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1.
  • Järhult, Josef D., et al. (författare)
  • Environmental levels of the antiviral oseltamivir induce development of resistance mutation H274Y in influenza A/H1N1 virus in mallards
  • 2011
  • Ingår i: PLoS ONE. - 1932-6203. ; 6:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Oseltamivir (Tamiflu®) is the most widely used drug against influenza infections and is extensively stockpiled worldwide as part of pandemic preparedness plans. However, resistance is a growing problem and in 2008-2009, seasonal human influenza A/H1N1 virus strains in most parts of the world carried the mutation H274Y in the neuraminidase gene which causes resistance to the drug. The active metabolite of oseltamivir, oseltamivir carboxylate (OC), is poorly degraded in sewage treatment plants and surface water and has been detected in aquatic environments where the natural influenza reservoir, dabbling ducks, can be exposed to the substance. To assess if resistance can develop under these circumstances, we infected mallards with influenza A/H1N1 virus and exposed the birds to 80 ng/L, 1 µg/L and 80 µg/L of OC through their sole water source. By sequencing the neuraminidase gene from fecal samples, we found that H274Y occurred at 1 µg/L of OC and rapidly dominated the viral population at 80 µg/L. IC₅₀ for OC was increased from 2-4 nM in wild-type viruses to 400-700 nM in H274Y mutants as measured by a neuraminidase inhibition assay. This is consistent with the decrease in sensitivity to OC that has been noted among human clinical isolates carrying H274Y. Environmental OC levels have been measured to 58-293 ng/L during seasonal outbreaks and are expected to reach µg/L-levels during pandemics. Thus, resistance could be induced in influenza viruses circulating among wild ducks. As influenza viruses can cross species barriers, oseltamivir resistance could spread to human-adapted strains with pandemic potential disabling oseltamivir, a cornerstone in pandemic preparedness planning. We propose surveillance in wild birds as a measure to understand the resistance situation in nature and to monitor it over time. Strategies to lower environmental levels of OC include improved sewage treatment and, more importantly, a prudent use of antivirals.
2.
  • Lahermo, Päivi, et al. (författare)
  • A quality assessment survey of SNP genotyping laboratories
  • 2006
  • Ingår i: Human Mutation. - 1059-7794. ; 27:7, s. 711-714
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • To survey the quality of SNP genotyping, a joint Nordic quality assessment (QA) round was organized between 11 laboratories in the Nordic and Baltic countries. The QA round involved blinded genotyping of 47 DNA samples for 18 or six randomly selected SNPs. The methods used by the participating laboratories included all major platforms for small- to medium-size SNP genotyping. The laboratories used their standard procedures for SNP assay design, genotyping, and quality control. Based on the joint results from all laboratories, a consensus genotype for each DNA sample and SNP was determined by the coordinator of the survey, and the results from each laboratory were compared to this genotype. The overall genotyping accuracy achieved in the survey was excellent. Six laboratories delivered genotype data that were in full agreement with the consensus genotype. The average accuracy per SNP varied from 99.1 to 100% between the laboratories, and it was frequently 100% for the majority of the assays for which SNP genotypes were reported. Lessons from the survey are that special attention should be given to the quality of the DNA samples prior to genotyping, and that a conservative approach for calling the genotypes should be used to achieve a high accuracy.
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3.
  • Wallensten, Anders, et al. (författare)
  • Surveillance of influenza A virus in migratory waterfowl in northern Europe
  • 2007
  • Ingår i: Emerging Infectious Diseases. - 1080-6040. - 1080-6040 ; 13:3, s. 404-411
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted large-scale, systematic sampling of influenza type A virus in migratory waterfowl (mostly mallards [Anas platyrhynchos]) at Ottenby Bird Observatory, southeast Sweden. As with previous studies, we found a higher prevalence in fall than spring, and among juveniles compared with adults. However, in contrast to other studies, we found that prevalence in spring was sometimes high (mean 4.0%, highest 9.5%). This finding raises the possibility that ducks are capable of perpetuating influenza A virus of different subtypes and subtype combinations throughout the year and from 1 year to the next. Isolation of the H5 and H7 subtypes was common, which suggests risk for transmission to sensitive domestic animals such as poultry. We argue that wild bird screening can function as a sentinel system, and we give an example of how it could have been used to forecast a remote and deadly outbreak of influenza A in poultry.
4.
  • Callaghan, Terry V., et al. (författare)
  • Multi-Decadal Changes in Tundra Environments and Ecosystems Synthesis of the International Polar Year-Back to the FutureProject (IPY-BTF)
  • 2011
  • Ingår i: Ambio. - Springer. - 0044-7447. ; 40:6, s. 705-716
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the responses of tundra systemsto global change has global implications. Most tundraregions lack sustained environmental monitoring and oneof the only ways to document multi-decadal change is toresample historic research sites. The International PolarYear (IPY) provided a unique opportunity for such researchthrough the Back to the Future (BTF) project (IPY project#512). This article synthesizes the results from 13 paperswithin this Ambio Special Issue. Abiotic changes includeglacial recession in the Altai Mountains, Russia; increasedsnow depth and hardness, permafrost warming, andincreased growing season length in sub-arctic Sweden;drying of ponds in Greenland; increased nutrient availabilityin Alaskan tundra ponds, and warming at mostlocations studied. Biotic changes ranged from relativelyminor plant community change at two sites in Greenland tomoderate change in the Yukon, and to dramatic increasesin shrub and tree density on Herschel Island, and in subarcticSweden. The population of geese tripled at one sitein northeast Greenland where biomass in non-grazed plotsdoubled. A model parameterized using results from a BTFstudy forecasts substantial declines in all snowbeds andincreases in shrub tundra on Niwot Ridge, Colorado overthe next century. In general, results support and provideimproved capacities for validating experimental manipulation,remote sensing, and modeling studies.
5.
  • Gillman, Anna, et al. (författare)
  • Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
  • 2015
  • Ingår i: Applied and Environmental Microbiology. - 0099-2240. ; 81:7, s. 2378-2383
  • Tidskriftsartikel (refereegranskat)abstract
    • Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.
6.
  • Jourdain, Elsa, et al. (författare)
  • Influenza Virus in a Natural Host, the Mallard Experimental Infection Data
  • 2010
  • Ingår i: PLoS ONE. - 1932-6203. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Wild waterfowl, particularly dabbling ducks such as mallards (Anas platyrhynchos), are considered the main reservoir of low-pathogenic avian influenza viruses (LPAIVs). They carry viruses that may evolve and become highly pathogenic for poultry or zoonotic. Understanding the ecology of LPAIVs in these natural hosts is therefore essential. We assessed the clinical response, viral shedding and antibody production of juvenile mallards after intra-esophageal inoculation of two LPAIV subtypes previously isolated from wild congeners. Six ducks, equipped with data loggers that continually monitored body temperature, heart rate and activity, were successively inoculated with an H7N7 LPAI isolate (day 0), the same H7N7 isolate again (day 21) and an H5N2 LPAI isolate (day 35). After the first H7N7 inoculation, the ducks remained alert with no modification of heart rate or activity. However, body temperature transiently increased in four individuals, suggesting that LPAIV strains may have minor clinical effects on their natural hosts. The excretion patterns observed after both reinoculations differed strongly from those observed after the primary H7N7 inoculation, suggesting that not only homosubtypic but also heterosubtypic immunity exist. Our study suggests that LPAI infection has minor clinically measurable effects on mallards and that mallard ducks are able to mount immunological responses protective against heterologous infections. Because the transmission dynamics of LPAIVs in wild populations is greatly influenced by individual susceptibility and herd immunity, these findings are of high importance. Our study also shows the relevance of using telemetry to monitor disease in animals.
7.
  • Hedov, Gerth, et al. (författare)
  • Swedish parents of children with Down's syndrome : Parental stress and sense of coherence in relation to employment rate and time spent in child care
  • 2002
  • Ingår i: Scandinavian Journal of Caring Sciences. - 0283-9318. ; 16:4, s. 424-430
  • Tidskriftsartikel (refereegranskat)abstract
    • Becoming parents of a child with Down's syndrome (DS) challenges the adjustment ability in parenthood. Individuals with higher sense of coherence (SOC) are supposed to manage stressors better than those with lower SOC. The aims of this study were to investigate parental self-perceived stress, SOC, frequency of gainful employment and amount of time spent on child care in Swedish DS parents (165 parents; 86 mothers, 79 fathers) and to compare those with control parents of healthy children (169 parents; 87 mothers, 82 fathers). The mean age of the children was 4.7 years. Parents responded to questionnaires separately including Hymovich's Parent Perception Inventory as stress measurement and Antonovsky's short version of the Orientation to Life. No differences concerning total employment rate were observed, but the DS mothers were more often employed part-time than control mothers. The DS parents did not spend more time on child care than the control parents and they did not differ in mean SOC score, but the DS parents perceived greater stress. The differences in stress, particularly between the DS and control mothers, were related to time-demanding areas. Parents with high SOC scores experienced significantly less self-perceived stress.
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8.
  • Isehed, Catrine, et al. (författare)
  • Effectiveness of enamel matrix derivative on the clinical and microbiological outcomes following surgical regenerative treatment of peri-implantitis : a randomized controlled trial
  • 2016
  • Ingår i: Journal of Clinical Periodontology. - 0303-6979. ; 43:10, s. 863-873
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: This randomized clinical trial aimed at comparing radiological, clinical and microbial effects of surgical treatment of peri-implantitis alone or in combination with enamel matrix derivative (EMD).METHODS: Twenty-six subjects were treated with open flap debridement and decontamination of the implant surfaces with gauze and saline preceding adjunctive EMD or no EMD. Bone level (BL) change was primary outcome and secondary outcomes were changes in pocket depth (PD), plaque, pus, bleeding and the microbiota of the peri-implant biofilm analyzed by the Human Oral Microbe Identification Microarray over a time period of 12 months.RESULTS: In multivariate modelling, increased marginal BL at implant site was significantly associated with EMD, the number of osseous walls in the peri-implant bone defect and a Gram+/aerobic microbial flora, whereas reduced BL was associated with a Gram-/anaerobic microbial flora and presence of bleeding and pus, with a cross-validated predictive capacity (Q(2) ) of 36.4%. Similar, but statistically non-significant, trends were seen for BL, PD, plaque, pus and bleeding in univariate analysis.CONCLUSION: Adjunctive EMD to surgical treatment of peri-implantitis was associated with prevalence of Gram+/aerobic bacteria during the follow-up period and increased marginal BL 12 months after treatment.
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9.
  • Westergren, Albert, 1967-, et al. (författare)
  • Measurement properties of the Minimal Insomnia Symptom Scale as an insomnia screening tool for adults and the elderly.
  • 2015
  • Ingår i: Sleep Medicine. - Elsevier. - 1878-5506.
  • Tidskriftsartikel (refereegranskat)abstract
    • The psychometric properties of the three-item Minimal Insomnia Symptom Scale (MISS) were evaluated using the classical test theory. Different cut-offs for identifying insomnia were suggested in two age groups (≥6 and ≥7 among adult and elderly people, respectively). The aim of the present study was to test the measurement properties of the MISS using the Rasch measurement model, with special emphasis on differential item functioning by gender and age.
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10.
  • Benson, M, et al. (författare)
  • A haplotype in the inducible T-cell tyrosine kinase is a risk factor for seasonal allergic rhinitis.
  • 2009
  • Ingår i: Allergy. - 1398-9995. ; 64:9, s. 1286-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:  Identification of disease-associated single nucleotide polymorphisms (SNPs) in seasonal allergic rhinitis (SAR) may be facilitated by focusing on genes in a disease-associated pathway.Objective:  To search for SNPs in genes that belong to the T-cell receptor (TCR) pathway and that change in expression in allergen-challenged CD4+ cells from patients with SAR.Methods:  CD4+ cells from patients with SAR were analysed with gene expression microarrays. Allele, genotype and haplotype frequencies were compared in 251 patients and 386 healthy controls.Results:  Gene expression microarray analysis of allergen-challenged CD4+ cells from patients with SAR showed that 25 of 38 TCR pathway genes were differentially expressed. A total of 62 SNPs were analysed in eight of the 25 genes; ICOS, IL4, IL5, IL13, CSF2, CTLA4, the inducible T-cell tyrosine kinase (ITK) and CD3D. Significant chi-squared values were identified for several markers in the ITK kinase gene region. A total of five SNPs were nominally significant at the 5% level. Haplotype analysis of the five significant SNPs showed increased frequency of a haplotype that covered most of the coding part of ITK. The functional relevance of ITK was supported by analysis of an independent material, which showed increased expression of ITK in allergen-challenged CD4+ cells from patients, but not from controls.Conclusion:  Analysis of SNPs in TCR pathway genes revealed that a haplotype that covers a major part of the coding sequence of ITK is a risk factor for SAR.
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