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.

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.

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.

The epidemiology and management of clusters of invasive meningococcal disease in England, 2010-15.

BACKGROUND: Guidance for public health management of invasive meningococcal disease (IMD) in in England recommends the use of antibiotic chemoprophylaxis and vaccination. We summarized clinical and epidemiological data collected during routine management of IMD clusters in England. METHODS: Data on epidemiology and operational decisions for public health management were reviewed for clusters between April 2010 and December 2015. RESULTS: Clusters were generally 2-3 cases (53/58; 91%) within a single age band <18-years. Nurseries (n = 20, 34%), households/social networks (n = 14, 24%) and schools (n = 10, 17%) were the commonest settings. Chemoprophylaxis alone was used in 36 (58%) clusters, including most serogroup B clusters (31/41; 76%). Chemoprophylaxis and vaccination was used in a further 20 (32%) clusters. Vaccine was delivered promptly (<7 days). Four clusters had cases with onset post-chemoprophylaxis; no clusters recorded cases with onset post-vaccination. No pattern was observed between interventions and setting/population at risk, and interventions were consistent with national guidance. Challenges to management included logistical issues related to intervention delivery. CONCLUSIONS: Public health management of IMD clusters presents challenges in decision-making and implementation of interventions. Nonetheless, few cases were observed following intervention. Responses were consistent with national guidance. A systematic data collection tool should be developed to support future evaluation.

Characteristics and patient pathways of Lyme disease patients: a retrospective analysis of hospital episode data in England and Wales (1998-2015).

BACKGROUND: Lyme disease is a tick-borne disease of increasing global importance. There is scant information on Lyme disease patient demographics in England and Wales, and how they interact with the National Health Service (NHS). Our aims were to explore the demographic characteristics of Lyme disease patients within the Hospital Episode Statistics (HES) and Patient Episode Database for Wales (PEDW), and to describe patient pathways. METHODS: Data from 1st January 1998 to 31st December 2015 was retrieved from the two administrative hospital datasets (HES and PEDW), based on patients coded with Lyme disease. Information was collected on demographic characteristics, home address and case management. Incidence rates were calculated, and demographics compared to the national population. RESULTS: Within HES and PEDW, 2361 patients were coded with Lyme disease. There was a significant increase (p < 0.01) in incidence from 0.08 cases/100,000 in 1998, to 0.53 cases/100,000 in 2015. There was a bimodal age distribution, patients were predominantly female, white and from areas of low deprivation. New cases peaked annually in August, with higher incidence rates in southern central and western England. Within hospital admission data (n = 2066), most cases were either referred from primary care (28.8%, n = 596) or admitted via accident and emergency (A&E) (29.5%, n = 610). This population entering secondary care through A&E suggest a poor understanding of the recommended care pathways for symptoms related to Lyme disease by the general population. CONCLUSIONS: These data can be used to inform future investigations into Lyme disease burden, and patient management within the NHS. They provide demographic information for clinicians to target public health messaging or interventions.

Challenges of investigating a large food-borne norovirus outbreak across all branches of a restaurant group in the United Kingdom, October 2016.

During October and November 2016, over 1,000 customers and staff reported gastroenteritis after eating at all 23 branches of a restaurant group in the United Kingdom. The outbreak coincided with a new menu launch and norovirus was identified as the causative agent. We conducted four retrospective cohort studies; one among all restaurant staff and three in customers at four branches. We investigated the dishes consumed, reviewed recipes, interviewed chefs and inspected restaurants to identify common ingredients and preparation methods for implicated dishes. Investigations were complicated by three public health agencies concurrently conducting multiple analytical studies, the complex menu with many shared constituent ingredients and the high media attention. The likely source was a contaminated batch of a nationally distributed ingredient, but analytical studies were unable to implicate a single ingredient. The most likely vehicle was a new chipotle chilli product imported from outside the European Union, that was used uncooked in the implicated dishes. This outbreak exemplifies the possibility of rapid spread of infectious agents within a restaurant supply chain, following introduction of a contaminated ingredient. It underlines the importance of appropriate risk assessments and control measures being in place, particularly for new ingredients and ready-to-eat foods.

Novel application of the matched case-control design to compare food supply chains during an Escherichia coli O157 outbreak, United Kingdom, 2016.

There is a need for innovative methods to investigate outbreaks of food-borne infection linked to produce with a complex distribution network. The investigation of a large outbreak of Escherichia coli O157 PT34 infection in the United Kingdom in 2016 indicated that catering venues associated with multiple cases had used salad leaves sourced from one supplier. Our aim was to investigate whether catering venues linked to cases were more likely to have used salad leaves from this supplier. We conducted a matched case-control study, with catering venues as the units of analysis. We compared venues linked to cases to those without known linked cases. We included 43 study pairs and obtained information on salad leaf products received by each venue. The odds of a case venue being supplied with salad leaves by Supplier A were 7.67 times (95% confidence interval: 2.30-25.53) those of control venues. This association provided statistical evidence to support the findings of the other epidemiological investigations undertaken for this outbreak. This is a novel approach which is labour-intensive but which addresses the challenge of investigating exposures to food across a complex distribution network.

The potential impact of media reporting in syndromic surveillance: an example using a possible Cryptosporidium exposure in North West England, August to September 2015.

During August 2015, a boil water notice (BWN) was issued across parts of North West England following the detection of Cryptosporidium oocysts in the public water supply. Using prospective syndromic surveillance, we detected statistically significant increases in the presentation of cases of gastroenteritis and diarrhoea to general practitioner services and related calls to the national health telephone advice service in those areas affected by the BWN. In the affected areas, average in-hours general practitioner consultations for gastroenteritis increased by 24.8% (from 13.49 to 16.84) during the BWN period; average diarrhoea consultations increased by 28.5% (from 8.33 to 10.71). Local public health investigations revealed no laboratory reported cases confirmed as being associated with the water supply. These findings suggest that the increases reported by syndromic surveillance of cases of gastroenteritis and diarrhoea likely resulted from changes in healthcare seeking behaviour driven by the intense local and national media coverage of the potential health risks during the event. This study has further highlighted the potential for media-driven bias in syndromic surveillance, and the challenges in disentangling true increases in community infection from those driven by media reporting.

The effectiveness of revaccination with pneumococcal polysaccharide vaccine for preventing pneumococcal disease in older adults in England: A population-based cohort study.

BACKGROUND: Pneumococcal disease in older adults in the United Kingdom is rising despite immunisation. A key gap in the literature is the clinical effectiveness of revaccination with the pneumococcal polysaccharide vaccine (PPV23). METHODS: A cohort study was performed in England, using electronic medical records in the Clinical Practice Research Datalink. Individuals aged ≥64 years and vaccinated with PPV23 were included. Rates of hospitalised pneumonia (HP) and invasive pneumococcal disease (IPD) were compared between individuals receiving a single PPV23 dose versus those receiving two doses using multi-level Cox proportional hazards models. Propensity score weighting was performed to minimise the effect of confounding covariates across the comparison groups. RESULTS: Between 2006 and 2019, there were 462 505 eligible participants. Of those, 6747 (1·5 %) received revaccination. Two doses compared to one dose was associated with an increased risk of HP (adjusted Hazard Ratio [aHR] 1·95; 95 %CI 1·74-2·20) and IPD (aHR 1·44; 95 %CI 1·41-1·46). In participants aged 64-74 years PPV23 revaccination was associated with more IPD (aHR 2·02; 95 %CI 1·75-2·33) and HP (aHR 1·46; 95 %CI 1·42-1.49). In those aged ≥75 years PPV23 revaccination was associated with more HP (aHR 1·12; 95 %CI 1·08-1·16) with no statistically significant difference detected in risk of IPD (aHR 1·20; 95 %CI 0·94-1·52). CONCLUSIONS: No clear benefit of PPV23 revaccination was measured in older adults in this observational study. The small proportion of revaccinated subjects limits the strength of the conclusions. Further research evaluating the clinical effectiveness of PPV23 revaccination is required.

Cross-sectional observational study of epidemiology of COVID-19 and clinical outcomes of hospitalised patients in North West London during March and April 2020.

OBJECTIVE: The aim of this paper is to describe evolution, epidemiology and clinical outcomes of COVID-19 in subjects tested at or admitted to hospitals in North West London. DESIGN: Observational cohort study. SETTING: London North West Healthcare NHS Trust (LNWH). PARTICIPANTS: Patients tested and/or admitted for COVID-19 at LNWH during March and April 2020 MAIN OUTCOME MEASURES: Descriptive and analytical epidemiology of demographic and clinical outcomes (intensive care unit (ICU) admission, mechanical ventilation and mortality) of those who tested positive for COVID-19. RESULTS: The outbreak began in the first week of March 2020 and reached a peak by the end of March and first week of April. In the study period, 6183 tests were performed in on 4981 people. Of the 2086 laboratory confirmed COVID-19 cases, 1901 were admitted to hospital. Older age group, men and those of black or Asian minority ethnic (BAME) group were predominantly affected (p<0.05). These groups also had more severe infection resulting in ICU admission and need for mechanical ventilation (p<0.05). However, in a multivariate analysis, only increasing age was independently associated with increased risk of death (p<0.05). Mortality rate was 26.9% in hospitalised patients. CONCLUSION: The findings confirm that men, BAME and older population were most commonly and severely affected groups. Only older age was independently associated with mortality.

Implementation of a Delayed Prescribing Model to Reduce Antibiotic Prescribing for Suspected Upper Respiratory Tract Infections in a Hospital Outpatient Department, Ghana.

Background: High levels of antimicrobial resistance (AMR) in Ghana require the exploration of new approaches to optimise antimicrobial prescribing. This study aims to establish the feasibility of implementation of different delayed/back-up prescribing models on antimicrobial prescribing for upper respiratory tract infections (URTIs). Methods: This study was part of a quality improvement project at LEKMA Hospital, Ghana, (Dec 2019-Feb 2020). Patients meeting inclusion criteria were assigned to one of four groups (Group 0: No prescription given; Group 1; Patient received post-dated antibiotic prescription; Group 2: Offer of a rapid reassessment of patient by a nurse practitioner after 3 days; and Group 3: Post-dated prescription forwarded to hospital pharmacy). Patients were contacted 10 days afterwards to ascertain wellbeing and actions taken, and patients were asked rate the service on a Likert scale. Post-study informal discussions were conducted with hospital staff. Results: In total, 142 patients met inclusion criteria. Groups 0, 1, 2 and 3 had 61, 16, 44 and 21 patients, respectively. Common diagnosis was sore throat (73%). Only one patient took antibiotics after 3 days. Nearly all (141/142) patients were successfully contacted on day 10, and of these, 102 (72%) rated their experiences as good or very good. Informal discussions with staff revealed improved knowledge of AMR. Conclusions: Delayed/back-up prescribing can reduce antibiotic consumption amongst outpatient department patients with suspected URTIs. Delayed/back-up prescribing can be implemented safely in low and middle-income countries (LMICs).

Routine laboratory surveillance of antimicrobial resistance in community-acquired urinary tract infections adequately informs prescribing policy in England.

OBJECTIVES: To assess whether resistance estimates obtained from sentinel surveillance for antimicrobial resistance (AMR) in community-acquired urinary tract infections (UTIs) differ from routinely collected laboratory community UTI data. METHODS: All patients aged ≥18 years presenting to four sentinel general practices with a suspected UTI, from 13 November 2017 to 12 February 2018, were asked to provide urine specimens for culture and susceptibility. Specimens were processed at the local diagnostic laboratory. Antibiotic susceptibility testing was conducted using automated methods. We calculated the proportion of Escherichia coli isolates that were non-susceptible (according to contemporaneous EUCAST guidelines) to trimethoprim, nitrofurantoin, cefalexin, ciprofloxacin and amoxicillin/clavulanic acid, overall and by age group and sex, and compared this with routine estimates. RESULTS: Sentinel practices submitted 740 eligible specimens. The specimen submission rate had increased by 28 specimens per 1000 population per year (95% CI 21-35). Uropathogens were isolated from 23% (169/740) of specimens; 67% were E. coli (113/169). Non-susceptibility of E. coli to trimethoprim was 28.2% (95% CI 20.2-37.7) on sentinel surveillance (33.4%; 95% CI 29.5-37.6 on routine data) and to nitrofurantoin was 0.9% (95% CI 0-5.7) (1.5%; 95% CI 0.7-3.0 on routine data). CONCLUSIONS: Routine laboratory data resulted in a small overestimation in resistance (although the difference was not statistically significant) and our findings suggest that it provides an adequate estimate of non-susceptibility to key antimicrobials in community-acquired UTIs in England. This study does not support the need for ongoing local sentinel surveillance.

Air-borne microbial contamination of surfaces in a UK dental clinic.

Little is known about the number, type, or antibiotic resistance profiles, of air-borne microbes present in hospital settings yet such information is important in designing effective measures to reduce cross-infection. In this study settle plates were used to identify and quantify the air-borne microbes present in a dental clinic. All isolates were identified to species level using partial 16S ribosomal RNA gene sequencing and their susceptibility to ampicillin, chloramphenicol, erythromycin, gentamicin, penicillin, tetracycline or vancomycin was performed. The mean numbers of viable bacteria detected for each sampling occasion during periods of clinical activity and in the absence of such activity were 21.9 x 10(2 )cfu/m2/h and 2.3 x 10(2 )cfu/m2/h respectively. One hundred ninety-three distinct colony morphotypes, comprising 73 species, were isolated during the study and 48% of these were resistant to at least one antibiotic. The mean numbers of different morphotypes detected per sampling occasion were 14.3 and 5 during periods of clinical activity and inactivity respectively. Propionibacterium acnes, Micrococcus luteus and Staphylococcus epidermidis were frequently isolated regardless of whether any clinical activities were taking place. These findings highlight the importance of preventing surfaces from becoming reservoirs of antibiotic-resistant bacteria and thereby contributing to cross-infection in the dental clinic.

Differences in travel-related incidence of chlamydia by age groups, gender and destination: Sweden 2000-2013.

BACKGROUND: The absolute number of travel-related Chlamydia cases in Sweden has consistently increased between 2000 and 2013. Given the growth in international travel, we aimed to study the trends of travel-related Chlamydia incidence to determine differences and identify high-risk groups and destinations. METHODS: For 2000-2013 we calculated annual Chlamydia incidence per 100,000 travels by dividing the number of notified travel-related cases by the number of travels; the latter were collected from a yearly survey among Swedish residents. For specific destinations 95% confidence intervals were calculated and monotonic yearly trends tested. RESULTS: The overall median annual travel-related Chlamydia incidence was higher for women than for men, but the opposite was true in age groups >25 years. For men, Thailand had the highest incidence, which was 3-7 times higher than the next highest destination in each age group. Spain, Turkey and Thailand had the highest incidence among women, but differences between countries were smaller than for men. For most destinations the yearly trends were stable. CONCLUSIONS: We showed different profiles for men and women and age groups in terms of high incidence destinations. This specific information could allow to better tailor safe sex messages and advocate post-travel Chlamydia testing to target groups travelling to certain destinations.

An assessment of the activity of a novel light-activated antimicrobial coating in a clinical environment.

Cellulose acetate coatings containing the light-activated antimicrobial agents toluidine blue O and rose bengal have previously been shown to be successful in killing a range of microorganisms. Here, we report on the ability of these coatings to achieve reductions in the microbial load on surfaces in a clinical environment.

Novel light-activated antimicrobial coatings are effective against surface-deposited Staphylococcus aureus.

Aerosols constitute a major route of transmission for a wide range of infectious diseases in the hospital setting. The aim of this study was to determine the survival of Staphylococcus aureus on a light-activated antimicrobial coating. S. aureus suspended in phosphate-buffered saline (PBS), saliva, or horse serum was sprayed onto cellulose acetate coatings containing toluidine blue O and rose bengal and the survival of the organism on these surfaces was determined following 6 h of exposure to a 28-W domestic fluorescent lamp (light intensity = 3700 +/- 20 lux). Kills ranging from 78.9% (in horse serum) to 99.8% (in PBS) were obtained when the bacterial density on the coatings was approximately 10(5) colony-forming units/m(2). The results of this study have shown that a coating containing toluidine blue and rose bengal can achieve significant kills of S. aureus when illuminated by a domestic light source. Light-activated coatings could provide a simple, low-cost means of reducing the microbial load in hospitals and other facilities.

Cellulose acetate containing toluidine blue and rose bengal is an effective antimicrobial coating when exposed to white light.

Simple methods of reducing the microbial load on surfaces in hospitals are needed to reduce the risk of hospital-associated infections. Here we report on the ability of a cellulose acetate coating containing the photosensitizers toluidine blue and rose bengal to kill microbes (Staphylococcus aureus, Escherichia coli, Clostridium difficile, a bacteriophage, and Candida albicans) on its surface when illuminated with white light.