European Practice for CDI Treatment.

Clostridioides difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) management guidance for CDI were updated in 2021. This guidance document outlines the treatment options for a variety of CDI clinical scenarios and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). One of the main changes is that metronidazole is no longer recommended as first-line CDI treatment. Rather, fidaxomicin is preferred on the basis of reduced recurrence rates with vancomycin as an acceptable alternative. Recommended options for recurrent CDI now include bezlotoxumab as well as FMT.A 2017 survey of 20 European countries highlighted variation internationally in CDI management strategies. A variety of restrictions were in place in 65% countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. This survey was repeated in November 2022 to assess the current landscape of CDI management practices in Europe. Of 64 respondents from 17 countries, national CDI guidelines existed in 14 countries, and 11 have already/plan to incorporate the ESCMID 2021 CDI guidance, though implementation has not been surveyed in 6. Vancomycin is the most commonly used first-line agent for the treatment of CDI (n = 42, 66%), followed by fidaxomicin (n = 30, 47%). Six (9%) respondents use metronidazole as first-line agent for CDI treatment, whereas 22 (34%) only in selected low-risk patient groups. Fidaxomicin is more likely to be used in high-risk patient groups. Availability of anti-CDI therapy influenced prescribing in six respondents (9%). Approval pre-prescription was required before vancomycin (n = 3, 5%), fidaxomicin (n = 10, 6%), bezlotoxumab (n = 11, 17%) and FMT (n = 10, 6%). Implementation of CDI guidelines is rarely audited.Novel anti-CDI agents are being evaluated; it is not yet clear what will be the roles of these agents. The treatment of recurrent CDI is particularly troublesome, and several different live biotherapeutics are being developed, in addition to FMT.

Establishing severe acute respiratory infection (SARI) surveillance in a sentinel hospital, Ireland, 2021 to 2022.

BackgroundIn 2020, due to the COVID-19 pandemic, the European Centre for Disease Prevention and Control (ECDC) accelerated development of European-level severe acute respiratory infection (SARI) surveillance.AimWe aimed to establish SARI surveillance in one Irish hospital as part of a European network E-SARI-NET.MethodsWe used routine emergency department records to identify cases in one adult acute hospital. The SARI case definition was adapted from the ECDC clinical criteria for a possible COVID-19 case. Clinical data were collected using an online questionnaire. Cases were tested for SARS-CoV-2, influenza and respiratory syncytial virus (RSV), including whole genome sequencing (WGS) on SARS-CoV-2 RNA-positive samples and viral characterisation/sequencing on influenza RNA-positive samples. Descriptive analysis was conducted for SARI cases hospitalised between July 2021 and April 2022.ResultsOverall, we identified 437 SARI cases, the incidence ranged from two to 28 cases per week (0.7-9.2/100,000 hospital catchment population). Of 431 cases tested for SARS-CoV-2 RNA, 226 (52%) were positive. Of 349 (80%) cases tested for influenza and RSV RNA, 15 (4.3%) were positive for influenza and eight (2.3%) for RSV. Using WGS, we identified Delta- and Omicron-dominant periods. The resource-intensive nature of manual clinical data collection, specimen management and laboratory supply shortages for influenza and RSV testing were challenging.ConclusionWe successfully established SARI surveillance as part of E-SARI-NET. Expansion to additional sentinel sites is planned following formal evaluation of the existing system. SARI surveillance requires multidisciplinary collaboration, automated data collection where possible, and dedicated personnel resources, including for specimen management.

SARS-CoV-2 Antibody Testing in Health Care Workers: A Comparison of the Clinical Performance of Three Commercially Available Antibody Assays.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies are an excellent indicator of past COVID-19 infection. As the COVID-19 pandemic progresses, retained sensitivity over time is an important quality in an antibody assay that is to be used for the purpose of population seroprevalence studies. We compared 5,788 health care worker (HCW) serum samples by using two serological assays (Abbott SARS-CoV-2 anti-nucleocapsid immunoglobulin G (IgG) and Roche anti-SARS-CoV-2 anti-nucleocapsid total antibody) and a subset of samples (all Abbott assay positive or grayzone, n = 485) on Wantai SARS-CoV-2 anti-spike antibody enzyme-linked immunosorbent assay (ELISA). For 367 samples from HCW with a previous PCR-confirmed SARS-CoV-2 infection, we correlated the timing of infection with assay results. Overall, seroprevalence was 4.2% on Abbott and 9.5% on Roche. Of those with previously confirmed infection, 41% (150/367) and 95% (348/367) tested positive on Abbott and Roche, respectively. At 21 weeks (150 days) after confirmed infection, positivity on Abbott started to decline. Roche positivity was retained for the entire study period (33 weeks). Factors associated (P ≤ 0.050) with Abbott seronegativity in those with previous PCR-confirmed infection included sex (odds ratio [OR], 0.30 male ; 95% confidence interval [CI], 0.15 to 0.60), symptom severity (OR 0.19 severe symptoms; 95% CI, 0.05 to 0.61), ethnicity (OR, 0.28 Asian ethnicity; 95% CI, 0.12 to 0.60), and time since PCR diagnosis (OR, 2.06 for infection 6 months previously; 95% CI, 1.01 to 4.30). Wantai detected all previously confirmed infections. In our population, Roche detected antibodies up to at least 7 months after natural infection with SARS-CoV-2. This finding indicates that the Roche total antibody assay is better suited than Abbott IgG assay to population-based studies. Wantai demonstrated high sensitivity, but sample selection was biased. The relationship between serological response and functional immunity to SARS-CoV-2 infection needs to be delineated. IMPORTANCE As the COVID-19 pandemic progresses, retained sensitivity over time is an important quality in an antibody assay that is to be used for the purpose of population seroprevalence studies. There is a relative paucity of published literature in this field to help guide public health specialists when planning seroprevalence studies. In this study, we compared results of 5,788 health care worker blood samples tested by using two assays (Roche and Elecsys, anti-nucleocapsid antibody) and by testing a subset on a third assay (Wantai enzyme-linked immunosorbent assay [ELISA] anti-spike antibody). We found significant differences in the performance of these assays, especially with distance in time from PCR-confirmed COVID-19 infection, and we feel these results may significantly impact the choice of assay for others conducting similar studies.

Prevalence of Antibodies to SARS-CoV-2 Following Natural Infection and Vaccination in Irish Hospital Healthcare Workers: Changing Epidemiology as the Pandemic Progresses.

BACKGROUND: In October 2020 SARS-CoV-2 seroprevalence among hospital healthcare workers (HCW) of two Irish hospitals was 15 and 4. 1%, respectively. We compare seroprevalence in the same HCW population 6 months later, assess changes in risk factors for seropositivity with progression of the pandemic and serological response to vaccination. METHODS: All staff of both hospitals (N = 9,038) were invited to participate in an online questionnaire and SARS-CoV-2 antibody testing in April 2021. We measured anti-nucleocapsid and anti-spike antibodies. Frequencies and percentages for positive SARS-CoV-2 antibodies were calculated and adjusted relative risks for participant characteristics were calculated using multivariable regression analysis. RESULTS: Five thousand and eighty-five HCW participated. Seroprevalence increased to 21 and 13%, respectively; 26% of infections were previously undiagnosed. Black ethnicity (aRR 1.7, 95% CI 1.3-2.2, p < 0.001), lower level of education (aRR 1.4 for secondary level education, 95% CI 1.1-1.8, p = 0.002), living with other HCW (aRR 1.2, 95% CI 1.0-1.4, p = 0.007) were significantly associated with seropositivity. Having direct patient contact also carried a significant risk being a healthcare assistant (aRR 1.8, 95% CI 1.3-2.3, p < 0.001), being a nurse (aRR 1.4, 95% CI 1.0-1.8, p = 0.022), daily contact with COVID-19 patients (aRR 1.4, 95% CI 1.1-1.7, p = 0.002), daily contact with patients without suspected or confirmed COVID-19 (aRR 1.3, 95% CI 1.1-1.5, p = 0.013). Breakthrough infection occurred in 23/4,111(0.6%) of fully vaccinated participants; all had anti-S antibodies. CONCLUSION: The increase in seroprevalence reflects the magnitude of the third wave of the pandemic in Ireland. Genomic sequencing is needed to apportion risk to the workplace vs. the household/community. Concerted efforts are needed to mitigate risk factors due to ethnicity and lower level of education, even at this stage of the pandemic. The undiagnosed and breakthrough infections call for ongoing infection prevention and control measures and testing of HCW in the setting of close contact. Vaccinated HCW with confirmed infection should be actively assessed, including SARS-CoV-2 whole genome sequencing (WGS), serology testing and assessment of host determinants, to advance understanding of the reasons for breakthrough infection.

Establishment of a national surveillance system to monitor community HIV testing, Ireland, 2018.

BACKGROUND: HIV continues to be an important public health issue. Voluntary community-based HIV testing (VCBT) helps to reduce the undiagnosed population of HIV-positive individuals, enabling early diagnosis and treatment. Monitoring is essential to determine whether at-risk groups are being effectively reached. AIMS: Our aim was to pilot and then introduce sustained monitoring of VCBT in Ireland, through collaboration between statutory and non-statutory organisations. METHODS: The study was initiated by the Health Protection Surveillance Centre in 2018. Steps included forming a multisectoral steering group and developing a minimum standardised dataset. De-identified case-based data were requested for VCBT carried out from 1 January 2017 onwards; this paper includes data for 2018. RESULTS: Six organisations participated; all four NGOs involved in VCBT, one medical charity, and the Health Service Executive National Social Inclusion Office. Methods were rapid point-of-care testing (POCT) (54%) or laboratory based (46%). Total HIV test reactivity was 1.7% (1.5% excluding persons later identified as previously diagnosed HIV positive). All POCT data were case based; the test reactivity rate was 0.8% and was higher in bar/club settings (1.2%). Most (74%) laboratory testing data were in aggregate format; the test positivity rate in one asylum centre was 5.0%. Ongoing challenges include testing among persons later identified as previously diagnosed HIV positive, monitoring case-based testing in asylum settings, and suboptimal data on confirmatory testing and linkage to care. CONCLUSIONS: Sustained national monitoring in community settings will help inform HIV testing guidelines and will enable assessment of the impact of local and regional community HIV testing strategies.

A proposal for changes to the European Union syphilis surveillance case definition using evidence from evaluations in Ireland.

Syphilis remains a disease of public health importance, with considerable health effects if not treated. Concurrent infection with syphilis and untreated HIV facilitates HIV transmission. The incidence of syphilis in Europe has been increasing, particularly among men who have sex with men (MSM) and in MSM with HIV. However, there is heterogeneity among countries in the case definition used for syphilis and in reported syphilis notification rates. In Ireland, we have undertaken a number of refinements of the national syphilis surveillance system since 2014, including refinement of the laboratory thresholds for notification (rapid plasma reagin 1:16 and/or positive IgM). This article outlines the steps taken and some of the challenges we faced. Our current case definition now accurately reflects the epidemiology of syphilis in Ireland and our current surveillance provides timely information for action, while not reducing the sensitivity of the system too much. For countries where surveillance is driven mainly by laboratory reporting and where obtaining clinical details is challenging, these thresholds for notification may be a pragmatic solution.

Piloting a surveillance system for HIV drug resistance in the European Union.

BackgroundA steady increase in HIV drug resistance (HIVDR) has been demonstrated globally in individuals initiating first-line antiretroviral therapy (ART). To support effective use of ART and prevent spread of HIVDR, monitoring is essential.AimWe piloted a surveillance system for transmitted HIVDR to assess the feasibility of implementation at the European level.MethodAll 31 countries in the European Union and European Economic Area were invited to retrospectively submit data on individuals newly diagnosed with HIV in 2015 who were tested for antiviral susceptibility before ART, either as case-based or as aggregate data. We used the Stanford HIV database algorithm to translate genetic sequences into levels of drug resistance.ResultsNine countries participated, with six reporting case-based data on 1,680 individuals and four reporting aggregated data on 1,402 cases. Sequence data were available for 1,417 cases: 14.5% of individuals (n = 244) showed resistance to at least one antiretroviral drug. In case-based surveillance, the highest levels of transmitted HIVDR were observed for non-nucleoside reverse-transcriptase inhibitors (NNRTIs) with resistance detected in 8.6% (n = 145), followed by resistance to nucleoside reverse-transcriptase inhibitors (NRTI) (5.1%; n = 85) and protease inhibitors (2.0%; n = 34).ConclusionWe conclude that standard reporting of HIVDR data was feasible in the participating countries. Legal barriers for data sharing, consensus on definitions and standardisation of interpretation algorithms should be clarified in the process of enhancing European-wide HIV surveillance with drug resistance information.

European Practice for CDI Treatment.

Clostridium difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used routinely for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases CDI treatment guidelines outline the treatment options for a variety of CDI clinical scenarios, including use of the more traditional anti-CDI therapies (e.g., metronidazole, vancomycin), the role of newer anti-CDI agents (e.g., fidaxomicin), indications for surgical intervention and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). A 2017 survey of 20 European countries found that while the majority (n = 14) have national CDI guidelines that provide a variety of recommendations for CDI treatment, only five have audited guideline implementation. A variety of restrictions are in place in 13 (65%) countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. Novel anti-CDI agents are being evaluated in Phase III trials; it is not yet clear what will be the roles of these agents. Prophylaxis is an optimum approach to reduce the impact of CDI especially in high-risk populations; monoclonal antibodies, antibiotic blocking approaches and multiple vaccines are currently in advanced clinical trials. The treatment of recurrent CDI is particularly troublesome, and several different live bio therapeutics are being developed, in addition to FMT.

Loss aversion in schizophrenia.

BACKGROUND: Loss aversion in decision-making refers to a higher sensitivity to losses than to gains. Loss aversion is conceived as an affective interference in cognitive processes such as judgment and decision-making. Loss aversion in non-risky choices has not been studied in schizophrenia. METHOD: Forty-two individuals with schizophrenia and 42 non-patient control subjects, matched by gender and age, were randomized to two different scenarios (a buying scenario and a selling scenario). Subjects were asked to evaluate the price of a decorated mug. Schizophrenia subjects were re-tested four weeks later with the other scenario. RESULTS: Contrary to non-patient controls, schizophrenia subjects did not show loss aversion. In the schizophrenia group, absence of loss aversion was correlated with age, duration of illness, number of months in State hospitals, and poorer performance in the Wisconsin Card Sorting Test, but not with current psychopathology and two domains of emotional experience. CONCLUSIONS: Absence of loss aversion in schizophrenia represents a deficit in the processing of emotional information during decision-making. It can be interpreted as a lack of integration between the emotional and the cognitive systems, or to a more diffuse and de-differentiated impact of emotional information on decision-making. Future studies should bring more clarity to this question.

The psychosocial impact of developmental dental defects in people with hereditary amelogenesis imperfecta.

BACKGROUND: Amelogenesis imperfecta (AI) is a hereditary dental condition with poor esthetics and dental sensitivity that frequently requires extensive dental treatment. The authors hypothesized that AI is associated with a negative psychosocial outcome. METHODS: Family members with and without AI completed a questionnaire including demographic and dental history questions, as well as a number of psychometric scales. The authors investigated the effects of AI status (with versus without), sex and age on each of the psychosocial outcomes using a generalized linear model. RESULTS: Subjects with AI (n = 30) had higher levels of social avoidance and distress, as well as higher levels of dysfunction, discomfort and disability attributable to their oral condition compared with subjects without AI (n = 29). The relationship of AI status to fear of negative evaluation, mastery and self-esteem was age-dependent. Younger subjects with AI tended to have higher fear of negative evaluation scores, while older subjects without AI tended to have higher fear of negative evaluation scores. Additionally, subjects without AI showed a definite decrease in mastery and self-esteem scores with age, while subjects with AI tended to show an increase in mastery and self-esteem scores with age. CONCLUSIONS: These results indicate that having AI has a marked impact on the psychosocial health of affected people comparable with the impact of systemic health conditions, especially at younger ages. CLINICAL IMPLICATIONS: Dental coverage for AI traditionally is excluded by third-party payers as being solely for esthetic reasons. The authors' study shows that AI has marked psychosocial effects, which suggests that dental treatment could be medically necessary and has far-reaching implications for the affected person's overall health.