Two cases of imported respiratory diphtheria in Edinburgh, Scotland, October 2019.

We report two cases of respiratory toxigenic Corynebacterium diphtheriae infection in fully vaccinated UK born adults following travel to Tunisia in October 2019. Both patients were successfully treated with antibiotics and neither received diphtheria antitoxin. Contact tracing was performed following a risk assessment but no additional cases were identified. This report highlights the importance of maintaining a high index of suspicion for re-emerging infections in patients with a history of travel to high-risk areas outside Europe.

Coronavirus disease (COVID-19) Community Testing Team in Scotland: A 14-day review, 6 to 20 February 2020.

In response to the outbreak of COVID-19, we set up a team to carry out sampling in the community. This enabled individuals to remain in self-isolation in their own homes and to prevent healthcare settings and services from being overwhelmed by admissions for sampling of suspected cases. There is evidence that this is a cost effective, safe and necessary service to complement COVID-19 testing in hospitals.

Evolution and effects of COVID-19 outbreaks in care homes: a population analysis in 189 care homes in one geographical region of the UK.

BACKGROUND: COVID-19 has affected care home residents internationally, but detailed information on outbreaks is scarce. We aimed to describe the evolution of outbreaks of COVID-19 in all care homes in one large health region in Scotland. METHODS: We did a population analysis of testing, cases, and deaths in care homes in the National Health Service (NHS) Lothian health region of the UK. We obtained data for COVID-19 testing (PCR testing of nasopharyngeal swabs for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) and deaths (COVID-19-related and non-COVID-19-related), and we analysed data by several variables including type of care home, number of beds, and locality. Outcome measures were timing of outbreaks, number of confirmed cases of COVID-19 in care home residents, care home characteristics associated with the presence of an outbreak, and deaths of residents in both care homes and hospitals. We calculated excess deaths (both COVID-19-related and non-COVID-19-related), which we defined as the sum of deaths over and above the historical average in the same period over the past 5 years. FINDINGS: Between March 10 and Aug 2, 2020, residents at 189 care homes (5843 beds) were tested for COVID-19 when symptomatic. A COVID-19 outbreak was confirmed at 69 (37%) care homes, of which 66 (96%) were care homes for older people. The size of care homes for older people was strongly associated with a COVID-19 outbreak (odds ratio per 20-bed increase 3·35, 95% CI 1·99-5·63). 907 confirmed cases of SARS-CoV-2 infection were recorded during the study period, and 432 COVID-19-related deaths. 229 (25%) COVID-19-related cases and 99 (24%) COVID-related deaths occurred in five (3%) of 189 care homes, and 441 (49%) cases and 207 (50%) deaths were in 13 (7%) care homes. 411 (95%) COVID-19-related deaths occurred in the 69 care homes with a confirmed COVID-19 outbreak, 19 (4%) deaths were in hospital, and two (<1%) were in one of the 120 care homes without a confirmed COVID-19 outbreak. At the 69 care homes with a confirmed COVID-19 outbreak, 74 excess non-COVID-19-related deaths were reported, whereas ten non-COVID-19-related excess deaths were observed in the 120 care homes without a confirmed COVID-19 outbreak. 32 fewer non-COVID-19-related deaths than expected were reported among care home residents in hospital. INTERPRETATION: The effect of COVID-19 on care homes has been substantial but concentrated in care homes with known outbreaks. A key implication from our findings is that, if community incidence of COVID-19 increases again, many care home residents will be susceptible. Shielding care home residents from potential sources of SARS-CoV-2 infection, and ensuring rapid action to minimise outbreak size if infection is introduced, will be important for any second wave. FUNDING: None.

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.

Heart Transplant Recipients Prefer a Telemental Health Cognitive-Behavioral Therapy Intervention Delivered by Telephone.

Background:Depression and anxiety are common after heart transplant, and in a regional heart transplant center servicing northern California, willingness to participate in treatment can be a major barrier.Introduction:Our primary aim is to design a remote cognitive-behavioral therapy (CBT) intervention. This study is the first step in the process. Through a survey to the cohort of heart transplant recipients (N = 230), managed within the Kaiser Permanente Northern California's Heart Transplant Service, we aimed to assess symptoms of stress, depression, and anxiety, patient willingness to participate in a CBT intervention, and preference between video and telephone. We proposed to patients a five-visit intervention, with the first and last visits in person and the three middle visits by video.Materials and Methods:One hundred twenty of 230 heart transplant recipients returned the 12-question Likert-like survey. Statistical tests included chi-square, fisher exact test, t-tests, and a logistic regression model.Results:Patients who reported two or more symptoms of stress, depression, and anxiety were 5.67 times more likely to engage in a remote CBT intervention (odds ratio = 5.67; 95% confidence interval 1.63-19.78; p = 0.006). Patients experiencing stress with depression were the most willing group to participate in a CBT intervention. The 12 patients who met the study criteria of 3 years post-transplant and experiencing at least one mental health symptom were invited to participate in the CBT intervention. All patients (12) who met the CBT intervention criteria were not willing to participate in the two in-person visits. All were willing to participate in a telephone-only CBT intervention.Discussion:Among the heart transplant recipients in this cohort, there is more willingness to participate in a CBT intervention when distress is higher and there is a preference for telephone visits as the modality for treatment delivery.Conclusions:Based on the findings, the CBT intervention will be shorter in duration; instead of five visits, there will be four visits; and it will be conducted by telephone only. The new intervention will be tested with 8 to 10 patients, changed, and then it will need to be empirically tested.

Outcome of paediatric acute flaccid myelitis associated with enterovirus D68: a case series.

Enterovirus D68 (EV-D68) is an emerging infection associated with acute flaccid myelitis (AFM). Cases of AFM associated with EV-D68 infection have increased in recent years and the evidence for a causal link is growing. However, our understanding of the epidemiology, clinical features, prognosis, and neurological sequelae of EV-D68 requires ongoing surveillance and investigation. We report five cases of AFM in previously typically developing children (2-6y) from South East Scotland during September and October 2016 after infection with EV-D68 (all detected in the nasopharyngeal aspirates). All cases presented with significant neurological symptoms, which were severe in two cases requiring intensive care support because of respiratory paralysis. At 18-month follow-up, two cases remain ventilator-dependent with other cases requiring ongoing community rehabilitation. These cases represent one of the largest reported paediatric cluster of AFM associated with EV-D68 in Europe. The epidemiology and clinical information add to the knowledge base and the 18-month outcome will help clinicians to counsel families. WHAT THIS PAPER ADDS: Nasopharyngeal aspirate is more sensitive for viral isolation and isolated in all cases. Clinical outcome at 18 months after enterovirus D68 with acute flaccid myelitis provides information on extent of recovery and level of disability.

Expression of Biglycan in First Trimester Chorionic Villous Sampling Placental Samples and Altered Function in Telomerase-Immortalized Microvascular Endothelial Cells.

OBJECTIVE: Biglycan (BGN) has reduced expression in placentae from pregnancies complicated by fetal growth restriction (FGR). We used first trimester placental samples from pregnancies with later small for gestational age (SGA) infants as a surrogate for FGR. The functional consequences of reduced BGN and the downstream targets of BGN were determined. Furthermore, the expression of targets was validated in primary placental endothelial cells isolated from FGR or control pregnancies. APPROACH AND RESULTS: BGN expression was determined using real-time polymerase chain reaction in placental tissues collected during chorionic villous sampling performed at 10 to 12 weeks' gestation from pregnancies that had known clinical outcomes, including SGA. Short-interference RNA reduced BGN expression in telomerase-immortalized microvascular endothelial cells, and the effect on proliferation, angiogenesis, and thrombin generation was determined. An angiogenesis array identified downstream targets of BGN, and their expression in control and FGR primary placental endothelial cells was validated using real-time polymerase chain reaction. Reduced BGN expression was observed in SGA placental tissues. BGN reduction decreased network formation of telomerase-immortalized microvascular endothelial cells but did not affect thrombin generation or cellular proliferation. The array identified target genes, which were further validated: angiopoetin 4 (ANGPT4), platelet-derived growth factor receptor α (PDGFRA), tumor necrosis factor superfamily member 15 (TNFSF15), angiogenin (ANG), serpin family C member 1 (SERPIN1), angiopoietin 2 (ANGPT2), and CXC motif chemokine 12 (CXCL12) in telomerase-immortalized microvascular endothelial cells and primary placental endothelial cells obtained from control and FGR pregnancies. CONCLUSIONS: This study reports a temporal relationship between altered placental BGN expression and subsequent development of SGA. Reduction of BGN in vascular endothelial cells leads to disrupted network formation and alterations in the expression of genes involved in angiogenesis. Therefore, differential expression of these may contribute to aberrant angiogenesis in SGA pregnancies.

Diminished hERG K+ channel activity facilitates strong human labour contractions but is dysregulated in obese women.

Human ether-a-go-go-related gene (hERG) potassium channels determine cardiac action potential and contraction duration. Human uterine contractions are underpinned by an action potential that also possesses an initial spike followed by prolonged depolarization. Here we show that hERG channel proteins (α-conducting and ß-inhibitory subunits) and hERG currents exist in isolated patch-clamped human myometrial cells. We show that hERG channel activity suppresses contraction amplitude and duration before labour, thereby facilitating quiescence. During established labour, expression of ß-inhibitory protein is markedly enhanced, resulting in reduced hERG activity that is associated with an increased duration of uterine action potentials and contractions. Thus, changes in hERG channel activity contribute to electrophysiological mechanisms that produce contractions during labour. We also demonstrate that this system fails in women with elevated BMI, who have enhanced hERG activity as a result of low ß-inhibitory protein expression, which likely contributes to the weak contractions and poor labour outcomes observed in many obese women necessitating caesarean delivery.

A Case of Adenomyosis with a High Titer of IgG Autoantibody to Calreticulin.

Background. High prevalence of autoantibodies to the calcium-binding, endoplasmic reticulum chaperone protein calreticulin has been reported in various autoimmune and parasitic diseases. It has been reported that adenomyosis is associated with the presence of autoantibodies, in particular to phospholipids; however, it is not known whether it is associated with autoimmunity to calreticulin. Results. A 35-year-old gravida 4 para 4 woman presented with a history of many years of intractable menorrhagia. Histopathological examination of a subsequent hysterectomy specimen revealed a bulky uterus, a poorly developed secretory endometrium with decidualization of the stroma and chronic endometritis, as well as the presence of adenomyosis uteri. IgG autoantibodies to calreticulin were measured in the plasma of this and 234 other patients. Nine (3.8%) patients tested positive. The titer of anticalreticulin IgG autoantibody in the sole case with adenomyosis was approximately 8 times the average of other positive-testing samples. Conclusions. The etiology of adenomyosis is unclear. The presence of a high titer, blocking anticalreticulin autoantibody may directly increase the risk that adenomyosis might develop. It is also possible that the expansion of endometrial glandular tissue, as well as elevated estrogens, during adenomyosis may lead to elevated calreticulin, which induces an autoimmune reaction to it. Further study is required to determine whether there is a significant association between adenomyosis and the prevalence of calreticulin autoantibodies.

Mumps in a boarding school: description of an outbreak and control measures.

BACKGROUND: The number of cases of mumps in the UK has increased during 2004-2005. Understanding why some people are more susceptible to mumps infection will help target vaccination and other control measures in the future. This paper describes a mumps outbreak in a boarding school in Scotland (October to November 2004). OBJECTIVES: To describe the characteristics of cases in a mumps outbreak; and to conduct a case-control study looking at the effect of previous measles-mumps-rubella (MMR) vaccination. DESIGN: Descriptive epidemiology. DATA SOURCES: Clinical, laboratory and surveillance data. SETTING: A private school with 600 boarding and day pupils. RESULTS: Fifty cases were notified to the public health department as having mumps. Twenty of the cases (40%) were confirmed virologically, all born between 1987-1991. A matched case-control study was conducted to explore the effect of prior MMR vaccination. Compared to no vaccine, MMR protected against mumps (odds ratio = 0.7), two doses offering best protection (odds ratio = 0.5), but the study was not large enough to detect a statistically significant difference. CONCLUSION: Some children and young people in the UK are currently incompletely vaccinated. This outbreak illustrates the potential of a mumps outbreak to disrupt the medical, educational and social life of a school. All children should be vaccinated with two doses of MMR vaccine before school entry. Children and young people born between 1979-1991 should be given the necessary additional dose(s) of MMR vaccine.