Timing and dosage of intrapartum prophylactic penicillin for preventing early-onset group B streptococcal disease: assessing maternal and umbilical cord blood concentration.

OBJECTIVE: Timing of administration of antibiotics and concentrations in maternal blood and the umbilical cord blood are important prerequisites for optimal intrapartum antibiotic prophylaxis (IAP) of neonatal early-onset group B streptococcus (GBS) disease. This cohort study aimed to explore penicillin concentrations in mothers and infants at birth in relation to time elapsed from administration to delivery and to the minimal inhibitory concentration (MIC) for GBS. MAIN OUTCOME MEASURES: Penicillin G concentrations in maternal and umbilical cord blood in relation to time and dose from administration to time of delivery. RESULTS: In 44 mother-infant dyads, median maternal penicillin G concentration was 0.2 mg/L (IQR 0-0.8 mg/L; range 0-1.6 mg/L). Median infant penicillin G concentration was 1.2 mg/L (IQR 0.5-5.0 mg/L; range 0-12.7 mg/L). In all infants (N=38) born less than 4 hours after the latest IAP administration, penicillin G concentrations far exceeded MIC (0.125 mg/L), even after short time intervals between IAP administration and birth. The highest plasma concentrations were reached in umbilical cord blood within 1 hour from IAP administration to birth.For 44 mother-infant dyads, maternal concentrations were very low compared with their infants'; particularly, very high concentrations were seen in the 20 infants with only one dose of IAP. CONCLUSION: High concentrations of penicillin G were found in umbilical cord blood of infants born less than 4 hours after IAP administration, well above the MIC for GBS.

Structural basis for kinase inhibition in the tripartite E. coli HipBST toxin-antitoxin system.

Many bacteria encode multiple toxin-antitoxin (TA) systems targeting separate, but closely related, cellular functions. The toxin of the Escherichia coli hipBA system, HipA, is a kinase that inhibits translation via phosphorylation of glutamyl-tRNA synthetase. Enteropathogenic E. coli O127:H6 encodes the hipBA-like, tripartite TA system; hipBST, in which the HipT toxin specifically targets the tryptophanyl-tRNA synthetase, TrpS. Notably, in the tripartite system, the function as antitoxin has been taken over by the third protein, HipS, but the molecular details of how activity of HipT is inhibited remain poorly understood. Here, we show that HipBST is structurally different from E. coli HipBA and that the unique HipS protein, which is homologous to the N-terminal subdomain of HipA, inhibits the kinase through insertion of a conserved Trp residue into the active site. We also show how auto-phosphorylation at two conserved sites in the kinase toxin serve different roles and affect the ability of HipS to neutralize HipT. Finally, solution structural studies show how phosphorylation affects overall TA complex flexibility.

Genome Characterisation of Invasive Haemophilus influenzae in Pregnancy: The Noticeable Placental Tissue Tropism Is Distributed across the Species Rather Than Linked with Capsulation or Particular Clones.

Pregnancy is associated with a 5-26 times increased risk of invasive Haemophilus influenzae infection and subsequent adverse pregnancy outcomes. Incidence rate and outcome are published in some regions, but the characterisation of bacterial isolates is limited. We performed comparative genomic analyses of isolates from 12 pregnancy-associated cases, cultured from maternal bacteraemia in pregnancy (nine), postpartum bacteraemia (one), neonatal bacteraemia (one), and placental tissue (one). In two bacteraemia cases, identical isolates were also cultured from cervical swabs. Eight cases occurred early in pregnancy (gestational week 7-26), and seven of them resulted in miscarriage or neonatal death. All bacterial genomes were devoid of capsule loci, and they were evenly distributed in the major phylogenetic group I of the species. The conspicuous tropism of H. influenzae for pregnancy and placental tissue is associated with the species rather than specific clonal subtypes.

Field Epidemiology and Public Health Microbiology training: capturing the alumni perspectives of the training's impact.

We present the findings from the European Programme for Intervention Epidemiology Training (EPIET) Alumni Network (EAN) Member Survey conducted in October to December 2021. The EAN consists of field epidemiologists (EPIET) and public health microbiologists (European Public Health Microbiology Training Programme (EUPHEM)) who stay connected after their 2-year fellowship. This active alumni network provides opportunities for career development, mentorship, knowledge exchange and sharing of best practices for community members, affiliated professionals and public health organisations in Europe. Overall, 281 of 732 members participated in the survey. Of the 192 European fellowship alumni respondents, 173 (90%) indicated that skills and competencies acquired during their fellowship improved performance in their role compared with their abilities before the fellowship. Reported skills and competencies that could be further strengthened included data management/analysis, communication, mathematical modelling and leadership/team management. The EAN Member Survey provides valuable feedback to the EAN, as well as the fellowship programme offices at the European Centre for Disease Prevention and Control (ECDC) and affiliated field epidemiology programmes. The COVID-19 pandemic was a stark reminder of how essential cross-border collaborations are for continued European health security. Maintaining and increasing the professional, well-trained workforce remains crucial for optimal response to infectious diseases and protection of public health.

Comparatively low rates of COVID-19 in women admitted in labor and their newborns prior to routine vaccination of pregnant women: insights from Denmark.

Background: In a country with a high-test frequency, societal lockdown, and pregnancy leave granted from 28 gestational weeks, we investigated SARS-CoV-2 infection in women admitted in labor and their newborn in the pre-vaccine period.Material and methods: A total of 1042 women admitted for delivery in two Danish hospitals agreed to a plasma sample and nasopharyngeal, vaginal, and rectal swabs and to sampling of umbilical cord blood and a nasopharyngeal swab from their newborn at delivery. Plasma samples from women were examined for SARS-CoV-2 antibodies. If antibodies were detected, or the woman had a positive nasopharyngeal swab upon admission or had a household contact with symptoms consistent with COVID-19, SARS-CoV-2 PCR was performed on plasma and swab samples from mother and child.Results: Seventeen women (1.6%) were seropositive. Half the newborn (n = 9 (53%)) of seropositive mothers were also seropositive. None of the seropositive women or newborns had clinical signs of COVID-19 and all had SARS-CoV-2 PCR negative plasma and swab samples.Conclusion: Adherence to specific national guidelines pertaining to testing, self-imposed isolation, and cautious behaviors among pregnant women likely contributed to the exceptionally low prevalence of both prior and current COVID-19 infections detected at the time of childbirth preceding the routine vaccination of pregnant women in Denmark.

Increase in invasive group A streptococcal infections and emergence of novel, rapidly expanding sub-lineage of the virulent Streptococcus pyogenes M1 clone, Denmark, 2023.

A highly virulent sub-lineage of the Streptococcus pyogenes M1 clone has been rapidly expanding throughout Denmark since late 2022 and now accounts for 30% of the new invasive group A streptococcal infections. We aimed to investigate whether a shift in variant composition can account for the high incidence rates observed over winter 2022/23, or if these are better explained by the impact of COVID-19-related restrictions on population immunity and carriage of group A Streptococcus.

DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia: is there a causal relationship?

Hepatotoxicity is a frequent complication during maintenance therapy of acute lymphoblastic leukemia (ALL) with 6-mercaptopurine and methotrexate. Elevated levels of methylated 6-mercaptopurine metabolites (MeMP) are associated with hepatotoxicity. However, not all mechanisms are known that lead to liver failure in patients with ALL. Variants in the POLG gene, which encodes the catalytic subunit of mitochondrial DNA polymerase gamma (POLG1), have been related to drug-induced hepatotoxicity, for example, by sodium valproate. The association of common POLG variants with hepatotoxicity during maintenance therapy was studied in 34 patients with childhood ALL. Of the screened POLG variants, four different variants were detected in 12 patients. One patient developed severe hepatotoxicity without elevated MeMP levels and harbored a heterozygous POLG p.G517V variant, which was not found in the other patients.

SARS-CoV-2 placentitis and severe pregnancy outcome after maternal infection: A Danish case series.

INTRODUCTION: SARS-CoV-2 infection during pregnancy may cause viral inflammation of the placenta, resulting in fetal demise even without fetal or newborn infection. The impact of timing of the infection and the mechanisms that cause fetal morbidity and mortality are not well understood. MATERIAL AND METHODS: To describe placental pathology from women with confirmed SARS-CoV-2 infection during pregnancy, a SARS-CoV-2 immunohistochemistry-positive placenta and late miscarriage, stillbirth, neonatal death, or medically indicated birth due to fetal distress. RESULTS: The triad of trophoblastic necrosis, inflammatory intervillous infiltrates, and increased perivillous fibrinoid deposition was present in all 17 placentas; the pregnancies resulted in eight stillbirths, two late miscarriages (19 and 21 weeks' gestation), and seven liveborn children, two of which died shortly after delivery. The severity of maternal COVID-19 was not reflected by the extent of the placental lesions. In only one case, SARS-CoV-2 was detected in lung tissue samples from the fetus. The majority events (miscarriage, stillbirth, fetal distress resulting in indicated birth, or livebirth, but neonatal death) happened shortly after maternal SARS-CoV-2 infection was diagnosed. Seven of eight sequenced cases were infected with the Delta (B.1.617.2) virus strain. CONCLUSION: We consolidate findings from previous case series describing extensive SARS-CoV-2 placentitis and placental insufficiency leading to fetal hypoxia. We found sparse evidence to support the notion that SARS-CoV-2 virus had infected the fetus or newborn.

Assessing welfare risks in unowned unsocialised domestic cats in Denmark based on associations with low body condition score.

BACKGROUND: Populations of unowned unsocialised cats are present worldwide. Generally, there is concern about their welfare. Low body condition score (BCS) is a potentially relevant indicator that is relatively easy to assess: emaciated cats are likely to have welfare problems while thin cats may be at risk of becoming emaciated. The objective of this study was to assess the association of low BSC with a selection of factors relating to the host, disease, and infection in unowned unsocialised domestic cats. We necropsied 598 euthanised unowned unsocialised cats from Denmark. We recorded each cat's age-group, sex, and neuter status, together with its pregnancy status, the season and location of trapping, as well as gross lesions at necropsy. We also tested for feline immunodeficiency virus and feline leukaemia virus, recorded presence of ectoparasites, and a subsample of the cats were also tested for endoparasites. Cats with no or sparse adipose deposits were categorised as having low BCS, and logistic regression was used to determine the factors associated with low BCS. RESULTS: Of the cats, 11.4% had low BCS. Season, age-group and sex were associated with low BCS and confounded potential associations with other variables. Intact adult males and females in spring and early summer were at highest risk of low BCS. When these factors were taken into account, cats with biting lice had 2.8 (95% confidence interval (CI) 1.4-5.4) times higher odds of low BCS, and cats with gastro-intestinal findings (i.e., enlarged mesenteric lymph nodes, abdominal hernia, diarrhoea, obstructive foreign bodies, or diaphragmatic hernia) had 50 (95% CI 10-417) times higher odds of low BCS, than cats with no such findings. Cats with low BCS were primarily adult intact cats with tooth lesions and skin lesions, ear mite infection, and positive test result for feline immunodeficiency virus. CONCLUSIONS: The results highlight associations that can be used to define a risk profile: low BCS, notably in summer-autumn, in an unowned unsocialised cat was associated with underlying, less visible problems. Thus, low BCS can be more than a step towards being emaciated; it can also be an indicator of other underlying welfare problems.

Transplacental transfer of SARS-CoV-2 antibodies: a cohort study.

The purpose of this study was to examine the transfer rate of SARS-CoV-2 IgG antibodies in pregnancy and newborns. Two Danish labor wards screened all women for SARS-CoV-2 by PCR upon arrival. Women (n = 99) with a SARS-CoV-2 PCR-positive nasopharyngeal (NP) swab or with a household member with a positive swab at labor or any time during pregnancy, or COVID-19 symptoms upon admission (November 2020 through August 2021), were included. Mother and infant were tested by NP swabs at delivery, and maternal and infant (umbilical cord) venous blood samples were collected. We obtained clinical information including previous PCR test results from the medical records. SARS-Cov-2 IgM and quantified IgG antibodies were measured by enzyme-linked immunosorbent assay and transfer ratios of IgG. We detected IgG antibodies in 73 women and 65 cord blood sera and found a strong correlation between SARS-CoV-2 IgG concentrations in maternal and umbilical cord sera (r = 0.9; p < 0.05). Transfer ratio was > 1.0 in 51 out of 73 (69%) infants and > 1.5 in 26 (35%). We found that transfer was proportional to time from a positive SARS-CoV-2 PCR NP swab to delivery (r = 0.5; p < 0.05). Transfer ratios of SARS-CoV-2 antibodies were associated with time from infection to delivery with transfer ratios of more than 1.0 in the majority of seropositive mother-infant dyads.

Increasing prevalence of chronic hepatitis B virus infection and low linkage to care in Denmark on 31 December 2016 - an update based on nationwide registers.

OBJECTIVES: We aimed to update the estimated prevalence of both diagnosed and undiagnosed chronic hepatitis B virus infection in Denmark. Moreover, we aimed to determine the number of people with chronic hepatitis B virus infection in specialised care and to assess the completeness of reporting to the national register of communicable diseases. METHODS: Using four registers with national coverage, we identified all individuals registered with chronic hepatitis B virus infection, aged 16 years or older, and alive in Denmark on 31 December 2016. The diagnosed population was then estimated using capture-recapture analysis. The undiagnosed population was estimated using data from the Danish pregnancy screening program. RESULTS: We estimated that 14,548 individuals were living with chronic hepatitis B virus infection corresponding to 0.3% of the Danish population. Of them, 13,530 (93%) were diagnosed and 7942 (55%) were registered in one or more of the source registers. Only 4297 (32%) diagnosed individuals had attended specialised care and only 3289 cases (24%) were reported to the Danish communicable disease register. CONCLUSION: The prevalence of chronic hepatitis B virus infection increased from 2007 to 2017. The majority that had been diagnosed did not receive care as recommended by national guidelines and were not reported to the communicable diseases register responsible for hepatitis B virus surveillance. Future efforts should focus on linking individuals diagnosed with chronic hepatitis B virus infection to specialised care and improving reporting to the hepatitis B virus surveillance system.

Invasive group B Streptococcus strains and clinical characteristics in Danish infants from 1999 to 2009.

Background: Group B Streptococcus (GBS) infection in infants may result in both respiratory, cardiovascular, and neurological dysfunction and ultimately death of the infant. Surveillance of GBS strains in infants and their clinical characteristics guide development of effective vaccines and other potential treatments and may have implications for future prognostics and infant care. Therefore, we aimed to study GBS serotypes and clonal complexes (CC) in Danish infants with early onset infection (EOD) (0-6 days of life) and late-onset infection (LOD) (7-89 days of life) and to estimate the association between GBS strain and different clinical outcomes. Methods: We included Danish infants less than 3 months of age with GBS isolates from blood or cerebrospinal fluid between 1999 and 2009. GBS isolates were analyzed by serotyping and multilocus sequence typing with classification of isolates into clonal complexes. Clinical characteristics were obtained by questionnaires completed by tending pediatrician including gestational age, Apgar scores, age at onset, meningitis, symptom severity, treatment duration, and mortality. Symptom severities were reported within neurological symptoms, need for respiratory or circulatory support, and treatment of disseminated intravascular coagulation. Results: A total of 212 GBS isolates were collected with 129 from EOD and 83 from LOD. The dominating GBS strains were III/CC17 (41%), Ia/CC23 (17%), III/CC19 (15%), Ib/CC8-10 (7%), and V/CC1 (6%). Strain Ia/CC23 was mostly found in EOD, while III/CC17 was widespread in LOD, though being the most common in both EOD and LOD. Strain III/CC17 and Ia/CC23 had highest percentage of samples from cerebrospinal fluid (26%), while III/CC19 had the least (8%). Strain III/CC19 had highest mortality with about one fifth of infected infants dying (22%) followed by Ia/CC23 (16%), Ib/CC8-10 (9%), and then III/CC17 (6%). The symptom severity varied between strains, but with no strain consistently resulting in more severe symptoms. Conclusion: Some potential differences in disease severity were observed between the different strains. These findings emphasize the continuous need for multimodal surveillance of infant GBS strains and their clinical characteristics to optimize development of GBS vaccines and other potential treatments.

First description of Onchocerca flexuosa infections in Danish red deer (Cervus elaphus).

The prevalence of Onchocerca infection in wild cervids from Denmark was studied in 119 fallow deer (Dama dama), 123 red deer (Cervus elaphus), 51 roe deer (Capreolus capreolus) and eight sika deer (Cervus Nippon) shot during the hunting season from October 2017 to January 2018 from 18 geographical locations across Denmark. The carcasses were macroscopic checked for nodules, and skin samples were examined for microfilaria. All roe deer, fallow deer and sika deer were negative for Onchocerca, while 30.9% red deer were positive for either microfilaria, nodules or both. Significantly more adult red deer (50.8%; 37.6-62.4; p < 0.0001) were infected with Onchocerca than juveniles <1 year (7.8%; 2.1-18.5), while there was an insignificant (p = 0.075) difference in prevalence observed between males (17.4%; 7.8-31.4) and females (41.7%; 30.2-53.9). Onchocerca-positive red deer were observed from 91.7% (11/12) of the sampled geographical locations. Species identification was done on adult worms from nodules taken from the lumbar region of 20 red deer of different geographical origin by sequencing the mitochondrial 12S, 16S and nad5 gene fragments. The sequences matched with previously published sequences for Onchocerca flexuosa. The high prevalence of Onchocerca infection caused by O. flexuosa in red deer in Denmark shows that Denmark has favourable vector conditions and a suitable environment for the maintenance of the parasite. To our knowledge, this is the first systematic study of Onchocerca in wild-living cervids in Denmark.

Occurrence and predictors of pericardial effusion requiring invasive treatment following heart valve surgery.

OBJECTIVES: To describe the occurrence of significant pericardial effusion, and to investigate characteristics associated with pericardial effusion within three months following heart valve surgery. METHODS: A retrospective, observational cohort study including adult patients undergoing heart valve surgery at Odense University Hospital from August 2013 to November 2017. Data were gathered from The Western Denmark Heart Registry and electronic patient records.Cox proportional hazard models were used to investigate the associations between characteristics associated with significant pericardial effusion during index admission and within 3 months. Results are presented as HR with 95% CI. RESULTS: In total, 1460 patients were included (70% men, median age 71 years (IQR 63-76)) and of those, n=230 patients (16%) developed significant pericardial effusion.EuroScore II was significantly associated with an increased risk of pericardial effusion during index admission and associated with a lower risk following discharge (index admission HR 1.05, 95% CI 1.02 to 1.08, after discharge HR 0.80, 95% CI 0.69 to 0.92). Increasing age (HR 0.97, 95% CI 0.95 to 0.98 per year) and concomitant coronary artery bypass grafting versus isolated valve surgery (HR 0.58, 95% CI 0.35 to 0.97) were significantly associated with a reduced risk of pericardial effusions in both periods. Being a man (HR 2.30, 95% CI 1.32 to 4.01) and aortic valve disease versus mitral valve disease (HR 2.16, 95% CI 1.20 to 3.90) were significantly associated with an increased risk after discharge. CONCLUSION: Significant pericardial effusions requiring drainage were present in 16% of cases following heart valve surgery, and different clinical characteristics were associated with the development of effusion.

Evidence-based art in the hospital.

BACKGROUND: Evidence-based art is the investigation of art effects and art investigated for effects. In this study the evidence regarding patient preferences for art styles and effects of art in nonpsychiatric hospitals and outpatient departments was reviewed. METHODS: Results from original articles were retrieved by a scoping PubMed search and by browsing the internet using the terms "evidence based art", "evidence based design", "art and hospital" and "design and hospital", "art effect", "design effect", "landscape preference" and "abstract art figurative art". The quality of art was not operationalized as a criterion. RESULTS: Of the articles 7 original sources showed patient preference for natural scenes and figurative art, 2 studies showed no preference, 16 studies showed positive art effects on well-being and behavior and 5 studies showed a positive effect of nature pictures on measurable findings. CONCLUSION: Controversial results together with theoretical aspects suggest natural scenes in patient rooms and diverse art in public areas.

DNA-thioguanine concentration and relapse risk in children and young adults with acute lymphoblastic leukemia: an IPD meta-analysis.

Methotrexate/6-mercaptopurine maintenance therapy improves acute lymphoblastic leukemia (ALL) outcome. Cytotoxicity is mediated by DNA incorporation of thioguanine nucleotides (DNA-TG). We investigated the association of DNA-TG to relapse risk in 1 910 children and young adults with non-high risk ALL. In a cohort-stratified Cox regression analysis adjusted for sex, age, and white cell count at diagnosis, the relapse-specific hazard ratio (HRa) per 100 fmol/µg increase in weighted mean DNA-TG (wmDNA-TG) was 0.87 (95% CI 0.78-0.97; p = 0.013) in the 839 patients who were minimal residual disease (MRD) positive at end of induction therapy (EOI), whereas this was not the case in EOI MRD-negative patients (p = 0.76). Validation analysis excluding the previously published Nordic NOPHO ALL2008 pediatric cohort yielded a HRa of 0.92 (95% CI 0.82-1.03; p = 0.15) per 100 fmol/µg increase in wmDNA-TG in EOI MRD-positive patients. If also excluding the United Kingdom cohort, in which samples were taken non-randomly in selected patients, the HRa for the EOI MRD-positive patients was 0.82 (95% CI 0.68-0.99; p = 0.044) per 100 fmol/µg increase in wmDNA-TG. The importance of DNA-TG as a biomarker for maintenance therapy intensity calls for novel strategies to increase DNA-TG, although its clinical value may vary by protocol backbone.

The Impact of IFNλ4 on the Adaptive Immune Response to SARS-CoV-2 Infection.

Genetic polymorphisms at the IFNL4 loci are known to influence the clinical outcome of several different infectious diseases. Best described is the association between the IFNL4 genotype and hepatitis C virus clearance. However, an influence of the IFNL4 genotype on the adaptive immune system was suggested by several studies but never investigated in humans. In this cross-sectional study, we have genotyped 201 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive participants for 3 IFNL4 polymorphisms (rs368234815, rs12979860, and rs117648444) and stratified them according to the IFNλ4 activity. Based on this stratification, we investigated the association between the IFNL4 genotype and the antibody as well as the CD8+ T cell response in the acute phase of the SARS-CoV-2 infection. We observed no differences in the genotype distribution compared with a Danish reference cohort or the 1,000 Genome Project, and we were not able to link the IFNL4 genotype to changes in either the antibody or CD8+ T cell responses of these patients.

The serotype distribution of Streptococcus agalactiae (GBS) carriage isolates among pregnant women having risk factors for early-onset GBS disease: a comparative study with GBS causing invasive infections during the same period in Denmark.

BACKGROUND: We describe the serotype distribution of Streptococcus agalactiae (GBS) carriage isolates from women in labor and among GBS isolates causing invasive infections during the same period to see if the distribution of carriage serotypes reflects the GBS serotypes causing invasive diseases including early-onset disease (EOGBS). METHODS: Data on invasive isolates from 2019 including serotype, erythromycin and clindamycin susceptibility was retrieved from the Danish national reference laboratory, Statens Serum Institut. Carriage isolates were collected from women with risk factors for EOGBS enrolled at delivery at the maternity ward at a Danish University Hospital, first half of 2019. RESULTS: Among carriage isolates, the dominant serotype was IX (21 %) followed by serotype III (19 %). The resistance to erythromycin and clindamycin was 21 and 26 %, respectively. Among invasive GBS isolates, no case of EOGBS with serotype IX was detected but the distribution of serotypes were otherwise similar to the GBS carrier strains. The corresponding resistance to erythromycin and clindamycin was 23 and 15 %, respectively. Penicillin resistance was not detected among carriage nor invasive isolates. CONCLUSIONS: The distribution of serotypes among carriage and invasive GBS reflects the assumption that EOGBS occur following transmission of GBS from mother to newborn, with the exception of serotype IX.

[Primary angle closure].

Glaucoma is the most common cause of irreversible blindness globally with a significant contribution from angle-closure glaucoma. Over the past 20 years, the terminology has been standardised with the term glaucoma being used exclusively for patients with signs of glaucomatous damage to the optic nerve. Prospective randomised clinical trials have changed treatment algorithms as summarised in this review. Prophylactic iridotomy is now only offered to selected at-risk patients, while removal of the lens with phacoemulsification is more often used as the primary treatment of patients with angle closure.