Early-onset group B streptococcal infections in five Nordic countries with different prevention policies, 1995 to 2019.

BackgroundNeonatal early-onset disease caused by group B Streptococcus (GBS) is a leading cause of infant morbidity. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing early-onset GBS disease, but there is no agreement on the optimal strategy for identifying the pregnant women requiring this treatment, and both risk-based prophylaxis (RBP) and GBS screening-based prophylaxis (SBP) are used.AimThe aim of this study was to evaluate the effect of SBP as a public health intervention on the epidemiology of early-onset GBS infections.MethodsIn 2012, Finland started the universal SBP, while Denmark, Iceland, Norway and Sweden continued with RBP. We conducted an interrupted time series analysis taking 2012 as the intervention point to evaluate the impact of this intervention. The incidences of early- and late-onset GBS infections during Period I (1995-2011) and Period II (2012-2019) were collected from each national register, covering 6,605,564 live births.ResultsIn Finland, a reduction of 58% in the incidence of early-onset GBS disease, corresponding to an incidence rate ratio (IRR) of 0.42 (95% CI: 0.34-0.52), was observed after 2012. At the same time, the pooled IRR of other Nordic countries was 0.89 (95% CI: 0.80-1.0), specifically 0.89 (95% CI: 0.70-1.5) in Denmark, 0.34 (95% CI: 0.15-0.81) in Iceland, 0.72 (95% CI: 0.59-0.88) in Norway and 0.97 (95% CI: 0.85-1.1) in Sweden.ConclusionsIn this ecological study of five Nordic countries, early-onset GBS infections were approximately halved following introduction of the SBP approach as compared with RBP.

Clinical phenotypes and outcomes of SARS-CoV-2, influenza, RSV and seven other respiratory viruses: a retrospective study using complete hospital data.

BACKGROUND: An understanding of differences in clinical phenotypes and outcomes COVID-19 compared with other respiratory viral infections is important to optimise the management of patients and plan healthcare. Herein we sought to investigate such differences in patients positive for SARS-CoV-2 compared with influenza, respiratory syncytial virus (RSV) and other respiratory viruses. METHODS: We performed a retrospective cohort study of hospitalised adults and children (≤15 years) who tested positive for SARS-CoV-2, influenza virus A/B, RSV, rhinovirus, enterovirus, parainfluenza viruses, metapneumovirus, seasonal coronaviruses, adenovirus or bocavirus in a respiratory sample at admission between 2011 and 2020. RESULTS: A total of 6321 adult (1721 SARS-CoV-2) and 6379 paediatric (101 SARS-CoV-2) healthcare episodes were included in the study. In adults, SARS-CoV-2 positivity was independently associated with younger age, male sex, overweight/obesity, diabetes and hypertension, tachypnoea as well as better haemodynamic measurements, white cell count, platelet count and creatinine values. Furthermore, SARS-CoV-2 was associated with higher 30-day mortality as compared with influenza (adjusted HR (aHR) 4.43, 95% CI 3.51 to 5.59), RSV (aHR 3.81, 95% CI 2.72 to 5.34) and other respiratory viruses (aHR 3.46, 95% CI 2.61 to 4.60), as well as higher 90-day mortality, ICU admission, ICU mortality and pulmonary embolism in adults. In children, patients with SARS-CoV-2 were older and had lower prevalence of chronic cardiac and respiratory diseases compared with other viruses. CONCLUSIONS: SARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics.

A Swedish population-based study of complications due to acute rhinosinusitis in children 5-18 years old.

BACKGROUND: There are few population-based studies of complications due to acute rhinosinusitis in children. The aim was to clarify the admission and complication rate and analyze bacterial cultures in children five to 18 years old in Stockholm, Sweden. METHODS: This was a population-based observational cohort study with retrospectively collected data from individual medical records, from 1 July 2003 to 30 June 2016 in Stockholm, Sweden. Hospital admissions of children with a discharge diagnosis of rhinosinusitis and related complications were reviewed. RESULTS: Incidence of admission due to acute rhinosinusitis was 7.8 per 100 000 children per year (boys 9.2, girls 6.2) and 61% of the admitted children were boys. A severe - postseptal orbital, intracranial or osseous - complication, was present in 34% of admissions (postseptal orbital 28%, intracranial 6%, osseous 4%), resulting in an incidence of 2.6 severe complications per 100 000 children per year (boys 3.6, girls 1.6). Orbital preseptal cellulitis was present in 88% of admissions. Incidence of surgery was 1.3 per 100 000 per year (boys 1.8, girls 0.8) and the percentage of admitted children that had surgery increased with age. S. pyogenes was the most common pathogen found in the whole cohort (29 admissions), while S. milleri was the most common pathogen found among the children with severe complication and surgery. CONCLUSIONS: There is a relative high risk of severe complications in children between five to 18 years that are admitted due to acute rhinosinusitis. There is a need for prospective studies to further analyze the pathogens involved in complications due to acute rhinosinusitis.

A 10-year retrospective survey of acute childhood osteomyelitis in Stockholm, Sweden.

AIM: Children with osteomyelitis present with a range of signs and symptoms and with varying degree of severity. The purpose of this study was to provide data on a population-based 10-year material of children with acute osteomyelitis. METHODS: All children, 0-14 years in Stockholm Region with acute osteomyelitis hospitalised in July 2005-June 2015, were retrospectively studied. Time to hospital presentation, disease localization, inflammation markers, imaging procedures, microbiology, severity classified by the presence of complications, surgical procedures, hospital length of stay and seasonal variation were recorded. RESULTS: There were 430 children with acute osteomyelitis; 61% were boys. The incidence per 100 000 person-years was 11.6; 9.3 in girls and 13.1 in boys. Median age at admission was 2.9 years with no peak later in childhood. Median time from first symptom to diagnosis was 4 days (range 1-21) and 48% of the cases were localised to femur or tibia. Mean C-reactive protein was 59 mg/L (range 1-376). Blood (n = 82) or tissue cultures (n = 54) were positive in 118 (28%) children. The most common pathogen was Staphylococcus aureus (n = 88) followed by Streptococcus pyogenes (n = 12). Surgery was performed in 71 children (17%). There was no mortality. Severe complications were seen in 14 (3.3%) children, five of whom were admitted to intensive care. Median hospital length of stay was 4 days (range 1-60). CONCLUSIONS: Osteomyelitis in children is a diagnostic challenge with a low yield of positive bacterial cultures. Few children with uncomplicated disease need surgery, but the risk of severe complications is not negligible.

Vitamin D strengthens the bladder epithelial barrier by inducing tight junction proteins during E. coli urinary tract infection.

Tight junction proteins are pivotal to prevent bacterial invasion of the epithelial barrier. We here report that supplementation with vitamin D can strengthen the urinary bladder lining. Vitamin D deficient and sufficient mice were infected with Escherichia coli (E. coli) transurethrally to cause urinary tract infection. In addition, bladder biopsies were obtained from postmenopausal women before and after a 3-month period of supplementation with 25-hydroxyvitamin D3 (25D3) and ex vivo infected with E. coli. In biopsies, obtained before E. coli infection, vitamin D had no impact on tight junction proteins. However, during E. coli infection, vitamin D induced occludin and claudin-14 in mature superficial umbrella cells of the urinary bladder, as demonstrated by immunohistochemistry. Increased cell-cell adhesion consolidating the epithelial integrity is thereby promoted. We here describe a novel role of vitamin D in the urinary tract supporting vitamin D supplementation to restore the bladder epithelial integrity.

An overview of how on-call consultant paediatricians can recognise and manage severe primary immunodeficiencies.

Severe primary paediatric immunodeficiency syndromes are rare and potentially fatal unless suspected, diagnosed and treated early. We provide clinical guidance and support for on-call consultant paediatricians working in secondary level hospitals on how to recognise and manage children with these conditions. Our paper addresses four conditions that risk the most severe outcomes if they are not adequately cared for during on-call periods, such as weekends: severe combined immunodeficiency, haemophagocytic lymphohistiocytosis, severe congenital neutropaenia and chronic granulomatous disease. CONCLUSION: On-call paediatricians are provided with advice on handling the most severe primary immunodeficiencies.

Fifteen-minute consultation: Recognising primary immune deficiencies in children.

Children with primary immunodeficiency syndromes present with broad variation of clinical features and the consequences are often severe if not promptly recognised. Here, support is provided for the general paediatrician to recognise primary immunodeficiencies among the many children they meet in their clinical practice.

Cytotoxic necrotizing factor 1 (CNF1) induces an inflammatory response in the urinary tract in vitro but not in vivo.

Cytotoxic necrotizing factor 1 (CNF1) is a well-defined virulence factor of uropathogenic Escherichia coli. We studied the role of CNF1 in uroepithelial cells as well as in children and adults with sporadic and recurrent UTI. Our study suggests that CNF1 may promote bacterial attachment and invasion and can induce an inflammatory response in the urinary tract in vitro but that its role in vivo is possibly minor in comparison with other virulence factors of the uropathogenic E. coli.

CAPD peritonitis induces the production of a novel peptide, daintain/allograft inflammatory factor-1.

OBJECTIVES: To study the occurrence of a novel macrophage-derived peptide, daintain/allograft inflammatory factor-1 (AIF-1), in dialysate from continuous ambulatory peritoneal dialysis (CAPD) patients at commencement and after a follow-up period of therapy and during peritonitis. In addition, we studied peptide production in response to bacterial stimulation of monocytes and macrophages. DESIGN: Peritoneal fluid and supernatants from cells stimulated with different bacteria were analyzed for daintain/AIF-1. PATIENTS AND SETTING: Peritoneal fluid was obtained from 5 patients at commencement of CAPD therapy and during 8 weeks' follow-up, and from 14 patients (10 males, 4 females) during CAPD peritonitis and during the noninfected steady state. All patients were admitted to the Karolinska Hospital. A human monocyte cell-line, THP-1 was differentiated to macrophages, and both monocytes and macrophages were stimulated with live and heat-inactivated Escherichia coli, Staphylococcus aureus, and S. epidermidis. Cells were also stimulated with interleukin (IL)-1beta and interferon gamma (IFNgamma). Daintain/AIF-1 was analyzed with radioimmunoassay technique and IL-8 with enzyme immunoassay technique. RESULTS: An increased production of daintain/AIF-1 was observed in the first spent dialysate in the newly started CAPD patients, with a decrease during the follow-up period (p < 0.05). During peritonitis, the first spent dialysate revealed significantly higher levels of daintain/AIF-1 (3.9 ng/mL) compared to the noninfected state (0.8 ng/mL), with production normalizing after 9-12 days. Bacterial stimulation with E. coli, S. aureus, or S. epidermidis induced higher daintain/AIF-1 response in monocytes compared to macrophages (p < 0.05). Live bacteria induced higher production of the peptide compared to heat-inactivated bacteria (p < 0.05). Interleukin-1beta and IFNgamma were used to stimulate monocytes and macrophages; however, no daintain/AIF-1 production was found, although increased IL-8 levels were detected. CONCLUSION: CAPD peritonitis induces a high and prominent daintain/AIF-1 response. Bacteria are able to induce a response of the peptide from monocytes and macrophages, and it is likely that the virulent parts of the bacteria are heat-labile structures. The early rise in daintain/ AIF-1 might be used as a marker of CAPD peritonitis.

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in acute pyelonephritis and renal scarring.

The aim of the present study was to elucidate the role of matrix metalloproteinase-9 (MMP-9), and its main inhibitor tissue inhibitor of metalloproteinases-1 (TIMP-1), in acute pyelonephritis and the process of renal scarring. Urine samples from 40 children with acute pyelonephritis, 16 children at 6-wk follow-up and 15 children with nonrenal fever were analyzed using ELISA. MMP-9 and TIMP-1 levels were compared with the outcome of pyelonephritis as measured by renal static scintigraphy. A mouse model of acute ascending pyelonephritis was used to localize the sites of production and the kinetics of MMP-9 and TIMP-1 using immunohistochemistry and ELISA. Human renal epithelial A498 cells, primary mesangial cells and monocytic THP-1 cells were stimulated by Escherichia coli. MMP-9 and TIMP-1 mRNA was analyzed by reverse transcription-PCR (RT-PCR) and protein production by ELISA. We demonstrate a significant increase of MMP-9 and TIMP-1 in the urine of children with acute pyelonephritis. Both proteins were produced mainly by leukocytes, and TIMP-1 also by resident kidney cells. Cells reacted differently after stimulation by bacteria. In mesangial cells and monocytes a decreased constitutive TIMP-1 production was found, which was in contrast to epithelial cells. Out of 40 children with pyelonephritis, 23 had higher urinary TIMP-1 than MMP-9 levels. These children had significantly more severe changes in both acute and follow-up scintigraphy scans indicating higher degree of acute tissue damage and renal scarring. Thus, our findings suggest an association between TIMP-1 and the process of renal scarring.