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Background: Scrub typhus, caused by Orientia tsutsugamushi involves infiltration of a mixture of perivascular lymphocytes and macrophages into affected organs. We investigated if this is characterized by chemokine dysregulation., Methods: mRNA expression of chemokines and receptors were screened in whole blood by cDNA microarray in a subgroup of patients and controls. Regulated transcripts were analyzed in plasma by enzyme immunoassays (chemokines) and in whole blood by qPCR (receptors) from scrub typhus patients (n=129), patients with similar febrile illness without Orentia tsutsugamushi infection (n=31) and healthy controls (n=31)., Results: (i) cDNA microarray identified dysregulation of the chemokines CCL18 and CCL23 and CCR3 receptor, in severe scrub typhus. (ii) Plasma CCL7, a ligand for CCR3, CCL18 and CCL23 were higher in scrub typhus patients, with a decline during follow-up. (iii) Conversely, mRNA levels of CCR3 and CCR8, the receptor for CCL18, were decreased in whole blood at hospital admission followed by an increase during follow-up. (iv) CCL7 was independently associated with disease severity. (v) Admission CCL7 levels were associated with short-time mortality., Conclusion: Our findings suggest CCL7 could represent a hitherto unknown pathogenic mediator in Orentia tsutsugamushi infection contributing to local and systemic inflammation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose: The mechanisms that control inflammation in scrub typhus are not fully elucidated. The Notch pathways are important regulators of inflammation and infection, but have not been investigated in scrub typhus., Methods: Plasma levels of the canonical Notch ligand Delta-like protein 1 (DLL1) were measured by enzyme immunoassay and RNA expression of the Notch receptors (NOTCH1, NOTCH2 and NOTCH4) in whole blood was analyzed by real-time PCR in patients with scrub typhus (n = 129), in patients with similar febrile illness without O. tsutsugamushi infection (n = 31) and in healthy controls (n = 31); all from the same area of South India., Results: Our main results were: (i) plasma DLL1 was markedly increased in scrub typhus patients at hospital admission with a significant decrease during recovery. (ii) RNA expression of NOTCH4 was decreased at admission in whole blood. (iii) A similar pattern for DLL1 and NOTCH4 was seen in febrile disease controls. (iv) Admission DLL1 in plasma was associated with disease severity and short-term survival. (vi) Regulation of Notch pathways in O. tsutsugamushi-infected monocytes as evaluated by public repository data revealed enhanced canonical Notch activation with upregulation of DLL1 and downregulation of NOTCH4., Conclusion: Our findings suggest that scrub typhus patients are characterized by enhanced canonical Notch activation. Elevated plasma levels of DLL1 were associated with organ dysfunction and poor outcomes in these patients., (© 2024. The Author(s).)

Background: Extensive measures to control spread of SARS-CoV-2 have led to limited access to education for millions of children and adolescents during the COVID-19 pandemic. Education and access to schools is vital for children and adolescents' learning, health, and wellbeing. Based on high vaccine uptake and low incidence levels, the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) decided to start the academic year 2021/22 with schools open for in-person teaching and moderate mitigation measures. We describe trends in SARS-CoV-2 infections and vaccination coverage among students during the first 12 weeks of the fall semester., Methods: In this multinational, retrospective, observational study, we have used surveillance and registry data from each of the Nordic countries to describe vaccine uptake (≥12 years), infection incidence (whole population) and transmission of SARS-CoV-2 among students. The study period, week 30 to 41 (Jul 26th - Oct 17th), represents the autumn semester from immediately before school started until fall break. In addition, we collected information on mitigation measures applied by the respective countries., Results: There were slight variations between the countries regarding existing infection prevention and control (IPC) measures, testing strategies and vaccination start-up among adolescents. All countries had high vaccine uptake in the adult population, while uptake varied more in the younger age groups. Incidence in the school-aged population differed between countries and seemed to be influenced by both vaccine uptake and test activity. Infection clusters among school-aged children were described for Denmark and Norway, and the number of clusters per week reflected the incidence trend of the country. Most events consisted of only 1-2 cases. Larger clusters appeared more frequently in the higher grades in Norway and in lower grades in Denmark., Conclusion: Data from the Nordic countries indicate that vaccination of adults and adolescents, in addition to mitigation measures, enabled full in-person learning. As SARS-CoV-2 infection does not represent a severe medical risk for most children as previously thought, measures targeting this group should be carefully adjusted and kept at a minimum. Our data add to the evidence on incidence and transmission of SARS-CoV-2 among students in schools open for in-person teaching, and may be valuable for decision makers worldwide., (© 2023. The Author(s).)

Objective: To assess the risk of transmission of SARS-CoV-2 in schools in Norway mainly kept open during the covid-19 pandemic in the academic year 2020-21., Design: Population wide, register based cohort study., Setting: Primary and lower secondary schools in Norway open during the academic year 2020-21, with strict infection prevention and control measures in place, such as organisation of students into smaller cohorts. Contact tracing, quarantine, and isolation were also implemented, and testing of students and staff identified as close contacts., Participants: All students and educational staff in primary and lower secondary schools in Norway, from August 2020 to June 2021., Main Outcome Measures: Overall attack rate of SARS-CoV-2 transmission (AR14) was defined as the number of individuals (among students, staff, or both) in the school with covid-19, detected within 14 days of the index case, divided by the number of students and staff members in the school. AR14 to students (attack rates from all index cases to students only) and AR14 to school staff (attack rates from all index cases to staff members only) were also calculated. These measures for student and school staff index cases were also calculated separately to explore variation in AR14 based on the characteristics of the index case., Results: From August 2020 to June 2021, 4078 index cases were identified; 3220 (79%) students and 858 (21%) school staff. In most (2230 (55%)) schools with an index case, no subsequent individuals with covid-19 were found within 14 days; in 631 (16%) schools, only one more individual with covid-19 within 14 days was found. Overall, AR14 was 0.33% (95% confidence interval 0.32% to 0.33%). When restricting index cases and subsequent individuals with covid-19 to students born in the same year, AR14 to students (0.56-0.78%) was slightly higher., Conclusions: Regarding the number of people infected with SARS-CoV-2 among students and staff, these results suggest that schools were not an important setting for transmission of the virus in Norway during the covid-19 pandemic in the academic year 2020-21., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Norwegian Institute for Public Health for the submitted work; PS has received a grant from the OAK Fellowships Programme in Molecular and Environmental Epidemiology (grant No OCAY-12-356) and has acted as an expert witness in court cases for the National Office for Health Service Appeals. No other author had financial relationships with any organisations that might have an interest in the submitted work in the previous three years or report other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)