This review aimed to explore the most contemporary evidence on whether poor oral health and cardiovascular disease occurs in the same individuals or populations, to outline the nature of the relationship between these two health outcomes and to discuss the implication of any findings for health services and future research.Methods The review was undertaken by a group comprising consultant clinicians from medicine and dentistry, trainees, public health and academics. The methodology involved a streamlined rapid review process and synthesis of the data.Results The results identified a number of systematic reviews of low to high quality, which suggests that there is: (1) fairly robust evidence of an increased risk of atherosclerotic vascular disease (ASVD) amongst individuals with chronic periodontitis, independent of other established cardiovascular risk factors; (2) there is some evidence that the incidence of caries and tooth loss is higher in patients with cardiovascular disease; and (3) that orofacial pain can presents as the sole symptom of stroke in some patients. The findings are discussed in relation to implications for service and future research.Conclusion There is high quality evidence to support an association between cardiovascular disease and oral health. This evidence is mainly related to the association between chronic periodontitis and atherosclerotic heart disease, and is independent of confounding factors as drawn from epidemiological observational studies.

A multifaceted approach to neural development.

The developing compound eye of the fruit fly, Drosophila offers notable advantages for a study of neural differentiation. It is a sensitive amplifier of a simple neural module; each eye is an approximately 700-fold repetition of the unit eye or ommatidium, which is a precise, stereotyped assembly of photoreceptors and accessory cells. The eye develops in a monolayer epithelium, which greatly reduces the complexities of cell-cell interactions often encountered in CNS development, and has permitted a detailed, cell-by-cell description of cell behavior during ommatidial development. Finally, the foundation of fly genetics permits a mutational analysis of eye development and the advanced molecular genetics of Drosophila allows close scrutiny of genes of interest. A recent convergence of cellular, genetic and molecular studies of ommatidial development suggests a model for neural differentiation in the fly eye.

Antibiotic resistance in the cultivable plaque microbiota of children from different ethnic groups.

The presence of ampicillin-, penicillin-, erythromycin- and tetracycline-resistant bacteria in the dental plaque of White, South Asian and Japanese children was investigated. There was a high prevalence of antibiotic-resistant bacteria in children from diverse ethnic groups. The median percentage of the cultivable plaque microbiota that was resistant to tetracycline was greater in South Asian (2.9%, range 0.1-17.5%) and Japanese (7.7%, range 1.3-56.2%) children than in White children (0.7%, range 0-5.6%), suggesting that ethnic differences exist in the oral load of tetracycline-resistant bacteria (P<0.01). Multiresistant bacteria were frequently isolated, with 42% of isolates exhibiting resistance to two or more antibiotics. This study has demonstrated that antibiotic-resistant bacteria can be readily isolated from the plaque microbiota of children from different ethnic groups.

Antimicrobial effect of silver-doped phosphate-based glasses.

In this study a range of phosphate-based glasses (PBG) doped with silver have been investigated for their antimicrobial activities. In disk diffusion assays, these compositions demonstrated microbistatic effects against a range of organisms including Staphylococcus aureus, Escherichia coli, Bacillus cereus, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and Candida albicans. The data obtained from the above studies allowed for an additional range of PBG containing lower amounts of silver to be studied for their effects on the growth and viability of S. aureus, E. coli, and C. albicans. PBG containing 3 and 5 mol % Ag were bactericidal for S. aureus and E. coli and significantly decreased the growth rate of C. albicans. A decrease in the dissolution rates of the glasses was seen with increasing Ag content over the range of concentrations investigated. Overall, 3 mol % Ag incorporated into the PBG investigated was sufficient to mount a potent antibacterial effect against the test organisms, and these compositions also gave excellent long-term release of Ag ions into the medium.

Virtual reality exposure therapy for Vietnam veterans with posttraumatic stress disorder.

BACKGROUND: Virtual reality (VR) integrates real-time computer graphics, body-tracking devices, visual displays, and other sensory input devices to immerse a participant in a computer-generated virtual environment that changes in a natural way with head and body motion. VR exposure (VRE) is proposed as an alternative to typical imaginal exposure treatment for Vietnam combat veterans with posttraumatic stress disorder (PTSD). METHOD: This report presents the results of an open clinical trial using VRE to treat Vietnam combat veterans who have DSM-IV PTSD. In 8 to 16 sessions, 10 male patients were exposed to 2 virtual environments: a virtual Huey helicopter flying over a virtual Vietnam and a clearing surrounded by jungle. RESULTS: Clinician-rated PTSD symptoms as measured by the Clinician Administered PTSD Scale, the primary outcome measure, at 6-month follow-up indicated an overall statistically significant reduction from baseline (p = .0021) in symptoms associated with specific reported traumatic experiences. All 8 participants interviewed at the 6-month follow-up reported reductions in PTSD symptoms ranging from 15% to 67%. Significant decreases were seen in all 3 symptom clusters (p < .02). Patient self-reported intrusion symptoms as measured by the Impact of Event Scale were significantly lower (p < .05) at 3 months than at baseline but not at 6 months, although there was a clear trend toward fewer intrusive thoughts and somewhat less avoidance. CONCLUSION: Virtual reality exposure therapy holds promise for treating PTSD in Vietnam veterans.