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  • 1.
    Assadian, Farzaneh
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sandström, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Laurell, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Lidian, Adnan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Svensson, Catharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Akusjärvi, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bergqvist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Punga, Tanel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Distribution and Molecular Characterization of Human Adenovirus and Epstein-Barr Virus Infections in Tonsillar Lymphocytes Isolated from Patients Diagnosed with Tonsillar Diseases2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, article id e0154814Article in journal (Refereed)
    Abstract [en]

    Surgically removed palatine tonsils provide a conveniently accessible source of T and B lymphocytes to study the interplay between foreign pathogens and the host immune system. In this study we have characterised the distribution of human adenovirus (HAdV), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) in purified tonsillar T and B cell-enriched fractions isolated from three patient age groups diagnosed with tonsillar hypertrophy and chronic/recurrent tonsillitis. HAdV DNA was detected in 93 out of 111 patients (84%), while EBV DNA was detected in 58 patients (52%). The most abundant adenovirus type was HAdV-5 (68%). None of the patients were positive for HCMV. Furthermore, 43 patients (39%) showed a co-infection of HAdV and EBV. The majority of young patients diagnosed with tonsillar hypertrophy were positive for HAdV, whereas all adult patients diagnosed with chronic/recurrent tonsillitis were positive for either HAdV or EBV. Most of the tonsils from patients diagnosed with either tonsillar hypertrophy or chronic/recurrent tonsillitis showed a higher HAdV DNA copy number in T compared to B cell-enriched fraction. Interestingly, in the majority of the tonsils from patients with chronic/recurrent tonsillitis HAdV DNA was detected in T cells only, whereas hypertrophic tonsils demonstrated HAdV DNA in both T and B cell-enriched fractions. In contrast, the majority of EBV positive tonsils revealed a preference for EBV DNA accumulation in the B cell-enriched fraction compared to T cell fraction irrespective of the patients' age.

  • 2.
    Atterby, Clara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Mourkas, Evangelos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Univ Bath, Dept Biol & Biochem, Milner Ctr Evolut, Bath, Avon, England.
    Meric, Guillaume
    Univ Bath, Dept Biol & Biochem, Milner Ctr Evolut, Bath, Avon, England.
    Pascoe, Ben
    Univ Bath, Dept Biol & Biochem, Milner Ctr Evolut, Bath, Avon, England;MRC CLIMB Consortium, Bath, Avon, England.
    Wang, Helen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Waldenström, Jonas
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, Kalmar, Sweden.
    Sheppard, Samuel K.
    Univ Bath, Dept Biol & Biochem, Milner Ctr Evolut, Bath, Avon, England;MRC CLIMB Consortium, Bath, Avon, England.
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Järhult, Josef D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Ellström, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    The Potential of Isolation Source to Predict Colonization in Avian Hosts: A Case Study in Campylobacter jejuni Strains From Three Bird Species2018In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 9, article id 591Article in journal (Refereed)
    Abstract [en]

    Campylobacter jejuni is the primary cause of bacterial gastroenteritis worldwide, infecting humans mostly through consumption of contaminated poultry. C. jejuni is common in the gut of wild birds, and shows distinct strain-specific association to particular bird species. This contrasts with farm animals, in which several genotypes co-exist. It is unclear if the barriers restricting transmission between host species of such specialist strains are related to environmental factors such as contact between host species, bacterial survival in the environment, etc., or rather to strain specific adaptation to the intestinal environment of specific hosts. We compared colonization dynamics in vivo between two host-specific C. jejuni from a song thrush (ST-1304 complex) and a mallard (ST-995), and a generalist strain from chicken (ST-21 complex) in a wild host, the mallard (Anas platyrhynchos). In 18-days infection experiments, the song thrush strain showed only weak colonization and was cleared from all birds after 10 days, whereas both mallard and chicken strains remained stable. When the chicken strain was given 4 days prior to co-infection of the same birds with a mallard strain, it was rapidly outcompeted by the latter. In contrast, when the mallard strain was given 4 days prior to co-infection with the chicken strain, the mallard strain remained and expansion of the chicken strain was delayed. Our results suggest strain-specific differences in the ability of C. jejuni to colonize mallards, likely associated with host origin. This difference might explain observed host association patterns in C. jejuni from wild birds.

  • 3.
    Baltekin, Özden
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology.
    Boucharin, Alexis
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Andersson, Dan I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Elf, Johan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Systems Biology.
    Antibiotic susceptibility testing in less than 30 min using direct single-cell imaging2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 34, p. 9170-9175Article in journal (Refereed)
    Abstract [en]

    The emergence and spread of antibiotic-resistant bacteria are aggravated by incorrect prescription and use of antibiotics. A core problem is that there is no sufficiently fast diagnostic test to guide correct antibiotic prescription at the point of care. Here, we investigate if it is possible to develop a point-of-care susceptibility test for urinary tract infection, a disease that 100 million women suffer from annually and that exhibits widespread antibiotic resistance. We capture bacterial cells directly from samples with low bacterial counts (10(4) cfu/mL) using a custom-designed microfluidic chip and monitor their individual growth rates using microscopy. By averaging the growth rate response to an antibiotic over many individual cells, we can push the detection time to the biological response time of the bacteria. We find that it is possible to detect changes in growth rate in response to each of nine antibiotics that are used to treat urinary tract infections in minutes. In a test of 49 clinical uropathogenic Escherichia coli (UPEC) isolates, all were correctly classified as susceptible or resistant to ciprofloxacin in less than 10 min. The total time for antibiotic susceptibility testing, from loading of sample to diagnostic readout, is less than 30 min, which allows the development of a point-of-care test that can guide correct treatment of urinary tract infection.

  • 4.
    Bergqvist, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Loss of DNA-binding and new transcriptional trans-activation function in polyomavirus large T-antigen with mutation of zinc finger motif.1990In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962Article in journal (Refereed)
  • 5.
    Borgmästars, Emmy
    et al.
    Natl Food Agcy, Div Sci, Dept Biol, Hamnesplanaden 5, S-75319 Uppsala, Sweden..
    Jazi, Mehrdad Mousavi
    Natl Food Agcy, Div Sci, Dept Biol, Hamnesplanaden 5, S-75319 Uppsala, Sweden..
    Persson, Sofia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Natl Food Agcy, Div Sci, Dept Biol, Hamnesplanaden 5, S-75319 Uppsala, Sweden.
    Jansson, Linda
    Lund Univ, Appl Microbiol, Naturvetarvagen 14, S-22362 Lund, Sweden..
    Radstrom, Peter
    Lund Univ, Appl Microbiol, Naturvetarvagen 14, S-22362 Lund, Sweden..
    Simonsson, Magnus
    Natl Food Agcy, Div Sci, Dept Biol, Hamnesplanaden 5, S-75319 Uppsala, Sweden..
    Hedman, Johannes
    Lund Univ, Appl Microbiol, Naturvetarvagen 14, S-22362 Lund, Sweden.;Swedish Natl Forens Ctr, Brigadgatan 13, S-58194 Linkoping, Sweden..
    Eriksson, Ronnie
    Natl Food Agcy, Div Sci, Dept Biol, Hamnesplanaden 5, S-75319 Uppsala, Sweden..
    Improved Detection of Norovirus and Hepatitis A Virus in Surface Water by Applying Pre-PCR Processing2017In: Food and Environmnetal Virology, ISSN 1867-0334, E-ISSN 1867-0342, Vol. 9, no 4, p. 395-405Article in journal (Refereed)
    Abstract [en]

    Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) detection of waterborne RNA viruses generally requires concentration of large water volumes due to low virus levels. A common approach is to use dead-end ultrafiltration followed by precipitation with polyethylene glycol. However, this procedure often leads to the co-concentration of PCR inhibitors that impairs the limit of detection and causes false-negative results. Here, we applied the concept of pre-PCR processing to optimize RT-qPCR detection of norovirus genogroup I (GI), genogroup II (GII), and hepatitis A virus (HAV) in challenging water matrices. The RT-qPCR assay was improved by screening for an inhibitor-tolerant master mix and modifying the primers with twisted intercalating nucleic acid molecules. Additionally, a modified protocol based on chaotropic lysis buffer and magnetic silica bead nucleic acid extraction was developed for complex water matrices. A validation of the modified extraction protocol on surface and drinking waters was performed. At least a 26-fold improvement was seen in the most complex surface water studied. The modified protocol resulted in average recoveries of 33, 13, 8, and 4% for mengovirus, norovirus GI, GII, and HAV, respectively. The modified protocol also improved the limit of detection for norovirus GI and HAV. RT-qPCR inhibition with C (q) shifts of 1.6, 2.8, and 3.5 for norovirus GI, GII, and HAV, respectively, obtained for the standard nucleic acid extraction were completely eliminated by the modified protocol. The standard nucleic acid extraction method worked well on drinking water with no RT-qPCR inhibition observed and average recoveries of 80, 124, 89, and 32% for mengovirus, norovirus GI, GII, and HAV, respectively.

  • 6.
    Gisselsson-Solen, Marie
    et al.
    Univ Lund Hosp, Dept Otorhinolaryngol Head & Neck Surg, S-22185 Lund, Sweden..
    Hermansson, Ann
    Univ Lund Hosp, Dept Otorhinolaryngol Head & Neck Surg, S-22185 Lund, Sweden..
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Individual-level effects of antibiotics on colonizing otitis pathogens in the nasopharynx2016In: International Journal of Pediatric Otorhinolaryngology, ISSN 0165-5876, E-ISSN 1872-8464, Vol. 88, p. 17-21Article in journal (Refereed)
    Abstract [en]

    Background: Although there is evidence of an association between antibiotic consumption and resistant bacteria on a population level, the relationship on an individual level has been less well studied, particularly in terms of nasopharyngeal colonization. We have therefore analysed this association, using data from a closely followed cohort of children taking part in a vaccination trial. Methods: 109 children with early onset of acute otitis media (AOM) were randomised to heptavalent pneumococcal conjugate vaccine (PCV7) or no vaccination. They were followed for three years with scheduled appointments as well as sick visits. Nasopharyngeal cultures were obtained at all visits. Antibiotic treatments were recorded, as were risk factors for AOM, including siblings, short breast-feeding and parental smoking. Data were entered into a Cox regression model, and the findings of Streptococcus pneumoniae and Haemophilus influenzae with reduced susceptibility to the penicillin group were related to the number of previous courses of antibiotics. Results: There was evidence of an association between the amount of previously consumed betalactams and colonization with beta-lactamasenegative ampicillin-resistant (BLNAR) H. influenzae (RR 1.21; 95% CI 1.03-1.43; p = 0.03), and also with the most commonly prescribed drug; amoxicillin (RR 1.39; 95% CI 1.09-1.76; p = 0.01). There was no evidence for an association between antibiotic consumption and betalactamase producing H. influenzae or S. pneumoniae with reduced susceptibility to penicillin. Furthermore, there was no evidence of an association between resistant bacteria and AOM risk factors or PCV7. Conclusion: In this subgroup of children, most of whom were given several courses of antibiotics in early childhood, there was evidence of an association between betalactam/amoxicillin consumption and nasopharyngeal colonization with BLNAR strains, bacteria that have increased in prevalence during the last 10-15 years, and that are notoriously difficult to treat with oral antibiotics.

  • 7.
    Gullsby, Karolina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    No detection of macrolide-resistant Mycoplasma pneumoniae from Swedish patients, 1996-2013.2016In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Infection ecology & epidemiology, Vol. 6, no 1, article id 31374Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Mycoplasma pneumoniae is a common cause of respiratory infections which can cause life-threatening pneumonia and serious extrapulmonary manifestations. Since the year 2000, the emergence of macrolide-resistant M. pneumoniae strains has increased with varying incidences across countries. In China more than 90% of the strains are resistant. M. pneumoniae diagnostics is mostly done with molecular methods, and in Sweden antibiotic resistance surveillance is not routinely performed. The prevalence of macrolide-resistant M. pneumoniae has not previously been studied in Sweden.

    MATERIAL AND METHODS: A total of 563 M. pneumoniae-positive respiratory samples, collected from four counties in Sweden between 1996 and 2013, were screened for mutations associated with macrolide resistance using a duplex FRET real-time PCR method. The real-time PCR targets the 23S rRNA gene, and differentiation between wild-type and resistant strains was achieved with a melting curve analysis.

    RESULTS: Of the 563 samples included, 548 were analyzed for mutations associated with macrolide resistance. No mutations were found. The detection rate of macrolide-resistant M. pneumoniae in this study was 0% [0.00-0.84%].

    CONCLUSION: No macrolide-resistant M. pneumoniae has been detected in Sweden. However, the emergence and spread of macrolide-resistant M. pneumoniae strains in many countries commands continuous epidemiological surveillance.

  • 8.
    Hanslin, Katja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Otterbeck, Alexander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hanslin, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Miklós, Lipscey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mitochondrial stress in early experimental sepsis revealed by electron transport chain inhibitionManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Increased plasma lactate in sepsis may not be due to insufficient oxygen

    delivery, but accelerated glycolysis and mitochondrial dysfunction may also contribute. To

    assess critical pathophysiological steps in non-ischemic lactate increase we studied the muscle metabolism with microdialysis in a sepsis model in pigs submitted to continuous E. coli infusion (sepsis group, n=12) for 3 hours (h). A control group (sham group, n=4) underwent the same procedures but did not receive E. coli. Protocolized interventions were applied to normalize oxygen delivery (DO2) and blood pressure. Metabolism was intervened locally via microdialysis catheters with the electron-transport chain inhibitor sodium cyanide and the inhibitor of the major energy consuming enzyme Na+/K+-ATPase ouabain.

    Results: All pigs in the sepsis group had positive blood cultures at 1 h. Median (range) Sequential Organ Failure Assessment (SOFA) score at 0 h was 0 (0-1) in both groups. At 3 h, SOFA increased to 6 (3-6) in the sepsis group but remained virtually unchanged in the sham group. Plasma lactate increased in the sepsis group despite that protocolized interventions maintained DO2.

    Sepsis accelerated glycolysis with a decrease in glucose, maintained or increased in lactate and pyruvate with a virtually normal lactate-to-pyruvate ratio (LPR) in microdialysate from catheters without intervention. The local cyanide intervention produced a severe energy crisis as evidenced by a dramatically elevated LPR, a lowered pyruvate and an increased lactate in both the sepsis and sham group. During sepsis, when the cyanide effect gradually diminished, this energy crisis normalized in the sham group but partly persisted in the sepsis group.

    Conclusions: Our findings suggest a reduction in mitochondrial oxidative capacity induced by sepsis, as revealed by cyanide inhibition. Decreasing energy consumption with a local ouabain intervention did not impact glucose and fat metabolism in sepsis or sham animals.

  • 9.
    Harvala, H.
    et al.
    Publ Hlth Agcy Sweden, Solna, Sweden.;European Ctr Dis Prevent & Control ECDC, European Programme Publ Hlth Microbiol Training E, Stockholm, Sweden..
    Ogren, J.
    Div Med Diagnost, Microbiol Lab, Jonkoping, Sweden..
    Boman, P.
    Univ Uppsala Hosp, Clin Microbiol, Uppsala, Sweden..
    Riedel, Hilde M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Univ Uppsala Hosp, Clin Microbiol, Uppsala, Sweden..
    Nilsson, P.
    Halland Cty Hosp, Dept Clin Microbiol, Halmstad, Sweden..
    Winiecka-Krusnell, J.
    Publ Hlth Agcy Sweden, Solna, Sweden..
    Beser, J.
    Publ Hlth Agcy Sweden, Solna, Sweden..
    Cryptosporidium infections in Sweden-understanding the regional differences in reported incidence2016In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 22, no 12, p. 1012-1013Article in journal (Refereed)
  • 10.
    Hoffman, Tove
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Lindeborg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Barboutis, Christos
    Hellen Ornithol Soc Birdlife, Athens, Greece.
    Erciyas-Yavuz, Kiraz
    Ondokuz Mayis Univ, Samsun, Turkey.
    Evander, Magnus
    Umea Univ, Umea, Sweden.
    Fransson, Thord
    Swedish Museum Nat Hist, Stockholm, Sweden.
    Figuerola, Jordi
    Estn Biol Donana, Seville, Spain;Ciber Epidemil & Salud Publ, Madrid, Spain.
    Jaenson, Thomas G.T.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Kiat, Yosef
    Hebrew Univ Jerusalem, Jerusalem, Israel.
    Lindgren, Per-Eric
    Linkoping Univ, Linkoping, Sweden.
    Lundkvist, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mohamed, Nahla
    Umea Univ, Umea, Sweden.
    Moutailler, Sara
    Agence Natl Secur Sanit Alimentat, Maisons Alfort, France.
    Nystrom, Fredrik
    Linkoping Univ, Linkoping, Sweden.
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Salaneck, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Alkhurma Hemorrhagic Fever Virus RNA in Hyalomma rufipes Ticks Infesting Migratory Birds, Europe and Asia Minor2018In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 24, no 5, p. 879-882Article in journal (Refereed)
    Abstract [en]

    Alkhurma hemorrhagic fever virus RNA was detected in immature Hyalomma rufipes ticks infesting northward migratory birds caught in the North Mediterranean Basin. This finding suggests a role for birds in the ecology of the Alkhurma hemorrhagic fever virus and a potential mechanism for dissemination to novel regions. Increased surveillance is warranted.

  • 11.
    Hurt, Aeron C.
    et al.
    WHO, Collaborating Ctr Reference & Res Influenza, Parkville, Vic, Australia.;Univ Melbourne, Melbourne Sch Populat & Global Hlth, Parkville, Vic, Australia..
    Su, Yvonne C. F.
    Duke NUS Med Sch, Program Emerging Infect Dis, Singapore, Singapore..
    Aban, Malet
    WHO, Collaborating Ctr Reference & Res Influenza, Parkville, Vic, Australia..
    Peck, Heidi
    WHO, Collaborating Ctr Reference & Res Influenza, Parkville, Vic, Australia..
    Lau, Hilda
    WHO, Collaborating Ctr Reference & Res Influenza, Parkville, Vic, Australia..
    Baas, Chantal
    WHO, Collaborating Ctr Reference & Res Influenza, Parkville, Vic, Australia..
    Deng, Yi-Mo
    WHO, Collaborating Ctr Reference & Res Influenza, Parkville, Vic, Australia..
    Spirason, Natalie
    WHO, Collaborating Ctr Reference & Res Influenza, Parkville, Vic, Australia..
    Ellström, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Hernandez, Jorge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Kalmar Cty Hosp, Dept Microbiol, Kalmar, Sweden..
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Barr, Ian G.
    WHO, Collaborating Ctr Reference & Res Influenza, Parkville, Vic, Australia..
    Vijaykrishna, Dhanasekaran
    Duke NUS Med Sch, Program Emerging Infect Dis, Singapore, Singapore..
    Gonzalez-Acuna, Daniel
    Univ Concepcion, Fac Ciencias Vet, Chillan, Chile..
    Evidence for the Introduction, Reassortment, and Persistence of Diverse Influenza A Viruses in Antarctica2016In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 90, no 21, p. 9674-9682Article in journal (Refereed)
    Abstract [en]

    Avian influenza virus (AIV) surveillance in Antarctica during 2013 revealed the prevalence of evolutionarily distinct influenza viruses of the H11N2 subtype in Adelie penguins. Here we present results from the continued surveillance of AIV on the Antarctic Peninsula during 2014 and 2015. In addition to the continued detection of H11 subtype viruses in a snowy sheathbill during 2014, we isolated a novel H5N5 subtype virus from a chinstrap penguin during 2015. Gene sequencing and phylogenetic analysis revealed that the H11 virus detected in 2014 had a >99.1% nucleotide similarity to the H11N2 viruses isolated in 2013, suggesting the continued prevalence of this virus in Antarctica over multiple years. However, phylogenetic analysis of the H5N5 virus showed that the genome segments were recently introduced to the continent, except for the NP gene, which was similar to that in the endemic H11N2 viruses. Our analysis indicates geographically diverse origins for the H5N5 virus genes, with the majority of its genome segments derived from North American lineage viruses but the neuraminidase gene derived from a Eurasian lineage virus. In summary, we show the persistence of AIV lineages in Antarctica over multiple years, the recent introduction of gene segments from diverse regions, and reassortment between different AIV lineages in Antarctica, which together significantly increase our understanding of AIV ecology in this fragile and pristine environment.

  • 12.
    Ianevski, Aleksandr
    et al.
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, N-7028 Trondheim, Norway.
    Zusinaite, Eva
    Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia.
    Kuivanen, Suvi
    Univ Helsinki, Dept Virol, FIN-00014 Helsinki, Finland.
    Strand, Mårten
    Umea Univ, Dept Clin Microbiol, S-90185 Umea, Sweden.
    Lysvand, Hilde
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, N-7491 Trondheim, Norway.
    Teppor, Mona
    Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia.
    Kakkola, Laura
    Univ Turku, Inst Biomed, FIN-20520 Turku, Finland.
    Paavilainen, Henrik
    Univ Turku, Inst Biomed, FIN-20520 Turku, Finland.
    Laajala, Mira
    Univ Jyvaskyla, Dept Biol & Environm Sci, Jyvaskyla 40500, Finland.
    Kallio-Kokko, Hannimari
    Univ Helsinki, Helsinki Univ Hosp, Dept Virol & Immunol, FIN-00014 Helsinki, Finland.
    Valkonen, Miia
    Helsinki Univ Hosp, Helsinki 00014, Finland.
    Kantele, Anu
    Helsinki Univ Hosp, Helsinki 00014, Finland.
    Telling, Kaidi
    Univ Tartu, Inst Med Microbiol, EE-50411 Tartu, Estonia.
    Lutsar, Irja
    Univ Tartu, Inst Med Microbiol, EE-50411 Tartu, Estonia.
    Letjuka, Pille
    Narva Haigla, EE-20104 Narva, Estonia.
    Metelitsa, Natalja
    Narva Haigla, EE-20104 Narva, Estonia.
    Oksenych, Valentyn
    Trondheim Reg & Univ Hosp, St Olays Hosp, Clin Med, N-7006 Trondheim, Norway.
    Bjorås, Magnar
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, N-7491 Trondheim, Norway.
    Nordbo, Svein Arne
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, N-7491 Trondheim, Norway;Trondheim Reg & Univ Hosp, St Olays Hosp, Dept Med Microbiol, N-7006 Trondheim, Norway.
    Dumpis, Uga
    Pouls Stradins Clin Univ Hosp, LV-1002 Riga, Latvia.
    Vitkauskiene, Astra
    Lithuanian Univ Hlth Sci, Dept Lab Med, LT-44307 Kaunas, Lithuania.
    Öhrmalm, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bergqvist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Aittokallio, Tero
    Univ Helsinki, Inst Mol Med Finland, FIMM, FIN-00290 Helsinki, Finland;Univ Turku, Dept Math & Stat, Turku 20014, Finland.
    Cox, Rebecca J.
    Univ Bergen, Influenza Ctr, Dept Clin Sci, N-5021 Bergen, Norway.
    Evander, Magnus
    Umea Univ, Dept Clin Microbiol, S-90185 Umea, Sweden.
    Hukkanen, Veijo
    Univ Turku, Inst Biomed, FIN-20520 Turku, Finland.
    Marjomaki, Varpu
    Univ Jyvaskyla, Dept Biol & Environm Sci, Jyvaskyla 40500, Finland.
    Julkunen, Ilkka
    Univ Turku, Inst Biomed, FIN-20520 Turku, Finland.
    Vapalahti, Olli
    Univ Helsinki, Dept Virol, FIN-00014 Helsinki, Finland;Helsinki Univ Hosp, Helsinki 00014, Finland;Univ Helsinki, Dept Vet Biosci, FIN-00014 Helsinki, Finland.
    Tenson, Tanel
    Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia.
    Merits, Andres
    Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia.
    Kainov, Denis
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, N-7028 Trondheim, Norway;Univ Tartu, Inst Technol, EE-50090 Tartu, Estonia.
    Novel activities of safe-in-human broad-spectrum antiviral agents2018In: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 154, p. 174-182Article in journal (Refereed)
    Abstract [en]

    According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-inhuman antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases.

  • 13.
    Isaksson, Jenny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Carlsson, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Airell, Asa
    Karolinska Univ Hosp Huddinge, Dept Clin Bacteriol, Stockholm, Sweden..
    Strömdahl, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bratt, Goran
    South Gen Hosp, Dept Infect Dis, Venhalsan, Stockholm, Sweden..
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Lymphogranuloma venereum rates increased and Chlamydia trachomatis genotypes changed among men who have sex with men in Sweden 2004-20162017In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 66, no 11, p. 1684-1687Article in journal (Refereed)
    Abstract [en]

    This study aimed to determine the incidence of lymphogranuloma venereum (LGV) in Sweden since 2004 and to study in detail a consecutive number of Chlamydia trachomatis cases in men who have sex with men (MSM) during a 10 month period (September 2014 to July 2015). LGV increased from sporadic import cases in 2004 to comprise a spread within Sweden in 2016. Initially, only the L2b ompA genotype was detected, but in 2015 half of the genotyped LGV cases were L2 genotype. The changing genotype distribution in Sweden is linked to increased LGV spread in Europe. High-resolution multilocus sequence typing of 168 C. trachomatis cases from MSM in 2015 resulted in 29 sequence types, of which 3 accounted for 49% of cases. The increased rates and different genotypes of LGV indicate that more concern for high-risk taking MSM is needed to avoid further spread of this invasive infection.

  • 14.
    Kileng, Hege
    et al.
    Univ Tromso Hosp, Tromso, Norway..
    Kjellin, Midori
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bergfors, Assar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Duberg, Ann-Sofi
    Orebro Univ Hosp, Orebro, Sweden..
    Wesslen, Lars
    Gavle Cent Hosp, Gavle, Sweden..
    Danielsson, Astrid
    Falun Cent Hosp, Falun, Sweden..
    Kristiansen, Magnhild G.
    Bodo Hosp, Bodo, Norway..
    Gutteberg, Tore
    Univ Tromso Hosp, Tromso, Norway..
    Lannergård, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Effect of pre-existing Hepatitis C NS3 Q80K variant in Genotype la and NS5A Y93H variant in Genotype 3 for interferon-free treatment combinations with direct antiviral agents (DAAs): Real-life experience from a multicenter study in Sweden and Norway2016In: Hepathology, ISSN 0270-9139, Vol. 63, no 1 SUPP, p. 1001A-1001AArticle in journal (Refereed)
  • 15.
    Kinch, Amelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Arvidson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
    Sällström, K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Pauksen, Karlis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Epstein-Barr virus-related disease after allogeneic HSCT and use of pre-emptive rituximab: Clinical Features And Outcome2017In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 52, no Supplement: 1, p. S88-S88Article in journal (Other academic)
  • 16.
    Liakopoulos, Apostolos
    et al.
    CVI Wageningen Univ, Dept Bacteriol & Epidemiol, Lelystad, Netherlands..
    Mevius, Dik J.
    CVI Wageningen Univ, Dept Bacteriol & Epidemiol, Lelystad, Netherlands.;Univ Utrecht, Dept Infect Dis & Immunol, Fac Vet Med, Utrecht, Netherlands..
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bonnedahl, Jonas
    Kalmar Cty Hosp, Dept Infect Dis, Kalmar, Sweden..
    The colistin resistance mcr-1 gene is going wild2016In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 8, p. 2335-2336Article in journal (Refereed)
  • 17.
    Liakopoulos, Apostolos
    et al.
    Wageningen Univ, CVI, Dept Bacteriol & Epidemiol, Lelystad, Netherlands..
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Geurts, Yvon
    Wageningen Univ, CVI, Dept Bacteriol & Epidemiol, Lelystad, Netherlands..
    Artursson, Karin
    Natl Vet Inst, SVA, Uppsala, Sweden..
    Berg, Charlotte
    Swedish Univ Agr Sci, Dept Anim Environm & Hlth, Uppsala, Sweden..
    Mevius, Dik J.
    Wageningen Univ, CVI, Dept Bacteriol & Epidemiol, Lelystad, Netherlands.;Univ Utrecht, Fac Vet Med, Dept Infect Dis & Immunol, Utrecht, Netherlands..
    Bonnedahl, Jonas
    Kalmar Cty Hosp, Dept Infect Dis, Kalmar, Sweden..
    Molecular Characterization of Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae from Wild Kelp Gulls in South America2016In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 60, no 11, p. 6924-6927Article in journal (Refereed)
    Abstract [en]

    Extended-spectrum-cephalosporin-resistant Enterobacteriaceae are a public health concern due to limited treatment options. Here, we report on the occurrence and the molecular characteristics of extended-spectrum-cephalosporin-resistant Enterobacteriaceae recovered from wild birds (kelp gulls). Our results revealed kelp gulls as a reservoir of various extended-spectrum cephalosporinase genes associated with different genetic platforms. In addition, we report for the first time the presence of a known epidemic clone of Salmonella enterica serotype Heidelberg (JF6X01.0326/XbaI. 1966) among wild birds.

  • 18.
    Lindahl-Rajala, Elisabeth
    et al.
    Swedish Univ Agr Sci, Div Reprod, Dept Clin Sci, Uppsala, Sweden..
    Hoffman, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Zoonosis Science Center.
    Fretin, David
    Vet & Agrochem Res Ctr, Unit Bacterial Zoonoses Livestock, Operat Direct Bacterial Dis, Brussels, Belgium..
    Godfroid, Jacques
    Arctic Univ Norway, Univ Tromso, Fac Biosci Fisheries & Econ, Dept Arctic & Marine Biol, Tromso, Norway..
    Sattorov, Nosirjon
    Tajik Acad Agr Sci, Inst Biosafety Problems, Ctr Natl Collect Pathogen Microorganisms, Dushanbe, Tajikistan..
    Boqvist, Sofia
    Swedish Univ Agr Sci, Div Food Safety & Bacteriol, Dept Biomed Sci & Vet Publ Hlth, Uppsala, Sweden..
    Lundkvist, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Zoonosis Science Center.
    Magnusson, Ulf
    Swedish Univ Agr Sci, Div Reprod, Dept Clin Sci, Uppsala, Sweden..
    Detection and characterization of Brucella spp. in bovine milk in small-scale urban and peri-urban farming in Tajikistan2017In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, no 3, article id e0005367Article in journal (Refereed)
    Abstract [en]

    Brucellosis is one of the most common zoonoses globally, and Central Asia remains a Brucella hotspot. The World Health Organization classifies brucellosis as a neglected zoonotic disease that is rarely in the spotlight for research and mainly affects poor, marginalized people. Urban and peri-urban farming is a common practice in many low-income countries, and it increases the incomes of families that are often restrained by limited economic resources. However, there is a concern that the growing number of people and livestock living close together in these areas will increase the transmission of zoonotic pathogens such as Brucella. This study investigates the presence of Brucella DNA in bovine milk in the urban and peri-urban area of Dushanbe, Tajikistan. Brucella DNA was detected in 10.3% of 564 cow milk samples by IS711-based real-time PCR. This finding is concerning because consumption of unpasteurized dairy products is common in the region. Furthermore, Brucella DNA was detected in the milk of all seropositive cows, but 8.3% of the seronegative cows also showed the presence of Brucella DNA. In addition, sequence analysis of the rpoB gene suggests that one cow was infected with B. abortus and another cow was most likely infected with B. melitensis. The discrepancies between the serology and real-time PCR results highlight the need to further investigate whether there is a need for implementing complementary diagnostic strategies to detect false serological negative individuals in Brucella surveillance, control, and eradication programmes. Furthermore, vaccination of cattle with S19 in addition to vaccination of small ruminants with Rev 1 might be needed in order to control Brucella infections in the livestock population but further research focusing on the isolation of Brucella is required to obtain a comprehensive understanding of the Brucella spp. circulating among the livestock in this region.

  • 19.
    Lindell, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Söderquist, Bo
    Orebro Univ, Sch Med Sci, Fac Med & Hlth, Orebro, Sweden;Orebro Univ Hosp, Dept Lab Med, Clin Microbiol, S-70185 Orebro, Sweden.
    Sundman, Kristina
    Orebro Univ Hosp, Dept Lab Med, Clin Microbiol, S-70185 Orebro, Sweden.
    Olaison, Lars
    Univ Gothenburg, Inst Biomed, Dept Infect Dis, Gothenburg, Sweden;Swedish Soc Infect Dis, Swedish Registry Infect Endocarditis, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Infect Dis, S-41685 Gothenburg, Sweden.
    Källman, Jan
    Orebro Univ, Fac Med & Hlth, Dept Infect Dis, Orebro, Sweden;Orebro Univ Hosp, Dept Infect Dis, S-70185 Orebro, Sweden.
    Prosthetic valve endocarditis caused by Propionibacterium species: a national registry-based study of 51 Swedish cases2018In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 37, no 4, p. 765-771Article in journal (Refereed)
    Abstract [en]

    Propionibacterium spp. are a rare cause of infective endocarditis (IE). The diagnosis is difficult because the bacteria are slow-growing and growth in blood cultures is often misinterpreted as contamination from the skin flora. The aim of this study was to describe all cases of Propionibacterium spp. endocarditis in the Swedish national registry of IE. The registry was searched for all cases of IE from 1995 to 2016 caused by Propionibacterium spp. Data concerning clinical characteristics, treatment, and outcome were registered. A total of 51 episodes of definitive prosthetic valve endocarditis (PVE) caused by Propionibacterium spp. were identified, comprising 8% of cases of PVE during the study period. Almost all cases (n = 50) were male. The median time from surgery to diagnosis of IE was 3 years. Most patients were treated mainly with beta-lactams, partly in combination with aminoglycosides. Benzyl-penicillin was the most frequently used beta-lactam. A total of 32 patients (63%) underwent surgery. Overall, 47 patients (92.1%) were cured, 3 (5.9%) suffered relapse, and 1 (2.0%) died during treatment. IE caused by Propionibacterium spp. almost exclusively affects men with a prosthetic valve and findings of Propionibacterium spp. in blood cultures in such patients favors suspicion of a possible diagnosis of IE. In patients with prosthetic valves, prolonged incubation of blood cultures up to 14 days is recommended. The prognosis was favorable, although a majority of patients required cardiac surgery during treatment. Benzyl-penicillin should be the first-line antibiotic treatment option for IE caused by Propionibacterium spp.

  • 20.
    Lytsy, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Engstrand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Gustafsson, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Kaden, Rene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Time to review the gold standard for genotyping vancomycin-resistant enterococci in epidemiology: Comparing whole-genome sequencing with PFGE and MLST in three suspected outbreaks in Sweden during 2013–20152017In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 54, p. 74-80Article in journal (Refereed)
    Abstract [en]

    Vancomycin-resistant enterococci (VRE) are a challenge to the health-care system regarding transmission rate and treatment of infections. VRE outbreaks have to be controlled from the first cases which means that appropriate and sensitive genotyping methods are needed.

    The aim of this study was to investigate the applicability of whole genome sequencing based analysis compared to Pulsed-Field Gel Electrophoresis (PFGE) and Multi-Locus Sequence Typing (MLST) in epidemiological investigations as well as the development of a user friendly method for daily laboratory use.

    Out of 14,000 VRE - screening samples, a total of 60 isolates positive for either vanA or vanB gene were isolated of which 38 were from patients with epidemiological links from three suspected outbreaks at Uppsala University Hospital. The isolates were genotypically characterised with PFGE, MLST, and WGS based core genome Average Nucleotide Identity analysis (cgANI). PFGE was compared to WGS and MLST regarding reliability, resolution, and applicability capacity.

    The PFGE analysis of the 38 isolates confirmed the epidemiological investigation that three outbreaks had occurred but gave an unclear picture for the largest cluster. The WGS analysis could clearly distinguish six ANI clusters for those 38 isolates.

    As result of the comparison of the investigated methods, we recommend WGS-ANI analysis for epidemiological issues with VRE. The recommended threshold for Enterococcus faecium VRE outbreak strain delineation with core genome based ANI is 98.5%.

    All referred sequences of this study are available from the NCBI BioProject number PRJNA301929.

  • 21.
    Merino, Leonardo
    et al.
    Natl Food Agcy, Dept Chem, Uppsala, Sweden.;CSIC, Inst Agroquim & Tecnol Alimentos, Dept Food Sci, Jaime Roig 11, E-46010 Valencia, Spain.;Swedish Univ Agr Sci, Dept Food Sci, Uppsala, Sweden..
    Darnerud, Per Ola
    Natl Food Agcy, Risk Benefit Assessment Dept, Uppsala, Sweden..
    Toldra, Fidel
    CSIC, Inst Agroquim & Tecnol Alimentos, Dept Food Sci, Jaime Roig 11, E-46010 Valencia, Spain..
    Ilbäck, Nils-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Natl Food Agcy, Risk Benefit Assessment Dept, Uppsala, Sweden.;Uppsala Univ, Dept Med Sci, Clin Microbiol & Infect Med, Uppsala, Sweden..
    Time-dependent depletion of nitrite in pork/beef and chicken meat products and its effect on nitrite intake estimation2016In: Food Additives & Contaminants, ISSN 1944-0049, E-ISSN 1944-0057, Vol. 33, no 2, p. 186-192Article in journal (Refereed)
    Abstract [en]

    The food additive nitrite (E249, E250) is commonly used in meat curing as a food preservation method. Because of potential negative health effects of nitrite, its use is strictly regulated. In an earlier study we have shown that the calculated intake of nitrite in children can exceed the acceptable daily intake (ADI) when conversion from dietary nitrate to nitrite is included. This study examined time-dependent changes in nitrite levels in four Swedish meat products frequently eaten by children: pork/beef sausage, liver pate and two types of chicken sausage, and how the production process, storage and also boiling (e.g., simmering in salted water) and frying affect the initial added nitrite level. The results showed a steep decrease in nitrite level between the point of addition to the product and the first sampling of the product 24 h later. After this time, residual nitrite levels continued to decrease, but much more slowly, until the recommended use-by date. Interestingly, this continuing decrease in nitrite was much smaller in the chicken products than in the pork/beef products. In a pilot study on pork/beef sausage, we found no effects of boiling on residual nitrite levels, but frying decreased nitrite levels by 50%. In scenarios of time-dependent depletion of nitrite using the data obtained for sausages to represent all cured meat products and including conversion from dietary nitrate, calculated nitrite intake in 4-year-old children generally exceeded the ADI. Moreover, the actual intake of nitrite from cured meat is dependent on the type of meat source, with a higher residual nitrite levels in chicken products compared with pork/beef products. This may result in increased nitrite exposure among consumers shifting their consumption pattern of processed meats from red to white meat products.

  • 22.
    Persson, Sofia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Eriksson, Ronnie
    Lowther, James
    Ellström, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Simonsson, Magnus
    Comparison between RT droplet digital PCR and RT real-time PCR for quantification of noroviruses in oysters.2018In: International Journal of Food Microbiology, ISSN 0168-1605, E-ISSN 1879-3460, Vol. 284, p. 73-83Article in journal (Refereed)
    Abstract [en]

    Oysters are frequently associated with norovirus outbreaks, but the presence of norovirus RNA in oysters does not necessarily imply a health risk to humans. There is a close link between human illness and consumption of oysters with high levels of norovirus RNA, but oysters with low levels of norovirus RNA are more unlikely to be associated with illness. Reliable and precise quantification methods are therefore important for outbreak investigations and risk assessments. This study optimised and validated RT droplet digital PCR (RT-ddPCR) assays for quantification of norovirus genogroups I and II in artificially contaminated oysters, and compared them with the standard method, RT real-time PCR (RT-qPCR). The two methods had comparable 95% limits of detection, but RT-ddPCR generally showed greater precision in quantification. Differences between fluorometric measurements and quantification with RT-ddPCR were determined on in vitro transcribed RNA with targets for norovirus genogroups I and II. Quantification by RT-ddPCR was on average 100 times lower than the fluorometric value for norovirus GI and 15.8 times lower than the fluorometric value for norovirus GII. The large inter-assay difference observed highlights the need for monitoring the RT efficiency in RT-ddPCR, especially when results from different assays are compared. Overall, this study suggests that RT-ddPCR can be a suitable method for precise quantification of norovirus genogroups I and II in oysters.

  • 23.
    Rehberg, L.
    et al.
    Rhine Waal Univ Appl Sci, Marie Curie Str 1, D-47533 Kleve, Germany..
    Frontzek, A.
    Med Care Ctr Dr Stein Colleagues, Monchengladbach, Germany..
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bockmuehl, D. P.
    Rhine Waal Univ Appl Sci, Marie Curie Str 1, D-47533 Kleve, Germany..
    Prevalence of beta-lactamase genes in domestic washing machines and dishwashers and the impact of laundering processes on antibiotic-resistant bacteria2017In: Journal of Applied Microbiology, ISSN 1364-5072, E-ISSN 1365-2672, Vol. 123, no 6, p. 1396-1406Article in journal (Refereed)
    Abstract [en]

    Aims: To investigate the prevalence of -lactamase genes in domestic washing machines and dishwashers, and the decontamination efficacy of laundering.

    Methods and Results: For the first investigation, swab samples from washing machines (n = 29) and dishwashers (n = 24) were analysed by real-time quantitative PCR to detect genes encoding beta-lactamases. To test the impact of laundering on resistant bacteria, cotton test swatches were artificially contaminated with susceptible and resistant strains of Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus within a second investigation. They were washed in a domestic washing machine with or without activated oxygen bleach (AOB)-containing detergent at 20-50 degrees C. beta-Lactamase genes (most commonly of the AmpC- and OXA-type) were detected in 79% of the washing machines and in 96% of the dishwashers and Pseudomonadaceae dominated the microbiota. The level of bacterial reduction after laundering was >= 80% for all Ps.aeruginosa and Kl.pneumoniae strains, while it was only 37-61% for the methicillin-resistant Staph.aureus outbreak strain. In general, the reduction was tendentially higher for susceptible bacteria than for the resistant outbreak strains, especially for Staph.aureus.

    Conclusions: beta-Lactamase genes seem to be frequently present in domestic appliances and may pose a potential risk for cross-contamination and horizontal transfer of genes encoding resistance against clinically important beta-lactams. In general, higher temperatures and the use of AOB can improve the reduction of antibiotic-resistant bacteria, including Staph.aureus which appears to be less susceptible to the decontamination effect of laundering.

    Significance and Impact of this Study: Data on the presence of antibiotic-resistant bacteria in the domestic environment are limited. This study suggests that -lactamase genes in washing machines and dishwashers are frequent, and that antibiotic-resistant strains are generally more resistant to the used washing conditions.

  • 24.
    Schönning, Caroline
    et al.
    Folkhälsomyndigheten.
    Jernberg, Cecilia
    Folkhälsomyndigheten.
    Klingenberg, D
    Folkhälsomyndigheten.
    Andersson, S
    Folkhälsomyndigheten.
    Pääjärvi, A
    Folkhälsomyndigheten.
    Alm, Erik
    Folkhälsomyndigheten.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Lytsy, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Legionellosis acquired through a dental unit: a case study2017In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 96, no 1, p. 89-92Article in journal (Refereed)
    Abstract [en]

    In 2012, an elderly immunocompromised man died from legionellosis at a hospital in Uppsala, Sweden. The patient had visited a dental ward at the hospital during the incubation period. Legionella spp. at a concentration of 2000 colony-forming units/L were isolated from the cupfiller outlet providing water for oral rinsing. Isolates from the patient and the dental unit were Legionella pneumophila serogroup 1, subgroup Knoxville and ST9. Pulsed-field gel electrophoresis and whole-genome sequencing strongly suggested that the isolates were of common origin. This report presents one of few documented cases of legionellosis acquired through a dental unit.

  • 25.
    Skorup, Paul
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Maudsdotter, Lisa
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Castegren, Markus
    Perioperative Medicine and Intensive Care (PMI) and CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model2018In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 46, no 7, p. e634-e641Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To investigate the dynamics of antibiotic-induced endotoxin liberation and inflammatory response in vivo in a clinically relevant large animal intensive care sepsis model and whether the addition of an aminoglycoside to a β-lactam antibiotic affects these responses.

    DESIGN: Prospective, placebo-controlled interventional experimental study.

    SETTING: University research unit.

    SUBJECTS: Thirty-six healthy pigs administered Escherichia coli as a 3-hour infusion.

    INTERVENTIONS: After 2 hours, during E. coli infusion, the animals were exposed to cefuroxime alone, the combination of cefuroxime and tobramycin, or saline.

    MEASUREMENTS AND MAIN RESULTS: Plasma endotoxin, interleukin-6, tumor necrosis factor-α, leucocytes, and organ dysfunction were recorded for 4 hours after antibiotic treatment, and differences to the values before treatment were calculated. In vitro experiments were performed to ascertain whether endotoxin is released during antibiotic-induced bacterial killing of this E. coli strain. Despite differences between the treatment arms in vitro, no differences in plasma endotoxin were observed in vivo. Antibiotic-treated animals demonstrated a higher interleukin-6 response (p < 0.001), greater leucocyte activation (p < 0.001), and more pronounced deterioration in pulmonary static compliance (p < 0.01) over time than controls. Animals treated with the combination showed a trend toward less inflammation.

    CONCLUSIONS: Treatment with antibiotics may elicit an increased inflammatory interleukin-6 response that is associated with leucocyte activation and pulmonary organ dysfunction. No observable differences were detected in plasma endotoxin concentrations. The reduction in cefuroxime-induced endotoxin release after the addition of an aminoglycoside in vitro could not be reproduced in this model.

  • 26. Smolle, C
    et al.
    Huss, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Lindblad, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Reischies, F
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Effectiveness of automated ultraviolet-C light for decontamination of textiles inoculated with Enterococcus faecium.2018In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 98, no 1, p. 102-104Article in journal (Refereed)
    Abstract [en]

    Healthcare textiles are increasingly recognized as potential vehicles for transmission of hospital-acquired infections. This study tested the ability of an automated ultraviolet-C (UV-C) room disinfection device (Tru-D Smart UV-C) to decontaminate textiles inoculated with Enterococcus faecium in a clinical setting. Contaminated polycotton (50/50 polyester/cotton) swatches were distributed to predefined locations in a ward room and exposed to UV-C light. UV-C decontamination reduced E. faecium counts by a mean log10 reduction factor of 1.37 (all P = 0.005, Wilcoxon signed rank test). UV-C decontamination may be a feasible adjunctive measure to conventional laundering to preserve the cleanliness of healthcare textiles in ward rooms.

  • 27.
    Sperber, Jesper
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Nyberg, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklos
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Protective ventilation reduces Pseudomonas aeruginosa growth in lung tissue in a porcine pneumonia model.2017In: Intensive care medicine experimental, ISSN 2197-425X, Vol. 5, no 1, article id 40Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Mechanical ventilation with positive end expiratory pressure and low tidal volume, i.e. protective ventilation, is recommended in patients with acute respiratory distress syndrome. However, the effect of protective ventilation on bacterial growth during early pneumonia in non-injured lungs is not extensively studied. The main objectives were to compare two different ventilator settings on Pseudomonas aeruginosa growth in lung tissue and the development of lung injury.

    METHODS: A porcine model of severe pneumonia was used. The protective group (n = 10) had an end expiratory pressure of 10 cm H2O and a tidal volume of 6 ml x kg(-1). The control group (n = 10) had an end expiratory pressure of 5 cm H2O and a tidal volume of 10 ml x kg(-1). 10(11) colony forming units of Pseudomonas aeruginosa were inoculated intra-tracheally at baseline, after which the experiment continued for 6 h. Two animals from each group received only saline, and served as sham animals. Lung tissue samples from each animal were used for bacterial cultures and wet-to-dry weight ratio measurements.

    RESULTS: The protective group displayed lower numbers of Pseudomonas aeruginosa (p < 0.05) in the lung tissue, and a lower wet-to-dry ratio (p < 0.01) than the control group. The control group deteriorated in arterial oxygen tension/inspired oxygen fraction, whereas the protective group was unchanged (p < 0.01).

    CONCLUSIONS: In early phase pneumonia, protective ventilation with lower tidal volume and higher end expiratory pressure has the potential to reduce the pulmonary bacterial burden and the development of lung injury.

  • 28.
    Sundberg, Isak
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lannergård, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Ramklint, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Cunningham, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Inflammatory Cytokines in a Repeated Measures Prospective Case Study of Interferon-Induced Depression2017In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10, p. S399-S399Article in journal (Other academic)
  • 29.
    Sundberg, Isak
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Lannergård, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Ramklint, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Cunningham, Janet L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Direct-acting antiviral treatment in real world patients with hepatitis C not associated with psychiatric side effects: a prospective observational study2018In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 18, article id 157Article in journal (Refereed)
    Abstract [en]

    Background: Treatment of Hepatitis C virus (HCV) infection has evolved from interferon (IFN)-based treatments to direct-acting antivirals (DAAs). Patients with HCV have an elevated psychiatric morbidity (including substance abuse) and patients with such comorbidity have often been excluded from treatment with IFN. To date, little is known about psychiatric adverse effects of DAA-based regimens. We therefore aimed to study the psychiatric side effects of new IFN-free treatment for HCV (including depressive symptoms and sleep) in real world patients also including those with a history of psychiatric diagnosis, substance abuse or drug dependence. Methods: Consecutive patients were monitored during treatment with three of the latest DAA agents (sofosbuvir, simeprevir and daclatasvir). Repeated expert psychiatric assessments from baseline to 12 weeks post-treatment were performed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) clinical version and the self-report versions of the Montgomery Asberg Depression Rating Scale (MADRS-S) and the Pittsburgh Sleep Quality Index (PSQI). Friedman's test was performed to calculate differences in the MADRS-S and PSQI over time. In a post-hoc analysis Wilcoxon's test was used to compare baseline depressive symptoms with those at post-treatment. Spearman's rank correlation test was conducted in another post-hoc analysis to evaluate the correlation between symptoms of depression and HCV viral load at baseline. Results: At baseline, 15/17 patients (88%) had a history of any psychiatric diagnosis; 11 (65%) had a history of substance abuse or dependence; and 11 (65%) had previously been treated with IFN and six of those had experienced psychiatric side effects. There was no correlation between depressive symptoms and HCV viral load at baseline. Symptoms of depression did not increase during DAA treatment and were lower 12 weeks post-treatment compared with baseline: MADRS-S 10.7 vs. 8.3 (p = 0.01). This observation held when excluding patients taking antidepressant medication. Sleep quality did not significantly change during treatment. Adherence to treatment was estimated to 95% and sustained virological response was 88%. Conclusions: Despite high psychiatric morbidity, including previous substance abuse, patients successfully completed DAA treatment without increasing depressive symptoms or sleep disturbance. Symptoms of depression were significantly reduced 12 weeks after DAA treatment.

  • 30.
    Thörn, Mari
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Rorsman, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Rönnblom, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Sangfelt, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Eriksson, Britt-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Active cytomegalovirus infection diagnosed by real-time PCR in patients with inflammatory bowel disease: a prospective, controlled observational study2016In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 9, p. 1075-1080Article in journal (Refereed)
    Abstract [en]

    Objective: It is assumed that cytomegaloviral (CMV) infection in inflammatory bowel disease (IBD) is caused by reactivation due to the immunosuppressive therapy, but the role of CMV as a pathophysiological factor and prognostic marker in IBD is unclear. The aim of this study was to investigate CMV infection in IBD, with real-time polymerase chain reaction (PCR) and immunohistochemistry, with emphasis on newly diagnosed disease.

    Materials and methods: In this prospective, controlled study, 67 patients with IBD and 34 control patients with irritable bowel syndrome (IBS) or rectal bleeding were included. Serology for CMV was analysed along with CMV DNA in plasma, mucosal biopsies, and faeces. Mucosal biopsies were further analysed with histopathology and CMV immunohistochemistry.

    Results: Detection of CMV IgM was more common in patients with IBD, compared to controls, 21% versus 3%. CMV DNA was found in 16% of patients with newly diagnosed, untreated IBD and in 38% of steroid-treated patients. Four of the five patients that needed urgent surgery were CMV-DNA positive in at least one of three sample types. None of the controls had detectable CMV DNA.

    Conclusions: Active CMV infection was found in high proportions of newly diagnosed untreated patients with IBD, in patients on immunosuppression and in patients in the need of surgery. Low CMV-DNA levels in non-immunosuppressed patients were not a risk factor for the development of more severe IBD, while the detection of CMV DNA in patients on immunosuppressive therapy may foresee disease progression.

  • 31.
    von Seth, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Otterberck, Alexander
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hanslin, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Miklós, Lipscey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Mitochondrial stress in early experimental sepsis revealed by electron transport chain inhibitionManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Increased plasma lactate in sepsis may not be due to insufficient oxygen

    delivery, but accelerated glycolysis and mitochondrial dysfunction may also contribute. To

    assess critical pathophysiological steps in non-ischemic lactate increase we studied the muscle metabolism with microdialysis in a sepsis model in pigs submitted to continuous E. coli infusion (sepsis group, n=12) for 3 hours (h). A control group (sham group, n=4) underwent the same procedures but did not receive E. coli. Protocolized interventions were applied to normalize oxygen delivery (DO2) and blood pressure. Metabolism was intervened locally via microdialysis catheters with the electron-transport chain inhibitor sodium cyanide and the inhibitor of the major energy consuming enzyme Na+/K+-ATPase ouabain.

    Results: All pigs in the sepsis group had positive blood cultures at 1 h. Median (range) Sequential Organ Failure Assessment (SOFA) score at 0 h was 0 (0-1) in both groups. At 3 h, SOFA increased to 6 (3-6) in the sepsis group but remained virtually unchanged in the sham group. Plasma lactate increased in the sepsis group despite that protocolized interventions maintained DO2.

    Sepsis accelerated glycolysis with a decrease in glucose, maintained or increased in lactate and pyruvate with a virtually normal lactate-to-pyruvate ratio (LPR) in microdialysate from catheters without intervention. The local cyanide intervention produced a severe energy crisis as evidenced by a dramatically elevated LPR, a lowered pyruvate and an increased lactate in both the sepsis and sham group. During sepsis, when the cyanide effect gradually diminished, this energy crisis normalized in the sham group but partly persisted in the sepsis group.

    Conclusions: Our findings suggest a reduction in mitochondrial oxidative capacity induced by sepsis, as revealed by cyanide inhibition. Decreasing energy consumption with a local ouabain intervention did not impact glucose and fat metabolism in sepsis or sham animals.

  • 32.
    von Seth, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Skorup, Paul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Miklós, Lipscey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    The role of oxygen delivery and inflammatory response on plasma lactate and organ dysfunction in experimental septic shockManuscript (preprint) (Other academic)
    Abstract [en]

    Elevated plasma lactate and organ dysfunction in septic shock may be due to insufficient oxygen delivery (DO2). However, other mechanisms, as mitochondrial dysfunction or adrenergic glycolysis may contribute to elevated lactate. We conducted a retrospective cohort analysis of 104 pigs in bacteremic and endotoxemic shock to investigate the impact of DO2, oxygen consumption (VO2), hemodynamics and inflammatory response on elevation in plasma lactate, tissue metabolism and organ dysfunction in experimental bacteremic and endotoxemic shock.

    Experimental septic shock was induced by continuous infusion of live bacteria and endotoxin for 6 hours (h). Hemodynamic parameters and DO2 were measured with pulmonary artery catheters and oximetry. Lactate, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were analyzed in plasma. Muscle metabolism was investigated with microdialysis. At 3 h, DO2 was 289±68 mL x min-1 x m-2 (mean±SD) and plasma lactate levels were 2.9±1.2 mmol x L-1. Elevated plasma lactate was dependent on DO2, but only at DO2 levels <250 mL x min-1 x m-2. Despite increased plasma lactate and decreased DO2, no decrease in VO2 was seen. Muscle pyruvate levels increased and lactate-to-pyruvate ratio decreased. Urinary output, but not static lung compliance, was DO2-dependent. In a multiple regression model DO2, mean arterial pressure and IL-6 were the strongest predictors of increased plasma lactate. Urinary output, but not static lung compliance, was DO2-dependent.

    In muscle accelerated glycolysis contributes to increased lactate. In addition, inflammatory response, manifested as plasma IL-6 but not as TNF-a, was associated with an elevation in plasma lactate levels. 

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