A population-based matched cohort study of major congenital anomalies following COVID-19 vaccination and SARS-CoV-2 infection.

Evidence on associations between COVID-19 vaccination or SARS-CoV-2 infection and the risk of congenital anomalies is limited. Here we report a national, population-based, matched cohort study using linked electronic health records from Scotland (May 2020-April 2022) to estimate the association between COVID-19 vaccination and, separately, SARS-CoV-2 infection between six weeks pre-conception and 19 weeks and six days gestation and the risk of [1] any major congenital anomaly and [2] any non-genetic major congenital anomaly. Mothers vaccinated in this pregnancy exposure period mostly received an mRNA vaccine (73.7% Pfizer-BioNTech BNT162b2 and 7.9% Moderna mRNA-1273). Of the 6731 babies whose mothers were vaccinated in the pregnancy exposure period, 153 had any anomaly and 120 had a non-genetic anomaly. Primary analyses find no association between any vaccination and any anomaly (adjusted Odds Ratio [aOR] = 1.01, 95% Confidence Interval [CI] = 0.83-1.24) or non-genetic anomalies (aOR = 1.00, 95% CI = 0.81-1.22). Primary analyses also find no association between SARS-CoV-2 infection and any anomaly (aOR = 1.02, 95% CI = 0.66-1.60) or non-genetic anomalies (aOR = 0.94, 95% CI = 0.57-1.54). Findings are robust to sensitivity analyses. These data provide reassurance on the safety of vaccination, in particular mRNA vaccines, just before or in early pregnancy.

Multi-Drug Resistant Staphylococcus aureus Carriage in Abattoir Workers in Busia, Kenya.

Abattoir workers have been identified as high-risk for livestock-associated Staphylococcus aureus carriage. This study investigated S. aureus carriage in abattoir workers in Western Kenya. Nasal swabs were collected once from participants between February-November 2012. S. aureus was isolated using bacterial culture and antibiotic susceptibility testing performed using the VITEK 2 instrument and disc diffusion methods. Isolates underwent whole genome sequencing and Multi Locus Sequence Types were derived from these data. S. aureus (n = 126) was isolated from 118/737 (16.0%) participants. Carriage was higher in HIV-positive (24/89, 27.0%) than HIV−negative participants (94/648, 14.5%; p = 0.003). There were 23 sequence types (STs) identified, and half of the isolates were ST152 (34.1%) or ST8 (15.1%). Many isolates carried the Panton-Valentine leucocidin toxin gene (42.9%). Only three isolates were methicillin resistant S. aureus (MRSA) (3/126, 2.4%) and the prevalence of MRSA carriage was 0.4% (3/737). All MRSA were ST88. Isolates from HIV-positive participants (37.0%) were more frequently resistant to sulfamethoxazole/trimethoprim compared to isolates from HIV-negative participants (6.1%; p < 0.001). Similarly, trimethoprim resistance genes were more frequently detected in isolates from HIV-positive (81.5%) compared to HIV-negative participants (60.6%; p = 0.044). S. aureus in abattoir workers were representative of major sequence types in Africa, with a high proportion being toxigenic isolates. HIV-positive individuals were more frequently colonized by antimicrobial resistant S. aureus which may be explained by prophylactic antimicrobial use.

A population-based matched cohort study of early pregnancy outcomes following COVID-19 vaccination and SARS-CoV-2 infection.

Data on the safety of COVID-19 vaccines in early pregnancy are limited. We conducted a national, population-based, matched cohort study assessing associations between COVID-19 vaccination and miscarriage prior to 20 weeks gestation and, separately, ectopic pregnancy. We identified women in Scotland vaccinated between 6 weeks preconception and 19 weeks 6 days gestation (for miscarriage; n = 18,780) or 2 weeks 6 days gestation (for ectopic; n = 10,570). Matched, unvaccinated women from the pre-pandemic and, separately, pandemic periods were used as controls. Here we show no association between vaccination and miscarriage (adjusted Odds Ratio [aOR], pre-pandemic controls = 1.02, 95% Confidence Interval [CI] = 0.96-1.09) or ectopic pregnancy (aOR = 1.13, 95% CI = 0.92-1.38). We undertook additional analyses examining confirmed SARS-CoV-2 infection as the exposure and similarly found no association with miscarriage or ectopic pregnancy. Our findings support current recommendations that vaccination remains the safest way for pregnant women to protect themselves and their babies from COVID-19.

Antibiotic prescribing for respiratory tract infection in patients with suspected and proven COVID-19: results from an antibiotic point prevalence survey in Scottish hospitals.

BACKGROUND: Bacterial co-infection is infrequently observed with SARS-CoV-2/COVID-19 infection outside of critical care, however, antibiotics are commonly prescribed. OBJECTIVES: To examine factors associated with antibiotic prescribing for suspected respiratory tract infection (RTI) and evaluate the nature and dynamics of prescribing in hospitalized patients with suspected and proven COVID-19 infection. METHODS: An antibiotic point prevalence survey in hospitalized adult patients was conducted in designated COVID-19 clinical areas (including critical care) in 15 Scottish hospitals. Antibiotics prescribed for RTI and factors associated with prescribing were investigated. RESULTS: Of 820 surveyed patients, 272 (prevalence 33.3%) received antibiotics for suspected RTI on the survey day and 58.8% were SARS-CoV-2 positive. Antibiotics were empirical in 91.9% and amoxicillin (24.6%), doxycycline (20.5%) and co-amoxiclav (15%) were most frequently prescribed. Oral antibiotics were prescribed in 54.5% and duration was recorded in 76.7% on wards for a median of 5 days. IV to oral switch occurred after a median of 2 days. Prescribing for RTI was independently and positively associated with COPD/chronic lung disease, purulent/bloody sputum, abnormal chest X-ray, and CRP ≥ 100 mg/L. Probable and definite hospital-acquired COVID-19 and diabetes were associated with a lower odds of receiving an antibiotic for RTI. CONCLUSIONS: Antibiotic prescribing for suspected RTI was commonly observed and predominantly empirical in suspected or proven COVID-19. Initiatives to reinforce stewardship principles including clinical review, effective use of microbiological diagnostics and better understanding of the role of biomarkers are central to further limit unnecessary antibiotic therapy in COVID-19.

Comparing national point prevalence surveys of healthcare-associated infection and antimicrobial prescribing: a methodological approach to adjust for differences in case-mix.

BACKGROUND: National point prevalence surveys (PPS) of healthcare-associated infection (HAI) and antimicrobial prescribing in hospitals were conducted in 2011 and 2016 in Scotland. When comparing results of PPS, it is important to adjust for any differences in patient case-mix that may confound the comparison. AIM: To describe the methodology used to compare prevalence for the two surveys and illustrate the importance of taking case-mix (patient and hospital stay characteristics) into account. METHODS: Multivariate models (clustered logistic regression) that adjusted for differences in patient case-mix were used to describe the difference in prevalence of six outcomes (HAI, antimicrobial prescribing and four devices: central vascular catheter, peripheral vascular catheter, urinary catheterisation and intubation) between the 2011 and 2016 PPS. Univariate models that did not adjust for these differences were also developed for comparison to show the importance of adjusting for confounders. RESULTS: Without adjustment for case-mix, HAI and intubation prevalence estimates were not significantly different in 2016 compared with 2011 although with adjustment, the prevalence of both was significantly lower (P=0.03 and P=0.02, respectively). These associations were only identified after adjustment for confounding by case-mix. CONCLUSIONS: While prevalence surveys do not provide intelligence on temporal trends as an incidence-based surveillance system would, if limitations and caveats are acknowledged, it is possible to compare two prevalence surveys to describe changing epidemiology. Adjusting for differences in case-mix is essential for robust comparisons. This methodology may be useful for other countries that are conducting large, repeated prevalence surveys.

Survey of antibiotic and antifungal prescribing in patients with suspected and confirmed COVID-19 in Scottish hospitals.

BACKGROUND: Concern regarding bacterial co-infection complicating SARS-CoV-2 has created a challenge for antimicrobial stewardship. Following introduction of national antibiotic recommendations for suspected bacterial respiratory tract infection complicating COVID-19, a point prevalence survey of prescribing was conducted across acute hospitals in Scotland. METHODS: Patients in designated COVID-19 units were included and demographic, clinical and antimicrobial data were collected from 15 hospitals on a single day between 20th and 30th April 2020. Comparisons were made between SARS-CoV-2 positive and negative patients and patients on non-critical care and critical care units. Factors associated with antibiotic prescribing in SARS-CoV-2 positive patients were examined using Univariable and multivariable regression analyses. FINDINGS: There were 820 patients were included, 64.8% were SARS-CoV-2 positive and 14.9% were managed in critical care, and 22.1% of SARS-CoV-2 infections were considered probable or definite nosocomial infections. On the survey day, antibiotic prevalence was 45.0% and 73.9% were prescribed for suspected respiratory tract infection. Amoxicillin, doxycycline and co-amoxiclav accounted for over half of all antibiotics in non-critical care wards and meropenem, piperacillin-tazobactam and co-amoxiclav accounted for approximately half prescribed in critical care. Of all SARS-CoV-2 patients, 38.3% were prescribed antibiotics. In a multivariable logistic regression analysis, COPD/chronic lung disease and CRP ≥ 100 mg/l were associated with higher odds and probable or confirmed nosocomial COVID-19, diabetes and management on an elderly care ward had lower odds of an antibiotic prescription. Systemic antifungals were prescribed in 9.8% of critical care patients and commenced a median of 18 days after critical care admission. INTERPRETATION: A relatively low prevalence of antibiotic prescribing in SARS-CoV-2 hospitalised patients and low proportion of broad spectrum antibiotics in non-critical care settings was observed potentially reflecting national antimicrobial stewardship initiatives. Broad spectrum antibiotic and antifungal prescribing in critical care units was observed indicating the importance of infection prevention and control and stewardship initiatives in this setting. FUNDING: The Scottish Antibiotic Prescribing Group is funded by Scottish Government.

Not just a matter of size: a hospital-level risk factor analysis of MRSA bacteraemia in Scotland.

BACKGROUND: Worldwide, there is a wealth of literature examining patient-level risk factors for methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. At the hospital-level it is generally accepted that MRSA bacteraemia is more common in larger hospitals. In Scotland, size does not fully explain all the observed variation among hospitals. The aim of this study was to identify risk factors for the presence and rate of MRSA bacteraemia cases in Scottish mainland hospitals. Specific hypotheses regarding hospital size, type and connectivity were examined. METHODS: Data from 198 mainland Scottish hospitals (defined as having at least one inpatient per year) were analysed for financial year 2007-08 using logistic regression (Model 1: presence/absence of MRSA bacteraemia) and Poisson regression (Model 2: rate of MRSA bacteraemia). The significance of risk factors representing various measures of hospital size, type and connectivity were investigated. RESULTS: In Scotland, size was not the only significant risk factor identified for the presence and rate of MRSA bacteraemia. The probability of a hospital having at least one case of MRSA bacteraemia increased with hospital size only if the hospital exceeded a certain level of connectivity. Higher levels of MRSA bacteraemia were associated with the large, highly connected teaching hospitals with high ratios of patients to domestic staff. CONCLUSIONS: A hospital's level of connectedness within a network may be a better measure of a hospital's risk of MRSA bacteraemia than size. This result could be used to identify high risk hospitals which would benefit from intensified infection control measures.

Measuring underreporting and under-ascertainment in infectious disease datasets: a comparison of methods.

BACKGROUND: Efficient and reliable surveillance and notification systems are vital for monitoring public health and disease outbreaks. However, most surveillance and notification systems are affected by a degree of underestimation (UE) and therefore uncertainty surrounds the 'true' incidence of disease affecting morbidity and mortality rates. Surveillance systems fail to capture cases at two distinct levels of the surveillance pyramid: from the community since not all cases seek healthcare (under-ascertainment), and at the healthcare-level, representing a failure to adequately report symptomatic cases that have sought medical advice (underreporting). There are several methods to estimate the extent of under-ascertainment and underreporting. METHODS: Within the context of the ECDC-funded Burden of Communicable Diseases in Europe (BCoDE)-project, an extensive literature review was conducted to identify studies that estimate ascertainment or reporting rates for salmonellosis and campylobacteriosis in European Union Member States (MS) plus European Free Trade Area (EFTA) countries Iceland, Norway and Switzerland and four other OECD countries (USA, Canada, Australia and Japan). Multiplication factors (MFs), a measure of the magnitude of underestimation, were taken directly from the literature or derived (where the proportion of underestimated, under-ascertained, or underreported cases was known) and compared for the two pathogens. RESULTS: MFs varied between and within diseases and countries, representing a need to carefully select the most appropriate MFs and methods for calculating them. The most appropriate MFs are often disease-, country-, age-, and sex-specific. CONCLUSIONS: When routine data are used to make decisions on resource allocation or to estimate epidemiological parameters in populations, it becomes important to understand when, where and to what extent these data represent the true picture of disease, and in some instances (such as priority setting) it is necessary to adjust for underestimation. MFs can be used to adjust notification and surveillance data to provide more realistic estimates of incidence.

The pathogen- and incidence-based DALY approach: an appropriate [corrected] methodology for estimating the burden of infectious diseases.

In 2009, the European Centre for Disease Prevention and Control initiated the 'Burden of Communicable Diseases in Europe (BCoDE)' project to generate evidence-based and comparable burden-of-disease estimates of infectious diseases in Europe. The burden-of-disease metric used was the Disability-Adjusted Life Year (DALY), composed of years of life lost due to premature death (YLL) and due to disability (YLD). To better represent infectious diseases, a pathogen-based approach was used linking incident cases to sequelae through outcome trees. Health outcomes were included if an evidence-based causal relationship between infection and outcome was established. Life expectancy and disability weights were taken from the Global Burden of Disease Study and alternative studies. Disease progression parameters were based on literature. Country-specific incidence was based on surveillance data corrected for underestimation. Non-typhoidal Salmonella spp. and Campylobacter spp. were used for illustration. Using the incidence- and pathogen-based DALY approach the total burden for Salmonella spp. and Campylobacter spp. was estimated at 730 DALYs and at 1,780 DALYs per year in the Netherlands (average of 2005-2007). Sequelae accounted for 56% and 82% of the total burden of Salmonella spp. and Campylobacter spp., respectively. The incidence- and pathogen-based DALY methodology allows in the case of infectious diseases a more comprehensive calculation of the disease burden as subsequent sequelae are fully taken into account. Not considering subsequent sequelae would strongly underestimate the burden of infectious diseases. Estimates can be used to support prioritisation and comparison of infectious diseases and other health conditions, both within a country and between countries.