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.

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.

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.

Multisystem inflammatory syndrome in children and adolescents after infection with SARS-CoV-2. / Multiorgan inflammatorisk syndrom hos barn og ungdom etter SARS-CoV-2-infeksjon.

Multisystem inflammatory syndrome is a rare immune-mediated complication of infection with SARS-CoV-2 in children and adolescents. The patients can rapidly become seriously ill with high fever, gastrointestinal symptoms and cardiogenic shock. The goal of treatment is to ensure adequate circulation and prevent late complications by providing anti-inflammatory therapy.

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.

Multiorgan inflammatory syndrome associated with SARS-CoV-2 in a child. / Multiorgan inflammatorisk syndrom assosiert med sars-CoV-2 hos et barn.

This case report describes a child with heart failure and incipient multiorgan failure following infection with SARS-CoV-2. This is not COVID-19, but a delayed immune response known as multiorgan inflammatory syndrome. We have treated a number of children with this condition, and similar cases have been reported internationally. Patients can quickly become seriously ill, with high fever, gastrointestinal symptoms and cardiogenic shock.

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.

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.

High frequency of enterovirus D68 in children hospitalised with respiratory illness in Norway, autumn 2014.

OBJECTIVES: An unexpectedly high proportion of children were admitted for severe respiratory infections at the Oslo University Hospital, Ullevål, Norway, during September and October, 2014. In light of the ongoing outbreak of enterovirus-D68 (EV-D68) in North America a real-time RT-PCR for screening of enterovirus and enterovirus D68 was established. DESIGN: We developed a duplex real-time RT-PCR for rapid screening of enterovirus D68. The method target the 5' non-translated region (NTR) of the HEV genome at a location generally used for enterovirus detection. SAMPLE: Nasopharyngeal samples (n = 354), from children <15 years of age, received for respiratory virus analysis in OUH during September 1st and October 31nd, 2014, were tested for enterovirus and screened for enterovirus D68. MAIN OUTCOME MEASURES AND RESULTS: The duplex real-time RT-PCR method was an efficient tool for rapid screening for EV-D68 in respiratory specimens. Enterovirus was detected in 66 (22%) of 303 pediatric nasopharyngeal samples collected from children hospitalised with acute respiratory infection within the two-month period. Out of these, 33 (50%) were EV-D68. EV-D68 was associated with acute flaccid paralysis in one child. CONCLUSIONS: An unexpectedly high proportion of children admitted for severe respiratory infections at the Oslo University Hospital, Ullevål, Norway, were diagnosed with EV- D68 during September 1st and October 31nd, 2014. These results emphasise that greater vigilance is required throughout Europe as enteroviruses are cause of severe respiratory disease.

Rotavirus gastroenteritis in Norway: analysis of prospective surveillance and hospital registry data.

We aimed to evaluate rotavirus morbidity and describe rotavirus epidemiology in hospitalized children in Norway to provide information before the introduction of new rotavirus vaccines. We retrospectively reviewed 14,973 gastroenteritis hospitalizations in children aged <5 y for the period 1995 to 2004, and prospectively surveyed for rotavirus in 311 children aged <5 y admitted with diarrhoea to 3 hospitals in 2006-2008. The proportion of rotavirus among all gastroenteritis hospitalizations was estimated at 14.5% from the retrospective data and at 62.9% in the prospective data. The annual incidence of rotavirus hospitalizations is estimated to be 3 per 1000 children <5 y of age, corresponding to approximately 900 (range 735-1092) hospitalizations each year. Children aged 6-23 months accounted for 61% of all confirmed rotavirus cases, and average duration of hospital stay for rotavirus cases was 1.3 days. We observed a predominance of rotavirus infections from March through May, similar to the seasonality of diarrhoea-associated hospitalizations with viral and unspecified aetiology. No rotavirus-associated deaths were reported. It is estimated that two thirds of all gastroenteritis hospitalizations in children <5 y of age may be attributable to rotavirus in Norway. Continued surveillance and further studies are needed to assess the full burden of rotavirus disease and its economic impact in Norway.

Detection and characterization of group A rotaviruses in children hospitalized with acute gastroenteritis in Norway, 2006-2008.

To assess the genetic diversity of rotavirus strains in Norway, the distribution of rotavirus genotypes was studied in children admitted to hospital with acute gastroenteritis. The detection of rotavirus in stool samples was compared using an enzyme-linked immunosorbent assay (ELISA), an immunochromatographic test and RT-PCR. Children <5 years of age admitted to hospital with diarrhea in three large hospitals were enrolled prospectively from March 2006 to February 2008. Rotavirus was detected in 58% of the children by the immunochromatographic test, in 63% by ELISA and 72% by RT-PCR. A total of 219 (70%) rotavirus isolates were characterized in order to determine the genotype. The predominant G types included G1 (53%), G9 (16%), and G3 (13%), and the frequency of G3 varied more than G9 between seasons (8-20%). The P[8] genotype was identified in 188 (86%) of samples, and the globally common genotype combinations G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8] accounted together for >80% of infection. No unusual rotavirus strains were detected, and only four samples contained mixed infections. This study demonstrates that ELISA has similar specificity but lower sensitivity compared to RT-PCR. The immunochromatographic test had the lowest sensitivity and specificity compared to the other assays. Rotaviruses causing severe gastroenteritis leading to hospitalization of children <5 years of age in Norway include the common genotypes, however, a considerable geographical and seasonal variation was observed in the distribution of these genotypes. These data may be important for assessing the need for introducing rotavirus vaccines into immunization programs in Norway.

Does granulocyte colony-stimulating factor ameliorate the proinflammatory response in human meningococcal septic shock?

OBJECTIVE: To test the hypothesis that granulocyte colony-stimulating factor acts cooperatively with interleukin-10 in down-regulating monocyte function in severe meningococcal septic shock. 1) We quantified the plasma levels of granulocyte colony-stimulating factor, interleukin-10, Neisseria meningitidis lipopolysaccharide and the number of N. meningitidis DNA copies in 28 patients with systemic meningococcal disease. 2) We studied the inhibitory effect of recombinant human granulocyte colony-stimulating factor on normal human monocytes stimulated with purified meningococcal lipopolysaccaride. 3) We monitored the inhibitory effects of endogenously produced granulocyte colony-stimulating factor and interleukin-10 in meningococcal shock plasmas on monocytes. DESIGN: Comparative, experimental study. SETTING: University Hospital and laboratory. SUBJECTS: Twenty-eight patients with systemic meningococcal disease, 13 with persistent shock, 7 died, and 15 without shock. MEASUREMENTS AND MAIN RESULTS: The median levels of granulocyte colony-stimulating factor in shock and nonshock patients were 1.7 x 10(6) and 8.1 x 10(2) pg/mL; interleukin-10, 2.1 x 10(4) and 4 x 10(1) pg/mL; number of N. meningitidis DNA copies, 2.9 x 10(7) and <10(3)/mL; and lipopolysaccharide, 105 and <0.04 endotoxin units/mL, respectively. The plasma levels of granulocyte colony-stimulating factor were reduced by 50% within 4 to 6 hrs after initiation of antibiotic treatment. In model experiments with lipopolysaccharide-stimulated human monocytes, recombinant human granulocyte colony-stimulating factor and interleukin-10 reduced the release of tumor necrosis factor-alpha by mean 30% and 92%, respectively. When plasmas from three shock patients were depleted of native granulocyte colony-stimulating factor or interleukin-10 by immunoprecipitation, no increase in tumor necrosis factor-alpha release occurred after removal of granulocyte colony-stimulating factor, whereas removal of interleukin-10 increased the tumor necrosis factor-alpha release eight-fold. CONCLUSIONS: Although granulocyte colony-stimulating factor in plasma increases by five orders of magnitude in patients with meningococcal shock, the anti-inflammatory effect on patients' monocytes is uncertain.

[Hepatitis C in children--diagnosis, follow-up and treatment]. / Hepatitt C hos barn--diagnostikk, oppfølging og behandling.

Hepatitis C-virus infection is relatively infrequent among children in the western world. Although most hepatitis C infections in children evolve to chronicity, liver damage is usually mild. In April 2001, a selected group of Norwegian paediatricians interested in infectious diseases convened to discuss the clinical management of hepatitis C in children. So far, no consensus reports concerning follow-up of hepatitis C infected mothers and their children or clinical management of chronic hepatitis C infection in childhood have been published. In view of the limited experience with hepatitis C among Norwegian children, strategies for the clinical management of hepatitis C infection are discussed based upon available literature and experience from England and Sweden. We present epidemiological data, the risk of vertical transmission and the clinical characteristics of hepatitis C in children. Procedures for follow-up of hepatitis C infected mothers and their children and guidelines for treatment of hepatitis C infected children are proposed. Long term follow-up to identify those who require treatment is important.

[Hepatitis B in children--diagnosis, follow-up and treatment]. / Hepatitt B hos barn--diagnostikk, oppfølging og behandling.

350 million people worldwide are chronic carriers of the hepatitis B virus. Mainly because of immigration, the number of children with chronic hepatitis B infection in Norway is also increasing, although the absolute number is still small. In April 2001, a group of Norwegian paediatricians interested in infectious diseases held a meeting to discuss the clinical management of chronic hepatitis B in children and develop recommendations. The recommendations are based on current European and American guidelines, experience from England and Sweden, and a review of the literature. International epidemiological data and data from Norway are briefly presented, followed by recommendations regarding diagnosis, follow-up and treatment of chronic hepatitis B infection in children. Children at risk of contracting hepatitis B from their mothers should be immunized shortly after birth. Paediatricians should follow up children with chronic hepatitis B infections in order to identify those who may be eligible for treatment.