| 1. |
- Hernroth, Bodil E., et al.
(författare)
-
Environmental factors influencing human viral pathogens and their potential indicator organisms in the blue mussel, Mytilus edulis : the first Scandinavian report
- 2002
-
Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 68:9, s. 4523-4533
-
Tidskriftsartikel (refereegranskat)abstract
- This study was carried out in order to investigate human enteric virus contaminants in mussels from three sites on the west coast of Sweden, representing a gradient of anthropogenic influence. Mussels were sampled monthly during the period from February 2000 to July 2001 and analyzed for adeno-, entero-, Norwalk-like, and hepatitis A viruses as well as the potential viral indicator organisms somatic coliphages, F-specific RNA bacteriophages, bacteriophages infecting Bacteroides fragilis, and Escherichia coli. The influence of environmental factors such as water temperature, salinity, and land runoff on the occurrence of these microbes was also included in this study. Enteric viruses were found in 50 to 60% of the mussel samples, and there were no pronounced differences between the samples from the three sites. E. coli counts exceeded the limit for category A for shellfish sanitary safety in 40% of the samples from the sites situated in fjords. However, at the site in the outer archipelago, this limit was exceeded only once, in March 2001, when extremely high levels of atypical indole-negative strains of E. coli were registered at all three sites. The environmental factors influenced the occurrence of viruses and phages differently, and therefore, it was hard to find a coexistence between them. This study shows that, for risk assessment, separate modeling should be done for every specific area, with special emphasis on environmental factors such as temperature and land runoff. The present standard for human fecal contamination, E. coli, seems to be an acceptable indicator of only local sanitary contamination; it is not a reliable indicator of viral contaminants in mussels. To protect consumers and get verification of "clean" mussels, it seems necessary to analyze for viruses as well. The use of a molecular index of the human contamination of Swedish shellfish underscores the need for reference laboratories with high-technology facilities.
|
|
| 2. |
- Formiga-Cruz, M, et al.
(författare)
-
Evaluation of potential indicators of viral contamination in shellfish and their applicability to diverse geographical areas.
- 2003
-
Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 69:3, s. 1556-63
-
Tidskriftsartikel (refereegranskat)abstract
- The distribution of the concentration of potential indicators of fecal viral pollution in shellfish was analyzed under diverse conditions over 18 months in diverse geographical areas. These microorganisms have been evaluated in relation to contamination by human viral pathogens detected in parallel in the analyzed shellfish samples. Thus, significant shellfish-growing areas from diverse countries in the north and south of Europe (Greece, Spain, Sweden, and the United Kingdom) were defined and studied by analyzing different physicochemical parameters in the water and the levels of Escherichia coli, F-specific RNA bacteriophages, and phages infecting Bacteroides fragilis strain RYC2056 in the shellfish produced, before and after depuration treatments. A total of 475 shellfish samples were studied, and the results were statistically analyzed. According to statistical analysis, the presence of human viruses seems to be related to the presence of all potential indicators in the heavily contaminated areas, where E. coli would probably be suitable as a fecal indicator. The F-RNA phages, which are present in higher numbers in Northern Europe, seem to be significantly related to the presence of viral contamination in shellfish, with a very weak predictive value for hepatitis A virus, human adenovirus, and enterovirus and a stronger one for Norwalk-like virus. However, it is important to note that shellfish produced in A or clean B areas can sporadically contain human viruses even in the absence of E. coli or F-RNA phages. The data presented here will be useful in defining microbiological parameters for improving the sanitary control of shellfish consumed raw or barely cooked.
|
|
| 3. |
- Johansen, Kari, et al.
(författare)
-
Norovirus strains belonging to the GII.4 genotype dominate as a cause of nosocomial outbreaks of viral gastroenteritis in Sweden 1997-2005 - Arrival of new variants is associated with large nation-wide epidemics
- 2008
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 42:2, s. 129-134
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In recent years an increase of the incidence of nosocomial outbreaks caused by noroviruses has been observed throughout Sweden, with high peaks noted in the winter seasons 2002/2003 and 2004/2005, respectively. Objectives: To phylogenetically characterize norovirus strains causing nosocomial outbreaks from 1997 to 2005 and estimate the impact of norovirus-like disease on the Swedish health care system during the peak season 2002/2003 when a new variant of norovirus occurred. Study design: Stool samples from 115 randomly selected nosocomial outbreaks occurring during 1997-2005 throughout Sweden were studied by RT-PCR and sequencing. In addition, to investigate the impact on the health-care system, a questionnaire was distributed to infection control units (n = 90) serving all Swedish hospitals, nursing homes and other health-care institutions during the largest epidemic of nosocomial outbreaks. Results: Sequencing of 279 nucleotides of the norovirus RNA polymerase gene in stools containing norovirus RNA showed that strains belonging to the GII.4 genotype dominated. Each of the two large epidemics was due to a new variant within this cluster. The questionnaire revealed that 30,000-35,000 episodes of nosocomial norovirus-like infections occurred in 80 of 82 major Swedish hospitals affected in 2002/2003. Conclusion: New norovirus variants within the cluster GGII.4 may have a major impact on the health-care system. (c) 2008 Elsevier B.V. All rights reserved.
|
|
| 4. |
- Allard, Annika, 1958-
(författare)
-
Enteric adenovirus type 41 : genome organization and specific detection procedures
- 1992
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Enteric adenoviruses (EAd) types 40 and 41 (Ad40 and Ad41) representing subgenus F, are primary pathogens of children being second only to rotaviruses as the most important cause of infantile diarrhea.The EAds differ from all other adenoviruses in their inability to grow in most conventional established cell lines and have been suggested to be deficient in some early gene functions since they could be complemented by Ad 5 early regions EIA and E1B. In order to search for differences that could explain its characteristic growth restriction, the early regions EIA and E1B of Ad41 (strain D389) were sequenced, analysed and compared with the corresponding regions of Adl2, Ad7, Ad2, and Ad4. As revealed by the analysis of Ad2, three major mRNAs of 9S, 12S and 13S are generated from region EIA. The EIA region of Ad41 encodes two mRNAs corresponding to the 12S and 13S mRNAs. Only the 13S mRNA is transcribed at detectable levels. This mRNA can be translated into a 251 aa putative protein that contains the three highly conserved domains found in all other human adenoviruses and shown to be responsible for many important regulatory functions during infection.The E1B region of Ad41 encodes three transcripts that correspond to 22S, 14S and 9S mRNA of Ad2. No equivalent to the 13S mRNA of Ad2 E1B is found. In addition the Ad41 14S mRNA exhibits an additional exon of 23 bp created by a donor and an acceptor splice sites not desribed for other adenovirus E1B sequences.Due to their growth restriction in conventional cultures, rapid diagnostic procedures developed for the enteric adenovirus infections have mainly been aimed at the detection of viral antigens or nucleic acids. This thesis also describes several procedures developed for the general detection of adenoviruses and specific detection of the enteric types in stools specimens. General and specific hybridization assays were developed by use of two BamHI clones obtained from the EIA region of Ad41. One- and two-step PCR procedures were also developed for the general detection of adenoviruses using primers corresponding to highly conserved sequences within the hexon gene. Subgenus F specific one- and two-step PCRs were developed by using primers located in the Ad41 E1B region.The one-step PCR systems were tested and validated against isolation in tissue culture, DNA restriction enzyme analysis and a commercial latex agglutination test in the study of 60 specimens obtained from children with rotavirus negative diarrhea. The asymptomatic fecal excretion of adenoviruses was evaluated by two-step PCR amplifications on samples from 50 healthy children, 50 healthy adults, and 50 adults suffering from diarrhea.Finally, a simplified procedure for detection, discrimination and typing of EAd was also designed by combining the one-step PCR amplification of the hexon region with the restriction of the 300 bp product.
|
|
| 5. |
|
|
| 6. |
- Allard, Karin, et al.
(författare)
-
A gender perspective in the relationship between work demands, boundary setting strategies and organizational flexibility in work-family conflict among managers in the public sector
- 2014
-
Ingår i: Threats and possibilities facing Nordic working life. - 9789198119558 ; , s. 169-169
-
Konferensbidrag (refereegranskat)abstract
- It is common to view work-family dilemmas like work-family conflict as the individual’s problem despite the fact that these kinds of dilemmas often have contextual sources. The aim of the present study is to explore the experience of work-family conflict among governmental employed managers by examining work demands, boundary setting strategies and organizational flexibility at the individual and at a contextual level where both the organizational belongingness and the gender composition is examined.Our results show that organizational and contextual research on work-family issues contributes with knowledge about organizational aspects and processes that managers in organizations have to be aware of instead of understanding work-family dilemmas as individuals’ problems. We also conclude that a gender perspective both at the individual and at the organizational level is needed in the field of work-family research.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
- Andersson, Emma K, 1978-, et al.
(författare)
-
Small molecule screening using a whole cell viral replication reporter gene assay identifies 2-{[2-(benzoylamino)benzoyl]amino}-benzoic acid as a novel anti-adenoviral compound
- 2010
-
Ingår i: Antimicrobial Agents and Chemotherapy. - : American society for microbiology. - 0066-4804 .- 1098-6596. ; 54:9, s. 3871-3877
-
Tidskriftsartikel (refereegranskat)abstract
- Adenovirus infections are widespread in society and are occasionally associated with severe, but rarely with life-threatening, disease in otherwise healthy individuals. In contrast, adenovirus infections present a real threat to immunocompromised individuals and can result in disseminated and fatal disease. The number of patients undergoing immunosuppressive therapy for solid organ or hematopoietic stem cell transplantation is steadily increasing, as is the number of AIDS patients, and this makes the problem of adenovirus infections even more urgent to solve. There is no formally approved treatment of adenovirus infections today, and existing antiviral agents evaluated for their anti-adenoviral effect give inconsistent results. We have developed a whole cell-based assay for high-throughput screening of potential anti-adenoviral compounds. The assay is unique in that it is based on a replication competent adenovirus type 11p GFP-expressing vector (RCAd11pGFP). This allows measurement of fluorescence changes as a direct result of RCAd11pGFP genome expression. Using this assay, we have screened 9,800 commercially available small organic compounds. Initially, we observed approximately 400 compounds that inhibited adenovirus expression in vitro by >/= 80% but only 24 were later confirmed as dose-dependent inhibitors of adenovirus. One compound in particular, 2-[[2-(benzoylamino)benzoyl]amino]-benzoic acid, turned out to be a potent inhibitor of adenovirus replication.
|
|
| 10. |
- Bergh, Johanna, et al.
(författare)
-
No link between viral findings in the prostate and subsequent cancer development
- 2007
-
Ingår i: British Journal of Cancer. - London : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 96:1, s. 137-139
-
Tidskriftsartikel (refereegranskat)abstract
- In an investigation of 201 prostate tissue samples from patients with benign prostate hyperplasia that later progressed to prostate cancer and 201 matched controls that did not, there were no differences in the prevalence of adenovirus, herpesvirus, papilloma virus, polyoma virus and Candida albicans DNA.
|
|
| 11. |
|
|
| 12. |
- Bofill-Mas, Silvia, et al.
(författare)
-
Quantification and stability of human adenoviruses and polyomavirus JCPyV in wastewater matrices.
- 2006
-
Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 72:12, s. 7894-6
-
Tidskriftsartikel (refereegranskat)abstract
- Human adenoviruses (HAdV) and human polyomavirus JCPyV have been previously proposed as indicators of fecal viral contamination in the environment. Different wastewater matrices have been analyzed by applying real-time quantitative PCR procedures for the presence, quantity, and stability of a wide diversity of excreted HAdV and JCPyV. High quantities of HAdV and JCPyV were detected in sewage, effluent wastewater, sludge, and biosolid samples. Both viruses showed high stability in urban sewage. These results confirm the suitability of both viruses as indicators of human fecal viral pollution.
|
|
| 13. |
- Brion, Gail, et al.
(författare)
-
Artificial neural network prediction of viruses in shellfish.
- 2005
-
Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 71:9, s. 5244-53
-
Tidskriftsartikel (refereegranskat)abstract
- A database was probed with artificial neural network (ANN) and multivariate logistic regression (MLR) models to investigate the efficacy of predicting PCR-identified human adenovirus (ADV), Norwalk-like virus (NLV), and enterovirus (EV) presence or absence in shellfish harvested from diverse countries in Europe (Spain, Sweden, Greece, and the United Kingdom). The relative importance of numerical and heuristic input variables to the ANN model for each country and for the combined data was analyzed with a newly defined relative strength effect, which illuminated the importance of bacteriophages as potential viral indicators. The results of this analysis showed that ANN models predicted all types of viral presence and absence in shellfish with better precision than MLR models for a multicountry database. For overall presence/absence classification accuracy, ANN modeling had a performance rate of 95.9%, 98.9%, and 95.7% versus 60.5%, 75.0%, and 64.6% for the MLR for ADV, NLV, and EV, respectively. The selectivity (prediction of viral negatives) was greater than the sensitivity (prediction of viral positives) for both models and with all virus types, with the ANN model performing with greater sensitivity than the MLR. ANN models were able to illuminate site-specific relationships between microbial indicators chosen as model inputs and human virus presence. A validation study on ADV demonstrated that the MLR and ANN models differed in sensitivity and selectivity, with the ANN model correctly identifying ADV presence with greater precision.
|
|
| 14. |
- Brion, G, et al.
(författare)
-
Probing Norwalk-like virus presence in shellfish, using artificial neural networks.
- 2004
-
Ingår i: Water Science and Technology. - 0273-1223 .- 1996-9732. ; 50:1, s. 125-9
-
Tidskriftsartikel (refereegranskat)abstract
- A database was examined using artificial neural network (ANN) models to investigate the efficacy of predicting PCR-identified Norwalk-like virus presence and absence in shellfish. The relative importance of variables in the model and the predictive power obtained by application of ANN modelling methods were compared with previously developed logistic regression models. In addition, two country-specific datasets were analysed separately with ANN models to determine if the relative importance of the input variables was similar for geographically diverse regions. The results of this analysis found that ANN models predicted Norwalk-like virus presence and absence in shellfish with equivalent, and better, precision than logistic regression models. For overall classification performance, ANN modelling had a rate of 93%, vs 75% for the logistic regression. ANN models were able to illuminate the site-specific relationships between indicators and pathogens.
|
|
| 15. |
- Duursma, Allard, et al.
(författare)
-
UN Peacekeeping at 75: Achievements, Challenges, and Prospects
- 2023
-
Ingår i: International Peacekeeping. - : Routledge. - 1353-3312 .- 1743-906X. ; 30:4, s. 415-476
-
Tidskriftsartikel (refereegranskat)abstract
- This year marks the 75th anniversary of what the UN itself understands to be its first peacekeeping operation. It is therefore an appropriate time to reflect on the track record of UN peacekeeping in its efforts to try to maintain and realize peace and security. Moreover, this milestone invites us to ponder what lies ahead in the realm of peacekeeping. For this reason, this forum article brings together both academics and UN officials to assess the achievements and challenges of UN peacekeeping over the past 75 years. Through a dialogue among peacekeeping scholars and practitioners, we hope to identify current trends and developments in UN peacekeeping, as well as explore priorities for the future to improve the effectiveness of peacekeeping operations in terms of achieving their mandate objectives, such as maintaining peace, protecting civilians, promoting human rights, and facilitating reconciliation. This forum article is structured into six thematic sections, each shedding light on various aspects of UN peacekeeping: (1) foundational principles of UN peacekeeping - namely, consent, impartiality, and the (non-)use of force; (2) protection of civilians; (3) the primacy of politics; (4) early warning; (5) cooperation with regional organizations; and (6) the changing geopolitical landscape in which UN peacekeeping operates.
|
|
| 16. |
- Edin, Alicia, et al.
(författare)
-
Development and Laboratory Evaluation of a Real-Time PCR Assay for Detecting Viruses and Bacteria of Relevance for Community-Acquired Pneumonia
- 2015
-
Ingår i: Journal of Molecular Diagnostics. - : Elsevier BV. - 1525-1578 .- 1943-7811. ; 17:3, s. 315-324
-
Tidskriftsartikel (refereegranskat)abstract
- Community-acquired pneumonia may present with similar clinical symptoms, regardless of viral or bacterial cause. Diagnostic assays are needed to rapidly discriminate between causes, because this will guide decisions on appropriate treatment. Therefore, a quantitative real-time PCR (qPCR) assay with duplex reactions targeting eight bacteria and six viruses was developed. Technical performance was examined with linear plasmids. Upper and Lower respiratory tract specimens were used to compare the qPCR assay with standard microbiological methods. The limit of detection was 5 to 20 DNA template copies with approximately 1000-fold differences in concentrations of the two competing templates. SDs for positive controls were <5%. The use of the qPCR assay resulted in 113 positive identifications in 94 respiratory specimens compared with 38 by using standard diagnostics. Diagnostic accuracy of the qPCR assay varied between 60% positive agreement with standard tests for Streptococcus pneumoniae and 100% for Mycoplasma pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus. Negative percentage of agreement was >95% for M. pneumoniae, Streptococcus pyogenes, respiratory syncytial virus, and influenza A virus; whereas it was only 56% for Haemophilus influenzae. Multiple microbial agents were identified in 19 of 44 sputum and 19 of 50 nasopharynx specimens. We conclude that in parallel qPCR detection of the targeted respiratory bacteria and viruses is feasible. The results indicate good technical performance of the assay in clinical specimens.
|
|
| 17. |
- Edin, Alicia, 1985-, et al.
(författare)
-
Evaluation of the Biofire Filmarray Pneumonia panel plus for lower respiratory tract infections
- 2020
-
Ingår i: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 52:7, s. 479-488
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Standard diagnostic methods for lower respiratory tract infections are currently too slow and insensitive to guide early clinical decisions concerning treatment and isolation. Syndrome-specific, diagnostic panels have potential to provide information about aetiology quickly. Available panels have been of limited use in lower respiratory tract infections due to slow turn-around-time, lack of quantification of important pathogens and lack of detection of resistance genes.Materials/methods: We evaluated the newly developed Biofire(R) Filmarray(R) Pneumonia Panel plus (Biomerieux). Eighty-eight consecutive lower respiratory tract samples were analyzed by both standard microbiological methods, as requested by the referring clinician, and by the panel. The agreement with standard methods, empirical treatment coverage and possible impact on isolation practices were assessed by comparing the results from standard diagnostic methods with the panel results in relation to clinical data and information of antimicrobial therapy.Results: Both qualitative and semi-quantitative results from the panel generally displayed good agreement with standard methods and by combining methods, a possible aetiology was detected in 73% of patients. Due to the panel approach, the panel detected viruses more frequently. In 25% of the 60 patients assessed for empirical treatment coverage, a pathogen not covered by current therapy was detected and in 30% of in-house patients the panel results were found to potentially influence clinical decisions related to isolation care.Conclusions: The new diagnostic panel shows promise in improving aetiological diagnostics of lower respiratory tract infections. Correctly applied it has potential to offer support in clinical decision-making within hours of sampling.
|
|
| 18. |
- Edin, Alicia, 1985-
(författare)
-
Improved diagnosis and prediction of community-acquired pneumonia
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. Although there is wide variation in the microbial etiology, CAP may manifest with similar symptoms, making institution of proper treatment challenging. Therefore, etiological diagnosis is important to ensure that correct treatment and necessary infection control measures are instituted. This provides a challenge for conventional microbial diagnostic methods, typically based on culture and direct antigen tests. Moreover, existing molecular biomarkers have poor prognostic value. Few studies have investigated the global metabolic response during infection and virtually nothing is known about early responses after the start of antimicrobial treatment. The aim of this work was to improve diagnostic and predictive methods for CAP.In paper I, a qPCR panel targeting 15 pathogens known to cause CAP was developed and evaluated. It combined identification of bacterial pathogens and viruses in the same diagnostic platform. The method proved to be robust and the results consistent with those obtained by standard methods. The panel approach, compared to conventional, selective diagnostics, detected a larger number of pathogens. In Paper II, whole blood samples from 65 patients with bacteremic sepsis were analyzed for metabolite profiles. Forty-nine patients with symptoms of sepsis, but later attributed to other diagnoses, were matched according to age and sex and served as a control group. Six metabolites were identified, all of which predicted growth of bacteria in blood culture. One of the metabolites, myristic acid, alone predicted bacteremic sepsis with a sensitivity of 100% and a specificity of 95%. Paper III and IV were based on a clinical study enrolling 35 patients with suspected CAP in need of hospital care. The aim was to study the metabolic response during the early phase of acute infection. The qPCR panel developed in Paper I was used to obtain the microbial etiological diagnosis. Paper IV focused on the global metabolic response and highlighted the dynamics of changes in major metabolic pathways during early recovery. A specific metabolite pattern for M. pneumoniae etiology was found. Four metabolites accurately predicted all but one patient as either M. pneumoniae etiology or not. Paper III looked at phospholipid levels during the first 48 hours after hospital admission. It was found that all major phospholipid species, especially the lysophosphatidyl-cholines, were pronouncedly decreased during acute infection. Levels started to increase the day after admission, reaching statistical significance at 48 hours. Paper II-IV showed that metabolomics might be used to study a number of different aspects of infection, such as etiology, disease progress and recovery. Knowledge of the metabolic profiles of patients may not only be utilized for biomarker discovery, as proposed in this work, but also for the future development of targeted therapies and supportive treatment.
|
|
| 19. |
- Evander, Magnus, et al.
(författare)
-
Puumala hantavirus viremia diagnosed by real-time reverse transcriptase PCR using samples from patients with hemorrhagic fever and renal syndrome
- 2007
-
Ingår i: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 45:8, s. 2491-2497
-
Tidskriftsartikel (refereegranskat)abstract
- Puumala virus (PUUV) is the endemic hantavirus in northern Sweden and causes nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome. There is a need for fast and reliable diagnostics to differentiate the disease from other infections. By aligning virus RNA sequences isolated from 11 different bank voles and one human patient, we designed a real-time reverse transcriptase (RT) PCR method for detection of PUUV RNA. The real-time RT-PCR assay showed linearity from 20 to 2 x 10(6) virus copies with a correlation coefficient above 0.98 to 0.99 for all experiments. The detection threshold for PUUV cDNA was two copies per reaction. A two-step qualitative RT-PCR to detect PUUV RNA showed 100% concordance with the real-time RT-PCR assay. PUUV RNA viremia was detected in 33 of 34 PUUV immunoglobulin M (IgM)-positive patients with typical clinical NE disease from the region of endemicity. One PUUV IgM-negative sample had PUUV RNA, and 4 days later, the patient was IgM positive. Of samples with indeterminate IgM, 43% were PUUV RNA positive. The kinetics of antibody titers and PUUV viremia were studied, and five of six NE patients displayed a decrease in PUUV viremia a few days after disease outbreak coupled with an increase in PUUV IgM and IgG. In one patient with continuously high PUUV RNA levels but low IgM and no IgG response, the infection was lethal. These findings demonstrated that real-time RT-PCR is a useful method for diagnosis of PUUV viremia and for detecting PUUV RNA at early time points, before the appearance of IgM antibodies.
|
|
| 20. |
- Filén, Finn, et al.
(författare)
-
Duplex real-time polymerase chain reaction assay for detection and quantification of herpes simplex virus type 1 and herpes simplex virus type 2 in genital and cutaneous lesions
- 2004
-
Ingår i: Sexually Transmitted Diseases. - 0148-5717 .- 1537-4521. ; 31:6, s. 331-6
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A sensitive and specific method for detecting herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) is important for diagnosing genital and cutaneous infections. GOAL: The goal of this study was to compare quantitative real-time polymerase chain reaction (qPCR) with virus culture for diagnosis of genital and cutaneous HSV-1 and HSV-2. STUDY DESIGN: A duplex qPCR system for quantification of DNA from HSV-1 and HSV-2 was developed. Duplicate swabs for PCR and virus culture were collected from 89 patients attending our sexually transmitted infection and dermatology clinic. RESULTS: The duplex qPCR had a linear measure interval of 10-10 copies/mL. The detection limit was between 1 and 5 copies per reaction. qPCR detected HSV in 57 (64%) specimens and virus was isolated in 45 (50%) cases. First-episode infections showed higher viral quantities with a median value of 4.2 x 10 copies per reaction compared with recurrent infections with 1.0 x 10 (P = 0.0002). HSV-1 was more likely to be the cause of first-episode genital infections (72%), and HSV-2 of recurrent and atypical genital manifestations (73%). CONCLUSION: Real-time PCR is a sensitive method for diagnosing genital herpes, and the duplex format is convenient for typing. The method increased the detection rate by 27% compared with virus culture.
|
|
| 21. |
- Formiga-Cruz, M, et al.
(författare)
-
Evaluation of potential indicators of viral contamination in shellfish and their applicability to diverse geographical areas
- 2003
-
Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 69:3, s. 1556-1563
-
Tidskriftsartikel (refereegranskat)abstract
- The distribution of the concentration of potential indicators of fecal viral pollution in shellfish was analyzed under diverse conditions over 18 months in diverse geographical areas. These microorganisms have been evaluated in relation to contamination by human viral pathogens detected in parallel in the analyzed shellfish samples. Thus, significant shellfish-growing areas from diverse countries in the north and south of Europe (Greece, Spain, Sweden, and the United Kingdom) were defined and studied by analyzing different physicochemical parameters in the water and the levels of Escherichia coli, F-specific RNA bacteriophages, and phages infecting Bacteroides fragilis strain RYC2056 in the shellfish produced, before and after depuration treatments. A total of 475 shellfish samples were studied, and the results were statistically analyzed. According to statistical analysis, the presence of human viruses seems to be related to the presence of all potential indicators in the heavily contaminated areas, where E. coli would probably be suitable as a fecal indicator. The F-RNA phages, which are present in higher numbers in Northern Europe, seem to be significantly related to the presence of viral contamination in shellfish, with a very weak predictive value for hepatitis A virus, human adenovirus, and enterovirus and a stronger one for Norwalk-like virus. However, it is important to note that shellfish produced in A or clean B areas can sporadically contain human viruses even in the absence of E. coli or F-RNA phages. The data presented here will be useful in defining microbiological parameters for improving the sanitary control of shellfish consumed raw or barely cooked.
|
|
| 22. |
- Formiga-Cruz, Meritxell, et al.
(författare)
-
Nested multiplex PCR assay for detection of human enteric viruses in shellfish and sewage.
- 2005
-
Ingår i: Journal of Virological Methods. - : Elsevier BV. - 0166-0934 .- 1879-0984. ; 125:2, s. 111-8
-
Tidskriftsartikel (refereegranskat)abstract
- Environmental samples and contaminated shellfish present frequently low concentrations of more than one viral species. For this reason, a nested multiplex RT-PCR was developed for the detection of adenoviruses, enteroviruses and hepatitis A viruses in different environmental samples such as urban sewage and shellfish. This assay will save time and cost for detection of these enteric viruses with a smaller sample volume, which otherwise can be a limiting factor in routine analysis. The limit of detection was approximately 1 copy for adenovirus and 10 copies for enterovirus and hepatitis A virus per PCR reaction using titrated cell-cultured viruses as template material. In shellfish and environmental samples, this multiplex PCR was optimized to detect all three viruses simultaneously when the concentration of each virus was equal or lower than 1000 copies per PCR reaction. This is the level found predominantly in the environment and in shellfish when the numbers of fecal bacterial and phage indicators are low. The detection of human adenoviruses by PCR has been suggested as a molecular index of fecal contamination of human origin in the environment and food and the multiplex assay developed may be a tool for evaluating the presence of viral contamination in shellfish and water and to expand microbiological control to include viral markers.
|
|
| 23. |
- Fresard, Laure, et al.
(författare)
-
Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
-
Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
-
Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
|
|
| 24. |
- Hernroth, Bodil, 1951, et al.
(författare)
-
Environmental factors influencing human viral pathogens and their potential indicator organisms in the blue mussel, Mytilus edulis: the first Scandinavian report
- 2002
-
Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 68:9, s. 4523-4533
-
Tidskriftsartikel (refereegranskat)abstract
- This study was carried out in order to investigate human enteric virus contaminants in mussels from three sites on the west coast of Sweden, representing a gradient of anthropogenic influence. Mussels were sampled monthly during the period from February 2000 to July 2001 and analyzed for adeno-, entero-, Norwalk-like, and hepatitis A viruses as well as the potential viral indicator organisms somatic coliphages, F-specific RNA bacteriophages, bacteriophages infecting Bacteroides fragilis, and Escherichia coli. The influence of environmental factors such as water temperature, salinity, and land runoff on the occurrence of these microbes was also included in this study. Enteric viruses were found in 50 to 60% of the mussel samples, and there were no pronounced differences between the samples from the three sites. E. coli counts exceeded the limit for category A for shellfish sanitary safety in 40% of the samples from the sites situated in fjords. However, at the site in the outer archipelago, this limit was exceeded only once, in March 2001, when extremely high levels of atypical indole-negative strains of E. coli were registered at all three sites. The environmental factors influenced the occurrence of viruses and phages differently, and therefore, it was hard to find a coexistence between them. This study shows that, for risk assessment, separate modeling should be done for every specific area, with special emphasis on environmental factors such as temperature and land runoff. The present standard for human fecal contamination, E. coli, seems to be an acceptable indicator of only local sanitary contamination; it is not a reliable indicator of viral contaminants in mussels. To protect consumers and get verification of "clean" mussels, it seems necessary to analyze for viruses as well. The use of a molecular index of the human contamination of Swedish shellfish underscores the need for reference laboratories with high-technology facilities.
|
|
| 25. |
- Holm, Anna, et al.
(författare)
-
Absence de papillomavirus humain à risque élevé dans le papillome inversé naso-sinusien p16 positif : [Absence of high-risk human papillomavirus in p16 positive inverted sinonasal papilloma]
- 2020
-
Ingår i: Annales Francaises d'Oto-Rhino-Laryngologie et de Pathologie Cervico-Faciale. - : Elsevier. - 1879-7261. ; 137:3, s. 186-191
-
Tidskriftsartikel (refereegranskat)abstract
- Le papillome inversé naso-sinusien (PINS) est une tumeur relativement rare dont l’étiologie est mal connue. Elle se caractérise par une agressivité locale et un fort potentiel de récidive en dépit d’une histologie bénigne.Objectif: L’objectif de cette étude était d’identifier la présence du papillomavirus humain (HPV) et de son marqueur de substitution, la protéine p16, dans des prélèvements tissulaires de PINS issus d’une cohorte régionale.Matériels et méthodes: À partir de notre cohorte régionale de 88 patients atteints de PINS traités entre 1984 et 2014, 54 sujets ont été sélectionnés et inclus dans cette étude. La technologie PCR a été réalisée sur 53 prélèvements et la coloration immunohistochimique pour recherche de p16 a été réalisée sur 54 prélèvements. L’ADN a été extrait après confirmation histopathologique du PINS. Un génotypage pour 13 types de HPV à risque élevé, 5 types de HPV à risque oncogène et 6 types de HPV à faible risque a été réalisé à l’aide du test de dépistage HPV PapilloCheck®.Résultats: L’analyse HPV a été réalisable sur 38 des 53 prélèvements. Sur ces 38 prélèvements, seuls 2 étaient positifs pour HPV 11. L’analyse immunohistochimique a montré que p16 était présent dans l’épithélium de tous les prélèvements, et dans les régions papillomateuses de 37 prélèvements.Conclusion: Étant donné que seuls 2 sur 38 PINS étaient positifs pour HPV (type 11) et que, dans le même temps, p16 était positif dans l’épithélium de tous les prélèvements et dans 37 des 38 régions papillomateuses, nous avons conclu que p16 ne peut pas être utilisé comme marqueur de substitution pour l’infection HPV à risque élevé dans le PINS. Nous préparons actuellement une étude multicentrique prospective afin d’augmenter la puissance de l’étude et de pouvoir mieux évaluer les implications cliniques de HPV et de p16 dans le PINS.
|
|
| 26. |
- Holm, Anna, et al.
(författare)
-
Absence of high-risk human papilloma virus in p16 positive inverted sinonasal papilloma
- 2020
-
Ingår i: European Annals of Otorhinolaryngology, Head and Neck Diseases. - : Elsevier Masson SAS. - 1879-7296 .- 1879-730X. ; 137:3, s. 201-206
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Sinonasal inverted papilloma (SIP) is a relatively rare disease, and its etiology is not understood. It is characterized by locally aggressive growth and a strong tendency to recur despite its benign histology.Aims: The aim of this study was to identify the presence of human papilloma virus (HPV) and its surrogate marker p16 in SIP tissue samples from a regional cohort.Material and methods: Subjects were identified from our regional center cohort of 88 SIP patients treated between 1984–2014. From these subjects, 54 were included in this study. Of these, 53 biopsies were analyzed with PCR, and 54 samples were immunohistochemically stained for p16. DNA was extracted from histopathologically verified SIP. Genotype screening for 13 high risk-, 5 oncogenic and 6 low risk HPV types was performed using the PapilloCheck® HPV-screening test.Results: HPV analysis was successful for 38 of 53 samples. Of the 38 successfully analyzed samples, only 2 samples were positive for HPV 11. Notably, p16 was present in the epithelia in all samples, and in the papilloma lesions in 37 samples.Conclusion: Since only 2 out of 38 SIPs were positive for HPV (type 11), and at the same time p16 was positive in epithelia in all samples and in 37 of 38 papilloma lesions of the samples, it is concluded that p16 cannot be used as a surrogate marker for high-risk HPV-infection in SIP. We are currently planning a prospective, multicenter study in order to increase the study power and in order to be able to better evaluate the clinical implications of HPV-and p16 in SIP.
|
|
| 27. |
- Holm, Anna, et al.
(författare)
-
Mapping of Human Papilloma Virus, p16, and Epstein-Barr Virusin Non-Malignant Tonsillar Disease
- 2019
-
Ingår i: Laryngoscope Investigative Otolaryngology (LIO). - : Wiley-Blackwell. - 2378-8038. ; 4:3, s. 285-291
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Due to their location in the entrance of the aero‐digestive tract, tonsils are steadily exposed to viruses. Human papilloma virus (HPV) and Epstein‐Barr virus (EBV) are two potentially oncogenic viruses that tonsils encounter. The incidence of HPV positive tonsillar cancer is on the rise and it is unknown when infection with HPV occurs.Aim: To investigate if tonsils are infected with HPV and EBV, to study the co‐expression of HPV and its surrogate marker p16, and to evaluate the number of EBV positive cells in benign tonsillar disease.Materials and Methods: Tonsils from 40 patients in a university hospital were removed due to hypertrophy, chronic or recurrent infection. These were analyzed for presence of HPV, its surrogate marker p16, and EBV. HPV was studied using PapilloCheck (a PCR method), while p16 was identified in epithelial and lymphoid tissue with immunohistochemistry and EBV using EBER‐ISH (Epstein‐Barr encoding region–in situ hybridization).Results: HPV was not detected, and p16 was present at low numbers in all epithelial samples as well as in 92.5% of the lymphoid tonsillar samples. At least one EBER‐positive cell was seen in 65% of cases. Larger numbers of EBER‐expressing cells were only seen in two cases.Conclusion: These findings demonstrate that EBV and HPV infect tonsils independently, but further studies are warranted to confirm their infectious relationship.Level of Evidence: Cross‐sectional study
|
|
| 28. |
- Kaján, Gyõzõ L., et al.
(författare)
-
A multigene typing system for human adenoviruses reveals a new genotype in a collection of Swedish clinical isolates
- 2018
-
Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 13:12
-
Tidskriftsartikel (refereegranskat)abstract
- Human adenoviruses (HAdVs) are common pathogens that can cause respiratory, gastrointestinal, urogenital, and ocular infections. They are divided into seven species containing 85 genotypes. Straightforward typing systems might help epidemiological investigations. As homologous recombination frequently shapes the evolution of HAdVs, information on a single gene is seldom sufficient to allow accurate and precise typing, and complete genome-based methods are recommended. Even so, complete genome analyses are not always easy to perform for practical reasons, and in such cases a multigene system can provide considerably more information about the strain under investigation than single-gene-based methods. Here we present a rapid, generic, multigene typing system for HAdVs based on three main deterministic regions of these viruses. Three PCR systems were used to amplify the genes encoding the DNA polymerase, the penton base hypervariable Arg-Gly-Asp-containing loop, and the hexon loop 1 (hypervariable region 1–6). Using this system, we typed 281 clinical isolates, detected members of six out of seven HAdV species (Human mastadenovirus A–F), and could also detect not only divergent strains of established types but also a new recombinant strain with a previously unpublished combination of adenovirus genomes. This strain was accepted by the Human Adenovirus Working Group as a novel genotype: HAdV-86. Seven strains that could not be typed with sufficient accuracy were also investigated using a PCR based on part of the fiber gene. By analysis of corresponding sequences of the 86 known HAdV genotypes, we determined that the proposed typing system should be able to distinguish all non-recombinant types, and with additional fiber information, all known HAdV genotypes.
|
|
| 29. |
- Kuoppa, Yvonne, et al.
(författare)
-
Quantitative detection of respiratory Chlamydia pneumoniae infection by real-time PCR
- 2002
-
Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 40:6, s. 2273-2274
-
Tidskriftsartikel (refereegranskat)abstract
- Real-time PCR was evaluated as a quantitative diagnostic method for Chlamydia pneumoniae infection using different respiratory samples. Real-time PCR had efficiency equal to or better than that of nested touchdown PCR. This study confirmed sputum as the best sampling material to detect an ongoing C. pneumoniae infection.
|
|
| 30. |
- Larsson, Nirina, et al.
(författare)
-
Are Swedish swingers a risk group for sexually transmitted infections?
- 2021
-
Ingår i: International Journal of STD and AIDS (London). - : Sage Publications. - 0956-4624 .- 1758-1052. ; 32:5, s. 427-434
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate whether Swedish swingers constitute a risk group for sexually transmitted infections (STIs). Two swinger clubs were invited to participate. At swinger meetings, members were offered an STI sampling kit and a questionnaire. Samples were analyzed for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis using a multiplex real-time polymerase chain reaction assay. In total, 235 swingers participated (118 women and 117 men). Urogenital C. trachomatis prevalence was 1.7%. Urogenital M. genitalium prevalence was 7.6% for women and 4.3% for men. No one tested positive for N. gonorrhoeae or T. vaginalis. For women, the mean number of unprotected temporary sex partners within the last 12 months was four men (range 0–35) and three women (range 0–50). Among men, the mean number of unprotected temporary sex partners within the last 12 months was five women (range 0–50) and 0 men (range 0–10). During vaginal sex, 46.6% women and 38.5% men always used protection with a temporary sex partner. Swedish swingers did not seem to have an increased prevalence of STIs. However, there was high-risk sexual behavior with unprotected sex and multiple sex partners, thereby making them a vulnerable group for acquiring STIs.
|
|
| 31. |
- Larsson, Nirina, et al.
(författare)
-
Are Urogenital Symptoms Caused by Sexually Transmitted Infections and Colonizing Bacteria?
- 2021
-
Ingår i: Journal of Lower Genital Tract Disease. - : Wolters Kluwer. - 1089-2591 .- 1526-0976. ; 25:3, s. 232-235
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to investigate the prevalence of sexually transmitted infections (STIs) and colonizing bacteria in relation to urogenital symptoms.Materials and Methods: In this cross-sectional study, patients visiting the STI clinic at Umeå University Hospital were asked for symptoms and condom use. Samples from 759 patients (465 male and 294 female) were analyzed for 4 STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium) and 3 colonizing bacteria (Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum).Results: Chlamydia trachomatis prevalence was 11% among women and 9.5% among men. Neisseria gonorrhoeae prevalence was 0.7% among women and 0.9% among men. Mycoplasma genitalium was found in 11% and 5.6% of women and men, respectively. Asymptomatic men and women had similar distribution patterns of microorganisms as those with urogenital symptoms, with the exceptions of Neisseria gonorrhoeae- and Mycoplasma genitalium-infected men who declared symptoms more frequently. Of 158 men with urogenital symptoms, 55% were test-negative. Of 129 women with urogenital symptoms, 12% were test-negative.Conclusions: This study reveals a complex picture, where a large number of multi-positive tests made it complicated to correlate urogenital symptoms with microorganisms. A high number of test-negative but symptomatic patients indicate a need of searching for additional pathogens.
|
|
| 32. |
- Lång, Mika, et al.
(författare)
-
Multicenter evaluation of the GenomEra SARS-CoV-2 assay kit
- 2022
-
Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 17
-
Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in late 2019, and quickly spread to every continent causing the global coronavirus disease 2019 (COVID-19) pandemic. Fast propagation of the disease presented numerous challenges to the health care industry in general and especially placed enormous pressure on laboratory testing. Throughout the pandemic, reverse transcription-PCR (RT-PCR)-based nucleic acid amplification tests have been the primary technique to identify acute infections caused by SARS-CoV-2. Since the start of the pandemic, there has been a constantly growing need for accurate and fast tests to enable timely protective and isolation means, as well as rapid therapeutic interventions. Here we present an evaluation of the GenomEra test for SARS-CoV-2. Analytical and clinical performance was evaluated in a multicenter setting with specimens analyzed using standard-of-care (SOC) techniques. Analytical sensitivity was assessed from spiked respiratory swab samples collected into different viral transport media, and in the best performer eSwab, the limit of detection was found to be 239 IU/mL in a heat processed sample. The GenomEra SARS-CoV-2 Assay Kit did not show specificity/cross-reactivity issues with common micro-organisms or other substances commonly found in respiratory specimens when analyzed both in vitro and in silico. Finally, the clinical performance was assessed in comparison to SOC techniques used at four institutions. Based on the analysis of 274 clinical specimens, the positive agreement of the GenomEra SARS-CoV-2 Assay Kit was 90.7%, and the negative agreement was 100%. The GenomEra SARS-CoV-2 Assay Kit provided accurate detection of SARS-CoV-2 with a short turnaround time in under 90 min.
|
|
| 33. |
- Nanda Biswas, Urmi, et al.
(författare)
-
Cognitive Interviews as a Method for Effective Cross-Cultural Research : A Study of Organisational Leaders in Sweden and India
- 2015
-
Ingår i: Indian journal of social work. - 0019-5634. ; 76:4, s. 521-536
-
Tidskriftsartikel (refereegranskat)abstract
- The research attempts to demonstrate the effectiveness of cognitive interview (CI) techniques used while finalising the survey instrument for establishing the conceptual equivalence of ethical values practiced by the managers of the selected organisations from Sweden and India. The results provided substantive insight into the cultural differences that influence ethical values in the organisations. The paper highlights the types and applications of CI in the study of the different fields of human behaviour.
|
|
| 34. |
- Nanda Biswas, Urmi, et al.
(författare)
-
Understanding Attractive Work in a Globalized World : Studies from India and Sweden
- 2017
-
Bok (refereegranskat)abstract
- This book discusses organizational values and their implications for perceived attractiveness and effectiveness of the workplace through cross-cultural research in India and Sweden. The authors provide information on how organizational values are conceptualized, presented and perceived by manager-level employees through cases from manufacturing, information technology (IT), healthcare, and education sectors in a developing and fast-growing economy like India versus a developed and stabilized economy like Sweden. Comparative results from these two very different countries provide knowledge that can be applied to make the workplace attractive in the context of globalized business processes. The authors present corporate social responsibility (CSR) and equal opportunities for men and women in the organization (EO) as important values in making the workplace attractive, where attractiveness is conceived in terms of organizational commitment and employees' intention to leave. The two selected values are particularly important as India is the first country in the world to come up with a mandatory CSR law, whereas Sweden has a long history of CSR and EO. The book demonstrates how work organizations in both countries are promoting these values to meet the challenges of attraction and retention of employees. The findings in this book are based on data gathered from various sources and sample groups in India and Sweden. The book generates insight and valuable information for researchers of organizational psychology, human resource management, cross-cultural management, as well as for work managers and HR professionals.
|
|
| 35. |
|
|
| 36. |
- Pettersson, Lisa, 1975-
(författare)
-
TRANSMISSION AND PATHOGENESIS OF HANTAVIRUS
- 2015
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hantaviruses are the causative agents of hemorrhagic fever with renal syndrome (HFRS) in Eurasia, and of hantavirus cardiopulmonary syndrome (HCPS) in the Americas. Transmission to humans usually occurs by inhalation of aerosolized virus-contaminated rodent excreta. To date, human-to-human transmission has only been described for the Andes hantavirus. The mode of transmission of Andes hantavirus is not yet known, but transmission through saliva has been suggested. In Sweden, we have one hantavirus that is pathogenic to humans, Puumala virus (PUUV), which is endemic in Central and Northern Europe. It induces a relatively mild form of HFRS, also called nephropathia epidemica (NE). The rodent reservoir is the bank vole (Myodes glareolus). The mechanism behind the pathogenesis of hantavirus is complex and probably involves both virus-mediated and host-mediated mechanisms. The aim of this project was to investigate the transmission mechanisms and pathogenesis of hantavirus disease in humans.In our first study, we described the largest outbreak of PUUV so far in Sweden. We investigated factors that might be important for causing the outbreak, and suggested that a peak in the bank vole population together with concurrent extreme weather conditions most probably contributed to the outbreak.Our next studies concentrated on human-to-human transmission of hantaviruses. We found PUUV RNA in saliva from PUUV-infected patients, suggesting that there is PUUV in the saliva of infected humans, although no person-to person transmission appears to occur with PUUV. In the studies that followed, we showed that human saliva and human salivary components could inhibit hantavirus replication. We also found PUUV-specific IgA in the saliva of PUUV-infected patients, which might prevent person-to-person transmission of the virus. In the final study, we focused on the pathogenesis of NE. One hundred five patients were included in a prospective study. They were divided into a group with mild disease and a group with moderate or severe disease. We found that the immune response had a dual role in disease development. It was partly responsible for development of severe disease, with significantly higher amounts of neutrophils in severely ill patients, but it was also protective against severe disease, because patients with mild disease had higher levels of PUUV-specific IgG.In conclusion, a peak in the bank vole population in combination with extreme weather will increase the risk of human infection, PUUV RNA is present in saliva, PUUV-specific IgA and salivary components inhibit person-to-person transmission of PUUV, and the immune response is important for the pathogenesis of PUUV and the severity of the disease.
|
|
| 37. |
- Rusiol, Marta, et al.
(författare)
-
Application of human and animal viral microbial source tracking tools in fresh and marine waters from five different geographical areas
- 2014
-
Ingår i: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 59, s. 119-129
-
Tidskriftsartikel (refereegranskat)abstract
- Integrated river basin management planning to mitigate the impacts of economic, demographic and climate change is an important issue for the future protection of water resources. Identifying sources of microbial contamination via the emerging science of Microbial Source Tracking (MST) plays a key role in risk assessment and the design of remediation strategies. Following an 18-month surveillance program within the EU-FP7-funded VIROCLIME project, specific MST tools were used to assess human markers such as adenoviruses (HAdV) and JC polyomaviruses (JCPyV) and porcine and bovine markers such as porcine adenoviruses (PAdV) and bovine polyomaviruses (BPyV) via quantification with real-time PCR to analyze surface water collected from five sites within different climatic zones: the Negro River (Brazil), Glafkos River (Greece), Tisza River (Hungary), Llobregat River (Spain) and Umealven River (Sweden). The utility of the viral MST tools and the prevalence and abundance of specific human and animal viruses in the five river catchments and adjacent seawater, which is impacted by riverine contributions from the upstream catchments, were examined. In areas where no sanitation systems have been implemented, sewage can directly enter surface waters, and river water exhibited high viral loads; HAdV and JCPyV could be detected at mean concentrations of 10(5) and 10(4) Genome Copies/Liter (GC/L), respectively. In general, river water samples upstream of urban discharges presented lower human viral loads than downstream sampling sites, and those differences appeared to increase with urban populations but decrease in response to high river flow, as the elevated river water volume dilutes microbial loads. During dry seasons, river water flow decreases dramatically, and secondary effluents can represent the bulk of the riverine discharge. We also observed that ice cover that formed over the river during the winter in the studied areas in North Europe could preserve viral stability due to the low temperatures and/or the lack of solar inactivation. Porcine and bovine markers were detected where intensive livestock and agricultural activities were present; mean concentration values of 10(3) GC/L indicated that farms were sometimes unexpected and important sources of fecal contamination in water. During spring and summer, when livestock is outdoors and river flows are low, animal pollution increases due to diffuse contamination and direct voiding of feces onto the catchment surface. The field studies described here demonstrate the dynamics of fecal contamination in all catchments studied, and the data obtained is currently being used to develop dissemination models of fecal contamination in water with respect to future climate change scenarios. The results concerning human and animal targets presented in this study demonstrate the specificity and applicability Of the viral quantitative parameters developed to widely divergent geographical areas and their high interest as new indicators of human and animal fecal contamination in water and as MST tools.
|
|
| 38. |
|
|
| 39. |
- Schindele, Alexandra, et al.
(författare)
-
Low Epstein-Barr virus count in sinonasal inverted papilloma
- 2020
-
Ingår i: Acta Oto-Laryngologica. - : Taylor & Francis. - 0001-6489 .- 1651-2251. ; 140:5, s. 413-417
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Sinonasal inverted papilloma (SIP) is a benign tumour originating from the sinonasal mucosa showing an extensive growth pattern, a high risk of recurrence and a 5–10% risk to malignify. Epstein-Barr virus (EBV) is an oncogenic herpesvirus which infects most individuals via the saliva eliciting a latent infection. Previous studies have been reporting variable data on EBV in SIP, and there is no present appreciation regarding the association between these.Aims/objectives: The aims were to investigate the presence and count of EBV in SIP and map the viral distribution in the epithelium versus the connective tissue.Material and method: Fifty-three SIP patients were identified in the Pathology Department register at the University Hospital of Umeå. The biopsies were analysed with Epstein-Barr Encoded Region (EBER) in situ hybridization. EBER-positive cells were counted in the epithelium and connective tissue.Results: We found EBER-stained cells in 30% of the cases, where 19% of these had an abundance of stained cells, and the rest showed a low count.Conclusions/significance: These findings demonstrate a low EBV count in SIP. EBV is less likely to be a causative agent in the formation of SIP, or its malignant transformation.
|
|
| 40. |
- Schindele, Alexandra, et al.
(författare)
-
Mapping human papillomavirus, Epstein–Barr virus, cytomegalovirus, adenovirus, and p16 in laryngeal cancer
- 2022
-
Ingår i: Discover Oncology. - : Springer. - 2730-6011. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Apart from tobacco and alcohol, viral infections are proposed as risk factors for laryngeal cancer. The occurrence of oncogenic viruses including human papilloma virus (HPV) and Epstein–Barr virus (EBV), in laryngeal squamous cell carcinoma (LSCC) varies in the world. Carcinogenesis is a multi-step process, and the role of viruses in LSCC progression has not been clarified. We aimed to analyze the presence and co-expression of HPV, EBV, human cytomegalovirus (HCMV) and human adenovirus (HAdV) in LSCC. We also investigated if p16 can act as surrogate marker for HPV in LSCC.Methods: Combined PCR/microarrays (PapilloCheck®) were used for detection and genotyping of HPV DNA, real-time PCR for EBV, HCMV and HAdV DNA detection, and EBER in situ hybridization (EBER-ISH) for EBV detection in tissue from 78 LSCC patients. Additionally, we analyzed p16 expression with immunohistochemistry.Results: Thirty-three percent (26/78) of LSCC tumor samples were EBV positive, 9% (7/78) HCMV positive and 4% (3/78) HAdV positive. Due to DNA fragmentation, 45 samples could not be analyzed with PapilloCheck®; 9% of the remaining (3/33) were high-risk HPV16 positive and also over-expressed p16. A total of 14% (11/78) of the samples over-expressed p16.Conclusion: These findings present a mapping of HPV, EBV, HCMV and HAdV, including the HPV surrogate marker p16, in LSCC in this cohort. Except for EBV, which was detected in a third of the samples, data show viral infection to be uncommon, and that p16 does not appear to be a specific surrogate marker for high-risk HPV infection in LSCC.
|
|
| 41. |
- Schindele, Alexandra, 1967-
(författare)
-
Mapping viruses in non-malignant tonsils, nasal polyps, sinonasal inverted papilloma and laryngeal cancer
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The upper respiratory tract is exposed to viruses, which can lead to infection and cancer development. We chose to study common and/or chronic diseases along with common and cancer related viruses in the upper airway. High-risk human papillomavirus (HPV) causes cancer in tonsils and base of tongue, and Epstein-Barr virus (EBV) in the nasopharynx. p16 is used as a site-specific tumor marker for HPV. Human cytomegalovirus (HCMV) and human adenovirus (HAdV) are proposed to be oncomodulatory. It is unclear what significance these viruses have in benign tonsillar disease, chronic rhinosinusitis with nasal polyps (CRSwNP), sinonasal inverted papillomas (SIP) and laryngeal squamous cell carcinoma (LSCC). If virus is identified, it could make possible the use of current vaccines in prevention and treatment, as well as protection of healthcare providers.Material and Methods: We analyzed 40 benign tonsils, 45 paired nasal polyp and healthy nasal mucosa samples, 53 SIP and 78 LSCC samples. We used PCR/microarrays (PapilloCheck®) for HPV detection and genotyping, immunohistochemistry (IHC) for p16 expression and real-time PCR for EBV, HCMV and HAdV detection. Additionally, Epstein-Barr encoding region (EBER) in situ hybridization (ISH) was used for EBV localization and count.Results: HPV and p16 were not co-expressed, and p16 levels were low in benign tonsils, nasal polyps, and paired controls. Also, 9% of LSCC samples were high-risk HPV 16 positive and over-expressed p16.EBV-positive cells were detected in 65% of the tonsils, nasal polyps (36%) versus controls (12%), 30% of SIP cases and 33% of LSCC samples.Conclusions: EBV is commonly identified in benign tonsils, nasal polyps, SIP and LSCC, when using sensitive and robust detection methods. At the same time, viral infection with HPV, HCMV or HAdV appears to be uncommon in these conditions. p16 does not emerge as a reliable marker for HPV infection in LSCC.
|
|
| 42. |
- Segerman, Anna, et al.
(författare)
-
Adenovirus types 11p and 35 attach to and infect primary lymphocytes and monocytes, but hexon expression in T-cells requires prior activation.
- 2006
-
Ingår i: Virology. - : Elsevier BV. - 0042-6822 .- 1096-0341. ; 349:1, s. 96-111
-
Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic cells are attractive targets for gene therapy, but the conventional adenovirus (Ad) vectors, based on Ad5, transduce these cells inefficiently. One reason for low permissiveness of hematopoietic cells to infection by species C Ads appears to be inefficient attachment. Vectors pseudotyped with species B fibers are clearly more efficient at transducing hematopoietic cells than Ad5. To evaluate which Ad species B type(s) would be the most efficient vector(s) for primary T-cells, B-cells and monocytes, attachment to and entry of the species B1 serotypes 3p and 7p and the species B2 serotypes 11p and 35 into primary PBMCs was studied. Ad11p and Ad35 were the only serotypes to show efficient binding and for which uptake by PBMCs could be detected. Infection of PBMCs by Ad5, Ad11p and Ad35 was compared. Expression of Ad hexons was detected in stimulated PBMCs, most frequently in T-cells, and in unstimulated monocytes, although B-cells appear to be refractory to productive infection. Replication of Ad DNA was severely restricted in most PBMCs. Neither hexon expression nor genome replication could be detected in unstimulated lymphocytes, but FISH and a real-time PCR-based assay suggested that Ad11p and Ad35 DNA reach the nucleus. Activation thus appears to be required for T-cells to be permissive to Ad gene expression. In summary, there are substantial differences between Ad3p and Ad7p on the one hand and Ad11p and Ad35 on the other, in their ability to interact with PBMCs. Ad11p and Ad35 probably represent vectors of choice for these cell types.
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
- Strand, Mårten, et al.
(författare)
-
2-[4,5-Difluoro-2-(2-fluorobenzoylamino)-benzoylamino]benzoic acid, an antiviral compound with activity against acyclovir-resistant isolates of herpes simplex virus type 1 and 2
- 2012
-
Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society Microbiology. - 0066-4804 .- 1098-6596. ; 56:11, s. 5735-5743
-
Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex viruses (HSV-1 and HSV-2) are responsible for life-long latent infections in humans, with periods of viral reactivation associated with recurring ulcerations in the orofacial and genital tract. In immunosuppressed patients and neonates, HSV infections are associated with severe morbidity, and in some cases even mortality. Today, acyclovir is the standard therapy for management of HSV infections. However, the need for novel antiviral agents is apparent since HSV isolates resistant to acyclovir therapy are frequently isolated in immunosuppressed patients. In this study, we assessed the anti-HSV activity of the anti-adenoviral compounds 2-[2-(2-benzoylamino)-benzoylamino]benzoic acid, (Benzavir-1) and 2-[4,5-difluoro-2-(2-fluorobenzoylamino)-benzoylamino]benzoic acid, (Benzavir-2) on HSV-1 and HSV-2. Both compounds were active against both viruses. Importantly, Benzavir-2 had similar potency to acyclovir against both HSV types and it was active against clinical acyclovir-resistant HSV isolates.
|
|
| 46. |
|
|
| 47. |
- Swartling, L., et al.
(författare)
-
Prolonged outbreak of adenovirus A31 in allogeneic stem cell transplant recipients
- 2015
-
Ingår i: Transplant Infectious Disease. - : Wiley. - 1398-2273 .- 1399-3062. ; 17:6, s. 785-794
-
Tidskriftsartikel (refereegranskat)abstract
- Background: An outbreak of human adenovirus (HAdV) A31 occurred from December 2011 to March 2012 at the Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital in Sweden. We analyzed the outbreak, the routes of transmission, and report the medical consequences.Methods: The medical records of all patients admitted to CAST during the outbreak period were studied. Phylogenetic analysis of the patient HAdV strains was performed by sequencing the hexon gene and the more variable E3 gene.Results: We identified 9 cases of HAdV A31. Hygiene measures were implemented, but transmission continued for 2 months. All 9 patients had been admitted to the ward, but 2 had no connection in time to other known HAdV A31 cases. DNA sequencing of the patient strains strongly suggested nosocomial transmission. Transplantation was postponed and then cancelled in 1 patient, and 5 patients were treated with cidofovir because of high levels of viremia. In 7 patients, concomitant graft-versus-host disease (GVHD) grade II–V complicated the clinical picture, as it was difficult to distinguish symptoms of GVHD from those of HAdV infection.Conclusion: An outbreak of HAdV in HSCT recipients can be difficult to control. Although none of the patients had severe disease, the medical consequences were significant. It is possible that unidentified cases with mild symptoms may have caused continuous transmission at the unit. Regular testing of all patients several weeks beyond the last case identified may be an important measure to control transmission.
|
|
| 48. |
- Welén, Karin, 1970, et al.
(författare)
-
A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome : No Evidence of Benefit, Supported by Epidemiology and In Vitro Data
- 2022
-
Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:3, s. 285-293
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response.Objective: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection.Designs, settings, and participants: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2–positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells.Intervention: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care.Outcome measurements: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition.Results and limitations: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20–0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52–4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders.Conclusions: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted.Patient summary: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.
|
|
| 49. |
- Westerberg, Sonja, et al.
(författare)
-
Interaction of Human Enterochromaffin Cells with Human Enteric Adenovirus 41 Leads to Serotonin Release and Subsequent Activation of Enteric Glia Cells
- 2018
-
Ingår i: Journal of Virology. - : AMER SOC MICROBIOLOGY. - 0022-538X .- 1098-5514. ; 92:7
-
Tidskriftsartikel (refereegranskat)abstract
- Human adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The main characteristics of HAdV-41 infection are diarrhea and vomiting. Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a suitable small-animal model has not been described. In this study, we used the human midgut carcinoid cell line GOT1 to investigate the effect of HAdV-41 infection and the individual HAdV-41 capsid proteins on serotonin release by enterochromaffin cells and on enteric glia cell (EGC) activation. We first determined that HAdV-41 could infect the enterochromaffin cells. Immunofluorescence staining revealed that the cells expressed HAdV-41-specific coxsackievirus and adenovirus receptor (CAR); flow cytometry analysis supported these findings. HAdV-41 infection of the enterochromaffin cells induced serotonin secretion dose dependently. In contrast, control infection with HAdV-5 did not induce serotonin secretion in the cells. Confocal microscopy studies of enterochromaffin cells infected with HAdV-41 revealed decreased serotonin immunofluorescence compared to that in uninfected cells. Incubation of the enterochromaffin cells with purified HAdV-41 short fiber knob and hexon proteins increased the serotonin levels in the harvested cell supernatant significantly. HAdV-41 infection could also activate EGCs, as shown in the significantly altered expression of glia fibrillary acidic protein (GFAP) in EGCs incubated with HAdV-41. The EGCs were also activated by serotonin alone, as shown in the significantly increased GFAP staining intensity. Likewise, EGCs were activated by the cell supernatant of HAdV-41-infected enterochromaffin cells.
|
|
