Rutger Bennet

Complications attributable to rotavirus-induced diarrhoea in a Swedish paediatric population: Report from an 11-year surveillance

The aim of this retrospective observational study was to evaluate age, length of hospital stay and development of complications in children hospitalized with community- or nosocomially- acquired rotavirus gastroenteritis (RV GE). In total, medical records of 984 children with RV GE were analysed retrospectively. The median age was 13.8 months (3 weeks to 99 months) in children with community acquired RV GE (n=723) and 9.0 months (range 3 weeks to 82 months) in children with nosocomially acquired RV GE (n=261). During this 11-y surveillance, only 2 children were admitted twice for a RV GE, suggesting development of subsequent protective immunity against severe rotavirus gastroenteritis after the first episode. Complications occurred in 16.5% of the children with community acquired RV GE and only in 1.9% of the nosocomially acquired RV GE. Identified complications in children with community acquired RV GE were: severe dehydration resulting in intensive care (1.7%), death (0.1%), hypertonic dehydration (9.1%), seizures (4.0%) and encephalitis with abnormal EEG (1.7%). The median age of children in need of intensive care was 9.1 months and in those developing hypertonic dehydration 10.8 months, both significantly lower than in children with no complications (p<0.05). Interestingly, the age of children developing seizures and signs of encephalitis was significantly higher than in children with no complications (p<0.01).

Burden of severe rotavirus disease leading to hospitalization assessed in a prospective cohort study in Sweden

Abstract Background: The aim of this prospective cohort study was to estimate the burden of severe disease caused by rotavirus-induced gastroenteritis in Swedish children aged < 5 y. Methods: Rotavirus-positive children admitted to hospitals serving 3 geographical regions with 155,838 children aged < 5 y, were offered inclusion in this 1-year study. Rotavirus strains identified were genotyped using multiplex PCR. Disease progression was documented through interviews and chart reviews. Results: In total, 604 children with rotavirus-induced gastroenteritis were included in the study. Forty-nine of 604 (8.1%) fulfilled the criteria for nosocomial infection. The minimum incidence was 388 per 100,000, with significant variability between study regions, ranging from 280 to 542 per 100,000. In all regions, the peak season occurred in February–April, but the season start varied, with first cases observed in October in the eastern region and December in the northern region. Genotypes identified differed between the regions: G1[P8] was most prevalent in all regions (77%), while the most varied pattern was observed in the western region, with G1[P8] observed in 61%, G4[P8] in 13%, G9[P8] in 10%, G2[P4] in 8%, and G3[P8] in 8% of the children. The median age of hospitalized children was 14 months and the median total duration of diarrhoea was 6.9 days. Sixty-eight percent reported a temperature > 38.5°C upon admission. Complications occurred in > 10% of the children, with hypertonic dehydration (32/604) and seizures (10/604) occurring most frequently. Conclusions: Rotaviruses may cause severe febrile acute gastroenteritis leading to dehydration requiring acute rehydration in hospital. In addition, further complications occurred in > 10% of hospitalized children.

Effectiveness of the monovalent AS03-adjuvanted influenza A(H1N1)pdm09 vaccine against hospitalization in children because of influenza

We studied the effectiveness of the AS03-adjuvanted monovalent vaccine (Pandemrix(®)) for the prevention of severe pandemic influenza A(H1N1)pdm09 in children, in 2009. All children hospitalized for influenza-like illness in Stockholm County during the peak of the pandemic were included. We compared the frequency of vaccinated children between influenza A(H1N1)pdm09 PCR positive cases and PCR negative controls in a retrospective case-control study. 95 cases and 177 controls were identified. About half of the children in both groups were between 6 months and 2 years of age. Only 1/95 (1%) cases had been vaccinated more than 14 days prior to admission, compared to 23/177 controls (13%), corresponding to a vaccine effectiveness, adjusted for co-morbid conditions, of 91% (95% confidence interval [CI] 30-99). In contrast, the risk for being a case was significantly higher among children vaccinated between 1 and 14 days prior to hospitalization, than among those who were non-vaccinated 13/95 vs. 7/177 (OR 3.6, 95% CI 1.4-9.5). We conclude that a single dose of adjuvanted vaccine was highly protective against hospitalization for influenza A(H1N1)pdm09 in children 6 month to 17 years. The reason for the increased rate of hospitalizations with confirmed influenza in children just following immunization is unclear and should be studied further.

Long term effectiveness of adjuvanted influenza A(H1N1)pdm09 vaccine in children

BACKGROUNDnImmunological studies have indicated that the effectiveness of AS03 adjuvanted monovalent influenza A(H1N1)pdm09 vaccine (Pandemrix) may be of longer duration than what is seen for non-adjuvanted seasonal influenza vaccines. Sixty-nine percent of children 6 months-18 years of age in Stockholm County received at least one dose of Pandemrix during the 2009 pandemic. We studied the effectiveness of the vaccine during the influenza seasons 2010-2011 and 2012-2013 in children hospitalized with virologically confirmed influenza. The season 2011-2012 was not included, since influenza A(H3N2) was the predominant circulating strain.nnnMETHODSnIn a retrospective case-control study using a modified test-negative design we compared the percentage vaccinated with Pandemrix among children diagnosed with influenza A(H1N1)pdm09 (cases), with that of those diagnosed with influenza A(H3N2) or influenza B (controls) during the two seasons. We excluded children born after July 1, 2009, since only children who were 6 months of age or older received the pandemic vaccine in October-December 2009.nnnRESULTSnDuring the 2010-2011 season, 3/16 (19%) of children diagnosed with influenza A(H1N1)pdm09, vs. 32/41 (78%) of those with influenza A(H3N2) or influenza B had been vaccinated with Pandemrix in 2009. The odds ratio, after adjustment for sex, age and underlying diseases, for becoming a case when vaccinated with Pandemrix was 0.083 (95%CI 0.014, 0.36), corresponding to a VE of 91.7%. During the season 2012-2013, there was no difference between the two groups; 59% of children diagnosed with influenza A(H3N2)/B and 60% of those with influenza A(H1N1)pdm09 had been vaccinated with Pandemrix in 2009.nnnCONCLUSIONnThe AS03 adjuvanted monovalent influenza A(H1N1) pdm09 vaccine (Pandemrix) was effective in preventing hospital admission for influenza A(H1N1)pdm09 in children during at least two seasons.

Tuberculosis infection and disease in the 2015 cohort of unaccompanied minors seeking asylum in Northern Stockholm, Sweden

Abstract Background: Minors with a stated age <18 years unaccompanied by a responsible adult form an increasing part of refugees to Europe. They are older than other asylum-seeking children and many come from countries with a high tuberculosis (TB) incidence. During the 2015 refugee crisis, 35,369 of 162,877 refugees (22%) seeking asylum in Sweden were unaccompanied minors, which gave us the opportunity to study their burden of TB infection and disease. Methods: Of the unaccompanied minors seeking asylum in Sweden during 2015, 2936 (8.3%) were allocated to northern Stockholm. Of these, 2422 were from countries with an incidence of TB exceeding 100/105, and were screened for TB infection with a Mantoux tuberculin skin test or a QuantiFERON-TB Gold®. Those from countries with a lower TB incidence were screened only if they had other risk factors for TB exposure. Results: Of those screened, 349 had a positive test and were referred to the northern paediatric TB clinic at Astrid Lindgren Children’s Hospital. Of these, 16 had TB disease and 278 latent tuberculosis infection (LTBI), while we considered 53 uninfected. In addition, eight sought medical attention with symptomatic TB outside the screening system. Cohort rates were 6.8% of LTBI and 0.5% of TB in minors from Afghanistan and 26–32% of LTBI and 3.4–3.5% of TB among those from Eritrea, Ethiopia or Somalia. Conclusion: We conclude that TB infection and disease is common among asylum-seeking unaccompanied minors, especially among those from the Horn of Africa.

Complexity in estimating recent tuberculosis transmission among predominantly immigrant school children in Stockholm, Sweden 2006.

In January 2006, an after-school carer in Stockholm was diagnosed with open pulmonary tuberculosis (TB) after having been symptomatic for 3 months. The aim of this paper is to illustrate the difficulties encountered in estimating recent transmission of TB among children in an immigrant school population. A tuberculin skin test was performed on 261 pupils aged 6–15 y and an additional interferon-gamma release assay was performed on 20 children. In total, 76% of the children were born in Sweden; however, 95% of the parents originated from countries with TB incidence >25/100,000. Three active TB cases were identified, 1 of whom was culture-positive with the same strain as the index case. Latent tuberculous infection (LTBI) was diagnosed in 35 children. However, the increased risk of earlier infection in this population makes it difficult to evaluate when transmission occurred. The magnitude of recent transmission from the index case will thus be uncertain and indications to treat less clear.

Paediatric tuberculosis cases increased in Stockholm from 1971 to 2015 following the rising number of children with immigrant backgrounds

This study described the epidemiology and clinical features of childhood tuberculosis (TB) in Stockholm over a 45‐year period, when there was a resurge of tuberculosis concomitant with increased immigration.

Interferon‐gamma release assays can effectively screen migrants for the tuberculosis infection, but urgent, active cases need clinical recognition

Increasing numbers of migrants to Sweden are screened for tuberculosis (TB), and a rational approach to screening is required. We evaluated positive tuberculin skin tests (TSTs) and interferon‐gamma release assays (IGRAs) on paediatric migrants in relation to the TB incidence in the corresponding foreign‐born populations in Stockholm.

Changing diagnosis coding routines may confound the results of longitudinal childhood pneumonia studies

This Swedish study compared the discharge diagnosis codes used for children up to the age of five hospitalised for acute lower respiratory tract infections before and after the introduction of the pneumococcal conjugate vaccine in 2007.

Impact on affected families and society of severe rotavirus infections in Swedish children assessed in a prospective cohort study

Abstract Background: Few prospective cohort studies have estimated the overall impact of severe rotavirus gastroenteritis (RVGE) leading to hospitalization on families and society. We assessed human and economic resources needed to care for an affected average child aged <5 years in Sweden. Methods: The study was conducted in Astrid Lindgren Children’s Hospital which serves approximately 14% of all Swedish children <5 years of age. All children admitted with acute gastroenteritis in the study period were tested for rotavirus. Health care consumption was collected prospectively and publically available unit costs used to calculate direct costs. Non-medical and indirect costs were collected in interviews with families using a standardized questionnaire during the hospital stay and approximately 14 days post-discharge. Results: 144/206 children (70%) with laboratory-confirmed RVGE were included. The median age was 14 months. The average total cost per hospitalized child was €3894, of which €2169 (56%) was due to direct healthcare-related costs (including Emergency Department visits and in-patient care), €104 (2%) to non-medical direct costs and €1621 (42%) to indirect costs due to productivity loss. Carers of children with severe RVGE were absent from work on average five days per study child: four days during hospitalization of affected child and one day due to gastroenteritis in the carer. Conclusions: Costs for RVGE are dominated by direct costs which are similar to some other countries in Europe, but indirect costs due to productivity loss are also important, and should be considered in decisions to introduce rotavirus vaccines into national vaccination programmes.