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In Stockholm, Sweden, rotavirus vaccination was offered to children born after 1 March 2014. Our aim was to describe rates of hospitalisation due to community-acquired gastroenteritis before and after the introduction of the vaccine, and aetiology, underlying medical conditions and complications in admitted children.We retrospectively included patients from our catchment area hospitalised with a diagnosis of gastroenteritis during ten infection seasons 2008/2009-2017/2018, whereof six seasons prevaccination and four seasons postvaccination. We studied virus detection data and the patients' medical records.We included 3718 episodes in 3513 children. In 2967 (80%), stools were tested with virus isolation, ELISA, PCR, or bacterial culture; 479 (16%) tested negative. The incidence rates, with 95% confidence intervals, for children5 years hospitalised for rotavirus gastroenteritis were 2.9 (2.8-3.1) per 1000 person-years prevaccination and 0.65 (0.56-0.74) postvaccination, for a rate ratio (RR) of 0.22 (0.19-0.26,Rotavirus vaccination reduced the number of children5 years requiring hospital care for gastroenteritis. We saw no replacement of rotavirus by other viruses.

Since the beginning of the Covid-19 pandemic, the scientific community has explored determinants of Covid 19 disease severity. However, the majority of studies are based on in-hospital patients with high risk of collider- or selection bias. The present investigation details risk factors associated with overall mortality, hospitalization and intensive care unit (ICU) admission in Covid-19 infections, with complete population coverage and high-resolution data on patient characteristics and comorbid conditions. Methods: This population-based observational study comprises all residents 18 years and older in Stockholm Region – 1.8 million inhabitants - using the real-time Covid-19 monitoring framework. The observation period lasted between March 1 to December 31, 2020. Hazard ratios (HR) for risk factors of Covid-19 disease severity were assessed using Cox proportional hazard models. Results: In total, 3,322 deaths, 11,508 hospitalizations and 1,423 ICU-admissions related to Covid-19 occurred during the study period. Kidney failure, diabetes and obesity increased risk of mortality and so did heart failure and ischemic heart disease. However, atrial fibrillation and hypertension did not. Risk of hospitalization follow a similar pattern, whereas admission to intensive care differs; triage processes where clearly present as certain co-morbid conditions were associated with lower ICU-admission. Conclusions: Observed differences in risk of mortality and hospitalization among patients with Covid 19 raise important questions about potentially protective co-medication which will be further addressed using the real-time Covid-19 monitoring framework.

AIM Since the introduction in 1979 of rapid testing using immunofluorescence, we have collected information about children hospitalised for confirmed respiratory syncytial virus (RSV) infection in the northern Stockholm area. We here report hospitalisation rates, risk factors and complications in 2008-2016 compared with 1986-1998. METHODS Microbiological laboratory reports and retrospective chart review. Comparison of the two periods was complicated by changing testing routines, with a more sensitive method and increased testing of older children in the late period. RESULTS In infants, there was an 12.3% increase in the population-based rate of hospital admission for RSV infection from 12.2 to 13.7/1000. Including all children

In 2014, an outbreak of enterovirus D68 (EV-D68) was observed in North America, with cases of severe respiratory illness and a possible etiological link to cases of acute flaccid paralysis. EV-D68 has also been reported from European countries, but no data from Sweden are available. This study investigated respiratory specimens collected during July-October 2014 from 30 Swedish children aged 0-9 years who were positive for enterovirus and/or rhinovirus in routine clinical PCR. Seven samples were typed as EV-D68 by VP4/VP2 sequencing. Two genetically distinct EV-D68 variants coexisted. Six viruses belonged to clade B, the variant involved in the North American outbreak, and one virus belonged to clade A. Respiratory illness was the major symptom among EV-D68 infected patients and all fully recovered. This is the first report of EV-D68 in Sweden. Considering the current epidemiological situation, genotyping and specific EV-D68 testing should be considered in patients with severe respiratory illness who test positive for enterovirus or rhinovirus in routine diagnostics.

BACKGROUND: Acute respiratory illness (ARI) accounts for a large proportion of all visits to pediatric health facilities. Quantitative real-time polymerase chain reaction (qPCR) analyses allow sensitive detection of viral nucleic acids, but it is not clear to what extent specific viruses contribute to disease because many viruses have been detected in asymptomatic children. Better understanding of how to interpret viral findings is important to reduce unnecessary use of antibiotics. OBJECTIVE: To compare viral qPCR findings from children with ARI versus asymptomatic control subjects. METHODS: Nasopharyngeal aspirates were collected from children aged ≤5 years with ARI and from individually matched, asymptomatic, population-based control subjects during a noninfluenza season. Samples were analyzed by using qPCR for 16 viruses. RESULTS: Respiratory viruses were detected in 72.3% of the case patients (n = 151) and 35.4% of the control subjects (n = 74) (P = .001). Rhinovirus was the most common finding in both case patients and control subjects (47.9% and 21.5%, respectively), with a population-attributable proportion of 0.39 (95% confidence interval: 0.01 to 0.62). Metapneumovirus, parainfluenza viruses, and respiratory syncytial virus were highly overrepresented in case patients. Bocavirus was associated with ARI even after adjustment for coinfections with other viruses and was associated with severe disease. Enterovirus and coronavirus were equally common in case patients and control subjects. CONCLUSIONS: qPCR detection of respiratory syncytial virus, metapneumovirus, or parainfluenza viruses in children with ARI is likely to be causative of disease; detection of several other respiratory viruses must be interpreted with caution due to high detection rates in asymptomatic children.

Aim To study the clinical impact of multiple viral respiratory infections compared to single infections. Methods Demographic data from 37 multiple infection periods in children

We report an enterovirus D68 (EV-D68) outbreak in Stockholm Sweden in 2016. Between 22 August and 25 September EV-D68 was detected in 74/495 respiratory samples analysed at the Karolinska University Hospital. During the peak week, 30/91 (33%) samples were EV-D68 positive. Viral protein (VP)P4/VP2 sequencing revealed that cases were caused by B3 lineage strains. Forty-four (59%) EV-D68-positive patients were children aged ≤ 5 years. Ten patients had severe respiratory or neurological symptoms and one died.

Objective. To evaluate how common pharyngeal Chlamydia trachomatis (CT) is among mainly heterosexual women and men with a confirmed or a highly suspicious genital infection having had recent unprotected active oral sex. Design. Prospective observational study. Setting. Out-patient clinics for sexually transmitted infections in Stockholm. Population. A total of 143 women and 138 men with a confirmed or suspected genital CT infection and a history of active oral sex. Methods. Pharyngeal samples from men and women in the study population were analyzed for the presence of CT. Main outcome measures. Number of positive CT in pharyngeal samples in relation to positive CT in genital samples. Results. Of the women, 9/128 (7.0%) were positive in the pharyngeal samples. None were exclusively positive in the pharynx. Three of 110 men (2.7%) had pharyngeal involvement. One man was positive in the pharynx as well as in the urine sample, and two men were exclusively pharyngeal CT positive. Conclusions. The finding of CT in the pharynx is not common in spite of the presence of a genital infection and a history of active oral sex.

Acute respiratory tract infections are caused by a large number of viruses. Diagnostic methods have until recently been available only for a limited number of these viruses. With the objective to achieve sensitive assays for all respiratory viruses, a rational workflow in the laboratory, and a short turn-around time, a real-time PCR diagnostic platform for daily rapid detection of 15 respiratory viruses was developed. The system was evaluated on 585 stored nasopharyngeal aspirates from hospitalized children. Previous analysis by immunofluorescence and virus isolation identified viruses in 37% of the samples while the new PCR diagnostic panel detected 57% virus positive samples. The new platform was introduced in the laboratory in October 2007 and has then fully replaced the standard immunofluorescence assay for rapid detection of viruses and virus isolation.

Background Influenza remains a common reason for the hospitalization of children. There is a need for long term studies that are also population based. We describe the epidemiology of severe influenza in a defined population 1998–2014. Method Retrospective study of annually collected data of virologically confirmed influenza in hospitalized children 0–17 years living in the catchment area (230,000 children). We gathered information about comorbidity and complications from case records, and compared Influenza A, B and A(H1N1)pdm09 with respect to these factors. Results A total of 922 children with influenza were hospitalized. The mean rate remained unchanged at 22.5–24.2 per 100,000 children per year. There were two major outbreaks: influenza A(H3N2) in 2003–2004 and the A(H1N1) pandemic in 2009–2010. The proportion of children with influenza B increased from 8% during the first half of the study period to 28% during the second half. The highest admission rate was found in children

A retrospective analysis of the virological findings in all respiratory samples (7303) analysed at the laboratory of Karolinska Hospital between 1993 and 2000 was performed. The findings were studied according to age and seasonal variation, and the methods were evaluated. Most samples were from children. RSV was the dominant agent, found in 34% of all samples from children 0-1 y of age. Influenza A was found in 13% of samples from the age group 2-5 y. Influenza A dominated among adults and the elderly. RSV was found only in 2% of samples from patients 81 y or older. Adenovirus was found among children and adults, but not at all among the elderly. Both antigen detection and virus isolation were performed on 79% (5776) of the samples. For diagnosis of influenza A, virus isolation was more sensitive than immunofluorescence, but for diagnosis of RSV immunofluorescence was more sensitive than virus isolation. Thus, the analysis verified that influenza A is common not only among adults and the elderly, but also among small children. RSV was an uncommon finding among the elderly. Immunofluorescence is sensitive and rapid for the diagnosis of particularly RSV among small children and influenza in all age groups.

Purpose The study goal was to investigate the occurrence of serum antibodies to Chlamydia trachomatis , Chlamydia pneumoniae , and Chlamydia psittaci in patients with temporomandibular joint (TMJ) monoarthritis or chronic closed lock and in control subjects. Patients and methods An indirect microimmunofluorescence test for detecting antibodies against C trachomatis was used. Twenty-three patients (12 with monoarthritis and 11 with chronic closed lock) and 42 control subjects were evaluated. Results Six patients with monoarthritis, 5 patients with chronic closed lock of the TMJ, and 6 control individuals were considered to have had a past C trachomatis infection based on their immunoglobulin G titers. Corresponding groups for C pneumoniae investigation included 3 patients with monoarthritis, 4 patients with chronic closed lock, and 17 control subjects, and for C psittaci , 1 patient with monoarthritis, 2 patients with chronic closed lock, and 1 control subject. Statistically significant differences between patients and control subjects were found for C trachomatis only; monoarthritis versus control ( P = .016), chronic closed lock versus control ( P = .038), and all patients versus control ( P = .007). Patients with monoarthritis did not differ from patients with chronic closed lock with regard to antibodies against C trachomatis . Conclusion The occurrence of serum antibodies to C trachomatis was significantly higher in patients than in control subjects, but this occurrence did not correlate with severity of observed tissue changes. Nevertheless, an association may exist between the presence of C trachomatis and TMJ disease.

Background Community-acquired pneumonia (CAP) is the leading cause of death in children worldwide and a substantial proportion of childhood CAP is caused by viruses. A better understanding of the role of virus infections in this condition is needed to improve clinical management and preventive measures. The aim of the study was therefore to assess the association between specific respiratory viruses and childhood CAP. Methods A case–control study was conducted during 3 years in Stockholm, Sweden. Cases were children aged ≤5 years with radiological CAP. Healthy controls were consecutively enrolled at child health units during routine visits and matched to cases on age and calendar time. Nasopharyngeal aspirates were obtained and analysed by real-time PCR for 15 viruses. Multivariate conditional logistic regression was used to account for coinfections with other viruses and baseline characteristics. Results A total of 121 cases, of which 93 cases met the WHO criteria for radiological pneumonia, and 240 controls were included in the study. Viruses were detected in 81% of the cases (n=98) and 56% of the controls (n=134). Influenza virus, metapneumovirus and respiratory syncytial virus were detected in 60% of cases and were significantly associated with CAP with ORs >10. There was no association with parainfluenza virus, human enterovirus or rhinovirus and coronavirus and bocavirus were negatively associated with CAP. Conclusions Our study indicates viral CAP is an underestimated disease and points out hMPV as a new important target for the prevention of childhood CAP.

Molecular assays for diagnosis of influenza A, influenza B, and respiratory syncytial virus (RSV) with short turnaround time are of considerable clinical importance. We have evaluated the diagnostic performance of the Simplexa(™) Flu A/BRSV Direct Kit, which has a run time of 60 min, using different types of respiratory samples collected from patients with a suspected respiratory tract infection, including materials not previously evaluated on this kit.In total, 210 clinical respiratory samples were analyzed using both the Simplexa direct assay and a laboratory-developed assay (LDA). The 210 clinical samples included 99 nasopharyngeal aspirates collected in 0.9% saline, 91 nasopharyngeal swabs in Σ-Virocult transport medium, 9 tracheal secretions, 8 bronchoalveolar lavages (BAL), and 3 other respiratory sample materials.The specificity of the Simplexa assay, using the LDA as gold standard and excluding secondary viral findings, was 100% for all three viruses, whereas the sensitivity was 94.0% for influenza A (47/50), 90.7% for influenza B (49/54), and 90.1% for RSV (46/51), respectively. Discordant results were only observed for samples with cycle threshold values (Ct)31 in the LDA. The Simplexa assay generated higher Ct values than the LDA for all three viruses and performed equally well on nasopharyngeal swabs and aspirates.The short run time of the Simplexa direct assay, in combination with high specificity and good sensitivity regarding the sample materials used in this study, make it an interesting option for rapid detection of these three important viral respiratory pathogens in a variety of clinical sample materials.

Background Several studies have compared nasal swabs to the more invasive nasopharyngeal aspirate (NPA) for detection of respiratory viruses. Mostly, the comparisons have been performed on immunocompetent children with upper respiratory tract symptoms. The results range from a relatively poor sensitivity for the swabs to an even higher sensitivity than for the NPA. We aimed to investigate the sensitivity of a flocked nasal swab (fNS) on immunocompromised adults with febrile neutropenia. Methods During 16 months, adults with a hematological disorder presenting with febrile neutropenia were enrolled in the study. Paired samples of the fNS and NPA were collected in the outer part of the nasal cavity and the nasopharynx, respectively. The samples were analyzed regarding a panel of 15 respiratory viruses by means of quantitative polymerase chain reaction. Furthermore, as an indirect measure of cell yield by either method, the copy number of the human beta actin gene was also determined. Cohen's kappa was calculated as a measure of agreement of the results obtained from either method. Wilcoxon signed-rank test was used for comparison of cell yield. Results A total of 98 paired samples from a total of 89 patients were collected. Twenty of the pairs had virus detected in at least one of the specimens; 11 in both, 7 in NPA only, and 2 in fNS only. For the fNS, the overall sensitivity for any virus and for rhinovirus only was 65% and 78%, respectively. NPA was significantly superior to the fNS in collecting epithelial cells. Conclusion We found the overall sensitivity of 65% to be too low to replace NPA with this sampling technique in this patient category.

This short communication hypothesises that rhinovirus epidemics occurring after start of school may interfere with the spread of influenza during the period when warm and humid climate decreases the influenza spread by aerosol. Limited laboratory data supporting this hypothesis are included in the article, but the report is written mainly to stimulate interest and research concerning the possibility that viral interaction may affect influenza epidemiology.

The epidemiology and genetic variability of circulating respiratory syncytial virus (RSV) strains in Stockholm during the season 2002–2003 were studied in consecutive RSV isolates derived from respiratory samples and diagnosed in the laboratory. Two hundred thirty-four viruses were sequenced. The samples were mainly from children under 1 year old (79%). The phylogeny of the N-terminal part of the G gene was studied after amplification and sequencing. One hundred fifty-two viruses belonged to subgroup B and 82 to subgroup A. The subgroup A viruses could be further divided into genotypes GA2 (25) and GA5 (57) and the subgroup B viruses into GB3 (137) and SAB1 (15) strains. These strains clustered with subgroup A and subgroup B strains from Kenya from the same period, as well as with strains from Great Britain from 1995 to 1998. The dominance of subgroup B strains in Stockholm during 2002–2003 is in agreement with findings from other parts of the world during the same years. Only two genotypes of subgroup A, GA2 and GA5, were circulating during this time, and GA2 has been circulating in Sweden for more than 20 years. Consecutive strains from the same individual displayed no variability in the sequenced region, which was also true of strains that had been passaged in cell cultures. J. Med. Virol. 80:159–167, 2008. © 2007 Wiley-Liss, Inc.

In 2006, a genetic variant of Chlamydia trachomatis not detectable with the most commonly used diagnostic tests was identified. Initial reports suggested that as many as 10% to 13% of all chlamydia cases would have remained undiagnosed. The aim of the study was to find the occurrence and clinical findings of this genetic variant among a high-risk population in Stockholm, Sweden.Samples were analyzed using the Cobas TaqMan CT test (Roche Diagnostics). To detect the new variant, an additional PCR-analysis, artus C. trachomatis LC MOMP PCR Kit (Qiagen) was performed on all negative samples. Positive results in the artus test were confirmed by a mutant specific PCR. Clinical data were retrospectively collected from medical records.Among 1009 samples analyzed, 115 were positive for C. trachomatis and among those, 27 were found to belong to the genetic altered strain. This variant constituted 23% of all chlamydia cases diagnosed, and 29% were found in the age group 20 to 29 years. Women with the new variant were younger and had more often performed another chlamydia test within the previous 6 months compared with those infected with the wild type.These results indicate that a large number of sexually active individuals might be infected despite a negative chlamydia test, thus facilitating a rapid transmission of the new variant. Accordingly, it is of great importance to be aware of limitations of the diagnostic methods used.

Japanese encephalitis (JE) is a rare diagnosis outside endemic areas. A case report of the disease in an 80-y-old man after a short time visit to Java and Bali is presented.

Viral diagnosis of respiratory tract infections has so far required sampling by health professionals, hampering large-scale epidemiological studies of virus-specific disease outcomes. As part of a population-based, prospective study of work-related risk factors for transmission of viral infections (SWEDE-I), we developed a scheme for self-sampling with nasal swabs. Random selection from the gainfully employed population of a medium-sized town in central Sweden resulted in a study cohort of 2,237 men and women aged 25 to 63 years. From September 2011 through May 2012, the cohort reported all instances of respiratory tract infection or gastroenteritis and participants concomitantly sent self-sampled nasal swabs for analysis using regular mail. Diagnosis of 14 viruses was performed. A total of 1,843 samples were received. The week-wise average delay between disease onset and arrival of the specimens at the laboratory varied between four and six days, and the corresponding median delay was between 3.5 and six days. In line with previous community-based studies, picorna- and coronaviruses dominated in specimens obtained from the self-sampling scheme. The results of self-sampling were contrasted to those from contemporaneous routine clinical sampling, on the same age group, in the adjacent Stockholm county. Although higher proportions of positive samples for respiratory syncytial virus and influenza were observed in the clinical sampling scheme, estimations of seasonality for influenza A and picornaviruses derived from both schemes were similar. Our findings show that nasal self-sampling is feasible in large-scale surveillance of respiratory infections and opens new prospects for population-based, virologically verified research on virus spread, burden of disease, and effects of environmental factors or interventions.

Background Infection with genital Chlamydia trachomatis (Ct) is the most common notifiable sexually transmitted infection (STI) in Sweden. A mutated Chlamydia, nvCT, has contributed to the increase. The occurrence of repeat infections is not investigated in Sweden. The current paper presents the study protocol for the first Swedish clinical investigation of repeat Chlamydial infection. The concern of the study is whether a Chlamydia infection at inclusion indicates an increased risk for Chlamydia at follow-up after 6–8 months, gender-specific risk factors for and clinical presentation of repeat infections. Methods and design Sesam City is a drop-in clinic in the city centre of Stockholm. Patients 20 years and older are admitted. During 2007, the clinic had 15 000 visits, 60% made by men. In December 2007, a cohort study began, and data collection was finished in April 2009. A total of 2813 study participants aged 20–39 years were recruited. Data collection included an anonymous self-administered paper-and-pen questionnaire on sexual behaviour, reproductive health and history of Chlamydia, and condom use. Chlamydia tests were performed by self-sampled specimens, analyzed by the ProbeTec (Becton Dickinson) method, Ct-positive specimens also analyzed with a nvCT-specific method. Data from medical records were summarized in clinical report forms. Patients positive for Chlamydia were retested 4 weeks after treatment. Contact tracing covered sexual contacts during the last 12 months. At follow-up 6–8 months after inclusion, Chlamydia tests were performed, and a new questionnaire and CRF completed. Discussion A STI-clinic-based prospective cohort study allowed us to survey 2813 adult patients. The collected data will provide gender-specific information on the occurrence of and risk for repeat Chlamydia infection, the occurrence of nvCT, and clinical data and information on sexual behaviour and reproductive health, risk-taking and condom use.