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BACKGROUND Use of rotavirus vaccines worldwide since 2006 has led to a significant impact on the burden of rotavirus disease. However, only a third of European countries have introduced rotavirus vaccination in their immunization programs. In October 2014, rotavirus vaccination was introduced for Norwegian infants under strict age restrictions. Exclusive use of the monovalent rotavirus vaccine (RV1) and high vaccination coverage from the beginning enabled evaluation of the impact of this vaccine during the first 4 years after introduction. METHODS Prospective laboratory-based surveillance among children

Objectives To estimate the risk of hospitalization among reported cases of the Delta variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) compared with the Alpha variant in Norway, and the risk of hospitalization by vaccination status. Methods A cohort study was conducted on laboratory-confirmed cases of SARS-CoV-2 in Norway, diagnosed between 3 May and 15 August 2021. Adjusted risk ratios (aRR) with 95% confidence intervals (CI) were calculated using multi-variable log-binomial regression, accounting for variant, vaccination status, demographic characteristics, week of sampling and underlying comorbidities. Results In total, 7977 cases of the Delta variant and 12,078 cases of the Alpha variant were included in this study. Overall, 347 (1.7%) cases were hospitalized. The aRR of hospitalization for the Delta variant compared with the Alpha variant was 0.97 (95% CI 0.76–1.23). Partially vaccinated cases had a 72% reduced risk of hospitalization (95% CI 59–82%), and fully vaccinated cases had a 76% reduced risk of hospitalization (95% CI 61–85%) compared with unvaccinated cases. Conclusions No difference was found between the risk of hospitalization for Delta cases and Alpha cases in Norway. The results of this study support the notion that partially and fully vaccinated cases are highly protected against hospitalization with coronavirus disease 2019. publishedVersion

ObjectivesWith most of the Norwegian population vaccinated against COVID-19, an increasing number and proportion of COVID-19 related hospitalisations are occurring among vaccinated patients. We estimated the length of stay (LoS) in hospital and an intensive care unit (ICU), and risk of admission to ICU and in-hospital death among COVID-19 patients ≥18 years who had been fully vaccinated with an mRNA vaccine, compared to unvaccinated patients.MethodsUsing national registry data, we conducted a cohort study on SARS-CoV-2 positive patients hospitalised in Norway between 1 February and 30 November 2021, with COVID-19 as the main cause of hospitalisation. We ran Cox proportional hazards models to analyse differences in our outcomes. Explanatory variables included vaccination status, age, sex, county of residence, regional health authority, date of admission, country of birth, virus variant and underlying risk factors.ResultsWe included 3,203 patients, of whom 716 (22%) were fully vaccinated (at least two doses or one dose and previous SARS-CoV-2 infection). Fully vaccinated patients had a shorter overall LoS in hospital (aHR for discharge: 1.61, 95%CI: 1.24–2.08), shorter LoS without ICU (aHR: 1.27, 95%CI: 1.07–1.52), and lower risk of ICU admission (aHR: 0.50, 95%CI: 0.37–0.69) compared to unvaccinated patients. We observed no difference in the LoS in ICU, nor risk of in-hospital death between fully vaccinated and unvaccinated patients.ConclusionsFully vaccinated patients hospitalised with COVID-19 in Norway have a shorter LoS and lower risk of ICU admission than unvaccinated patients. These findings can support patient management and ongoing capacity planning in hospitals.

ObjectivesTo estimate the risk of hospitalisation among reported cases of the Delta-variant of SARS-CoV-2 compared to the Alpha variant in Norway. We also estimated the risk of hospitalisation by vaccination status.MethodsWe conducted a cohort study on laboratory-confirmed cases of SARS-CoV-2 in Norway, diagnosed between 3 May and 15 August 2021. We calculated adjusted risk ratios (aRR) with 95% confidence intervals (CIs) using multivariable binomial regression, accounting for variant, vaccination status, demographic characteristics, week of sampling and underlying comorbidities.ResultsWe included 7,977 cases of Delta and 12,078 cases of Alpha. Overall, 347 (1.7%) cases were hospitalised. The aRR of hospitalisation for Delta compared to Alpha was 0.97 (95%CI 0.76–1.23). Partially vaccinated cases had a 72% reduced risk of hospitalisation (95%CI 59%–82%), and fully vaccinated cases had a 76% reduced risk (95%CI 61%–85%), compared to unvaccinated cases.ConclusionsWe found no difference in the risk of hospitalisation for Delta cases compared to Alpha cases in Norway. Further research from a wide variety of settings is needed to better understand the association between the Delta variant and severe disease. Our results support the notion that partially and fully vaccinated persons are highly protected against hospitalisation with COVID-19.HighlightsThe SARS-CoV-2 Delta variant has dominated in Norway since July 2021There was no difference in the risk of hospitalisation for Delta cases compared to AlphaPartially and fully vaccinated cases had >70% decreased risk of hospitalisation

BackgroundThe SARS-CoV-2 variant of concern (VOC) B.1.1.7 has spread worldwide and has been associated with increased risk of severe disease. Studies on patient trajectories and outcomes among hospitalised patients infected with B.1.1.7 are essential for hospital capacity planning.MethodsUsing linked individual-level data from national registries, we conducted a cohort study on cases of SARS-CoV-2 in Norway hospitalised between 21 December 2020 and 25 April 2021. We calculated adjusted hazard ratios using survival analysis to examine the association between B.1.1.7 and time from symptom onset to hospitalisation, and length of stay (LoS) in hospital and an intensive care unit compared to non-VOC. We calculated adjusted odds ratios using logistic regression to examine the association between B.1.1.7 and mortality (up to 30 days post discharge) compared to non-VOC.ResultsWe included 946 B.1.1.7 patients and 157 non-VOC. The crude median time from symptom onset to hospitalisation was 8 days (IQR: 5–10) for B.1.1.7 and 8 days (IQR: 4–11) for non-VOC. The crude median LoS in hospital was 5.0 days (IQR: 2.6–10.0) for B.1.1.7 patients and 5.1 days (IQR: 2.5–9.9) for non-VOC. Fifty-four (6%) B.1.1.7 patients died, compared to 14 (9%) non-VOC. There was no difference in the unadjusted or adjusted estimates of our outcome measures for B.1.1.7 and non-VOC patients.ConclusionsB.1.1.7 does not appear to influence hospitalised patient trajectories, compared to non-VOC. These findings, along with the success of ongoing vaccination programmes, are encouraging for ongoing capacity planning in the hospital sector.

IntroductionSince their emergence, SARS-CoV-2 variants of concern (VOC) B.1.1.7 and B.1.351 have spread worldwide. We estimated the risk of hospitalisation and admission to an intensive care unit (ICU) for infections with B.1.1.7 and B.1.351 in Norway, compared to infections with non-VOC.Materials and methodsUsing linked individual-level data from national registries, we conducted a cohort study on laboratory-confirmed cases of SARS-CoV-2 in Norway diagnosed between 28 December 2020 and 2 May 2021. Variants were identified based on whole genome sequencing, partial sequencing by Sanger sequencing or PCR screening for selected targets. The outcome was hospitalisation or ICU admission. We calculated adjusted risk ratios (aRR) with 95% confidence intervals (CIs) using multivariable binomial regression to examine the association between SARS-CoV-2 variants B.1.1.7 and B.1.351 with i) hospital admission and ii) ICU admission compared to non-VOC.ResultsWe included 23,169 cases of B.1.1.7, 548 B.1.351 and 4,584 non-VOC. Overall, 1,017 cases were hospitalised (3.6%) and 206 admitted to ICU (0.7%). B.1.1.7 was associated with a 1.9-fold increased risk of hospitalisation (aRR 95%CI 1.6–2.3) and a 1.8-fold increased risk of ICU admission (aRR 95%CI 1.2–2.8) compared to non-VOC. Among hospitalised cases, no difference was found in the risk of ICU admission between B.1.1.7 and non-VOC. B.1.351 was associated with a 2.4-fold increased risk of hospitalisation (aRR 95%CI 1.7–3.3) and a 2.7-fold increased risk of ICU admission (aRR 95%CI 1.2–6.5) compared to non-VOC.DiscussionOur findings add to the growing evidence of a higher risk of severe disease among persons infected with B.1.1.7 or B.1.351. This highlights the importance of prevention and control measures to reduce transmission of these VOC in society, particularly ongoing vaccination programmes, and preparedness plans for hospital surge capacity.

Background To minimise vaccine-associated risk of intussusception following rotavirus vaccination, Norway adopted very strict age limits for initiating and completing the vaccine series at the time rotavirus vaccination was included in the national immunisation programme, October 2014. Although Norway has a high coverage for routine childhood vaccines, these stringent age limits could negatively affect rotavirus coverage. We documented the status and impact of rotavirus vaccination on other infant vaccines during the first year after its introduction. Methods We used individual vaccination data from the national immunisation register to calculate coverage for rotavirus and other vaccines and examine adherence with the recommended schedules. We identified factors associated with completing the full rotavirus series by performing multiple logistic regression analyses. We also evaluated potential changes in uptake and timeliness of other routine vaccines after the introduction of rotavirus vaccine using the Kaplan-Meier method. Results The national coverage for rotavirus vaccine achieved a year after the introduction was 89% for one dose and 82% for two doses, respectively. Among fully rotavirus-vaccinated children, 98% received both doses within the upper age limit and 90% received both doses according to the recommended schedule. The child’s age at the initiation of rotavirus series and being vaccinated with diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b (DTaP/IPV/Hib) and pneumococcal vaccines were the strongest predictors of completing the full rotavirus series. No major changes in uptake and timeliness of other paediatric vaccines were observed after introduction of rotavirus vaccine. Conclusions Norway achieved a high national coverage and excellent adherence with the strict age limits for rotavirus vaccine administration during the first year of introduction, indicating robustness of the national immunisation programme. Rotavirus vaccination did not impact coverage or timeliness of other infant vaccines.

Norway has initiated a publicly funded rotavirus immunization program for all age-eligible children in 2014. We aimed to estimate the healthcare costs of rotavirus gastroenteritis in children younger than 5 years old.We identified all gastroenteritis cases in children younger than 5 years old treated during 2009-2013 through the national claims database for primary care and the national hospital registry. We estimated direct medical costs of rotavirus-associated primary care consultations and hospital encounters (inpatient admission, outpatient visit and ambulatory care). We performed a range of one-way sensitivity analyses to explore uncertainty in the cost estimates.Before vaccine introduction, the mean healthcare cost of rotavirus gastroenteritis in children younger than 5 years old was €4,440,337 per year. Among rotavirus-associated costs, 92% were hospital costs and the remaining 8% were primary care costs. The mean annual cost of rotavirus-associated hospital encounters was €4,083,691, of which 95% were costs of inpatient hospital admissions. The average healthcare cost of medically attended gastroenteritis in children younger than 5 years old was approximately €8 million per year, of which rotavirus-related costs represented 56%.Healthcare costs of rotavirus gastroenteritis in Norway are substantial. The cost-effectiveness of ongoing rotavirus immunization program should be reassessed.

Background Rotavirus vaccination was included into the Norwegian childhood immunisation programme in 2014. Before implementation, rotavirus vaccination was found to be cost–effective from a societal perspective, but not from a healthcare perspective. Since introduction, new data on the incidence and economic effects of rotavirus disease have become available. We assessed early epidemiological effects of the rotavirus vaccination programme and re–evaluated its cost–effectiveness in Norway for the years 2015–2019. Methods Using a dynamic transmission model, we compared the epidemiological effects of the ongoing two–dose vaccination programme with Rotarix®, and a hypothetical 3–dose programme with RotaTeq® with no vaccination. A baseline cost of € 54 per fully vaccinated child was used. Cost–effectiveness was computed from a healthcare and societal perspective, using a decision analytical model. Data on healthcare use and costs, productivity losses and health utilities were based on published and own estimates. Uncertainty was accounted for in one–way, multi–way, and probabilistic sensitivity analyses. Results During 2015–2019, 114,658 home care cases, 34,571 primary care cases, 7,381 severe cases, and 2 deaths associated with rotavirus disease were avoided due to vaccination. Under baseline assumptions vaccination was cost–effective from a healthcare perspective with a cost per QALY of € 47,447 for Rotarix® and € 52,709 for RotaTeq®. The break–even price was € 70 for Rotarix® and € 67 for RotaTeq®. Vaccination was cost–saving from the societal perspective, and also from a healthcare perspective for vaccine prices below € 25 and € 22 per vaccinated child for Rotarix® and RotaTeq®, respectively. Conclusion Ongoing childhood rotavirus vaccination in Norway has reduced the rotavirus disease burden substantially, and is cost–effective compared with no vaccination.

Background Bulk stool specimens are traditionally used for rotavirus detection but may be challenging to obtain from young children. Immediate and easy sampling may however be required in different situations, such as outbreak investigation. Objectives We assessed the diagnostic performance of rectal swabs compared to bulk stools for the detection of rotavirus by Enzyme Immunoassay (EIA) and multiplex semi-nested reverse transcription PCR (semi-nested RT-PCR) in children recruited through active hospital-based surveillance of acute gastroenteritis in Norway. Study design We obtained 265 paired bulk stool and rectal swab specimens from children under 5 years of age hospitalized with acute gastroenteritis (AGE). Both types of specimens were analyzed for rotavirus by EIA and semi-nested RT-PCR. In addition, VP6-spesific real-time PCR was used to evaluate the detection performance in the two specimen types. Results Concordant results were obtained in 257 (97%) paired specimens by EIA and in 248 (94%) pairs by semi-nested RT-PCR. Results of VP6-specific real-time PCR obtained from 100 pairs of specimens showed concordance in 91% of the pairs. Sensitivity and specificity for rectal swab specimens were 95% and 100% by EIA; 95% and 92% by semi-nested RT-PCR, respectively. Conclusion Both EIA and semi-nested RT-PCR showed a high accuracy, and rectal swab specimens are appropriate for rotavirus diagnosis and may be used as an alternate specimen type when collection of bulk stool is not feasible. © 2017. This is the authors’ accepted and refereed manuscript to the article. Locked until 1.11.2018 due to copyright restrictions. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Background Currently Norway does not recommend universal varicella vaccination for healthy children. This study assessed susceptibility to varicella-zoster virus (VZV) in the Norwegian population for the first time. Methods A national convenience sample of residual sera was tested for anti-VZV IgG by ELISA. We estimated age-specific seropositivity to VZV, controlling for sex and geographical distribution. We assessed differences between the proportions using the chi-square test and multivariable logistic regression. Seroprevalence data were compared to the varicella and herpes zoster-associated consultation rates in patients attending primary healthcare. Results Although 73.2 % (n = 1,540) of all samples were positive for VZV, only 11.2 % of samples collected from 1-year-olds were seropositive. There was a sharp increase in the proportion of seropositive in 3- and 5-year-olds (40.2 % and 65.4 %, respectively). By the school entry age of 6 years, 69.8 % of children were seropositive. The age-specific annual consultation rate for varicella in primary healthcare peaked in 1-year-olds, with 2,627 cases per 100,000 population. The profile of varicella-related consultations in primary healthcare mirrored the VZV seropositivity profile. The herpes zoster-related consultations in primary healthcare peaked in people over 70 years of age (702 cases per 100,000 population). Conclusions VZV seroprevalence in Norway was somewhat lower than in some other European countries. The age-specific varicella–related consultation rates in primary healthcare mirrored the age profile of VZV seroprevalence. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1581-4) contains supplementary material, which is available to authorized users.

In this study, we propose a novel statistical framework for detecting progressive changes in molecular traits as response to a pathogenic stimulus. In particular, we propose to employ Bayesian hierarchical models to analyse changes in mean level, variance and correlation of metabolic traits in relation to covariates. To illustrate our approach we investigate changes in urinary metabolic traits in response to cadmium exposure, a toxic environmental pollutant. With the application of the proposed approach, previously unreported variations in the metabolism of urinary metabolites in relation to urinary cadmium were identified. Our analysis highlights the potential effect of urinary cadmium on the variance and correlation of a number of metabolites involved in the metabolism of choline as well as changes in urinary alanine. The results illustrate the potential of the proposed approach to investigate the gradual effect of pathogenic stimulus in molecular traits.