SARS-CoV-2 in first trimester pregnancy: a cohort study.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Evaluating next-generation sequencing for direct clinical diagnostics in diarrhoeal disease.

The accurate microbiological diagnosis of diarrhoea involves numerous laboratory tests and, often, the pathogen is not identified in time to guide clinical management. With next-generation sequencing (NGS) becoming cheaper, it has huge potential in routine diagnostics. The aim of this study was to evaluate the potential of NGS-based diagnostics through direct sequencing of faecal samples. Fifty-eight clinical faecal samples were obtained from patients with diarrhoea as part of the routine diagnostics at Hvidovre University Hospital, Denmark. Ten samples from healthy individuals were also included. DNA was extracted from faecal samples and sequenced on the Illumina MiSeq system. Species distribution was determined with MGmapper and NGS-based diagnostic prediction was performed based on the relative abundance of pathogenic bacteria and Giardia and detection of pathogen-specific virulence genes. NGS-based diagnostic results were compared to conventional findings for 55 of the diarrhoeal samples; 38 conventionally positive for bacterial pathogens, two positive for Giardia, four positive for virus and 11 conventionally negative. The NGS-based approach enabled detection of the same bacterial pathogens as the classical approach in 34 of the 38 conventionally positive bacterial samples and predicted the responsible pathogens in five of the 11 conventionally negative samples. Overall, the NGS-based approach enabled pathogen detection comparable to conventional diagnostics and the approach has potential to be extended for the detection of all pathogens. At present, however, this approach is too expensive and time-consuming for routine diagnostics.

Monitoring meticillin resistant Staphylococcus aureus and its spread in Copenhagen, Denmark, 2013, through routine whole genome sequencing.

Typing of meticillin resistant Staphylococcus aureus (MRSA) by whole genome sequencing (WGS) is performed routinely in Copenhagen since January 2013. We describe the relatedness, based on WGS data and epidemiological data, of 341 MRSA isolates. These comprised all MRSA (n = 300) identified in Copenhagen in the first five months of 2013. Moreover, because MRSA of staphylococcal protein A (spa)-type 304 (t304), sequence type (ST) 6 had been associated with a continuous neonatal ward outbreak in Copenhagen starting in 2011, 41 t304 isolates collected in the city between 2010 and 2012 were also included. Isolates from 2013 found to be of t304, ST6 (n=14) were compared to the 41 earlier isolates. In the study, isolates of clonal complex (CC) 22 were examined in detail, as this CC has been shown to include the hospital-acquired epidemic MRSA (EMRSA-15) clone. Finally, all MRSA ST80 were also further analysed, as representatives of an important community-acquired MRSA in Europe. Overall the analysis identified 85 spa-types and 35 STs from 17 CCs. WGS confirmed the relatedness of epidemiologically linked t304 neonatal outbreak isolates. Several non-outbreak related patients had isolates closely related to the neonatal isolates suggesting unrecognised community chains of transmission and insufficient epidemiological data. Only four CC22 isolates were related to EMRSA-15. No community spread was observed among the 13 ST80 isolates. WGS successfully replaced conventional typing and added information to epidemiological surveillance. Creation of a MRSA database allows clustering of isolates based on single nucleotide polymorphism (SNP) calling and has improved our understanding of MRSA transmission.

Increased risk of venous thromboembolism within the first year after Staphylococcus aureus bacteraemia: a nationwide observational matched cohort study.

OBJECTIVES: Recent evidence suggests that there is an association between infection and venous thromboembolism (VTE). Here, we examined the risk of VTE after Staphylococcus aureus bacteraemia (SAB) compared to the risk in control subjects. DESIGN AND SETTING: Register-based nationwide observational cohort study of hospitalized patients and matched control subjects from the general population in Denmark between 1995 and 2008. RESULTS: Amongst 15 669 SAB cases and 156 690 controls, 182 and 511, respectively, experienced VTE within 1 year. The overall incidence rate (IR) of VTE amongst cases was highest within the first 30 days [IR of deep vein thrombosis (DVT), 39.3 (95% confidence interval (CI) 28.9-53.4)/1000 person-years (PYs); IR of pulmonary embolism (PE), 16.3 (95% CI 10.1-26.2)/1000 PYs]. IRs of DVT were particularly increased amongst cases with a previous diagnosis of VTE, community-acquired infection, a history of injection drug use and in younger age groups. The overall hazard ratio of VTE for cases compared to controls declined from 15.6 (95% CI 10.3-23.5) in the first 30 days after SAB to 4.5 (95% CI 3.2-6.2) from 181 to 365 days after infection. The increased risk of VTE amongst SAB patients persisted after excluding cases with identified VTE risk factors. CONCLUSIONS: There was a particularly high risk of VTE during the first month following an episode of SAB. The risk declined over time, but remained at a threefold increased level compared to control subjects, suggesting that there are shared risk factors for SAB and VTE. Patients with SAB and well-documented risk factors for VTE may benefit from thromboprophylaxis.

Repeated introduction and spread of the MRSA clone t304/ST6 in northern Europe.

OBJECTIVES: During the last decades several methicillin-resistant Staphylococcus aureus (MRSA) clones with the capability of global spread have emerged in the community. Here, we have investigated a large collection of clinical isolates belonging to MRSA clone t304/ST6, which has emerged in many European countries over the last years, in order to retrace its phylogeny and its spread. METHODS: We characterized 466 ST6 isolates from Denmark (n = 354), France (n = 10), Norway (n = 24), Sweden (n = 27) and the UK (n = 51). All had spa-type t304 (n = 454) or t304-related spa-types (n = 12) and whole genome sequencing (WGS) was carried out on Illumina Miseq or Hiseq with 100-300 bp reads. cgMLST was performed using Ridom SeqSphere. RESULTS: A minimum spanning tree (MST) of all 466 isolates showed one large cluster including 182 isolates collected only from Denmark and related to a long-term neonatal outbreak in Copenhagen. This cluster contrasted with numerous small clusters, including the remaining Danish isolates and isolates from the other countries that interspersed throughout the tree. Most isolates were Panton-Valentine leukocidin (PVL) negative (95%) and harboured SCCmec IVa. One genome was closed using Oxford Nanopore technology and Illumina MiSeq. It contained a plasmid of 19.769 bp including the blaZ gene. A similar plasmid was found in 78% of all isolates. DISCUSSION: t304/ST6 is a successful emerging clone and the fact that isolates from five countries are interspersed throughout the MST indicates a common origin. This clone is commonly described in the Middle East and its emergence in Europe coincides with influx of refugees from the Syrian Civil War.

Semi-selective broth improves screening for methicillin-resistant Staphylococcus aureus.

OBJECTIVES: To evaluate two enrichment broths for methicillin-resistant Staphylococcus aureus (MRSA) detection and compare results with direct plating. METHODS: Swabs from 1224 patients were re-analysed for MRSA in a central laboratory (Münster) using six methods. Swabs were suspended in 0.5 mL of non-selective enrichment broth (NB) and vortexed. Aliquots of 100 microL were inoculated on/into: (I) ChromID MRSA agar; (II) Columbia sheep blood (5%) agar (BA) and ChromID MRSA; (III, IV) NB incubated overnight followed by plating on BA and ChromID MRSA; and (V, VI) a semi-selective broth containing cefoxitin and aztreonam (TSB-SSI) incubated overnight followed by plating on BA and ChromID MRSA. In III-VI, 100 microL of the enriched broth was plated on each agar. RESULTS: The combined MRSA-positive rate was 21.5%. MRSA isolates detected by each method were: TSB-SSI, n = 223; NB, n = 205; BA and ChromID MRSA, n = 203; ChromID MRSA alone, n = 183. TSB-SSI detected more positive throat samples than the comparators and significantly reduced methicillin-susceptible S. aureus (MSSA) growth. The maximum sensitivity obtained was only 85%, possibly due to the study design using pre-used swabs and dilution of swab material. For 997 samples, results from Münster were compared with initial results. Peripheral laboratories identified 172 MRSA compared with Münster where 186, 186 and 204 MRSA were found for direct plating, NB and TSB-SSI broth, respectively. CONCLUSIONS: TSB-SSI was superior to both NB and direct plating on ChromID MRSA and BA. Despite re-using swabs for the study, we showed that routine diagnostic screening could be significantly improved, using a semi-selective enrichment broth.

Core genome multi-locus sequence typing as an essential tool in a high-cost livestock-associated meticillin-resistant Staphylococcus aureus CC398 hospital outbreak.

BACKGROUND: Livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex (CC) 398 may be transmitted and cause morbidity and mortality in hospitals. The economic cost of stopping hospital transmission of LA-MRSA CC398 is poorly described. Early detection of transmission may limit the extent of the intervention. AIM: To evaluate core genome multi-locus sequence typing (cgMLST) for detecting transmission chains and to estimate the costs for interventions to prevent further spread after discovery of hospital transmission of LA-MRSA CC398. METHODS: Five patients were involved in two episodes of transmission of LA-MRSA CC398 in a hospital. Standard interventions including MRSA screening of patients and healthcare workers were initiated. Whole genome sequences of the five isolates and 17 epidemiologically unrelated MRSA CC398 isolates from other hospitalized patients were analysed by single nucleotide polymorphism (SNP) comparisons and cgMLST. The economic costs of constraining transmission were calculated from relevant sources. FINDINGS: The five isolates suspected to be involved in hospital transmission clustered with ≤2 SNPs in the draft genome sequences with some distance to other isolates. cgMLST allocated the five isolates to the same type, which was different from all but two of the sporadic isolates. Furthermore, cgMLST separated the five transmission isolates from all other isolates. The economic costs of the outbreak interventions exceeded €11,000 per patient. CONCLUSION: LA-MRSA CC398 is transmittable in hospitals, and intervention against transmission may reach considerable costs. cgMLST is useful in surveillance of hospital transmission of LA-MRSA.

Implications of identifying the recently defined members of the Staphylococcus aureus complex S. argenteus and S. schweitzeri: a position paper of members of the ESCMID Study Group for Staphylococci and Staphylococcal Diseases (ESGS).

BACKGROUND: Staphylococcus argenteus and Staphylococcus schweitzeri, previously known as divergent Staphylococcus aureus clonal lineages, have been recently established as novel, difficult-to-delimit, coagulase-positive species within the S. aureus complex. Methicillin-resistant strains of S. argenteus are known from Australia and the UK. Knowledge of their epidemiology, medical significance and transmission risk is limited and partly contradictory, hampering definitive recommendations. There is mounting evidence that the pathogenicity of S. argenteus is similar to that of 'classical' S. aureus, while as yet no S. schweitzeri infections have been reported. AIM: To provide decision support on whether and how to distinguish and report both species. SOURCES: PubMed, searched for S. argenteus and S. schweitzeri. CONTENT: This position paper reviews the main characteristics of both species and draws conclusions for microbiological diagnostics and surveillance as well as infection prevention and control measures. IMPLICATIONS: We propose not distinguishing within the S. aureus complex for routine reporting purposes until there is evidence that pathogenicity or clinical outcome differ markedly between the different species. Primarily for research purposes, suitably equipped laboratories are encouraged to differentiate between S. argenteus and S. schweitzeri. Caution is urged if these novel species are explicitly reported. In such cases, a specific comment should be added (i.e. 'member of the S.aureus complex') to prevent confusion with less- or non-pathogenic staphylococci. Prioritizing aspects of patient safety, methicillin-resistant isolates should be handled as recommended for methicillin-resistant Staphylococcus aureus (MRSA). In these cases, the clinician responsible should be directly contacted and informed by the diagnosing microbiological laboratory, as they would be for MRSA. Research is warranted to clarify the epidemiology, clinical impact and implications for infection control of such isolates.

Low prevalence of the new variant of Chlamydia trachomatis in Denmark.

We estimated the prevalence of the new variant of Chlamydia trachomatis in Denmark. Fifty consecutive C trachomatis urine samples from each of the 14 regional microbiology laboratories were initially tested and re-analysed with a real-time C trachomatis PCR assay targeting the 16S rRNA gene and with the Becton Dickinson ProbeTec with confirmation of positives with a plasmid PCR with the primers CTP200/CTP201 flanking the deletion. The positive rate for 691 samples was 17% by real-time C trachomatis PCR and by ProbeTec. One specimen was positive for the new variant of C trachomatis (0.14% of all samples; 0.8% of the positives). The prevalence of the new variant of C trachomatis is very low despite very close contact between Denmark and Sweden and extensive cross-border commuting.

Environmental meticillin-resistant Staphylococcus aureus (MRSA) disinfection using dry-mist-generated hydrogen peroxide.

Meticillin-resistant Staphylococcus aureus (MRSA) is a major problem in hospitals worldwide. Hand hygiene is recognised as crucial in limiting the spread of MRSA but less is known about the role of MRSA reservoirs in the inanimate hospital environment. We evaluated the effect of hydrogen peroxide vapour diffused by Sterinis((R)) against MRSA in two experimental hospital settings and in two field trials. Dipslides were used for MRSA detection and quantification before and after using the Sterinis disinfection process. In the first experimental hospital setting, four epidemic MRSA strains were placed at five locations and left for one week. All strains survived the week but not the disinfection process. In field trial one 14 upholstered chairs from a department with many MRSA positive patients were left for one month in a closed room prior to disinfection. MRSA was found on the upholstery of four of the 14 chairs. Three chairs became MRSA negative immediately after the disinfection, the fourth 24h later. The second field trial was in the private home of a MRSA positive family of four individuals. One location was found MRSA positive, remaining so after the Sterinis cycles. We found Sterinis to be effective against MRSA in the experimental hospital setting and upholstered chairs, but not in the private home of heavily colonised MRSA patients.

Identification of a PVL-negative SCCmec-IVa sublineage of the methicillin-resistant Staphylococcus aureus CC80 lineage: understanding the clonal origin of CA-MRSA.

OBJECTIVES: Community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates belonging to clonal complex 80 (CC80) are recognized as the European CA-MRSA. The prevailing European CA-MRSA clone carries a type IVc staphylococcal cassette chromosome mec (SCCmec) and expresses Panton-Valentine leukocidin (PVL). Recently, a significant increase of PVL-negative CC80 MRSA has been observed in Denmark. The aim of this study was to examine their genetics and epidemiology, and to compare them to the European CA-MRSA clone in order to understand the emergence of PVL-negative CC80 MRSA. METHODS: Phylogenetic analysis of the CC80 S. aureus lineage was conducted from whole-genome sequences of 217 isolates (23 methicillin-susceptible S. aureus and 194 MRSA) from 22 countries. All isolates were further genetically characterized in regard to resistance determinants and PVL carriage, and epidemiologic data were obtained for selected isolates. RESULTS: Phylogenetic analysis revealed the existence of three distinct clades of the CC80 lineage: (a) an methicillin-susceptible S. aureus clade encompassing Sub-Saharan African isolates (n = 13); (b) a derived clade encompassing the European CA-MRSA SCCmec-IVc clone (n = 185); and (c) a novel and genetically distinct clade encompassing MRSA SCCmec-IVa isolates (n = 19). All isolates in the novel clade were PVL negative, but carried remnant parts (8-12 kb) of the PVL-encoding prophage ΦSa2 and were susceptible to fusidic acid and kanamycin/amikacin. Geospatial mapping could link these isolates to regions in the Middle East, Asia and South Pacific. CONCLUSIONS: This study reports the emergence of a novel CC80 CA-MRSA sublineage, showing that the CC80 lineage is more diverse than previously assumed.

Clinical and analytical evaluation of the new Aptima Mycoplasma genitalium assay, with data on M. genitalium prevalence and antimicrobial resistance in M. genitalium in Denmark, Norway and Sweden in 2016.

OBJECTIVES: Mycoplasma genitalium (MG) causes urethritis and cervicitis, potentially causing reproductive complications. Resistance in MG to first-line (azithromycin) and second-line (moxifloxacin) treatment has increased. We examined the clinical and analytical performance of the new Conformité Européene (CE)/in vitro diagnostics (IVD) Aptima Mycoplasma genitalium assay (CE/IVD AMG; Hologic); the prevalence of MG, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); and MG resistance to azithromycin and moxifloxacin in Denmark, Norway and Sweden in 2016. METHODS: From February 2016 to February 2017, urogenital and extragenital (only in Denmark) specimens from consecutive attendees at three sexually transmitted disease clinics were tested with the CE/IVD AMG, the research-use-only MG Alt TMA-1 assay (Hologic), Aptima Combo 2 (CT/NG) assay and a laboratory-developed TaqMan real-time mgpB quantitative real-time PCR (qPCR). Resistance-associated mutations were determined by sequencing. Strains of MG and other mycoplasma species in different concentrations were also tested. RESULTS: In total 5269 patients were included. The prevalence of MG was 7.2% (382/5269; 4.9-9.8% in the countries). The sensitivity of the CE/IVD AMG, MG Alt TMA-1 and mgpB qPCR ranged 99.13-100%, 99.13-100% and 73.24-81.60%, respectively, in the countries. The specificity ranged 99.57-99.96%, 100% and 99.69-100%, respectively. The prevalence of resistance-associated mutations for azithromycin and moxifloxacin was 41.4% (120/290; 17.7-56.6%) and 6.6% (18/274; 4.1-10.2%), respectively. Multidrug resistance was found in all countries (2.7%; 1.1-4.2%). CONCLUSIONS: Both transcription-mediated amplification (TMA)-based MG assays had a highly superior sensitivity compared to the mgpB qPCR. The prevalence of MG and azithromycin resistance was high. Validated and quality-assured molecular tests for MG, routine resistance testing of MG-positive samples and antimicrobial resistance surveillance are crucial.

A new multiplex PCR for easy screening of methicillin-resistant Staphylococcus aureus SCCmec types I-V.

A multiplex PCR with four primer-pairs was designed to identify the five main known SCCmec types. A clear and easily discriminated band pattern was obtained for all five types. The SCCmec type was identified for 98% of 312 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). SCCmec type IV was by far the most common SCCmec type among both hospital- and community-acquired MRSA isolates in Denmark.

Increasing incidence but decreasing in-hospital mortality of adult Staphylococcus aureus bacteraemia between 1981 and 2000.

Staphylococcus aureus is a leading cause of bacteraemia. This study analysed temporal trends from 18,702 adult cases of S. aureus bacteraemia in Denmark between 1981 and 2000. After stratification for mode of acquisition, 57% of cases were hospital-acquired (HA), 28% were community-acquired (CA) and 15% were of undetermined acquisition (UA). Incidence rates increased from 18.2 to 30.5 cases/100,000 population. Annual rates increased by 6.4% for CA, by 2.2% for HA and by 3.6% for UA cases, respectively. Case-mortality associated with HA bacteraemia decreased from 36.2% to 20.7% (43% rate reduction, p 0.0001), compared with a decrease from 34.5% to 26.5% (23% rate reduction, p 0.0001) for CA bacteraemia. Following multivariate analysis, age, pneumonia, endocarditis and chronic illness were associated with increased mortality, regardless of the mode of acquisition. Overall, mortality associated with S. aureus bacteraemia declined significantly between 1981 and 2000, but incidence rates doubled, so that the total number of deaths increased. These data emphasise the public health importance of S. aureus bacteraemia and the need for further preventive measures and improved care in order to reduce incidence rates and improve outcomes.

Excretion patterns of human metapneumovirus and respiratory syncytial virus among young children.

BACKGROUND: As respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause serious respiratory tract infections, the routes of transmission of these viruses are important to elucidate. We examined the modes of virus shedding and shedding duration of RSV and hMPV in young children. METHODS: From each child in a group of 44 children (37 RSV-positive, 6 hMPV-positive, and 1 co-infected child), aged between 0.5-38 months, hospitalised at Hvidovre Hospital, Copenhagen, Denmark, one nasopharyngeal aspirate (NPA), saliva, urine, and faeces sample were collected at inclusion and weekly in a three-week period. Sweat and blood samples were obtained at inclusion. The presence of RSV and hMPV RNA was detected using real-time RT-PCR. RESULTS: We detected RSV RNA in 28 saliva specimens, 5 stool samples, and 3 sweat samples. hMPV RNA was detected in one saliva specimen and two sweat samples. Four of the five children shedding RNA in faeces had diarrhoea and children shedding RNA in sweat were either less than five weeks of age or had a chronic lung disease. RSV and hMPV RNA was shed in nasal secretions for a median of 11.5 and 5.0 days respectively (p = 0.001). More than 75% of the family members of the infected children showed to have an upper respiratory tract infection when following up. CONCLUSION: Viral RNA was present in nasal secretions, saliva, sweat, and faeces, but whether or not the virions were infectious and constitute a potential mode of transmission remains to be shown in future studies.

Increased risk of arterial thromboembolic events after Staphylococcus aureus bacteremia: A matched cohort study.

OBJECTIVES: An association between infection and arterial thromboembolic events (ATE) has been suggested. Here we examined the risk of myocardial infarction (MI), stroke and other ATE after Staphylococcus aureus bacteremia (SAB). METHODS: Danish register-based nation-wide observational cohort study between 1995 and 2008 with matched control subjects from the general population. RESULTS: Within a year, 278 of 15,669 SAB patients and 2570 of 156,690 controls developed MI, stroke or another ATE. The incidence rates among SAB patients were highest within the first 30 days and decreased over a year. The adjusted relative risk of MI, stroke and other ATE during the first 30 days after SAB in patients compared to controls were 2.2 (95% CI: 1.6-3.1), 5.5 (95% CI: 3.8-8.3) and 15.5 (95% CI: 6.9-35), respectively. Compared to controls, the increased adjusted relative risk persisted for 30 days for MI, 180 days for stroke and one year for other ATE. Increasing age, hypertension, atrial flutter/fibrillation, prior ATE and endocarditis in SAB patients were associated with an increased risk of ATE. CONCLUSIONS: SAB was associated with a short-term increased risk of ATE that persisted longer dependent on type of event. Studies are warranted to investigate treatment strategies to diminish ATE after SAB.

Staphylococcus aureus spa type t437: identification of the most dominant community-associated clone from Asia across Europe.

Methicillin-resistant Staphylococcus aureus (MRSA) belonging to the multilocus sequence type clonal complex 59 (MLST CC59) is the predominant community-associated MRSA clone in Asia. This clone, which is primarily linked with the spa type t437, has so far only been reported in low numbers among large epidemiological studies in Europe. Nevertheless, the overall numbers identified in some Northern European reference laboratories have increased during the past decade. To determine whether the S. aureus t437 clone is present in other European countries, and to assess its genetic diversity across Europe, we analysed 147 S. aureus t437 isolates from 11 European countries collected over a period of 11 years using multiple locus variable number tandem repeat fingerprinting/analysis (MLVF/MLVA) and MLST. Additionally 16 S. aureus t437 isolates from healthy carriers and patients from China were included. Most isolates were shown to be monophyletic with 98% of the isolates belonging to the single MLVA complex 621, to which nearly all included isolates from China also belonged. More importantly, all MLST-typed isolates belonged to CC59. Our study implies that the European S. aureus t437 population represents a genetically tight cluster, irrespective of the year, country and site of isolation. This underpins the view that S. aureus CC59 has been introduced into several European countries, not being restricted to particular geographical regions or specific host environments. The European S. aureus t437 isolates thus bear the general hallmarks of a high-risk clone.

Pituitary-thyroid axis in critical illness.

Severe nonthyroidal illness has been claimed to cause secondary hypothyroidism. We reevaluated this concept measuring serum free T4 and free T3 by an ultrafiltration method and serum TSH by an ultrasensitive technique (detection limit, and serum TSH by an ultrasensitive technique (detection limit, 0.05 mU/L). Forty-five critically ill patients suffering from hepatic coma (n = 10), terminal cancer (n = 9), stroke (n = 8), and respiratory insufficiency not treated (n = 7) and treated (n = 11) with dopamine were studied. The mortality rate was 80%. No patients received glucocorticoids, and only patients in the last group received dopamine. Serum total as well as free thyroid hormone index values were grossly reduced in the majority of the patients. The 34 patients not receiving dopamine in general had normal values of serum free T4 (32 of 34) and free T3 (31 of 34), measurable TSH (33 of 34), and detectable TSH responses to iv TRH (33 of 34). In contrast, the dopamine-treated patients had reduced serum free T4 and TSH levels compared to normal subjects (P less than 0.05), as well as reduced TSH responses to TRH (P less than 0.01). Serum free T4 and free T3 were below the normal range in 3 patients and 1 patient, respectively, and serum TSH was below the detection limit in 2 patients. We conclude that critically ill patients with nonthyroidal illness not receiving dopamine have normal pituitary-thyroid function, whereas dopamine induces some degree of secondary hypothyroidism.