Genetic diversity of rotavirus strains circulating in Norway before and after the introduction of rotavirus vaccination in children.

Globally, rotavirus (RV) is the leading cause of acute gastroenteritis (AGE) in young children under 5 years of age. Implementation of RV vaccination is expected to result in fewer cases of RV in the target population, but it is unknown if this also results in vaccine-induced virus strain replacement. Rotarix, a monovalent vaccine based on G1P[8] RV, was introduced in Norway in the children's immunization program in September 2014. The main aim of this study was to describe the diversity of RV circulating pre and post introduction of the RV vaccine in Norway and investigate changes in genotype distribution during the first 4 years after implementation. A total of 1108 samples were collected from children under 5 years enrolled with AGE from five large hospitals in Norway and were analyzed for RV by enzyme immunoassay (EIA). All positive results were genotyped by multiplex semi-nested reverse transcription PCR for identification of G and P types. In total, 487 of the 1108 (44%) samples, collected from the enrolled children, were positive for RV by EIA method which were further genotyped. G1P[8] was found to be the most common type of RV pre and post RV vaccine implementation followed by G9P[8]. There were neither geographical nor temporal differences in genotype dominance. Also, no apparent changes were shown in the genotype distribution in the postvaccine era for years from 2015 to 2018. In 21.4% of the cases, vaccine strains were detected. Continuous RV genotype surveillance is vital for assessing the effectiveness of a vaccine program and monitoring for any emergence of vaccine-escape strains. Genotyping is also necessary to detect vaccine strains to avoid reporting false-positive cases of active RV infection in newly vaccinated cases.

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.

Intussusception among Norwegian children: What to expect after introduction of rotavirus vaccination?

BACKGROUND: To reduce the risk of vaccine-associated intussusception, rotavirus vaccination in Norway was implemented under strict age limits (the first dose given by 12 weeks of age and the second dose by 16 weeks of age) in 2014. We estimated the incidence of intussusception in children <2 years old before vaccine introduction and the number of vaccine-associated cases under current and extended age limits for vaccine administration in Norway. METHODS: To estimate the baseline incidence, we validated all diagnoses in children <2 years old registered in the national hospital registry during the pre-vaccine period of 2008-2013. Using national vaccine coverage data and international estimates of intussusception risk after rotavirus vaccination, we calculated the numbers of expected vaccine-associated intussusception cases to compare with the estimated numbers of averted rotavirus cases. Uncertainty was accounted for by several scenario analyses using current and extended age limits for vaccine administration. RESULTS: The pre-vaccine incidence of intussusception was 26.7 (95% CI 23.1-30.6) cases/year per 100,000 children <2 years old and 37.1 (95% CI 31.2-43.8) cases/year per 100,000 children <1 year old. In the 2016 birth cohort (approx. 60,000) vaccinated under the current age limits, 1.3 (95% CI 0.7-2.0) vaccine-associated intussusception cases were expected to occur. If age limits were extended to 16 weeks for the first vaccine dose and 24 weeks for the second dose, leading to more children vaccinated at an older age, 2.2 (95% CI 1.2-3.5) excess cases would be expected in the same cohort. Simultaneously, an estimated 1768 rotavirus hospitalizations/year in children <5 years old would be averted under current age limits, with 98 additional rotavirus hospitalizations averted under extended age limits. CONCLUSIONS: Administering rotavirus vaccines beyond current age limits in Norway would lead to a marginal increase in the number of intussusception cases, which would be offset by the benefits of vaccination.

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.

Risk Factors for Sporadic Domestically Acquired Campylobacter Infections in Norway 2010-2011: A National Prospective Case-Control Study.

BACKGROUND: Campylobacteriosis is the most frequently reported food- and waterborne infection in Norway. We investigated the risk factors for sporadic Campylobacter infections in Norway in order to identify areas where control and prevention measures could be improved. METHODS: A national prospective case-control study of factors associated with Campylobacter infection was conducted from July 2010 to September 2011. Cases were recruited from the Norwegian Surveillance System of Communicable Diseases (MSIS). Controls were randomly selected from the Norwegian Population Registry. Cases and controls were mailed a paper questionnaire with a prepaid return envelope. Univariable analyses using logistic regression were conducted for all exposures. A final parsimonious multivariable model was developed using regularized/penalized logistic regression, and adjusted odds ratios were calculated. RESULTS: A total of 995 cases and 1501 controls were included in the study (response proportion 55% and 30%, respectively). Exposures that had significant increases in odds of Campylobacter infection in multivariable analysis were drinking water directly from river, stream, or lake (OR: 2.96), drinking purchased bottled water (OR: 1.78), eating chicken (1.69), eating meat that was undercooked (OR: 1.77), eating food made on a barbecue (OR: 1.55), living on a farm with livestock (OR: 1.74), having a dog in the household (OR: 1.39), and having household water supply serving fewer than 20 houses (OR: 1.92). CONCLUSIONS: Consumption of poultry and untreated water remain important sources of Campylobacter infection in Norway, despite ongoing control efforts. The results justify the need for strengthening education for consumers and food handlers about the risks of cross-contamination when preparing poultry and with consuming raw or undercooked chicken. The public should also be reminded to take precautions when drinking untreated water in nature and ensure continued vigilance in order to protect and maintain the quality of water from small-scale water supply systems.