Impact of the Rotavirus Vaccination Program in Norway After Four Years With High Coverage.

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 <5 years of age hospitalized for acute gastroenteritis at 5 Norwegian hospitals was used to assess the vaccine effectiveness of 2 vaccine doses against rotavirus hospitalization in a case-control study. We used community controls selected from the national population-based immunization registry, and test-negative controls recruited through hospital surveillance. We also assessed the vaccine impact by using time-series analysis of retrospectively collected registry data on acute gastroenteritis in primary and hospital care during 2009-2018. RESULTS: Vaccine effectiveness against rotavirus-confirmed hospitalization was 76% (95% confidence interval [CI]: 34%-91%) using test-negative controls, and 75% (95% CI: 44%-88%) using community controls. In the postvaccine period, acute gastroenteritis hospitalizations in children <5 years were reduced by 45% compared with the prevaccine years (adjusted incidence rate ratios 0.55; 95% CI: 0.49-0.61). Reduction in hospitalizations was also seen in cohorts not eligible for vaccination. Rates in primary care decreased to a lesser degree. CONCLUSIONS: Four years after introduction of rotavirus vaccination in the national childhood immunization program, we recorded a substantial reduction in the number of children hospitalized for acute gastroenteritis in Norway, attributable to a high vaccine effectiveness.

Rotavirus detection in bulk stool and rectal swab specimens in children with acute gastroenteritis in Norway.

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.

Re-evaluation of the cost-effectiveness and effects of childhood rotavirus vaccination in Norway.

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.

Varicella-zoster virus susceptibility and primary healthcare consultations in Norway.

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.

Burden of Rotavirus Disease in Norway: Using National Registries for Public Health Research.

BACKGROUND: Norway introduced routine rotavirus immunization for all children born on or after September 1, 2014. We estimated the healthcare burden of all-cause gastroenteritis and rotavirus disease in children <5 years old to establish the prevaccine baseline and support the ongoing immunization program. METHODS: We examined national registry data on gastroenteritis-associated primary care consultations and hospitalizations for 2009-2013 and data on all deaths in children <5 years old reported during 2000-2013. We also established rotavirus hospital surveillance from February 2014 through January 2015. RESULTS: Before vaccine introduction, 114.5 cases per 1000 children <5 years old were treated in primary care and 11.8 children per 1000 were hospitalized with gastroenteritis annually. During hospital surveillance, rotavirus was detected in 65% (95% confidence interval: 60-70) of inpatient gastroenteritis cases. We estimated that 4.0 inpatient and 2.3 outpatient cases per 1000 children were seen in hospital with rotavirus disease annually, suggesting that 1 in 32 children was hospitalized by age 5. Additional 30.6 rotavirus cases per 1000 children consulted primary care annually or 1 in every 7 children by the age of 5 years. Rotavirus-associated mortality was estimated at 0.17 deaths per 100,000 children <5 years old, corresponding to 1 death every second year. CONCLUSIONS: Rotavirus remains the primary cause of severe gastroenteritis in children in Norway. The unique population-based registers, in combination with an established rotavirus surveillance platform, provide a well-suited setting to evaluate the impact of rotavirus vaccination.

Healthcare Costs of Rotavirus and Other Types of Gastroenteritis in Children in Norway.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: Healthcare costs of rotavirus gastroenteritis in Norway are substantial. The cost-effectiveness of ongoing rotavirus immunization program should be reassessed.

Variance and covariance heterogeneity analysis for detection of metabolites associated with cadmium exposure.

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.