No association between disease severity and respiratory syncytial virus subtypes RSV-A and RSV-B in hospitalized young children in Norway.

OBJECTIVE: There is conflicting evidence whether subtypes of Respiratory syncytial virus have different seasonality or are differentially associated with clinical severity. We aimed to explore the associations between disease severity and RSV subtypes RSV-A and RSV-B and to describe the circulation of RSV subtypes pattern by season and age. METHODS: Active prospective hospital surveillance for RSV-A and RSV-B in children <59 months of age was conducted during 2015-2018. All febrile children 12-59 months of age were enrolled, whereas children <12 months were eligible if presenting with fever or respiratory symptoms. Risk factors and upper and lower respiratory tract infection was identified by linkage to national registry data and analyzed using penalized maximum likelihood logistic regression. RESULTS: Both RSV-A and B were found to co-circulate throughout all three study seasons, and no clear seasonal pattern was identified. Likewise, we found no association between sex or measures of severity with RSV-A or RSV-B. There was significantly more RSV-A than RSV-B among children with comorbidities. CONCLUSIONS: No association was found between disease severity or sex and RSV subtypes RSV-A and RSV-B in hospitalized young children in Norway.

Effectiveness of one and two doses of acellular pertussis vaccines against laboratory-confirmed pertussis requiring hospitalisation in infants: Results of the PERTINENT sentinel surveillance system in six EU/EEA countries, December 2015 - December 2019.

BACKGROUND: Monitoring effectiveness of pertussis vaccines is necessary to adapt vaccination strategies. PERTINENT, Pertussis in Infants European Network, is an active sentinel surveillance system implemented in 35 hospitals across six EU/EEA countries. We aim to measure pertussis vaccines effectiveness (VE) by dose against hospitalisation in infants aged <1 year. METHODS: From December 2015 to December 2019, participating hospitals recruited all infants with pertussis-like symptoms. Cases were vaccine-eligible infants testing positive for Bordetella pertussis by PCR or culture; controls were those testing negative to all Bordetella spp. For each vaccine dose, we defined an infant as vaccinated if she/he received the corresponding dose >14 days before symptoms. Unvaccinated were those who did not receive any dose. We calculated (one-stage model) pooled VE as 100*(1-odds ratio of vaccination) adjusted for country, onset date (in 3-month categories) and age-group (when sample allowed it). RESULTS: Of 1,393 infants eligible for vaccination, we included 259 cases and 746 controls. Median age was 16 weeks for cases and 19 weeks for controls (p < 0.001). Median birth weight and gestational age were 3,235 g and week 39 for cases, 3,113 g and week 39 for controls. Among cases, 119 (46 %) were vaccinated: 74 with one dose, 37 two doses, 8 three doses. Among controls, 469 (63 %) were vaccinated: 233 with one dose, 206 two doses, 30 three doses. Adjusted VE after at least one dose was 59 % (95 %CI: 36-73). Adjusted VE was 48 % (95 %CI: 5-71) for dose one (416 eligible infants) and 76 % (95 %CI: 43-90) for dose two (258 eligible infants). Only 42 infants were eligible for the third dose. CONCLUSIONS: Our results suggest moderate one-dose and two-dose VE in infants. Larger sample size would allow more precise estimates for dose one, two and three.

Risk factors associated with severe disease in respiratory syncytial virus infected children under 5 years of age.

Objective: To evaluate risk factors for severe disease in children under 59 months of age hospitalized with respiratory syncytial virus (RSV) infection. Study design: We prospectively enrolled 1,096 cases of laboratory confirmed RSV infection during three consecutive RSV seasons in 2015-2018. Potential risk factors for severe disease were retrieved through patient questionnaires and linkage to national health registries. Need for respiratory support (invasive ventilation, bi-level positive airway pressure, or continuous positive airway pressure), and length of stay exceeding 72 h were used as measures of disease severity. Associations were investigated using multivariable logistic regression analyses. Multiple imputation was used to avoid bias and inference induced by missing data. Results: Risk factors associated with a need for respiratory support included age younger than 3 months of age [aOR: 6.73 (95% CI 2.71-16.7)], having siblings [aOR: 1.65 (95% CI 1.05-2.59)] and comorbidity [aOR: 2.40 (95% CI 1.35-4.24)]. The length of hospital stay >72 h was significantly associated with being younger than 3 months of age [aOR: 3.52 (95% CI 1.65-7.54)], having siblings [aOR: 1.45 (95% CI 1.01-2.08)], and comorbidity [aOR: 2.18 (95% CI 1.31-3.61)]. Sub-group analysis of children younger than 6 months of age confirmed the association between both young age and having siblings and the need for respiratory support. Conclusion: In a large cohort of children <59 months hospitalized with RSV infection, young age, comorbidity, and having siblings were associated with more severe disease.

The burden of hospital-attended influenza in Norwegian children.

Background: Norwegian health authorities do not recommend universal pediatric vaccination against seasonal influenza. We aimed to estimate the incidence of influenza by age and underlying medical conditions in hospitalized Norwegian children aged <18 years. Methods: Active surveillance for influenza in children <18 years was implemented in five hospitals during 2015-18. Children with respiratory symptoms and/or fever were prospectively enrolled and tested for influenza. Surveillance data were linked to health registry data to estimate the national burden of influenza in hospitals. Results: In 309 (10%) out of 3,010 hospital contacts, the child tested positive for influenza, corresponding to an average incidence of 0.96 hospital-attended influenza cases per 1,000 children <18 years of age. Children <1 year of age (3.8 per 1,000 children) and children with underlying medical conditions (17 per 1,000 children with bronchopulmonary dysplasia) had the highest average incidence. Among <1 year old children, 3% tested positive for influenza, compared to 25% for children aged 6-17. Few children were vaccinated against influenza. Conclusions: Children <1 year of age and children with underlying medical conditions had a higher incidence of influenza requiring hospital treatment compared to the general population. Effective interventions against seasonal influenza for children in Norway should be considered.

Cost and health impact analysis of herpes zoster vaccination in Norway.

BACKGROUND: A decision analytic model was developed to estimate the cost-effectiveness of a national vaccination program against herpes zoster in Norway. METHODS: The model analyzed six vaccination scenarios that included the live-attenuated zoster vaccine under different target ages of vaccination (60, 65, and 70 years) compared with no vaccination. A catch-up program implemented in the first year of the vaccination was included in three of the scenarios. The model followed the population of Norway over a 40-year time horizon to estimate costs and outcomes associated with vaccination. Immunization costs, costs related to herpes zoster (both healthcare sector and non-healthcasre sector), the quality of life gains due to avoided cases of herpes zoster, and quality-of-life losses due to vaccine-related adverse events were estimated. RESULTS AND CONCLUSIONS: A national vaccination program would result in reduction of the number of herpes zoster cases and decreased burden of illness. Vaccinating adults at 65 years of age with catch-up up to 70 years in the first year of the program was the most cost-effective strategy with the incremental cost per quality-adjusted life-year gained at NOK (Norwegian Krone) 245,459 from the societal perspective and NOK 248,637 from the health care system perspective.

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.

The burden of respiratory syncytial virus in children under 5 years of age in Norway.

OBJECTIVES: To estimate age-specific incidence of medically attended respiratory syncytial virus (RSV) infections in hospitalised Norwegian children and describe disease epidemiology. METHODS: Active prospective hospital surveillance for RSV in children <59 months of age was conducted during 2015-2018. All febrile children 12-59 months of age were enrolled, whereas children <12 months were enrolled based on respiratory symptoms regardless of fever. Surveillance data were linked to national registry data to estimate the clinical burden of RSV. RESULTS: Of the children enrolled, 1096 (40%) were infected with RSV. The highest incidence rates were found in children 1 month of age, with a peak incidence of 43 per 1000 during the 2016-2017 season. In comparison, children 24-59 months of age had an infection rate of 1.4 per 1000 during the same winter season. The peak season was during the 2016-2017 winter, with an incidence rate of 6.0 per 1000 children 0-59 months of age. In the study population a total of 168 (15%) of the infected children had pre-existing medical conditions predisposing for more severe disease. High infection rates were found in this population. CONCLUSIONS: Children with comorbidities showed high hospital contact rates, but the majority of children in need of medical attention associated with RSV infection were previously healthy.

Economic burden of varicella in Europe in the absence of universal varicella vaccination.

BACKGROUND: Though the disease burden of varicella in Europe has been reported previously, the economic burden is still unknown. This study estimated the economic burden of varicella in Europe in the absence of Universal Varicella Vaccination (UVV) in 2018 Euros from both payer (direct costs) and societal (direct and indirect costs) perspectives. METHODS: We estimated the country specific and overall annual costs of varicella in absence of UVV in 31 European countries (27 EU countries, plus Iceland, Norway, Switzerland and the United Kingdom). To obtain country specific unit costs and associated healthcare utilization, we conducted a systematic literature review, searching in PubMed, EMBASE, NEED, DARE, REPEC, Open Grey, and public heath websites (1/1/1999-10/15/2019). The number of annual varicella cases, deaths, outpatient visits and hospitalizations were calculated (without UVV) based on age-specific incidence rates (Riera-Montes et al. 2017) and 2018 population data by country. Unit cost per varicella case and disease burden data were combined using stochastic modeling to estimate 2018 costs stratified by country, age and healthcare resource. RESULTS: Overall annual total costs associated with varicella were estimated to be €662,592,061 (Range: €309,552,363 to €1,015,631,760) in Europe in absence of UVV. Direct and indirect costs were estimated at €229,076,206 (Range €144,809,557 to €313,342,856) and €433,515,855 (Range €164,742,806 to €702,288,904), respectively. Total cost per case was €121.45 (direct: €41.99; indirect: €79.46). Almost half of the costs were attributed to cases in children under 5 years, owing mainly to caregiver work loss. The distribution of costs by healthcare resource was similar across countries. France and Germany accounted for 49.28% of total annual costs, most likely due to a combination of high numbers of cases and unit costs in these countries. CONCLUSIONS: The economic burden of varicella across Europe in the absence of UVV is substantial (over 600 M€), primarily driven by caregiver burden including work productivity losses.

Clinical and economic impact of universal varicella vaccination in Norway: A modeling study.

BACKGROUND: Norway has not implemented universal varicella vaccination, despite the considerable clinical and economic burden of varicella disease. METHODS: An existing dynamic transmission model of varicella infection was calibrated to age-specific seroprevalence rates in Norway. Six two-dose vaccination strategies were considered, consisting of combinations of two formulations each of a monovalent varicella vaccine (Varivax® or Varilrix®) and a quadrivalent vaccine against measles-mumps-rubella-varicella (ProQuad® or PriorixTetra®), with the first dose given with a monovalent vaccine at age 15 months, and the second dose with either a monovalent or quadrivalent vaccine at either 18 months, 7 or 11 years. Costs were considered from the perspectives of both the health care system and society. Quality-adjusted life-years saved and incremental cost-effectiveness ratios relative to no vaccination were calculated. A one-way sensitivity analysis was conducted to assess the impact of vaccine efficacy, price, the costs of a lost workday and of inpatient and outpatient care, vaccination coverage, and discount rate. RESULTS: In the absence of varicella vaccination, the annual incidence of natural varicella is estimated to be 1,359 per 100,000 population, and the cumulative numbers of varicella outpatient cases, hospitalizations, and deaths over 50 years are projected to be 1.81 million, 10,161, and 61, respectively. Universal varicella vaccination is projected to reduce the natural varicella incidence rate to 48-59 per 100,000 population, depending on the vaccination strategy, and to reduce varicella outpatient cases, hospitalizations, and deaths by 75-85%, 67-79%, and 75-79%, respectively. All strategies were cost-saving, with the most cost-saving as two doses of Varivax® at 15 months and 7 years (payer perspective) and two doses of Varivax® at 15 months and 18 months (societal perspective). CONCLUSIONS: All modeled two-dose varicella vaccination strategies are projected to lead to substantial reductions in varicella disease and to be cost saving compared to no vaccination in Norway.

Incidence and severity of pertussis hospitalisations in infants aged less than 1 year in 37 hospitals of six EU/EEA countries, results of PERTINENT sentinel pilot surveillance system, December 2015 to December 2018.

IntroductionPERTINENT is a pilot active surveillance system of infants hospitalised with pertussis in six European Union/European Economic Area countries (37 hospitals, seven sites).AimThis observational study aimed to estimate annual pertussis incidence per site from 2016 to 2018 and respective trends between 2017 and 2018. Pertussis cases were described, including their severity.MethodsWe developed a generic protocol and laboratory guidelines to harmonise practices across sites. Cases were hospitalised infants testing positive for Bordetella pertussis by PCR or culture. Sites collected demographic, clinical, laboratory data, vaccination status, and risk/protective factors. We estimated sites' annual incidences by dividing case numbers by the catchment populations.ResultsFrom December 2015 to December 2018, we identified 469 cases (247 males; 53%). The median age, birthweight and gestational age were 2.5 months (range: 0-11.6; interquartile range (IQR): 2.5), 3,280 g (range: 700-4,925; IQR: 720) and 39 weeks (range: 25-42; IQR: 2), respectively. Thirty cases (6%) had atypical presentation either with cough or cyanosis only or with absence of pertussis-like symptoms. Of 330 cases with information, 83 (25%) were admitted to intensive care units including five deceased infants too young to be vaccinated. Incidence rate ratios between 2018 and 2017 were 1.43 in Czech Republic (p = 0.468), 0.25 in Catalonia (p = 0.002), 0.71 in France (p = 0.034), 0.14 in Ireland (p = 0.002), 0.63 in Italy (p = 0.053), 0.21 in Navarra (p = 0.148) and zero in Norway.ConclusionsIncidence appeared to decrease between 2017 and 2018 in all but one site. Enhanced surveillance of hospitalised pertussis in Europe is essential to monitor pertussis epidemiology and disease burden.

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.

Effect of rotavirus vaccine implementation on the prevalence of coinfections with enteric viruses in Norway.

Acute gastroenteritis (AGE) is a common illness in both adults and children worldwide and is caused by several microorganisms including viruses, bacteria, and parasites. Rotavirus (RV), which is the main cause of AGE, can occur as a mixed infection with other viruses. The aim of this study is to assess the molecular epidemiology of viral enteric viruses and assess RV coinfections with other enteric viruses and their influence on disease severity before and after RV vaccine introduction in children under 5 years of age. A total of 600 samples collected from children hospitalized for AGE in five large hospitals in Norway, and were analyzed for viral gastroenteritis agents by enzyme immunoassay and quantitative real-time polymerase chain reaction (qRT-PCR). Positive results confirmed either by Sanger sequencing or genotyped by multiplex semi-nested RT-PCR. In total, 243 of the 300 (81%) samples, collected from the prevaccine cohort, were positive for at least one of the four viruses tested in this study. RV was most frequently identified in 82.6% of the samples. In the postvaccine cohort, 114 of the 300 (38%) samples were positive for at least one of the viruses tested. RV found in 36.5% of the samples. Coinfections found less frequently in the postvaccine cohort. Among circulating enteric viruses in Norway, RV is the most important cause of viral gastrointestinal infection. As expected, there were fewer RV positive and fewer coinfections after RV vaccine implementation. The results provide valuable data that can aid in further evaluation of the vaccine impact.

The burden of herpes zoster disease in Norway.

BACKGROUND: No national vaccination program against herpes zoster (HZ) is currently in place in Norway. We aimed to quantify the burden of medically attended HZ to assess the need for a vaccination program. METHODS: We linked data from several health registries to identify medically attended HZ cases during 2008-2014 and HZ-associated deaths during1996-2012 in the entire population of Norway. We calculated HZ incidences for primary and hospital care by age, sex, type of health encounter, vaccination status, and co-morbidities among hospital patients. We also estimated HZ-associated mortality and case-fatality. RESULTS: The study included 82,064 HZ patients, of whom none were reported as vaccinated against HZ. The crude annual incidence of HZ was 227.1 cases per 100,000 in primary healthcare and 24.8 cases per 100,000 in hospitals. Incidence rates were higher in adults aged ≥50 years (461 per 100,000 in primary care and 57 per 100,000 in hospitals), and women than in men both in primary healthcare (267 vs 188 per 100,000), and hospitals (28 vs 22 per 100,000). Among hospital patients, 47% had complicated zoster and 25% had comorbidities, according to the Charlson comorbidity index. The duration of hospital stay (median 4 days) increased with the severity of comorbidities. The estimated mortality rate was 0.18 per 100,000; and in-hospital case-fatality rate was 1.04%. CONCLUSIONS: Medically attended HZ poses a substantial burden in the Norwegian healthcare sector. The majority of the zoster cases occurred among adults aged ≥50 years - the group eligible for zoster vaccination - and increased use of zoster vaccination may be warranted, especially among persons with co-morbidities.

Immunity to varicella zoster virus among pregnant women in the Norwegian Mother and Child Cohort Study.

INTRODUCTION: Infection with varicella zoster virus (VZV) in pregnancy may lead to serious outcomes both for the mother and the newborn. Targeted screening and vaccination of non-immune women during reproductive age could prevent varicella infection in pregnancy. Currently, no universal varicella screening of pregnant women is implemented in Norway, but serological testing in pregnancy is recommended in particular situations. We examined seroprevalence of VZV in a national pregnancy cohort in order to help assess a need for VZV screening of women during reproductive age. METHODS: We determined the susceptibility to VZV and the reliability of self-reported history of VZV infection in the Norwegian obstetric population by using a random sample of 1,184 pregnant women from the Norwegian Mother and Child Cohort study (MoBa). The MoBa study included approximately 95,200 pregnant women in Norway between 1998 and 2009. Blood samples taken at gestational week 17-18 were analysed using a commercial enzyme immunoassay for specific IgG antibodies to Varicella-Zoster virus. Second sample taken at birth was tested if the first sample result was negative or equivocal. RESULTS: Of the 1,184 pregnant women, 98.6% (n = 1,167) were seropositive, 0.83% (n = 10) remained seronegative, and four women (0.34%) seroconverted during their pregnancy. No significant associations were found between serological status and women's age at birth, gestational age, women's country of birth and year of child's birth. One woman reported prior history of varicella, whereas 143 (12.1%) women reported a household exposure to childhood diseases with fever and rash, of which 25 reported exposure to varicella, of which all were seropositive. CONCLUSIONS: The findings support antenatal screening recommendations in Norway advising testing for VZV in pregnant women with unknown immunity to VZV. Further studies are however needed to better identify target groups for screening and vaccination.

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.

Healthcare costs associated with varicella and herpes zoster in Norway.

BACKGROUND: Norway does not implement routine vaccination against varicella or herpes zoster. Despite substantial health burden associated with both diseases, their economic impact is not well described. The aim of the present study was to document the healthcare costs associated with both conditions in a Norwegian setting. METHODS: We used registry data about patients' contacts with primary and specialized healthcare services from 2008 to 2014 to estimate the costs associated with varicella and herpes zoster in the primary and hospital care sector. We calculated the individual costs by treatment facility (general practitioner and emergency primary care clinic) in primary care and by treatment level (inpatient, outpatient or ambulatory treatment) at hospitals. RESULTS: We estimate that the annual healthcare cost of patients with varicella and herpes zoster are NOK 85 million (approximately € 9 million). Of the annual costs, 73% are associated with herpes zoster and 27% are due to varicella. The majority (54%) of the total annual cost is represented by patients with herpes zoster treated in hospital. CONCLUSION: Varicella and herpes zoster impose a substantial financial burden on the national healthcare services in Norway. Most of the costs are incurred by herpes zoster, which could be prevented by vaccination.

Hypoglycaemia was common in acute gastroenteritis in a prospective hospital-based study, but electrolyte imbalances were not.

AIM: Using routine blood sampling in a gastroenteritis diagnostic workup is debatable. This study examined the relationship between the severity of acute gastroenteritis and blood test abnormalities. METHODS: We prospectively enrolled children under five years of age referred for outpatient or inpatient management for gastroenteritis from February 2014 to April 2016. The four study hospitals cared for 30% of Norwegian children. The severity of gastroenteritis was assessed using Vesikari scores. Blood samples were analysed at each hospital. RESULTS: The 659 children had a median age of 19 months. The rotavirus was found in 314/514 children with stool samples (61%). Severe gastroenteritis, indicated by a Vesikari score of ≥11, was found in 392/549 (71%) with completed scores, but only 40 of 649 (6%) assessed for dehydration were more than 5% dehydrated. None had sodium <130 mmol/L. Glucose of 3.0-3.3 mmol/L was detected in 52/578 (9%) and <3.0 mmol/L in 33/578 (6%). Hypoglycaemia, elevated urea, low bicarbonate and negative base excess were associated with disease severity. The duration of vomiting and the rotavirus infection were associated with hypoglycaemia. Elevated urea, low bicarbonate and negative base excess had high specificities, but low sensitivities. CONCLUSION: Hypoglycaemia was common in acute gastroenteritis, but major electrolyte disturbances were infrequent.

Modeling the impact of combined vaccination programs against varicella and herpes zoster in Norway.

BACKGROUND: Adoption of varicella immunization in Europe is limited due to a predicted increase in the incidence of herpes zoster (HZ) resulting from a removal of exogenous boosting by varicella vaccination. Most available assessments of immunization strategies only considered universal varicella vaccination (alone or in combination with HZ by the live vaccine). The development of a new subunit recombinant zoster vaccine may provide new perspectives of HZ control. METHODS: We used a mathematical model for VZV in Norway based on the progressive immunity formulation of exogenous boosting. We evaluated a complete range of alternative immunization options against varicella and HZ including both universal and targeted varicella vaccination, either alone or with zoster immunization, and zoster immunization alone. We considered all values of the boosting intensity consistent with the Norwegian HZ incidence and compared the performance of the currently available live vaccine vs. a new recombinant vaccine. RESULTS: Universal varicella vaccination alone resulted in a marked increase in the incidence of HZ under all scenarios considered. Even under the most favorable hypotheses on the magnitude of the boosting intensity, this increase could be mitigated only by a parallel HZ immunization with a recombinant vaccine, assuming a long duration of protection. Targeted varicella immunization of adolescents resulted in a modest increase in the HZ incidence which could be counterbalanced by both the live and, especially, the recombinant vaccine. CONCLUSIONS: Given current knowledge on HZ pathogenesis and exogenous boosting, targeted varicella vaccination of adolescents was the only strategy that was not predicted to impact the epidemiology of HZ, and therefore it may represent a suitable alternative to universal vaccination. These results are aimed to support vaccine policy decisions in Norway and other countries with a similar VZV epidemiology.