| 51. |
- Ydreborg, Magdalena, 1974, et al.
(author)
-
A Novel Fibrosis Index Comprising a Non-Cholesterol Sterol Accurately Predicts HCV-Related Liver Cirrhosis
- 2014
-
In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4
-
Journal article (peer-reviewed)abstract
- Diagnosis of liver cirrhosis is essential in the management of chronic hepatitis C virus (HCV) infection. Liver biopsy is invasive and thus entails a risk of complications as well as a potential risk of sampling error. Therefore, non-invasive diagnostic tools are preferential. The aim of the present study was to create a model for accurate prediction of liver cirrhosis based on patient characteristics and biomarkers of liver fibrosis, including a panel of non-cholesterol sterols reflecting cholesterol synthesis and absorption and secretion. We evaluated variables with potential predictive significance for liver fibrosis in 278 patients originally included in a multicenter phase III treatment trial for chronic HCV infection. A stepwise multivariate logistic model selection was performed with liver cirrhosis, defined as Ishak fibrosis stage 5-6, as the outcome variable. A new index, referred to as Nordic Liver Index (NoLI) in the paper, was based on the model:Log-odds (predicting cirrhosis) =-12.17+ (agex0.11) + (BMI (kg/m(2))x0.23) + (D-7-lathosterol (mu g/100 mg cholesterol)x(-0.013)) + (Platelet count (x10(9)/L)x(-0.018)) + (Prothrombin-INRx3.69). The area under the ROC curve (AUROC) for prediction of cirrhosis was 0.91 (95% CI 0.86-0.96). The index was validated in a separate cohort of 83 patients and the AUROC for this cohort was similar (0.90; 95% CI: 0.82-0.98). In conclusion, the new index may complement other methods in diagnosing cirrhosis in patients with chronic HCV infection.
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| 52. |
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| 53. |
- Ydreborg, Magdalena, 1974, et al.
(author)
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Impact of IL28B-Related Single Nucleotide Polymorphisms on Liver Transient Elastography in Chronic Hepatitis C Infection
- 2013
-
In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
-
Journal article (peer-reviewed)abstract
- Background and Aims: Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of hepatitis C virus (HCV) infection as well as outcome following pegylated interferon and ribavirin therapy among genotype 1 infected patients. Additionally the presence of the otherwise favorable IL28B genetic variants in the context of HCV genotype 3 infection reportedly entail more pronounced liver fibrosis and steatosis. The present study aimed to evaluate the impact of IL28B SNP variability on liver stiffness as accessed by transient elastography. Methods: Seven hundred and seventy-one Swedish HCV infected patients sequentially undergoing liver stiffness measurement by means of Fibroscan (R) in the context of a real-life trial had samples available for IL28B genotyping (rs12979860) and HCV genotyping. Results: CCrs12979860 was more common among HCV genotype 2 or 3 infected treatment-naive patients than among those infected with genotype 1 (P<0.0001). Additionally CCrs12979860 among HCV genotype 3 infected patients was associated with higher liver stiffness values (P = 0.004), and higher AST to platelet ratio index (APRI; p = 0.02) as compared to carriers of the T allele. Among HCV genotype 1 infected patients, CCrs12979860 was significantly associated with higher viral load (P = 0.001), with a similar non-significant trend noted among HCV genotype 3 infected patients. Conclusion: This study confirms previous reports that the CCrs12979860 SNP is associated with more pronounced liver pathology in patients chronically infected with HCV genotype 3 as compared to genotype 1, suggesting that IL28B genetic variants differently regulates the course of HCV infection across HCV genotypes.
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| 54. |
- Andreasson, Thomas, et al.
(author)
-
Evaluation of anamnestic criteria for the identification of patients with acute community onset viral gastroenteritis in the emergency department-A prospective observational study.
- 2014
-
In: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 46:8, s. 561-565
-
Journal article (peer-reviewed)abstract
- Background: To our knowledge no clinical criteria for the identification of community onset viral gastroenteritis in individual patients have been evaluated systematically with modern PCR-based diagnostic assays as gold standard. Objective: The aim of this study was to identify factors independently associated with the detection of virus by PCR in rectal swab samples from patients with acute community onset gastroenteritis. Methods: A prospective observational study was conducted from December 2010 through March 2011 at the emergency department (ED) of a large teaching hospital. All patients who reported vomiting and/or diarrhoea up to 48 h prior to their visit to the ED were asked to participate. A rectal swab sample was obtained from each patient. Symptoms, date of onset, and epidemiological data were recorded. Samples were analysed with a multiple real-time PCR targeting 6 viral agents (astrovirus, adenovirus, rotavirus, sapovirus, and norovirus GI and GII). Results: Two hundred and five patients fulfilled the inclusion criteria, of whom 66 agreed to participate; their median (IQR) age was 65 (38-84) y and 43 (65%) were females. Thirty-one (47%) were positive by PCR for at least 1 of the agents examined (26 norovirus, 2 sapovirus, 2 rotavirus, and 1 adenovirus). Diarrhoea and a short duration of symptoms (≤ 2 days) were independently associated with a positive rectal swab sample, with odds ratios of 7.5 (95% confidence interval (CI) 2.0-28) and 10.4 (95% CI 1.9-56), respectively (p < 0.01 for both). A multivariate model including these 2 variables had a sensitivity of 81% (25/31) and a specificity of 69% (24/35). Conclusions: Diarrhoea and a short duration of symptoms were the only anamnestic criteria independently associated with acute community onset viral gastroenteritis confirmed by PCR.
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| 55. |
- Andreen, Niklas, et al.
(author)
-
Mortality of COVID-19 is associated with comorbidity in patients with chronic obstructive pulmonary disease
- 2022
-
In: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 54:7, s. 508-513
-
Journal article (peer-reviewed)abstract
- Background The aim of this study was to compare the outcome of coronavirus disease 2019 (COVID-19) in hospitalised patients with chronic obstructive pulmonary disease (COPD) with the outcome in matched COVID-19 patients without COPD. Methods Sixty-three COPD patients hospitalised for acute COVID-19 from March through August 2020 were retrospectively identified and 63 hospitalised COVID-19 patients without COPD were selected and matched for age, gender and month of hospital admission. Results COPD patients had a higher rate of comorbidities, especially cardiovascular disease, and a trend towards a higher 30-day mortality than control patients (35% vs. 22%). In the COPD group, high Charlson comorbidity index (p = 0.03) and previous cerebrovascular disease (p = 0.04) were associated with 30-day mortality in univariate analysis. Inhaled corticosteroids maintenance therapy was not associated with lower mortality. Conclusion COPD patients hospitalised for acute COVID-19 disease had significantly more comorbidities and a high risk of severe outcome and death within 30 days. Comorbidity, especially cardiovascular diseases, was associated with mortality among COPD patients.
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| 56. |
- Beck-Friis, Thomas, et al.
(author)
-
Burden of rotavirus infection in hospitalized elderly individuals prior to the introduction of rotavirus vaccination in Sweden
- 2019
-
In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 119, s. 1-5
-
Journal article (peer-reviewed)abstract
- Background: Rotavirus gastroenteritis (GE) in the elderly has been much less studied than in children. Objectives: The aim of this study was to determine the morbidity and mortality for elderly hospitalized patients with rotavirus GE prior to the introduction of rotavirus vaccination in Sweden, and to investigate the epidemiology of rotavirus genotypes in these patients. Study design: All patients 60 years or older who were hospitalized at Sahlgrenska University Hospital, Gothenburg, Sweden, and were rotavirus positive in a clinical diagnostic test from 2009 to 2016, were included. Medical records were reviewed and rotavirus genotyping real-time PCR was performed. Results: One hundred and fifty-nine patients were included, corresponding to an annual incidence of hospitalization due to rotavirus GE of 16/100 000 inhabitants aged 60 years or older. G2P[4] was the most common genotype, followed by G1P[8] and G4P[8]. The majority of patients had community-onset of symptoms and no or few pre-existing health disorders. Four patients (2.5%) died within 30 days of sampling. Patients with hospital-onset rotavirus GE had a longer median length of stay following diagnosis compared with patients with community-onset of symptoms (19 vs. 5 days, p = 0.001) and higher 30-day mortality (8.6% (3/35) vs. < 1% (1/124), p = 0.03). Conclusions: Hospitalization due to rotavirus GE among the elderly seems to mainly affect otherwise healthy individuals and is associated with low 30-day mortality.
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| 57. |
- Beck-Friis, Thomas, et al.
(author)
-
Outdoor Absolute Humidity Predicts the Start of Norovirus GII Epidemics
- 2023
-
In: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 11:2
-
Journal article (peer-reviewed)abstract
- Seasonal variation of viral gastroenteritis is related to weather conditions, but the relationship with the incidence of viral gastroenteritis (GE) is not fully understood. This study examined the impact of outdoor climate factors on seasonal variation in detection rates of gastroenteritis viruses, with emphasis on norovirus. Weekly detection rates of norovirus genogroup I (GI) and II (GII), rotavirus, adenovirus, astrovirus, and sapovirus were analyzed in relation to average weekly means of meteorological parameters. Associations between rates of PCR detection of the viral GE pathogens and climate factors were investigated with generalized linear models. Low absolute humidity was correlated with increased detection of adenovirus (P = 0.007), astrovirus (P = 0.005), rotavirus (P = 0.004), norovirus GI (P = 0.001), and sapovirus (P = 0.002). In each investigated season, a drop in absolute humidity preceded the increase in norovirus GII detections. We found a correlation between declining absolute humidity and increasing norovirus GII detection rate. Absolute humidity was a better predictor of gastrointestinal virus seasonality compared to relative humidity.IMPORTANCE Viral gastroenteritis causes considerable morbidity, especially in vulnerable groups such as the elderly and chronically ill. Predicting the beginning of seasonal epidemics is important for the health care system to withstand increasing demands. In this paper we studied the association of outdoor climate factors on the detection rates of gastrointestinal viruses and the association between these factors and the onset of annual norovirus epidemics. Declining absolute humidity preceded the increase in diagnosed norovirus GII cases by approximately 1 week. These findings contribute to the understanding of norovirus epidemiology and allow health care services to install timely preventive measures and can help the public avoid transmission. Viral gastroenteritis causes considerable morbidity, especially in vulnerable groups such as the elderly and chronically ill. Predicting the beginning of seasonal epidemics is important for the health care system to withstand increasing demands.
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| 58. |
- Bergbrant, Susanna, et al.
(author)
-
Syndromic testing for respiratory pathogens but not National Early Warning Score can be used to identify viral cause in hospitalised adults with lower respiratory tract infections
- 2024
-
In: INFECTIOUS DISEASES. - 2374-4235 .- 2374-4243. ; 56:7
-
Journal article (peer-reviewed)abstract
- BackgroundCommunity-acquired lower respiratory tract infection (LRTI) is a common reason for hospitalisation. Antibiotics are frequently used while diagnostic microbiological methods are underutilised in the acute setting.ObjectivesWe aimed to investigate the relative proportion of viral and bacterial infections in this patient group and explore methods for proper targeting of antimicrobial therapy.MethodsWe collected nasopharyngeal samples prospectively from adults hospitalised with LRTIs during three consecutive winter seasons (2016-2019). Syndromic nasopharyngeal testing was performed using a multiplex PCR panel including 16 viruses and four bacteria. Medical records were reviewed for clinical data.ResultsOut of 220 included patients, a viral pathogen was detected in 74 (34%), a bacterial pathogen in 63 (39%), both viral and bacterial pathogens in 49 (22%), while the aetiology remained unknown in 34 (15%) cases. The proportion of infections with an identified pathogen increased from 38% to 85% when syndromic testing was added to standard-of-care testing. Viral infections were associated with a low CRP level and absence of pulmonary infiltrates. A high National Early Warning Score did not predict bacterial infections.ConclusionsSyndromic testing by a multiplex PCR panel identified a viral infection or viral/bacterial coinfection in a majority of hospitalised adult patients with community-acquired LRTIs.
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| 59. |
- Bjarnason, A., et al.
(author)
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Incidence, etiology, and outcomes of community-acquired pneumonia: A population-based study
- 2018
-
In: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 5:2
-
Journal article (peer-reviewed)abstract
- Background. The microbial etiology of community-acquired pneumonia (CAP) is often unclear in clinical practice, and previous studies have produced variable results. Population-based studies examining etiology and incidence are lacking. This study examined the incidence and etiology of CAP requiring hospitalization in a population-based cohort as well as risk factors and outcomes for specific etiologies. Methods. Consecutive admissions due to CAP in Reykjavik, Iceland were studied. Etiologic testing was performed with cultures, urine-antigen detection, and polymerase chain reaction analysis of airway samples. Outcomes were length of stay, intensive care unit admission, assisted ventilation, and mortality. Results. The inclusion rate was 95%. The incidence of CAP requiring hospitalization was 20.6 cases per 10 000 adults/year. A potential pathogen was detected in 52% (164 of 310) of admissions and in 74% (43 of 58) with complete sample sets. Streptococcus pneumoniae was the most common pathogen (61 of 310, 20%; incidence: 4.1/10 000). Viruses were identified in 15% (47 of 310; incidence: 3.1/10 000), Mycoplasma pneumoniae were identified in 12% (36 of 310; incidence: 2.4/10 000), and multiple pathogens were identified in 10% (30 of 310; incidence: 2.0/10 000). Recent antimicrobial therapy was associated with increased detection of M pneumoniae (P ≤ .001), whereas a lack of recent antimicrobial therapy was associated with increased detection of S pneumoniae (P = .02). Symptoms and outcomes were similar irrespective of microbial etiology. Conclusions. Pneumococci, M pneumoniae, and viruses are the most common pathogens associated with CAP requiring hospital admission, and they all have a similar incidence that increases with age. Symptoms do not correlate with specific agents, and outcomes are similar irrespective of pathogens identified. © The Author(s) 2018.
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| 60. |
- Bjarnason, A, et al.
(author)
-
Utility of oropharyngeal real-time PCR for S. pneumoniae and H. influenzae for diagnosis of pneumonia in adults.
- 2017
-
In: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. - : Springer Science and Business Media LLC. - 1435-4373. ; 36:3, s. 529-536
-
Journal article (peer-reviewed)abstract
- A lack of sensitive tests and difficulties obtaining representative samples contribute to the challenge in identifying etiology in pneumonia. Upper respiratory tract swabs can be easily collected and analyzed with real-time PCR (rtPCR). Common pathogens such as S. pneumoniae and H. influenzae can both colonize and infect the respiratory tract, complicating the interpretation of positive results. Oropharyngeal swabs were collected (n=239) prospectively from adults admitted to hospital with pneumonia. Analysis with rtPCR targeting S. pneumoniae and H. influenzae was performed and results compared with sputum cultures, blood cultures, and urine antigen testing for S. pneumoniae. Different Ct cutoff values were applied to positive tests to discern colonization from infection. Comparing rtPCR with conventional testing for S. pneumoniae in patients with all tests available (n=57) resulted in: sensitivity 87%, specificity 79%, PPV 59% and NPV 94%, and for H. influenzae (n=67): sensitivity 75%, specificity 80%, PPV 45% and NPV 94%. When patients with prior antimicrobial exposure were excluded sensitivity improved: 92% for S. pneumoniae and 80% for H. influenzae. Receiver operating characteristic curve analysis demonstrated for S. pneumoniae: AUC=0.65 (95% CI 0.51-0.80) and for H. influenzae: AUC=0.86 (95% CI 0.72-1.00). Analysis of oropharyngeal swabs using rtPCR proved both reasonably sensitive and specific for diagnosing pneumonia caused by S. pneumoniae and H. influenzae. This method may be a useful diagnostic adjunct to other methods and of special value in patients unable to provide representative lower airway samples.
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| 61. |
- Brittain-Long, Robin, 1969, et al.
(author)
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Access to a polymerase chain reaction assay method targeting 13 respiratory viruses can reduce antibiotics: a randomised, controlled trial.
- 2011
-
In: BMC medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 9
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Viral respiratory infections are common worldwide and range from completely benign disease to life-threatening illness. Symptoms can be unspecific, and an etiologic diagnosis is rarely established because of a lack of suitable diagnostic tools. Improper use of antibiotics is common in this setting, which is detrimental in light of the development of bacterial resistance. It has been suggested that the use of diagnostic tests could reduce antibiotic prescription rates. The objective of this study was to evaluate whether access to a multiplex polymerase chain reaction (PCR) assay panel for etiologic diagnosis of acute respiratory tract infections (ARTIs) would have an impact on antibiotic prescription rate in primary care clinical settings. METHODS: Adult patients with symptoms of ARTI were prospectively included. Nasopharyngeal and throat swabs were analysed by using a multiplex real-time PCR method targeting thirteen viruses and two bacteria. Patients were recruited at 12 outpatient units from October 2006 through April 2009, and samples were collected on the day of inclusion (initial visit) and after 10 days (follow-up visit). Patients were randomised in an open-label treatment protocol to receive a rapid or delayed result (on the following day or after eight to twelve days). The primary outcome measure was the antibiotic prescription rate at the initial visit, and the secondary outcome was the total antibiotic prescription rate during the study period. RESULTS: A total sample of 447 patients was randomised. Forty-one were excluded, leaving 406 patients for analysis. In the group of patients randomised for a rapid result, 4.5% (9 of 202) of patients received antibiotics at the initial visit, compared to 12.3% (25 of 204) (P = 0.005) of patients in the delayed result group. At follow-up, there was no significant difference between the groups: 13.9% (28 of 202) in the rapid result group and 17.2% (35 of 204) in the delayed result group (P = 0.359), respectively. CONCLUSIONS: Access to a rapid method for etiologic diagnosis of ARTIs may reduce antibiotic prescription rates at the initial visit in an outpatient setting. To sustain this effect, however, it seems necessary to better define how to follow and manage the patient according to the result of the test, which warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01133782.
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| 62. |
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| 63. |
- Brittain-Long, Robin, 1969, et al.
(author)
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Seasonal variations of 15 respiratory agents illustrated by the application of a multiplex polymerase chain reaction assay.
- 2011
-
In: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548.
-
Journal article (peer-reviewed)abstract
- Abstract Background: Nucleic acid amplification tests are increasingly being used to diagnose viral and bacterial respiratory tract infections. The high sensitivity of these tests affects our understanding of the epidemiology of respiratory tract infections. We have assessed the detection rate of a multiplex real-time polymerase chain reaction (PCR) test, with emphasis on epidemiology and seasonal distribution of the most common respiratory tract infections. Methods: Seven thousand eight hundred and fifty-three nasopharyngeal samples from 7220 patients (age range 0-98 y, median 22 y) obtained during 36 consecutive months (November 2006-October 2009), were analyzed with a multiplex PCR panel including influenza A (IfA) and B (IfB) virus, parainfluenza virus (PIV) 1-3, respiratory syncytial virus (RSV), human rhinovirus (HRV), human coronavirus (CoV) OC43, NL63, and 229E, human metapneumovirus (HMPV), adenovirus (AdV), enterovirus (EV), and 2 bacteria - Mycoplasma pneumoniae and Chlamydophila pneumoniae. Results: Of the total samples, 44.5% (n = 3496) were positive for at least 1 agent, with HRV being the most common (n = 1482, 38.0%), followed by RSV (n = 526, 13.5%) and IfA (n = 403, 10.3%). The diagnostic yield was significantly higher during the winter and early spring compared to the summer (n = 2439 of 4458 samples, 54.7% and n = 1057 of 3395 samples, 31.1%, respectively; p < 0.001). Conclusions: The diagnostic yield was highly dependent on the month of sampling and the age of the patient. However, the overall detection rate per month was above 30%, apart for August and September. Our findings support the use of similar tests in routine clinical care all year round. HRV was the most common finding in the respiratory tract, independent of season.
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| 64. |
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| 65. |
- Ekerfors, Ulrika, et al.
(author)
-
Muscle performance and fatigue in compensated chronic liver disease.
- 2019
-
In: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 54:7, s. 925-933
-
Journal article (peer-reviewed)abstract
- Background: A common and debilitating symptom in patients with chronic liver disease is fatigue (CLD). Muscle dysfunction has been suggested to be a key mechanism of fatigue in CLD. Objective: We aimed to evaluate fatigue and the potential association with muscle performance and physical activity in outpatients with CLD. Methods: Two-hundred seventy outpatients with CLD were included, (52±15years, mean±SD; 151 females) with autoimmune hepatitis (n=49), primary biliary cholangitis (n=45), primary sclerosing cholangitis (n=46), chronic hepatitis B (n=57) or C (n=73). Patients with a Child-Pugh >6 were excluded. The questionnaire Fatigue Impact Scale (FIS) was used to evaluate fatigue, and physical activity was evaluated through a self-reported level of physical activity. Muscle function was assessed with four muscle tests, walking speed, handgrip strength, standing heel-rise test (SHT) and 'Timed Up and Go' test (TUG). Results: The median total FIS score was 30 (40% had FIS > 40, considered high-fatigue). Diminished muscle performance was observed in the SHT (% of predicted value: 53±26%) and with maximum grip strength (85±20%). The FIS score was significantly different between groups of CLDs (p=.004). In multivariate analysis the TUG (p=.001), SHT (p=.005), antidepressants (p<.001), and level of physical activity (p=.001) were associated with fatigue (R2=29%). Subjects with higher levels of physical activity had lower FIS (p<.001). Conclusions: In patients with CLD, fatigue was associated with low muscle performance and reduced level of physical activity, which could be a potential therapeutic target.
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| 66. |
- Gustavsson, Lars, et al.
(author)
-
Excess mortality following community-onset norovirus enteritis in the elderly.
- 2011
-
In: The Journal of hospital infection. - : Elsevier BV. - 1532-2939 .- 0195-6701. ; 79:1, s. 27-31
-
Journal article (peer-reviewed)abstract
- Norovirus has been associated with excess deaths. A retrospective study of mortality following norovirus enteritis (NVE) was undertaken. All hospitalized adult patients with a stool sample positive for norovirus genogroup II on polymerase chain reaction, treated at Sahlgrenska University Hospital, Gothenburg, Sweden between August 2008 and June 2009, were included as cases (N=598, aged 18-101 years). Matched controls without enteritis (N=1196) were selected for comparison. Medical records were reviewed and deaths up to 90 days following positive sampling were noted, as well as comorbidities and length of hospital stay. Thirty- and 90-day survival rates were calculated. Total 30-day mortality was 7.6% and no deaths were recorded in cases aged 18-59 years. Thirty-day mortality was higher in cases with underlying medical conditions compared with those without these comorbidities (age 60-101 years: 89.5% vs 94.7% alive at Day 30, respectively; P<0.05). In cases aged >80 years, mortality was higher in those with community-onset NVE (N=64) compared with hospital-onset NVE (N=305) (81.2% vs 90.2% alive at Day 30, respectively; P<0.05), and compared with controls (N=128) (81.2% vs 91.4% alive at Day 30, respectively; P<0.05). Median length of hospital stay was 20 [interquartile range (IQR) 12-29] days for cases with hospital-onset NVE, and seven (IQR 2-13) days for controls (P<0.001). In conclusion, community-onset NVE requiring hospitalization was associated with higher mortality compared with hospital-onset NVE and matched controls in hospitalized elderly patients.
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| 67. |
- Gustavsson, Lars, et al.
(author)
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Low serum levels of CCL5 are associated with longer duration of viral shedding in norovirus infection
- 2015
-
In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 69, s. 133-137
-
Journal article (peer-reviewed)abstract
- Background: The mechanisms that determine the duration of fecal shedding of norovirus in humans have not been described in detail. Objectives: We investigated serum inflammatory mediator levels in relation to the duration of viral shedding in norovirus infection. Study design: A prospective cohort study of patients hospitalized with acute norovirus genogroup II infection. Rectal swab samples were obtained at inclusion and day 7, 14, 21 and 28. Serum levels of 42 inflammatory mediators were determined with a Luminex-based cytokine assay. Sera from 20 healthy blood donors served as controls. Results: Altogether, 28 patients (54% women, median age 83 years, median duration of symptoms 3 days) were included. Twelve subjects cleared the virus within 14 days and 16 were norovirus-RNA positive for >21 days, constituting the two study groups ("rapid" vs. "slow" clearance). Individuals with norovirus infection had higher levels of IL-18, CXCL9, CXCL10, soluble IL-2 receptor and macrophage migration inhibitory factor (MIF), compared to controls (p < 0.05), with the highest median concentrations in the slow clearance group. In contrast, CCL5 levels were lower in the slow compared to the rapid clearance group (median 54 vs. 134 ng/mL, p < 0.05), and lower in norovirus-infected patients than in controls. Conclusion: Low levels of CCL5 were associated with longer duration of viral shedding, suggesting that CCL5 may influence the clearance of norovirus. (C) 2015 Elsevier B.V. All rights reserved.
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| 68. |
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| 69. |
- Gustavsson, Lars, et al.
(author)
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Rectal swabs can be used for diagnosis of viral gastroenteritis with a multiple real-time PCR assay
- 2011
-
In: Journal of Clinical Virology. - 1386-6532. ; 51, s. 275-278
-
Journal article (peer-reviewed)abstract
- Background: Viral agents, especially norovirus, are the most common cause of nosocomial spread of epidemic gastroenteritis (GE). Rapid and reliable detection of these agents could reduce the risk of outbreaks. Objective: To evaluate the diagnostic performance of rectal swab samples compared to standard stool samples for detection of agents causing viral GE by PCR. Study design: Complete pairs of rectal swab and stool samples, obtained simultaneously from patients with symptoms of acute onset GE, were analysed with a multiple real-time PCR targeting six different gastroenteritis agents (astro-, adeno-, rota-, sapo- and norovirus GI and II). Cycle threshold (Ct) values were registered for positive samples. A positive PCR result in either sample for any virus was considered gold standard. Results: 69 sample pairs were included of which 29 were negative in both sample types and 38 were positive in both sample types. One pair was positive in the stool sample only and another pair was positive in the rectal swab sample only. Sensitivity for both sample types was 97.5% (39/40). Conclusion: Rectal swab samples are as reliable as stool samples for PCR-based diagnosis of viral gastroenteritis in patients with a short duration of symptoms and may be used as a complement to stool samples, especially when immediate sampling is desirable.
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| 70. |
- Gustavsson, Lars, et al.
(author)
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Slow Clearance of Norovirus following Infection with Emerging Variants of Genotype GII.4 Strains.
- 2017
-
In: Journal of clinical microbiology. - 1098-660X. ; 55:5, s. 1533-1539
-
Journal article (peer-reviewed)abstract
- The emergence of new norovirus genotype GII.4 strains is associated with widespread norovirus epidemics. Extended periods of viral shedding can contribute to the epidemic potential of norovirus. To describe the duration of viral shedding in infections with novel emerging GII.4 strains versus infections with previously circulating strains, we performed a prospective cohort study of patients hospitalized with norovirus gastroenteritis during separate winter seasons. Rectal swab samples were obtained at the time of inclusion and weekly during follow-ups. The subgenotype strain was determined from capsid sequences. The outcome was defined by the detection of virus for >14 days (slow clearance) or by the detection of negative samples within 14 days (rapid clearance). Two major epidemic GII.4 strains emerged during the study period, GII.4 New Orleans 2009, in 2010, and GII.4 Sydney 2012, in 2012. From these two seasons, sequences were available from 24 cases where the duration of shedding could be determined. The median age of the patients was 83 years and 50% were women. The majority of patients were infected with virus that clustered with the respective season's epidemic strain (n = 19), whereas 5 patients had previously circulating strains (3 were Den Haag 2006b, in 2010, and 2 were New Orleans 2009, in 2012). Among the patients infected with an epidemic strain, the proportion who shed virus for >14 days was significantly higher (16/19 [84%] versus 1/5 [20%], P = 0.01). In summary, a slow clearance of norovirus from stool was more common in infections with novel epidemic GII.4 strains. This suggests that the average duration of shedding may be longer during seasons when new GII.4 strains have emerged.
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| 71. |
- Gustavsson, Lars, et al.
(author)
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Venous lactate levels can be used to identify patients with poor outcome following community-onset norovirus enteritis
- 2012
-
In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 44:10, s. 782-787
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Journal article (peer-reviewed)abstract
- Background: Norovirus enteritis (NVE) can be fatal in frail patients. High blood lactate levels indicate hypoperfusion and predict mortality in many infectious diseases. The objective was to determine the frequency and association with mortality of elevated lactate levels in patients with community-onset NVE. Methods: A retrospective cohort study was performed. All hospitalized adult patients with community-onset NVE verified by polymerase chain reaction during the period August 2008 to June 2009 were included. Vital signs and venous lactate on arrival, co-morbid conditions, and time of death were registered. The outcome measure was 30-day all-cause mortality. Results: Eighty-two patients with a median age of 77 y (interquartile range (IQR) 53-86 y) were included, of whom 47 (57%) were female and 49 (60%) had at least 1 major co-morbid condition. Lactate levels were above the upper limit of normal (ULN; 1.6 mmol/l) in 45 patients (55%). The overall 30-day mortality rate was 7% (6/82). Mortality was 18% (5/28) with lactate >= 2.4 mmol/l (> 50% above the ULN) on admission compared to 2% (1/54) with lactate < 2.4 mmol/l (p < 0.05). Patients who died had a higher median lactate level compared to survivors: 4.5 (IQR 2.7-7.9) mmol/l vs 1.7 (IQR 1.3-2.5) mmol/l, respectively (p < 0.01). The adjusted odds ratio for death within 30 days for a 1 mmol/l increase in lactate was 2.5 (95% confidence interval 1.003-6.3, p = 0.049). Conclusions: We observed a high proportion of patients with elevated lactate levels in community-onset NVE. Lactate elevation could predict mortality. Measurement of blood lactate may be a valuable tool in the clinical management of patients with a suspected norovirus infection.
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| 72. |
- Hansen, Karin B., et al.
(author)
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Flocked nasal swab versus nasopharyngeal aspirate in adult emergency room patients: similar multiplex PCR respiratory pathogen results and patient discomfort
- 2016
-
In: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 48:3, s. 246-250
-
Journal article (peer-reviewed)abstract
- Fifty adult emergency room patients with symptoms of respiratory tract infections or acute onset of extreme fatigue were sampled by both nasopharyngeal aspirate (NPA) and flocked nasal swab (fNS). Respiratory agents were detected by a qualitative influenza PCR and an 18-valent multiplex PCR in 20 of 29 patients with a clinical diagnosis of respiratory tract infection, and in 3 of 21 without such a diagnosis. PCR detected influenza A and B in NPA samples from 11 patients and in fNS samples from 10 patients. Little or no discomfort was perceived by 60% of the patients when sampled by NPA and by 66% when sampled by fNS. We conclude that NPA and fNS were equally sensitive for detection of respiratory agents by multiplex PCR, and the two sampling methods did not differ significantly regarding discomfort perceived by patients (p=0.171, Wilcoxon signed rank test). Hence less invasive sampling by fNS might be preferable in certain settings and situations.
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| 73. |
- Harbin, N. J., et al.
(author)
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Does C-reactive protein predict time to recovery and benefit from oseltamivir treatment in primary care patients with influenza-like illness? A randomized controlled trial secondary analysis
- 2021
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In: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 39:4, s. 527-532
-
Journal article (peer-reviewed)abstract
- Objective Recovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-reactive protein (CRP) concentration of >= 30 mg/L can predict (1) ILI disease duration, and (2) which patients are most likely to benefit from oseltamivir treatment. Design Secondary analysis of randomized controlled trial data. Setting Primary care in Lithuania, Sweden and Norway during three consecutive influenza seasons 2016-2018. Subjects A total of 277 ILI patients aged one year or older and symptom duration of <= 72 h. Main outcome measures Capillary blood CRP concentration at baseline, and ILI recovery time defined as having 'returned to usual daily activity' with residual symptoms minimally interfering. Results At baseline, 20% (55/277) had CRP concentrations >= 30mg/L (range 0-210). CRP concentration >= 30 mg/L was not associated with recovery time (adjusted hazards ratio (HR) 0.80: 95% CI 0.50-1.3; p = 0.33). Interaction analysis of CRP concentration >= 30 mg/L and oseltamivir treatment did not identify which patients benefit more from oseltamivir treatment (adjusted HR 0.69: 95% CI 0.37-1.3; p = 0.23). Conclusion There was no association between CRP concentration of >= 30 mg/L and recovery time from ILI. Furthermore, CRP could not predict which ILI patients benefit more from oseltamivir treatment. Hence, we do not recommend CRP testing for predicting ILI recovery time or identifying patients who will receive particular benefit from oseltamivir treatment.
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| 74. |
- Landén, Mikael, 1966, et al.
(author)
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Respiratory infections during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder
- 2021
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In: International Journal of Bipolar Disorders. - : Springer Science and Business Media LLC. - 2194-7511. ; 9:1
-
Journal article (peer-reviewed)abstract
- Background In vitro studies have demonstrated that lithium has antiviral properties, but evidence from human studies is scarce. Lithium is used as a mood stabilizer to treat patients with bipolar disorder. Here, the aim was to investigate the association between lithium use and the risk of respiratory infections in patients with bipolar disorder. To rule out the possibility that a potential association could be due to lithium's effect on psychiatric symptoms, we also studied the effect of valproate, which is an alternative to lithium used to prevent mood episodes in bipolar disorder. Method We followed 51,509 individuals diagnosed with bipolar disorder in the Swedish Patient register 2005-2013. We applied a within-individual design using stratified Cox regression to estimate the hazard ratios (HRs) of respiratory infections during treated periods compared with untreated periods. Results During follow-up, 5,760 respiratory infections were documented in the Swedish Patient Register. The incidence rate was 28% lower during lithium treatment (HR 0.73, 95% CI 0.61-0.86) and 35% higher during valproate treatment (HR 1.35, 95% CI 1.06-1.73) compared with periods off treatment. Conclusions This study provides real-world evidence that lithium is associated with decreased risk for respiratory infections and suggests that the repurposing potential of lithium for potential antiviral or antibacterial effects is worthy of investigation.
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| 75. |
- Magnusson, Jesper, et al.
(author)
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Cell-free DNA as a biomarker after lung transplantation: A proof-of-concept study
- 2022
-
In: Immunity Inflammation and Disease. - : Wiley. - 2050-4527. ; 10:5
-
Journal article (peer-reviewed)abstract
- Background: Lung transplantation (LTx) is a lifesaving procedure burdened with limited long-term survival. The most common cause of death after LTx is chronic lung allograft dysfunction (CLAD). Today, useful biomarkers for the detection of CLAD are lacking. Circulating cell-free DNA (cfDNA) is released during cellular decay and can be detected using polymerase chain reaction (PCR). Thus, donor-derived cfDNA in recipient serum indicates cellular decay in the transplanted organ. In the current study, we explore the possibility of using a novel PCR method to detect cfDNA as a biomarker for clinical events, especially CLAD. Methods: Four patients were retrospectively tested for levels of both donor and recipient-derived cfDNA using digital droplet PCR after targeted preamplification. The results were correlated to recorded clinical events. Results: All available samples rendered results. Both patients that later developed CLAD showed a persistently elevated ratio between donor-and recipient-derived cfDNA. Also, the mean level of cfDNA was higher in the two patients who later developed CLAD than in patients who did not (p = .0015). Conclusions: This proof-of-concept study suggests that cfDNA quantified with PCR may be used as a biomarker of significant clinical events such as CLAD.
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| 76. |
- Magnusson, Jesper, et al.
(author)
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Incidence of Hepatitis E Antibodies in Swedish Lung Transplant Recipients
- 2015
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In: Transplantation Proceedings. - : Elsevier BV. - 0041-1345. ; 47:6, s. 1972-1976
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Journal article (peer-reviewed)abstract
- Background. Hepatitis E virus (REV) is an important cause of acute and chronic hepatitis in solid organ transplant recipients, especially liver transplant recipients. However, less is known of the incidence and prevalence of HEV in lung transplant recipients. Methods. In a prospective study, 62 patients were observed during the first year after lung transplantation. Sera were analyzed for anti-REV immunoglobulin G (IgG) and IgM at 12 months after transplantation. Samples positive for anti-REV were also analyzed for REV RNA by polymerase chain reaction. Pretransplantation samples were analyzed for patients with detectable anti-REV 1 year after transplantation. Results. Eight patients (13%) had anti-REV IgG at the 12-month follow-up sample. HEV RNA could not be detected in any of these samples. One of these patients seroconverted during the follow-up without developing acute or chronic hepatitis. Conclusions. Our results show that the prevalence of REV antibodies among Swedish lung transplant recipients is similar when compared to the general population. It also suggests that the risk for REV antibody seroconversion during first year is limited.
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| 77. |
- Magnusson, Jesper, et al.
(author)
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The Impact of Viral Respiratory Tract Infections on Long-Term Morbidity and Mortality following Lung Transplantation: A Retrospective Cohort Study Using a Multiplex PCR Panel.
- 2013
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In: Transplantation. - 1534-6080. ; 95:2, s. 383-388
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The major factor affecting morbidity and mortality after lung transplantation (LTX) is bronchiolitis obliterans syndrome. Earlier studies have suggested a connection between the presence of viral agents and morbidity in this patient group, but data are somewhat conflicting. The objective of this study was to investigate the development of bronchiolitis obliterans syndrome and graft loss after LTX in relation to the presence of respiratory viruses during the first year after LTX. METHOD: The study is a retrospective cohort study of 39 LTX recipients 11-13 years after surgery. Patients were operated between January 1, 1998 and December 31, 2000 at Sahlgrenska University Hospital. The presence of virus in bronchoalveolar lavage (BAL) fluids from patients during the first year after surgery was analyzed retrospectively using a multiplex polymerase chain reaction test capable of detecting 15 respiratory agents. The time to BOS or graft loss was analyzed in relation to the positive findings in BAL during the first year after LTX. RESULTS: Patients with one or more viruses detected in BAL during the first year after transplantation demonstrated a significantly faster development of BOS (P=0.005) compared with patients with no virus detected. No significant difference in graft survival was found. CONCLUSION: Our results suggest that the long-term prognosis after LTX may be negatively affected by viral respiratory tract infections during the first year after LTX.
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| 78. |
- Magnusson, Jesper, et al.
(author)
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Viral Respiratory Tract Infection During the First Postoperative Year Is a Risk Factor for Chronic Rejection After Lung Transplantation
- 2018
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In: Transplantation Direct. - : Ovid Technologies (Wolters Kluwer Health). - 2373-8731. ; 4:8
-
Journal article (peer-reviewed)abstract
- Background. Chronic lung allograft dysfunction (CLAD) is the major limiting factor for long-term survival in lung transplant recipients. Viral respiratory tract infection (VRTI) has been previously associated with CLAD development. The main purpose of this study was to evaluate the long-term effects of VRTI during the first year after lung transplantation in relation to CLAD development. Method. Ninety-eight patients undergoing lung transplantation were prospectively enrolled between 2009 and 2012. They were monitored for infections with predefined intervals and on extra visits during the first year, the total follow-up period ranged between 5 and 8 years. Nasopharyngeal swab and bronchoalveolar lavage samples were analyzed using a multiplex polymerase chain reaction panel for respiratory pathogens. Data regarding clinical characteristics and infectious events were recorded. Results. Viral respiratory tract infection during the first year was identified as a risk factor for long-term CLAD development (P = 0.041, hazard ratio 1.94 [1.03-3.66]) in a time-dependent multivariate Cox regression analysis. We also found that coronavirus in particular was associated with increased risk for CLAD development. Other identified risk factors were acute rejection and cyclosporine treatment. Conclusions. This study suggests that VRTI during the first year after lung transplantation is associated with long-term CLAD development and that coronavirus infections in particular might be a risk factor.
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| 79. |
- Nenonen, Nancy P, 1943, et al.
(author)
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Norovirus GII.4 Detection in Environmental Samples from Patient Rooms during Nosocomial Outbreaks
- 2014
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In: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 52:7, s. 2352-2358
-
Journal article (peer-reviewed)abstract
- Norovirus (NoV) is an important cause of nosocomial gastroenteric outbreaks. This 5-month study was designed to characterize NoV contamination and airborne dispersal in patient rooms during hospital outbreaks. Air vents, overbed tables, washbasins, dust, and virus traps designed to collect charged particles from the air were swabbed to investigate the possibility of NoV contamination in patient rooms during outbreaks in seven wards and in an outbreak-free ward. Symptomatic inpatients were also sampled. Nucleic acid extracts of the samples were examined for NoV RNA using genogroup I (GI) and GII real-time reverse transcription-PCR (RT-PCR). The NoV strains were characterized by RT-PCR, sequencing, and phylogenetic analysis of the RNA-dependent RNA-polymerase-N/S capsid-coding region (1,040 nucleotides [nt]). Patient strains from two outbreaks in one ward were sequenced across the RNA-dependent-RNA-polymerase major capsid-coding region (2.5 kb), including the hypervariable P2 domain. In the outbreak wards, NoV GII was detected in 48 of 101 (47%) environmental swabs and 63 of 108 patients (58%); NoV genotype II.4 was sequenced from 18 environmental samples, dust (n = 8), virus traps (n = 4), surfaces (n = 6), and 56 patients. In contrast, NoV GII was detected in 2 (GII. 4) of 28 (7%) environmental samples and in 2 (GII. 6 and GII. 4) of 17 patients in the outbreak-free ward. Sequence analyses revealed a high degree of similarity (>99.5%, 1,040 nt) between NoV GII.4 environmental and patient strains from a given ward at a given time. The strains clustered on 11 subbranches of the phylogenetic tree, with strong correlations to time and place. The high nucleotide similarity between the NoV GII.4 strains from patients and their hospital room environment provided molecular evidence of GII.4 dispersal in the air and dust; therefore, interventional cleaning studies are justified.
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| 80. |
- Nilsson, Anna, et al.
(author)
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Frequent detection of respiratory agents by multiplex PCR on oropharyngeal samples in Swedish school-attending adolescents
- 2012
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 44, s. 393-397
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Journal article (peer-reviewed)abstract
- Background: Respiratory agents may be detected in the oropharynx of healthy individuals. The extent of this condition and the reasons behind it are largely unknown. The objective of this study was to determine the factors associated with the presence of respiratory agents in the oropharynx of adolescents healthy enough to attend school activities. Methods: On a single day in December, samples from the posterior wall of the oropharynx of adolescents aged 1015 y were obtained using cotton-tipped swabs. The samples were analyzed by real-time polymerase chain reaction (PCR) for the presence of 13 respiratory viruses and 2 bacteria (Mycoplasma pneumoniae and Chlamydophila pneumoniae). Results: Out of the 232 adolescents sampled, 67 (29%) had any respiratory symptom. A positive PCR result was found in 50 individuals (22%). Human rhinovirus was the most commonly found agent. Respiratory agents were significantly more frequent in the younger age group (1013 y) than in the older age group (1415 y): 26% (38/148) vs 14% (12/84), respectively; p = 0.04. Cough was the only symptom that was more common among individuals with a positive PCR test than among those with a negative PCR test: 8/50 (16%) vs 11/182 (6%); p = 0.02. Family size and class size were not associated with the likelihood of a positive PCR test. Conclusions: The presence of respiratory agents in the oropharynx is a frequent finding among adolescents healthy enough to attend school activities. The high prevalence was found to be associated with young age, but not with the size of the family or class. © 2012 Informa Healthcare.
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| 81. |
- Nordén, Rickard, 1977, et al.
(author)
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Quantification of torque teno virus and Epstein-Barr virus is of limited value for predicting the net state of immunosuppression after lung transplantation
- 2018
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In: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 5:4
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Journal article (peer-reviewed)abstract
- Background. Major hurdles for survival after lung transplantation are rejections and infectious complications. Adequate methods for monitoring immune suppression status are lacking. Here, we evaluated quantification of torque teno virus (TTV) and Epstein-Barr virus (EBV) as biomarkers for defining the net state of immunosuppression in lung-transplanted patients. Methods. This prospective single-center study included 98 patients followed for 2 years after transplantation. Bacterial infections, fungal infections, viral respiratory infections (VRTI), cytomegalovirus (CMV) viremia, and acute rejections, as well as TTV and EBV levels, were monitored. Results. The levels of torque teno virus DNA increased rapidly after transplantation, likely due to immunosuppressive treatment. A modest increase in levels of Epstein-Barr virus DNA was also observed after transplantation. There were no associations between either TTV or EBV and infectious events or acute rejection, respectively, during follow-up. When Tacrolimus was the main immunosuppressive treatment, TTV DNA levels were significantly elevated 6-24 months after transplantation as compared with Cyclosporine treatment. Conclusions. Although replication of TTV, but not EBV, appears to reflect the functionality of the immune system, depending on the type of immunosuppressive treatment, quantification of TTV or EBV as biomarkers has limited potential for defining the net state of immune suppression.
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| 82. |
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| 83. |
- Novo, Mirza, et al.
(author)
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COMP: A Potential Early Biomarker of RAS After Lung Transplantation
- 2021
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In: Transplantation Direct. - : Ovid Technologies (Wolters Kluwer Health). - 2373-8731. ; 7:8
-
Journal article (peer-reviewed)abstract
- Background. Chronic rejection, defined as chronic lung allograft dysfunction (CLAD), is the major factor limiting longterm survival after lung transplantation (LTx). A specific subgroup of CLAD is restrictive allograft syndrome (RAS). CLAD's pathogenesis is largely unknown, but previous findings suggest that it is associated with increased fibrosis in the transplanted lung. Cartilage oligomeric matrix protein (COMP) has been associated with multiple fibrotic conditions. The current study aimed to explore the relation between COMP serum levels and development of CLAD, and RAS in particular, in a retrospective cohort of LTx patients. Methods. This study included retrospective data from patients who underwent LTx during 2009-2011. Blood samples and spirometry data were obtained at follow-up visits 1, 3, 6, 9, and 12 mo after transplantation. Serum samples were analyzed for COMP. CLAD and RAS were defined according to the 2019 International Society for Heart and Lung Transplantation consensus document. Results. Data from 38 patients (19 men and women, respectively) were collected. Twenty-three patients (60.5%) developed CLAD, of whom 6 (26.1 %) fulfilled the criteria for RAS. Patients who developed RAS had higher mean COMP levels between 1 and 3 mo after LTx than those who did not develop RAS (10.9 [3.9-17.5] U/L vs 7.4 [3.9-10.8] U/L, P=0.008). RAS was also associated with shorter survival. We found no association between COMP levels and CLAD of other types than RAS. Conclusions. Serum level of COMP early after LTx seems to be associated with RAS development and might serve as a biomarker suitable for clinical use in the LTx setting.
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| 84. |
- Olofsson, Sigvard, 1948, et al.
(author)
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PCR for detection of respiratory viruses: seasonal variations of virus infections
- 2011
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In: EXPERT REVIEW OF ANTI-INFECTIVE THERAPY. - 1478-7210. ; 9:8, s. 615-626
-
Research review (peer-reviewed)abstract
- Real-time PCR and related methods have revolutionized the laboratory diagnosis of viral respiratory infections because of their high detection sensitivity, rapidness and potential for simultaneous detection of 15 or more respiratory agents. Results from studies with this diagnostic modality have significantly expanded our knowledge about the seasonality of viral respiratory diseases, pinpointed the difficulties to make a reliable etiologic diagnosis without the aid of an unbiased multiplex molecular assay for respiratory viruses, and revealed previously unknown details as to possible infections with multiple agents as aggravating factors. The scope of this article is to review and discuss this new knowledge and its implications for diagnostic strategies and other measures essential for the clinical management of respiratory viral infections and for epidemiological surveillance of seasonal respiratory infections.
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| 85. |
- Sansone, Martina, et al.
(author)
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Extensive Hospital In-Ward Clustering Revealed By Molecular Characterization of Influenza A Virus Infection.
- 2020
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In: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 71:9
-
Journal article (peer-reviewed)abstract
- Nosocomial transmission of influenza A virus (InfA) infection is not fully recognized. The aim of this study was to describe the characteristics of hospitalized patients with InfA infections during an entire season and to investigate in-ward transmission at a large, acute-care hospital.During the 2016-17 season, all hospitalized patients≥18 years old with laboratory-verified (real-time polymerase chain reaction) InfA were identified. Cases were characterized according to age; sex; comorbidity; antiviral therapy; viral load, expressed as cycle threshold values; length of hospital stay; 30-day mortality; and whether the InfA infection met criteria for a health care-associated influenza A infection (HCAI). Respiratory samples positive for InfA that were collected at the same wards within 7 days were chosen for whole-genome sequencing (WGS) and a phylogenetic analysis was performed to detect clustering. For reference, concurrent InfA strains from patients with community-acquired infection were included.We identified a total of 435 InfA cases, of which 114 (26%) met the HCAI criteria. The overall 30-day mortality rate was higher among patients with HCAI (9.6% vs 4.6% among non-HCAI patients), although the difference was not statistically significant in a multivariable analysis, where age was the only independent risk factor for death (P<.05). We identified 8 closely related clusters (involving≥3 cases) and another 10 pairs of strains, supporting in-ward transmission.We found that the in-ward transmission of InfA occurs frequently and that HCAI may have severe outcomes. WGS may be used for outbreak investigations, as well as for evaluations of the effects of preventive measures.
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| 86. |
- Sansone, Martina, et al.
(author)
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Molecular characterization of a nosocomial outbreak of influenza B virus in an acute care hospital setting
- 2019
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In: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701. ; 101:1, s. 30-37
-
Journal article (peer-reviewed)abstract
- Aim: To describe a hospital outbreak of influenza B virus (InfB) infection during season 2015/2016 by combining clinical and epidemiological data with molecular methods. Methods: Twenty patients diagnosed with InfB from a hospital outbreak over a four-week-period were included. Nasopharyngeal samples (NPS) positive for InfB by multiplex real-time polymerase chain reaction were sent for lineage typing and whole genome sequencing (WGS). Medical records were reviewed retrospectively for data regarding patient characteristics, localization, exposure and outcome, and assembled into a timeline. In order to find possible connections to the hospital outbreak, all patients with a positive NPS for influenza from the region over an extended time period were also reviewed. Findings: All 20 cases of InfB were of subtype B/Yamagata, and 17 of 20 patients could be linked to each other by either shared room or shared ward. WGS was successful or partially successful for 15 of the 17 viral isolates, and corroborated the epidemiological link supporting a close relationship. In the main affected ward, 19 of 75 inpatients were infected with InfB during the outbreak period, resulting in an attack rate of 25%. One probable case of influenza-related death was identified. Conclusion: InfB may spread within an acute care hospital, and advanced molecular methods may facilitate assessment of the source and extent of the outbreak. A multifaceted approach, including rapid diagnosis, early recognition of outbreak situations, simple rules for patient management and the use of regular infection control measures, may prevent nosocomial transmission of influenza virus. (C) 2018 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
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| 87. |
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| 88. |
- Sansone, Martina, et al.
(author)
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System dynamic modelling of healthcare associated influenza -a tool for infection control
- 2022
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In: Bmc Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 22:1
-
Journal article (peer-reviewed)abstract
- Background The transmission dynamics of influenza virus within healthcare settings are not fully understood. Capturing the interplay between host, viral and environmental factors is difficult using conventional research methods. Instead, system dynamic modelling may be used to illustrate the complex scenarios including non-linear relationships and multiple interactions which occur within hospitals during a seasonal influenza epidemic. We developed such a model intended as a support for health-care providers in identifying potentially effective control strategies to prevent influenza transmission. Methods By using computer simulation software, we constructed a system dynamic model to illustrate transmission dynamics within a large acute-care hospital. We used local real-world clinical and epidemiological data collected during the season 2016/17, as well as data from the national surveillance programs and relevant publications to form the basic structure of the model. Multiple stepwise simulations were performed to identify the relative effectiveness of various control strategies and to produce estimates of the accumulated number of healthcare-associated influenza cases per season. Results Scenarios regarding the number of patients exposed for influenza virus by shared room and the extent of antiviral prophylaxis and treatment were investigated in relation to estimations of influenza vaccine coverage, vaccine effectiveness and inflow of patients with influenza. In total, 680 simulations were performed, of which each one resulted in an estimated number per season. The most effective preventive measure identified by our model was administration of antiviral prophylaxis to exposed patients followed by reducing the number of patients receiving care in shared rooms. Conclusions This study presents an system dynamic model that can be used to capture the complex dynamics of in-hospital transmission of viral infections and identify potentially effective interventions to prevent healthcare-associated influenza infections. Our simulations identified antiviral prophylaxis as the most effective way to control in-hospital influenza transmission.
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| 89. |
- Sundell, Nicklas, et al.
(author)
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A four year seasonal survey of the relationship between outdoor climate and epidemiology of viral respiratory tract infections in a temperate climate
- 2016
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In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 84, s. 59-63
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Journal article (peer-reviewed)abstract
- Background The relation between weather conditions, viral transmission and seasonal activity of respiratory viruses is not fully understood. Objectives To investigate the impact of outdoor weather in a temperate climate setting on the seasonal epidemiology of viruses causing respiratory tract infections, particularly influenza A (IFA). Study design In total, 20,062 clinical nasopharyngeal swab samples referred for detection of respiratory pathogens using a multiplex PCR panel, between October 2010 and July 2013, were included. Results of PCR detection were compared with local meteorological data for the same period. Results Low temperature and vapor pressure (VP) were associated with weekly incidence of IFA, respiratory syncytial virus, metapneumovirus, bocavirus and adenovirus but no association with relative humidity was found. The incidence of human rhinovirus and enterovirus was independent of temperature. During seasonal IFA outbreaks, the weekly drop of average temperature (compared with the week before) was strongly associated with the IFA incidence recorded the following week. Conclusion A sudden drop in outdoor temperature might activate the annual influenza epidemic in a temperate climate by facilitating aerosol spread in dry air. These conditions also seem to affect the incidence of other respiratory pathogens but not human rhino- or enterovirus, suggesting that routes of infection other than aerosol may be relevant for these agents. © 2016 Elsevier B.V.
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| 90. |
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| 91. |
- Sundell, Nicklas, et al.
(author)
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Measles outbreak in Gothenburg urban area, Sweden, 2017 to 2018: low viral load in breakthrough infections
- 2019
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In: Eurosurveillance. - 1560-7917. ; 24:17, s. 2-12
-
Journal article (peer-reviewed)abstract
- In an outbreak of measles in Gothenburg, Sweden, breakthrough infections (i.e. infections in individuals with a history of vaccination) were common. The objective of this study was to compare measles RNA levels between naive (i.e. primary) and breakthrough infections. We also propose a fast provisional classification of breakthrough infections. Medical records were reviewed and real-time PCR-positive samples geno-typed. Cases were classified as naive, break-through or vaccine infections. We compared clinical symptoms and measles RNA cycle threshold (Ct) values between breakthrough and naive infections. Sixteen of 28 confirmed cases of measles in this outbreak were breakthrough infections. A fast provisional classification, based on previous history of measles vaccination and detectable levels of measles IgG in acute serum, correctly identified 14 of the 16 breakthrough infections, confirmed by IgG avidity testing. Measles viral load was significantly lower in nasopharyngeal samples from individuals with breakthrough compared with naive infections (median Ct-values: 32 and 19, respectively, p < 0.0001). No onward transmission from break-through infections was identified. Our results indicate that a high risk of onward transmission is limited to naive infections. We propose a fast provisional classification of breakthrough measles that can guide contact tracing in outbreak settings.
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| 92. |
- Swartling, L., et al.
(author)
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Hepatitis E virus is an infrequent but potentially serious infection in allogeneic hematopoietic stem cell transplant recipients
- 2020
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In: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 55:7, s. 1255-63
-
Journal article (peer-reviewed)abstract
- Hepatitis E virus (HEV) can cause chronic infection and liver cirrhosis in immunocompromised individuals. The frequency and clinical importance of HEV was studied retrospectively in a cohort of 236 Swedish allogeneic hematopoietic stem cell transplantation (HSCT) recipients. In blood samples collected at 6 months after HSCT, HEV RNA was identified in 8/236 (3.4%) patients, and 11/236 (4.7%) patients had detectable anti-HEV IgG and/or IgM, eight of whom were HEV RNA negative. Two of the patients with positive HEV RNA died with ongoing signs of hepatitis: one of acute liver and multiple organ failure, the other of unrelated causes. The remaining six patients with HEV RNA had cleared the infection at 7-24 (median 8.5) months after HSCT. HEV infection was associated with elevated alanine aminotransferase at 6 months after HSCT (OR 15, 1.3-174, p = 0.03). Active graft-versus-host disease of the liver at 6 months after HSCT was present in 3/8 (38%) patients with HEV RNA, but was not significantly associated with HEV infection. In conclusion, HEV infection is an important differential diagnosis in patients with elevated liver enzymes after HSCT. Although spontaneous clearance was common, the clinical course may be severe.
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| 93. |
- Torén, Kjell, 1952, et al.
(author)
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Risk factors for norovirus infection in healthcare workers during nosocomial outbreaks: a cross-sectional study
- 2021
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In: Antimicrobial Resistance and Infection Control. - : Springer Science and Business Media LLC. - 2047-2994. ; 10:1
-
Journal article (peer-reviewed)abstract
- Background Norovirus outbreaks cause severe medico-socio-economic problems affecting healthcare workers and patients. The aim of the study was to investigate prevalence of norovirus infection and risk factors for infection in healthcare workers during nosocomial outbreaks. Methods A cross-sectional study of norovirus infections in healthcare workers was performed in seven outbreak wards in a large university hospital. Packs (swab for rectal sampling, and questionnaire) were posted to healthcare workers on notification of a ward outbreak. Rectal samples were examined with norovirus-specific real-time PCR. Replies from questionnaires were analysed using logistic regression models with norovirus genogroup (G)II positive findings as dependent variable. The results are expressed as odds ratios (OR) with 95% confidence intervals (CI). Sequencing and phylogenetic analyses (1040 nucleotides) were used to characterize norovirus strains from healthcare workers. Cluster analyses included norovirus GII.4 strains detected in ward patients during the ongoing outbreaks. Results Of 308 packs issued to healthcare workers, 129 (42%) were returned. norovirus GII was detected in 26 healthcare workers (20.2%). Work in cohort care (OR 4.8, 95% CI 1.4-16.3), work in wards for patients with dementia (OR 13.2, 95% CI 1.01-170.7), and having diarrhoea, loose stools or other gastrointestinal symptoms the last week (OR 7.7, 95% CI 2.5-27.2) were associated with increased norovirus prevalence in healthcare workers. Sequencing revealed norovirus GII.4 in healthcare workers samples, and strains detected in healthcare workers and ward patients during a given ward outbreak showed >= 99% similarity. Conclusion Norovirus positive findings in healthcare workers were strongly associated with symptomatic infection, close contact with sick patients, and dementia nursing.
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| 94. |
- Viklund, Emilia, et al.
(author)
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Severe acute respiratory syndrome coronavirus 2 can be detected in exhaled aerosol sampled during a few minutes of breathing or coughing
- 2022
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In: Influenza and other Respiratory Viruses. - : Wiley. - 1750-2640 .- 1750-2659. ; 16:3, s. 402-10
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Journal article (peer-reviewed)abstract
- Background: The knowledge on the concentration of viral particles in exhaled breath is limited. The aim of this study was to explore if severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be detected in aerosol from subjects with the coronavirus disease 2019 (COVID-19) during various types of breathing and coughing and how infection with SARS-CoV-2 may influence the number and size of exhaled aerosol particles. Methods: We counted and collected endogenous particles in exhaled breath in subjects with COVID-19 disease by two different impaction-based methods, during 20 normal breaths, 10 airway opening breaths, and three coughs, respectively. Breath samples were analyzed with reverse transcription real-time polymerase chain reaction (RT-PCR). Results: Detection of RNA in aerosol was possible in 10 out of 25 subjects. Presence of virus RNA in aerosol was mainly found in cough samples (n = 8), but also in airway opening breaths (n = 3) and in normal breaths (n = 4), with no overlap between the methods. No association between viral load in aerosol and number exhaled particles <5μm was found. Subjects with COVID-19 exhaled less particles than healthy controls during normal breathing and airway opening breaths (all P < 0.05), but not during cough. Conclusion: SARS-CoV-2 RNA can be detected in exhaled aerosol, sampled during a limited number of breathing and coughing procedures. Detection in aerosol seemed independent of viral load in the upper airway swab as well as of the exhaled number of particles. The infectious potential of the amount of virus detected in aerosol needs to be further explored.
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| 95. |
- Westin, Johan, 1965, et al.
(author)
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Dismal prognosis for cirrhotic patients with hepatitis C after initial failure of direct acting anti-virals, but salvage therapy may be life-saving
- 2023
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In: Infectious Diseases. - 2374-4235. ; 55:11, s. 786-793
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Journal article (peer-reviewed)abstract
- BackgroundEffective direct-acting antiviral treatment against hepatitis C virus infection is available in many countries worldwide. Despite good treatment results, a proportion of patients does not respond to treatment. The aim of this study was to investigate the long-term prognosis and the outcome of salvage therapy, after an initial treatment failure, in a nation-wide real-life setting.MethodData from all adult patients registered in the national Swedish hepatitis C treatment register who did not achieve sustained virological response after initial antiviral treatment, was retrieved from 2014 through 2018.ResultsIn total, 288 patients with primary treatment failure were included, of whom 236 underwent a second treatment course as salvage therapy after a median delay of 353 (IQR: 215-650) days. Fifteen patients received a third treatment course as second salvage treatment after a further median delay of 193 (IQR: 160-378) days. One-hundred-eleven out of 124 (90%) non-cirrhotic and 62/79 (78%) cirrhotic patients achieved sustained virological response following the first salvage treatment. Sustained virological response was achieved by 108/112 (96%) patients who received a triple antiviral regimen. In total 69 patients were lost to follow-up or died waiting for salvage treatment. Baseline cirrhosis was associated with poor long-term survival.ConclusionOur study indicates that salvage therapy was effective in most patients with primary treatment failure, in particular when a triple direct acting antiviral regimen was given. To avoid the risk of death or complications, patients with primary treatment failure should be offered salvage therapy with a triple regimen, as soon as possible.
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| 96. |
- Westin, Johan, 1965
(author)
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Hepatitis C virus infection. Viral genotypes and factors promoting liver fibrosis
- 2002
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Doctoral thesis (other academic/artistic)abstract
- Hepatitis C virus (HCV) is associated with chronic infection in a majority of infected individuals. Chronic hepatitis C may result in liver cirrhosis or hepatocellular cancer and is therefore considered a major health problem worldwide. In order to determine the relative prevalence of HCV genotypes in our catchment area, sera from 312 patients were analysed. Genotypes 1a (35%) and 3 (31%) were the most common types, followed by genotypes 2 (17%) and 1b (6%). The relative prevalence of genotype 1b decreased in favour of genotype 3 over time. The genotype distribution pattern was different compared with many other regions, which may be explained by relatively recent introduction of HCV to the Swedish population. Histological examination of liver biopsies is essential in the management of patients with chronic hepatitis. Several scoring systems have been proposed, aiming to facilitate interpretation of histological features, one of them by Ishak et al. To evaluate its interobserver reliability and criterion validity, 95 liver biopsies were independently examined by three observers. We found that if a deviance of one categorical level in any variable was not considered relevant, the method was highly reliable. The scale provided an acceptable compromise between complexity and reliability. Accordingly, it was used in the following studies. The progression of fibrosis over time was retrospectively investigated in 98 patients who underwent two liver biopsies before any treatment. Several host and virus-related factors may influence the fibrosis progression and we chose to study the effect of moderate alcohol intake and of fatty infiltration (steatosis) in the liver. Seventy-eight patients with moderate alcohol consumption responded to a self-administered questionnaire for evaluation of "lifetime drinking history". A subgroup of patients with progressive fibrosis had a higher alcohol intake, and higher "drinking frequency", during the period between the biopsies. Multivariate analysis showed that drinking frequency and time between the biopsies were independently associated with fibrosis progression. Thus, moderate alcohol intake seems to influence the fibrosis development. Analysis of the drinking pattern revealed that drinking frequency affects fibrosis more than the quantity consumed on each occasion. The 98 patients with two liver biopsies were examined for the effect of liver steatosis on fibrosis progression. Both prevalence and grade of steatosis were associated with HCV genotype 3, independent of sex, age, body mass index and alcohol use. Progressive fibrosis was more prevalent in patients with steatosis. This effect was mainly seen in genotype 3-infected patients. Our study thus confirms the hypothesis that steatosis is associated with HCV genotype 3, and, furthermore, with progressive fibrosis over time, especially in genotype 3 patients. These data imply that genotype 3-infected patients with steatosis ought to be selected for early antiviral therapy.
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| 97. |
- Westin, Johan, 1965, et al.
(author)
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Multiplex real-time PCR for detection of respiratory tract infections
- 2008
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In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 41:1, s. 53-56
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Journal article (peer-reviewed)abstract
- Background Broad diagnostics of respiratoryinfection by molecular assays has not yet won acceptance due to technical difficulties and high costs. Objectives To evaluate clinical applicability of multiplexreal-timePCR. Study design An assay targeting influenza virus A (IfA) and B (IfB), parainfluenza 1-3 (PIV), human metapneumovirus (MPV), respiratory syncytial virus (RSV), rhinovirus (RV), enterovirus (EV), adenovirus (AdV), human coronaviruses (229E, OC43, NL63), M. pneumoniae and Ch. pneumoniae was developed and run daily on consecutive clinical nasopharyngeal swab samples. Results An etiology was identified in 48% of the 954 samples, with IfA in 25%, RV in 20%, MPV in 10% and M. pneumoniae in 10% of the positive. By a rational procedure costs could be reduced and the customer price set relatively low (€33 per sample). Conclusion Streamlined testing and cost limitation is achievable and probably critical for implementation of a broad molecular diagnostics of respiratoryinfections.
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| 98. |
- Widström, Julia, et al.
(author)
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Complex norovirus transmission dynamics at hospital wards revealed by deep sequencing
- 2023
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In: Journal of Clinical Microbiology. - 0095-1137. ; 61:11
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Journal article (peer-reviewed)abstract
- Detailed knowledge regarding norovirus transmission within hospitals is limited. We investigated a norovirus hospital outbreak affecting 65 patients at five different wards. PCR showed that 61 (94%) of the patients were infected with genotype II.4 strains. Successful Ion Torrent deep sequencing of GII.4 positive samples from 59 patients followed by phylogenetic analysis revealed that all sequences but two clustered into four distinct clades. Two of the clades belonged to GII.4 Sydney 2012, while the other two belonged to GII.4 New Orleans 2009. One of the clades was predominant at two wards, while two clades were predominant at one ward each. The fourth clade was found in sporadic cases at several wards. Thus, at four out of five wards, variants from one clade were predominant. At one ward, a single clade accounted for all cases, while at three wards the predominant clade accounted for 60%-71% of cases. Analysis of quasispecies variation identified positions that could further discriminate between variants from separate wards. The results illustrate a complex transmission of healthcare-associated norovirus infections and show that sequencing can be used to discriminate between related and unrelated cases.
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