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  • 1.
    Ahlstrom, Christina A.
    et al.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Bonnedahl, Jonas
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden;Kalmar Cty Council, Dept Infect Dis, Kalmar, Sweden.
    Woksepp, Hanna
    Kalmar Cty Hosp, Res Sect, Dept Dev & Publ Hlth, Kalmar, Sweden.
    Hernandez, Jorge
    Kalmar Cty Hosp, Dept Clin Microbiol, Kalmar, Sweden.
    Reed, John A.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Tibbitts, Lee
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Douglas, David C.
    US Geol Survey, Alaska Sci Ctr, Juneau, AK USA.
    Ramey, Andrew M.
    US Geol Survey, Alaska Sci Ctr, Anchorage, AK 99508 USA.
    Satellite tracking of gulls and genomic characterization of faecal bacteria reveals environmentally mediated acquisition and dispersal of antimicrobial-resistant Escherichia coli on the Kenai Peninsula, Alaska2019In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 28, no 10, p. 2531-2545Article in journal (Refereed)
    Abstract [en]

    Gulls (Larus spp.) have frequently been reported to carry Escherichia coli exhibiting antimicrobial resistance (AMR E. coli); however, the pathways governing the acquisition and dispersal of such bacteria are not well described. We equipped 17 landfill-foraging gulls with satellite transmitters and collected gull faecal samples longitudinally from four locations on the Kenai Peninsula, Alaska to assess: (a) gull attendance and transitions between sites, (b) spatiotemporal prevalence of faecally shed AMR E. coli, and (c) genomic relatedness of AMR E. coli isolates among sites. We also sampled Pacific salmon (Oncorhynchus spp.) harvested as part of personal-use dipnet fisheries at two sites to assess potential contamination with AMR E. coli. Among our study sites, marked gulls most commonly occupied the lower Kenai River (61% of site locations) followed by the Soldotna landfill (11%), lower Kasilof River (5%) and upper Kenai River (<1%). Gulls primarily moved between the Soldotna landfill and the lower Kenai River (94% of transitions among sites), which were also the two locations with the highest prevalence of AMR E. coli. There was relatively high spatial and temporal variability in AMR E. coli prevalence in gull faeces and there was no evidence of contamination on salmon harvested in personal-use fisheries. We identified E. coli sequence types and AMR genes of clinical importance, with some isolates possessing genes associated with resistance to as many as eight antibiotic classes. Our findings suggest that gulls acquire AMR E. coli at habitats with anthropogenic inputs and subsequent movements may represent pathways through which AMR is dispersed.

  • 2.
    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.

  • 3.
    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.

  • 4.
    Atterby, Clara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Osbjer, Kristina
    Swedish Univ Agr Sci SLU, Dept Clin Sci, Div Reprod, Uppsala, Sweden; Food & Agr Org United Nations, Phnom Penh, Cambodia.
    Tepper, Viktoria
    Swiss Fed Inst Technol, Inst Environm Engn, Zurich, Switzerland.
    Rajala, Elisabeth
    Swedish Univ Agr Sci SLU, Dept Clin Sci, Div Reprod, Uppsala, Sweden.
    Hernandez, Jorge
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, Kalmar, Sweden; Linköping Univ, Kalmar Cty Council, Dept Infect Dis, Dept Clin & Expt Med, Linköping, Sweden; Kalmar Cty Hosp, Diagnost Ctr, Clin Microbiol Lab, Kalmar, Sweden.
    Seng, Sokerya
    Food & Agr Org United Nations, Phnom Penh, Cambodia.
    Holl, Davun
    Minist Agr Forestry & Fisheries, Gen Directorate Anim Hlth & Prod, Phnom Penh, Cambodia.
    Bonnedahl, Jonas
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, Kalmar, Sweden; Linköping Univ, Kalmar Cty Council, Dept Infect Dis, Dept Clin & Expt Med, Linköping, Sweden.
    Börjesson, Stefan
    Natl Vet Inst SVA, Dept Anim Hlth & Antimicrobial Strategies, Uppsala, Sweden; Linköping Univ, Dept Clin & Expt Med, Linköping, Sweden.
    Magnusson, Ulf
    Swedish Univ Agr Sci SLU, Dept Clin Sci, Div Reprod, Uppsala, Sweden.
    Järhult, Josef D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Carriage of carbapenemase- and extended-spectrum cephalosporinase-producing Escherichia coli and Klebsiella pneumoniae in humans and livestock in rural Cambodia: gender and age differences and detection of blaOXA-48 in humans2019In: Zoonoses and Public Health, ISSN 1863-1959, E-ISSN 1863-2378, Vol. 66, no 6, p. 603-617Article in journal (Refereed)
    Abstract [en]

    Objectives: This study investigates the frequency and characteristics of carbapenemase‐producing Escherichia coli/Klebsiella pneumoniae (CPE/K) and extended‐spectrum cephalosporinase‐producing E. coli/K. pneumoniae (ESCE/K) in healthy humans and livestock in rural Cambodia. Additionally, household practices as risk factors for faecal carriage of ESCE/K are identified.

    Methods: Faecal samples were obtained from 307 humans and 285 livestock including large ruminants, pigs and poultry living in 100 households in rural Cambodia in 2011. Each household was interviewed, and multilevel logistic model determined associations between household practices/meat consumption and faecal carriage of ESCE/K. CPE and ESCE/K were detected and further screened for colistin resistance genes.

    Results: CPE/K isolates harbouring blaOXA‐48 were identified in two humans. The community carriage of ESCE/K was 20% in humans and 23% in livestock. The same ESBL genes: blaCTX‐M‐15, blaCTX‐M‐14, blaCTX‐M‐27, blaCTX‐M‐55, blaSHV‐2, blaSHV‐12, blaSHV‐28; AmpC genes: blaCMY‐2, blaCMY‐42, blaDHA‐1; and colistin resistance genes: mcr‐1‐like and mcr‐3‐like were detected in humans and livestock. ESCE/K was frequently detected in women, young children, pigs and poultry, which are groups in close contact. The practice of burning or burying meat waste and not collecting animal manure indoors and outdoors daily were identified as risk factors for faecal carriage of ESCE/K.

    Conclusions: Faecal carriage of E. coli and K. pneumoniae harbouring extended‐spectrum cephalosporinase genes are common in the Cambodian community, especially in women and young children. Exposure to animal manure and slaughter products are risk factors for intestinal colonization of ESCE/K in humans.

     

  • 5.
    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.

  • 6.
    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)
  • 7.
    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.

  • 8.
    Bösl, Korbinian
    et al.
    Norwegian Univ Sci & Technol, Ctr Mol Inflammat Res, Trondheim, Norway;Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Ianevski, Aleksandr
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Than, Thoa T.
    Inst Pasteur Korea, Seongnam, South Korea.
    Andersen, Petter I.
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Kuivanen, Suvi
    Univ Helsinki, Dept Virol, Helsinki, Finland.
    Teppor, Mona
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Zusinaite, Eva
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Dumpis, Uga
    Pauls Stradins Clin Univ Hosp, Riga, Latvia.
    Vitkauskiene, Astra
    Lithuanian Univ Hlth Sci, Dept Lab Med, Kaunas, Lithuania.
    Cox, Rebecca J.
    Univ Bergen, Dept Clin Sci, Influenza Ctr, Bergen, Norway.
    Kallio-Kokko, Hannimari
    Univ Helsinki, Dept Virol & Immunol, Helsinki Univ Hosp, Helsinki, Finland.
    Bergqvist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Tenson, Tanel
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Merits, Andres
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Oksenych, Valentyn
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Björås, Magnar
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Anthonsen, Marit W.
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Shum, David
    Inst Pasteur Korea, Seongnam, South Korea.
    Kaarbö, Mari
    Oslo Univ Hosp, Dept Microbiol, Oslo, Norway.
    Vapalahti, Olli
    Univ Helsinki, Dept Vet Biosci, Helsinki, Finland.
    Windisch, Marc P.
    Inst Pasteur Korea, Seongnam, South Korea.
    Superti-Furga, Giulio
    Austrian Acad Sci, CeMM Res Ctr Mol Med, Vienna, Austria;Med Univ Vienna, Ctr Physiol & Pharmacol, Vienna, Austria.
    Snijder, Berend
    Swiss Fed Inst Technol, Inst Mol Syst Biol, Dept Biol, Zurich, Switzerland.
    Kainov, Denis
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway;Swiss Fed Inst Technol, Inst Mol Syst Biol, Dept Biol, Zurich, Switzerland.
    Kandasamy, Richard K.
    Norwegian Univ Sci & Technol, Ctr Mol Inflammat Res, Trondheim, Norway;Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway;Univ Oslo, Nord EMBL Partnership, Ctr Mol Med Norway NCMM, Oslo, Norway;Univ Massachusetts, Sch Med, Dept Med, Program Innate Immun,Div Infect Dis & Immunol, Worcester, MA 01655 USA.
    Common Nodes of Virus-Host Interaction Revealed Through an Integrated Network Analysis2019In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 2186Article in journal (Refereed)
    Abstract [en]

    Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.

  • 9.
    Cabrera-Pardo, Jaime R.
    et al.
    Univ Concepcion, Fac Ciencias Nat & Oceanog, Dept Bot, Concepcion, Chile;Univ Bio Bio, Fac Ciencias, Dept Quim, Ave Collao 1202, Concepcion, Chile.
    Lood, Rolf
    Lund Univ, Dept Clin Sci, Div Infect Med, Biomed Ctr B14, Solvegatan 19, SE-22362 Lund, Sweden.
    Udekwu, Klas
    Stockholm Univ, Dept Mol Biosci, TWGI Svante Arrheniusvag 20C, S-10691 Stockholm, Sweden.
    Gonzalez-Rocha, Gerardo
    Univ Concepcion, Fac Ciencias Biol, Dept Microbiol, Lab Invest Agentes Antibacterianos, Concepcion, Chile.
    Munita, Jose M.
    UT Hlth McGovern Med Sch, Ctr Antimicrobial Resistance & Microbial Genom, Houston, TX USA;Univ Desarrollo, Fac Med Clin Alemana, Genom & Resistant Microbes Grp, Santiago, Chile.
    Järhult, Josef D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Opazo-Capurro, Andres
    Univ Concepcion, Fac Ciencias Biol, Dept Microbiol, Lab Invest Agentes Antibacterianos, Concepcion, Chile.
    A One Health - One World initiative to control antibiotic resistance: A Chile - Sweden collaboration2019In: One Health, ISSN 2352-7714, Vol. 8, article id 100100Article in journal (Refereed)
    Abstract [en]

    Controlling antibiotic resistance is a global concern. The One Health initiative has provided a strategy to deal with this problem efficiently within a country. However, due to the global nature of the problem it is paramount not only to focus on specific countries, but to establish ways to avoid the development of antibiotic resistance in different geographical regions. In this letter, we propose a One Health - One World approach that would enable different countries to connect by sharing information about infections, outbreaks and surveillance. We believe such a strategy should be implemented worldwide in order to mitigate the development and dissemination of antibiotic resistance.

  • 10.
    Eriksson, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lindskog, Cecilia
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Lorente-Leal, Victor
    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.
    González-Acuna, Daniel
    Univ Concepcion, Fac Ciencias Vet, Chillan, Chile.
    Järhult, Josef D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Lundkvist, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Jourdain, Elsa
    INRA, UMR0346 EPIA, VetAgro Sup, St Genes Champanelle, France.
    Ellström, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Attachment Patterns of Human and Avian Influenza Viruses to Trachea and Colon of 26 Bird Species: Support for the Community Concept2019In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 10, article id 815Article in journal (Refereed)
    Abstract [en]

    Avian influenza A viruses (AIVs) have a broad host range, but are most intimately associated with waterfowl (Anseriformes) and, in the case of the H13 and H16 subtypes, gulls (Charadriiformes). Host associations are multifactorial, but a key factor is the ability of the virus to bind host cell receptors and thereby initiate infection. The current study aims at investigating the tissue attachment pattern of a panel of AIVs, comprising H3N2, H6N1, H12N5, and H16N3, to avian trachea and colon tissue samples obtained from host species of different orders. Virus attachment was not restricted to the bird species or order from which the virus was isolated. Instead, extensive virus attachment was observed to several distantly related avian species. In general, more virus attachment and receptor expression were observed in trachea than in colon samples. Additionally, a human seasonal H3N2 virus was studied. Unlike the studied AIVs, this virus mainly attached to tracheae from Charadriiformes and a very limited set of avian cola. In conclusion, the reported results highlight the importance of AIV attachment to trachea in many avian species. Finally, the importance of chickens and mallards in AIVs dynamics was illustrated by the abundant AIV attachment observed.

  • 11.
    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.

  • 12.
    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.

  • 13.
    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.
    Olsen, Björn
    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.
    Bondeson, Kåre
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Molecular typing of Mycoplasma pneumoniae strains in Sweden, 1996–2017, and the emergence of a new P1 cytadhesin gene, Variant 2e2019In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 57, no 6, article id e00049-19Article in journal (Refereed)
    Abstract [en]

    Mycoplasma pneumoniae causes respiratory infections, such as community-acquired pneumonia (CAP), with epidemics recurring every 3 to 7 years. In 2010 and 2011, many countries experienced an extraordinary epidemic peak. The cause of these recurring epidemics is not understood, but decreasing herd immunity and shifts in the strains' antigenic properties have been suggested as contributing factors. M. pneumoniae PCR-positive samples were collected between 1996 and 2017 from four neighboring counties inhabited by 12% of Sweden's population. A total of 578 isolates were characterized directly from 624 clinical samples using P1 typing by sequencing and multilocus variable number tandem repeat analysis (MLVA). A fluorescence resonance energy transfer (FRET)-PCR approach was also used to detect mutations associated with macrolide resistance in the 23S rRNA gene. Through P1 typing, the strains were classified into type 1 and type 2, as well as variants 2a, 2b, 2c, and a new variant found in nine of the strains, denoted variant 2e. Twelve MLVA types were distinguished, and 3-5-6-2 (42.4%), 4-5-7-2 (37.4%), and 3-6-6-2 (14.9%) predominated. Several P1 and MLVA types cocirculated each year, but type 2/variant 2 strains and MLVA types 3-5-6-2 and 4-5-7-2 predominated during the epidemic period comprising the peak of 2010 and 2011. In 2016 and 2017, type 1 became more common, and MLVA type 4-5-7-2 predominated. We also found that 0.2% (1/578) of the strains carried a macrolide resistance-associated mutation, indicating a very low prevalence of macrolide resistance in this region of Sweden.

  • 14.
    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.

  • 15.
    Hanslin, Katja
    et al.
    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.
    Skorup, Paul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Wilske, Frida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. 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, Clinical Chemistry.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Perioperative Medicine and Intensive Care, Karolinska University Hospital and CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    The impact of the systemic inflammatory response on hepatic bacterial elimination in experimental abdominal sepsis2019In: Intensive Care Medicine Experimental, ISSN 2197-425X, Vol. 7, no 1, article id 52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bacterial translocation from the gut has been suggested to induce a systemic inflammatory response syndrome (SIRS) and organ dysfunction. The liver has a pivotal role in eliminating circulating bacteria entering from the gut. We investigated whether pre-existing inflammation affects hepatic bacterial elimination.

    METHODS: Fifteen anaesthetised piglets were infused with E. coli in the portal vein for 3 h. The naive group (n = 6) received the bacterial infusion without endotoxin exposure. SIRS (SIRS group, n = 6) was induced by endotoxin infusion 24 h before the bacterial infusion. For effects of anaesthesia, controls (n = 3) received saline instead of endotoxin for 24 h. Bacterial counts and endotoxin levels in the portal and hepatic veins were analysed during bacterial infusion.

    RESULTS: The bacterial killing rate was higher in the naive group compared with the SIRS group (p = 0.001). The ratio of hepatic to portal venous bacterial counts, i.e. the median bacterial influx from the splanchnic circulation, was 0.06 (IQR 0.01-0.11) in the naive group and 0.71 (0.03-1.77) in the SIRS group at 3 h, and a magnitude lower in the naive group during bacteraemia (p = 0.03). Similar results were seen for hepatic endotoxin elimination. Peak log tumour necrosis factor alpha was higher in the naive 4.84 (4.77-4.89) vs. the SIRS group 3.27 (3.26-3.32) mg/L (p < 0.001).

    CONCLUSIONS: Our results suggest that hepatic bacterial and endotoxin elimination is impaired in pigs with pre-existing SIRS while the inflammatory response to bacterial infusion is diminished. If similar mechanisms operate in human critical illness, the hepatic elimination of bacteria from the gut could be impaired by SIRS.

  • 16.
    Hansson, D.
    et al.
    Stockholm Univ, Dept Math, SE-10691 Stockholm, Sweden.
    Leung, K. Y.
    Stockholm Univ, Dept Math, SE-10691 Stockholm, Sweden.
    Britton, T.
    Stockholm Univ, Dept Math, SE-10691 Stockholm, Sweden.
    Strömdahl, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Karolinska Inst, Dept Publ Hlth Sci, SE-17177 Stockholm, Sweden.
    A dynamic network model to disentangle the roles of steady and casual partners for HIV transmission among MSM2019In: Epidemics, ISSN 1755-4365, E-ISSN 1878-0067, Vol. 27, p. 66-76Article in journal (Refereed)
    Abstract [en]

    HIV is a sexually transmitted infection (STI) whose transmission process is highly dependent on the sexual network structure of the population under consideration. Most sexual behaviour data is egocentric in nature. We develop a stochastic dynamic sexual network model that utilises this type of egocentric network data. The model incorporates both steady and casual sex partners, and can be seen as a stochastic form of a generalised pair-formation model. We model the spread of an infection where individuals are susceptible, infectious, or successfully treated (and unable to transmit) and derive analytical expressions for several epidemiological quantities. We use sexual behaviour and HIV prevalence data that was gathered among 403 MSM at an STI clinic in Stockholm. To accurately capture transmission dynamics for this population, we need to explicitly model both casual sex partners and steady partnerships. Our model yields an estimate for the mean time until diagnosis followed by successful treatment that is in line with literature. This study indicates that small reductions in the time to diagnosis, and thereby, beginning of treatment, may substantially reduce HIV prevalence. Moreover, we find that moderate increases in condom use with casual sex partners have greater impact on reducing prevalence than the same increases in condom use with steady sex partners. This result demonstrates the relative importance of casual contacts on the HIV transmission dynamics among MSM in Sweden. Our results highlight the importance of HIV testing and condom-use interventions, and the role that casual and steady partners play in this, in order to turn the epidemiological trend in Sweden towards decreased HIV incidence.

  • 17.
    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)
  • 18.
    Helin, Anu S
    et al.
    Centre for Ecology and Evolution in Microbial Model Systems, Linnaeus University, Kalmar, Sweden.
    Wille, Michelle
    Centre for Ecology and Evolution in Microbial Model Systems, Linnaeus University, Kalmar, Sweden.
    Atterby, Clara
    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, Infectious Diseases.
    Waldenström, Jonas
    Centre for Ecology and Evolution in Microbial Model Systems, Linnaeus University, Kalmar, Sweden.
    Chapman, Joanne R.
    Centre for Ecology and Evolution in Microbial Model Systems, Linnaeus University, Kalmar, Sweden; Department of Molecular Biosciences, University of Kansas, Lawrence, USA.
    A rapid and transient innate immune response to avian influenza infection in mallards2018In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 95, p. 64-72Article in journal (Refereed)
    Abstract [en]

    The vertebrate innate immune system provides hosts with a rapid, non-specific response to a wide range of invading pathogens. However, the speed and duration of innate responses will be influenced by the co-evolutionary dynamics of specific host-pathogen combinations. Here, we show that low pathogenic avian influenza virus (LPAI) subtype H1N1 elicits a strong but extremely transient innate immune response in its main wildlife reservoir, the mallard (Anas platyrhynchos). Using a series of experimental and methodological improvements over previous studies, we followed the expression of retinoic acid inducible gene 1 (RIG-I) and myxovirus resistance gene (Mx) in mallards semi-naturally infected with low pathogenic H1N1. One day post infection, both RIG-I and Mx were significantly upregulated in all investigated tissues. By two days post infection, the expression of both genes had generally returned to basal levels, and remained so for the remainder of the experiment. This is despite the fact that birds continued to actively shed viral particles throughout the study period. We additionally show that the spleen plays a particularly active role in the innate immune response to LPAI. Waterfowl and avian influenza viruses have a long co-evolutionary history, suggesting that the mallard innate immune response has evolved to provide a minimum effective response to LPAIs such that the viral infection is brought under control while minimising the damaging effects of a sustained immune response.

  • 19.
    Herrmann, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Isaksson, Jenny
    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, Åsa
    Karolinska Univ Hosp, Stockholm, Sweden.
    Strömdahl, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Bratt, Göran
    South Gen Hosp, Stockholm, Sweden.
    LYMPHOGRANULOMA VENEREUM IN SWEDEN 2004-2016: INCREASED RATES AMONG HIV-NEGATIVE MEN WHO HAVE SEX WITH MEN AND CHANGED GENOTYPES2017In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 93, no Suppl. 2, p. A103-A103, article id P3.27Article in journal (Other academic)
  • 20.
    Hoffman, Tove
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    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 Sciences, Infection medicine.
    Salaneck, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    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.

  • 21.
    Howe, Anita
    et al.
    Univ Milan, Ctr Excellence HIV AIDS, Milan, Italy.
    Cento, Valeria
    Univ Milan, Microbiol & Virol, Milan, Italy.
    Knight, Nathaniel
    Ctr Excellence HIV AIDS, Res Lab, Frankfurt, Germany.
    Dietz, Julia
    Univ Hosp Frankfurt, Frankfurt, Germany.
    Di Maio, Velia Chiara
    Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy.
    De Salazar, Adolfo
    Hosp Univ San Cecilio, Jefe Serv Microbiol, Granada, Spain.
    Popping, Stephanie
    Erasmus MC, Dept Virosci, Rotterdam, Netherlands.
    Fourati, Slim
    Henri Mondor Univ Hosp, Virol, Creteil, France.
    Knops, Elena
    Univ Hosp Cologne, Inst Virol, Cologne, Germany.
    Kjellin, Midori
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Sayan, Murat
    Univ Res Ctr Expt Hlth Sci, Nicosia, Northern Cyprus, Cyprus.
    Mor, Orna
    Sheba Med Ctr, Cent Virol Lab, Ramat Gan, Israel.
    De Knegt, Robert J.
    Erasmus MC, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands.
    Mitchell, Robert
    Univ British Columbia, Vancouver, BC, Canada.
    Tam, Edward V.
    Lair Ctr, Vancouver, BC, Canada.
    Pai, Rohit
    Pereira, Oscar Octavio Cruz
    Royal Jubilee Hosp, Victoria, BC, Canada.
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Wang, Gary P.
    Univ Florida, Gainesville, FL 32611 USA.
    Wong, Alexander
    Univ Saskatchewan, Infect Dis, Saskatoon, SK, Canada.
    Parczewski, Milosz
    Pomeranian Med Univ, Dept Infect Trop Dis & Immune Deficiency, Szczecin, Poland.
    Applegate, Tanya
    Kirby Inst, Viral Hepatitis Clin Res Program, Kensington, NSW, Australia.
    Ramji, Alnoor
    Univ British Columbia, Div Gastroenterol, Vancouver, BC, Canada.
    Perno, Carlo Federico
    Univ Milan, Milan, Italy.
    Kaiser, Rolf
    7Univ Hosp Cologne, Virol, Cologne, Germany.
    Boucher, Charles A. B.
    Erasmus MC, Dept Virosci, Rotterdam, Netherlands.
    Feld, Jordan J.
    Univ Hlth Network, Toronto Ctr Liver Dis, Toronto, ON, Canada.
    Pawlotsky, Jean-Michel
    INSERM, Imrb U955, Team 18, Paris, France.
    Garcia, Federico
    Inst Invest Biosanitaria Ibs, Virol, Granada, Spain.
    Ceccherini-Silberstein, Francesca
    Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy.
    Sarrazin, Christoph
    Goethe Univ Hosp, Frankfurt, Germany.
    Harrigan, Richard
    Univ British Columbia, AIDS, Vancouver, BC, Canada.
    A Real World Resistance Profile of Virologic Failures Collected from an International Collaboration (SHARED)2018In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 68, p. 128A-128AArticle in journal (Other academic)
  • 22.
    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.

  • 23.
    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.

  • 24.
    Ianevski, Aleksandr
    et al.
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Zusinaite, Eva
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Shtaida, Nastassia
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Kallio-Kokko, Hannimari
    Univ Helsinki, Dept Virol & Immunol, Helsinki, Finland.
    Valkonen, Miia
    HUS, Helsinki, Finland; Univ Helsinki, Helsinki, Finland.
    Kantele, Anu
    HUS, Helsinki, Finland; Univ Helsinki, Helsinki, Finland.
    Telling, Kaidi
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Lutsar, Irja
    Univ Tartu, Inst Med Microbiol, Tartu, Estonia.
    Letjuka, Pille
    Narva Haigla, Narva, Estonia.
    Metelitsa, Natalja
    Narva Haigla, Narva, Estonia.
    Oksenych, Valentyn
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
    Dumpis, Uga
    Latvian Biomed Res & Study Ctr, Riga, Latvia.
    Vitkauskiene, Astra
    Lithuanian Univ Hlth Sci, Dept Lab Med, Kaunas, Lithuania.
    Stasaitis, Kestutis
    Lithuanian Univ Hlth Sci, Dept Emergency Med, 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.
    Cox, Rebecca J.
    Univ Bergen, Dept Clin Sci, Influenza Ctr, Bergen, Norway.
    Tenson, Tanel
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Merits, Andres
    Univ Tartu, Inst Technol, Tartu, Estonia.
    Kainov, Denis E.
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway; Univ Tartu, Inst Technol, Tartu, Estonia.
    Low Temperature and Low UV Indexes Correlated with Peaks of Influenza Virus Activity in Northern Europe during 2010-20182019In: Viruses, ISSN 1999-4915, E-ISSN 1999-4915, Vol. 11, no 3, article id 207Article in journal (Refereed)
    Abstract [en]

    With the increasing pace of global warming, it is important to understand the role of meteorological factors in influenza virus (IV) epidemics. In this study, we investigated the impact of temperature, UV index, humidity, wind speed, atmospheric pressure, and precipitation on IV activity in Norway, Sweden, Finland, Estonia, Latvia and Lithuania during 2010-2018. Both correlation and machine learning analyses revealed that low temperature and UV indexes were the most predictive meteorological factors for IV epidemics in Northern Europe. Our in vitro experiments confirmed that low temperature and UV radiation preserved IV infectivity. Associations between these meteorological factors and IV activity could improve surveillance and promote development of accurate predictive models for future influenza outbreaks in the region.

  • 25.
    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.

  • 26.
    Johansson, Håkan
    et al.
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, Kalmar, Sweden.
    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.
    Artursson, Karin
    National Veterinary Institute, Uppsala, Sweden.
    Berg, Charlotte
    Swedish Univ Agr Sci, Dept Anim Environm & Hlth, Skara, Sweden.
    Bonnedahl, Jonas
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, Kalmar, Sweden;Kalmar Cty Hosp, Dept Infect Dis, Kalmar, Sweden.
    Hansson, Ingrid
    Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Uppsala, Sweden.
    Hernandez, Jorge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Kalmar Cty Hosp, Lab Microbiol, Kalmar, Sweden.
    Lopez-Martin, Juana
    Univ Concepcion, Fac Ciencias & Vet, Dept Patol & Med Prevent, Chillan, Chile.
    Medina-Vogel, Gonzalo
    Univ Andres Bello, Ctr Invest Sustentabilidad, Santiago, Chile.
    Moreno, Lucile
    Univ Concepcion, Fac Ciencias Nat & Oceanograf, Concepcion, Chile.
    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.
    Engvall, Eva Olsson
    National Veterinary Institute, Uppsala, Sweden.
    Skarin, Hanna
    National Veterinary Institute, Uppsala, Sweden.
    Troell, Karin
    Natl Vet Inst, Uppsala, Sweden.
    Waldenström, Jonas
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, Kalmar, Sweden.
    Ågren, Joakim
    National Veterinary Institute, Uppsala, Sweden.
    Gonzalez-Acuna, Daniel
    Univ Concepcion, Fac Ciencias Vet, Chillan, Chile.
    Characterization of Campylobacter spp. isolated from wild birds in the Antarctic and Sub-Antarctic2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 11, article id e0206502Article in journal (Refereed)
    Abstract [en]

    A lack of knowledge of naturally occurring pathogens is limiting our ability to use the Antarctic to study the impact human-mediated introduction of infectious microorganisms have on this relatively uncontaminated environment. As no large-scale coordinated effort to remedy this lack of knowledge has taken place, we rely on smaller targeted efforts to both study present microorganisms and monitor the environment for introductions. In one such effort, we isolated Campylobacter species from fecal samples collected from wild birds in the Antarctic Peninsula and the sub-Antarctic island of South Georgia. Indeed, in South Georgia, we found Campylobacter lari and the closely related Campylobacter peloridis, but also distantly related human-associated multilocus sequence types of Campylobacter jejuni. In contrast, in the Antarctic Peninsula, we found C. tart and two closely related species, Campylobacter subantarcticus and Campylobacter volucris, but no signs of human introduction. In fact, our finding of human-associated sequence types of C. jejuni in South Georgia, but not in the Antarctic Peninsula, suggests that efforts to limit the spread of infectious microorganisms to the Antarctic have so far been successful in preventing the introduction of C. jejuni. However, we do not know how it came to South Georgia and whether the same mode of introduction could spread it from there to the Antarctic Peninsula.

  • 27.
    Jonsson, Johanna
    et al.
    Karolinska Inst, Unit Occupat Med, Inst Environm Med, Stockholm, Sweden.
    Stein, Mart
    Natl Inst Publ Hlth & Environm, Ctr Infect Dis Control, Bilthoven, Netherlands.
    Johansson, Gun
    Karolinska Inst, Unit Occupat Med, Inst Environm Med, Stockholm, Sweden.
    Bodin, Theo
    Karolinska Inst, Unit Occupat Med, Inst Environm Med, Stockholm, Sweden.
    Strömdahl, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Karolinska Inst, Dept Publ Hlth, Stockholm, Sweden.
    A performance assessment of web-based respondent driven sampling among workers with precarious employment in Sweden2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 1, article id e0210183Article in journal (Refereed)
    Abstract [en]

    Objectives: Precarious employment (PE) is a social determinant of poor health of workers. However, this population usually lack a sampling frame, making it challenging to identify the characteristics of this group. Web-based respondent driven sampling (webRDS) recruits individuals online through the social network and can provide population estimates. This study aims to assess the performance of webRDS in a population of workers with PE.

    Method: WebRDS was used for recruitment and data collection in the PRecarious EMployment In Stockholm (PREMIS) study. Cross-sectional questionnaire data was collected between November 2016 and May 2017. Eligible participants were living and/or working in Stockholm County, 18-65 years old, had a personal identification number and were currently employed. WebRDS performance was assessed by the total sample size, length of recruitment chains, sample composition, sample proportions and estimated RDSII population proportions with confidence intervals.

    Results: The webRDS process resulted in a sample of 358 recruits and a total sample of 415 participants, recruited over 1-15 waves. Of the participating seeds and recruits, 60% and 48%, respectively, successfully recruited at least one peer. The sample composition stabilized for all variables assessed. The sample proportions and RDSII estimates differed by 1-8% and the confidence intervals included the sample proportions for all variables except one.

    Conclusions: WebRDS successfully recruited a sufficient sample of workers with precarious employment from which population estimates could be made. Future studies should consider implementing webRDS on a national level in order to further study this population.

  • 28.
    Kaarme, Johan
    et al.
    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), Paediatric Inflammation Research.
    Riedel, Hilde M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Schaal, Wesley
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Yin, Hong
    Nevéus, Tryggve
    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), Paediatric Inflammation Research.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Rapid Increase in Carriage Rates of Enterobacteriaceae Producing Extended-Spectrum β-Lactamases in Healthy Preschool Children, Sweden2018In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 24, no 10, p. 1874-1881Article in journal (Refereed)
    Abstract [en]

    By collecting and analyzing diapers, we identified a >6-fold increase in carriage of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae for healthy preschool children in Sweden (p<0.0001). For 6 of the 50 participating preschools, the carriage rate was >40%. We analyzed samples from 334 children and found 56 containing >1 ESBL producer. The prevalence in the study population increased from 2.6% in 2010 to 16.8% in 2016 (p<0.0001), and for 6 of the 50 participating preschools, the carriage rate was >40%. Furthermore, 58% of the ESBL producers were multidrug resistant, and transmission of ESBL-producing and non-ESBL-producing strains was observed at several of the preschools. Toddlers appear to be major carriers of ESBL producers in Sweden.

  • 29. Kileng, Hege
    et al.
    Kjellin, Midori
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Akaberi, Dario
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Bergfors, Assar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Duberg, Ann-Sofi
    Wesslén, Lars
    Danielsson, Astrid
    Gangsøy Kristiansen, Magnhild
    Gutteberg, Tore
    Goll, Rasmus
    Lannergård, Anders
    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 Sciences, Infection medicine.
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Personalized treatment of hepatitis C genotype 1a in Norway and Sweden 2014-2016: a study of treatment outcome in patients with or without resistance-based DAA-therapy.2018In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 10-11, p. 1347-1353Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Resistance-associated substitutions (RASs) may impair treatment response to direct-acting antivirals (DAA) in hepatitis C virus (HCV) treatment. We investigated the effects of baseline NS3-RASs (Q80K and R155K) and clinically relevant NS5A-RASs in patients with HCV genotype (GT) 1a infection on treatment outcome, with or without resistance-based DAA-treatment. This multi-center study was carried out between 2014 and 2016.

    PATIENTS/METHODS: Treatment in the intervention group (n = 92) was tailored to baseline resistance. Detection of NS3-RAS led to an NS5A-inhibitor-based regimen and detection of NS5A-RAS to a protease-inhibitor regimen. Patients without baseline RAS in the intervention group and all patients in the control group (n = 101) received recommended standard DAA-treatment.

    RESULTS: The sustained virologic response rates (SVR) in the intervention and control groups were 97.8% (90/92) and 93.1% (94/101), respectively (p = .174). A trend toward higher SVR-rate in cirrhotic patients (p = .058) was noticed in the intervention group compared to the control group with SVR-rates 97.5% (39/40) and 83.3% (35/42), respectively. All patients with baseline NS3 (Q80K/R155K) or NS5A-RASs in the intervention group achieved SVR with personalized resistance-based treatment. In the control group, five patients with Q80K or R155K at baseline were treated with simeprevir + sofosbuvir and treatment failed in two of them. Furthermore, one of three patients who failed ledipasvir + sofosbuvir treatment had NS5A-RASs at baseline.

    CONCLUSIONS: In line with the findings of the OPTIMIST-2 trial for Q80K and the EASL-guidelines 2016 for NS5A-RASs, baseline RASs appeared to have an impact on treatment outcome albeit a statistical significance was not observed in this low-prevalence population.

  • 30.
    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)
  • 31.
    Kurland, Siri
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Löwdin, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Eliasson, E.
    Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Pharmacol, Stockholm, Sweden.
    Nielsen, Elisabet I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Pharmacokinetics of Caspofungin in Critically Ill Patients in Relation to Liver Dysfunction: Differential Impact of Plasma Albumin and Bilirubin Levels2019In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 63, no 6, article id e02466-18Article in journal (Refereed)
    Abstract [en]

    Caspofungin has a liver-dependent metabolism. Reduction of the dose is recommended based on Child-Pugh (C-P) score. In critically ill patients, drug pharmacokinetics (PK) may be altered. The aim of this study was to investigate the prevalence of abnormal liver function tests, increased C-P scores, their effects on caspofungin PK, and whether pharmacokinetic-pharmacodynamic (PK/PD) targets were attained in patients with suspected candidiasis. Intensive care unit patients receiving caspofungin were prospectively included. PK parameters were determined on days 2, 5, and 10, and their correlations to the individual liver function tests and the C-P score were analyzed. Forty-six patients were included with C-P class A (n = 5), B (n = 40), and C (n = 1). On day 5 (steady state), the median and interquartile range for area under the curve from 0 to 24 h (AUC(0-24)), clearance (CL), and central volume of distribution (V-1) were 57.8 (51.6 to 69.8) mg.h/liter, 0.88 (0.78 to 1.04) liters/h, and 11.9 (9.6 to 13.1) liters, respectively. The C-P score did not correlate with AUC(0-24) (r = 0.03; P = 0.84), CL (r = -0.07; P = 0.68), or V-1 (r = 0.19; P = 0.26), but there was a bilirubin-driven negative correlation with the elimination rate constant (r = -0.46; P = 0.004). Hypoalbuminemia correlated with low AUC(0-24) (r = 0.45; P = 0.005) and was associated with higher clearance (r = -0.31; P = 0.062) and somewhat higher V-1 (r = -0.15; P = 0.37), resulting in a negative correlation with the elimination rate constant (r = -0.34; P = 0.042). For Candida strains with minimal inhibitory concentrations of >= 0.064 mu g/ml, PK/PD targets were not attained in all patients. The caspofungin dose should not be reduced in critically ill patients in the absence of cirrhosis, and we advise against the use of the C-P score in patients with trauma- or sepsis-induced liver injury.

  • 32.
    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)
  • 33.
    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.

  • 34.
    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.

  • 35.
    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.

  • 36.
    Lipcsey, Miklós
    et al.
    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 Surgical Sciences, Hedenstierna laboratory.
    Hanslin, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Stålberg, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Smekal, David
    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, Clinical Chemistry.
    The time course of calprotectin liberation from human neutrophil granulocytes after Escherichia coli and endotoxin challenge2019In: Innate Immunity, ISSN 1753-4259, E-ISSN 1753-4267, Vol. 25, no 6, p. 369-373Article in journal (Refereed)
    Abstract [en]

    Plasma calprotectin has previously been reported as a biomarker for sepsis. The aim of the present study was to elucidate the kinetics of calprotectin release from neutrophils exposed to Escherichia coli and endotoxin. Whole blood samples were exposed to E. coli bacteria or endotoxin in vitro. Blood samples were collected after 0, 1, 2, 3 and 4 h and plasma calprotectin was analysed by particle enhanced turbidimetric immunoassay while TNF-α, IL-6, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were analyzed by ELISA. When neutrophils were exposed to either E. coli or endotoxin, calprotectin levels began to increase within a couple of hours after the challenge. Calprotectin increases early in response to bacterial challenge. Given the logistic advantages of the calprotectin analysis, this may be of interest for early diagnosis of bacterial infections.

  • 37.
    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.

  • 38.
    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.

  • 39.
    Nilsson, Anna J. E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Tervahartiala, Taina
    Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Stenbäckinkatu 9, PO Box 100, 00029 Helsinki, Finland.
    Lennebratt, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Lannergård, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Sorsa, Timo
    Department of Dental Medicine, Division of Periodontology, Karolinska Institute, SE-17177 Stockholm, Sweden.
    Rautelin, Hilpi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology.
    Enhanced Systemic Response of Matrix Metalloproteinases and Their Regulators in Campylobacter and Salmonella Patients2018In: Diagnostics (Basel), ISSN 2075-4418, Vol. 8, no 4, article id 82Article in journal (Refereed)
    Abstract [en]

    Campylobacters are major enteropathogens worldwide with a substantial financial burden. Matrix metalloproteinases (MMPs) are proteolytic metalloendopeptidases with ability to modify immune response and shown to be upregulated in patients with several tissue destructive diseases, including infections. We measured here serum concentrations of MMP-8 and MMP-9 together with their regulators myeloperoxidase (MPO), human neutrophil elastase (HNE), and tissue inhibitor of metalloproteinases (TIMP)-1 in 80 Campylobacter and 25 Salmonella patients as well as in 27 healthy controls. Paired serum samples were available for 73 and 23 patients, respectively. When the initial serum samples were compared to those from controls, both Campylobacter and Salmonella patients showed elevated concentrations of all biomarkers tested (p ≤ 0.037). In the follow-up samples, collected about 25 days afterwards, MMP-8 levels of Campylobacter patients had already turned to normal but all the other biomarkers still showed elevated, although from the initial levels significantly dropped, levels. For the follow-up samples of Salmonella patients, only MMP-9 and MPO levels were at a significantly higher level than in controls. It remains to be studied if the systematically enhanced neutrophil-derived proteolytic and oxidative stress, induced by Campylobacter infection as shown here and persisting for several weeks, is important for the development of late sequelae.

  • 40.
    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.

  • 41.
    Persson, Sofia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Natl Food Agcy, European Union Reference Lab EURL Foodborne Viru, Hamnesplanaden 5, S-45323 Uppsala, Sweden.
    Karlsson, Mans
    Stockholm Univ, Dept Math, Stockholm, Sweden.
    Borsch-Reniers, Henrik
    Southern Roslagen Environm & Hlth Author, Taby, Sweden.
    Ellström, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Eriksson, Ronnie
    Natl Food Agcy, European Union Reference Lab EURL Foodborne Viru, Hamnesplanaden 5, S-45323 Uppsala, Sweden.
    Simonsson, Magnus
    Natl Food Agcy, European Union Reference Lab EURL Foodborne Viru, Hamnesplanaden 5, S-45323 Uppsala, Sweden.
    Missing the Match Might Not Cost You the Game: Primer-Template Mismatches Studied in Different Hepatitis A Virus Variants2019In: Food and Environmnetal Virology, ISSN 1867-0334, E-ISSN 1867-0342, Vol. 11, no 3, p. 297-308Article in journal (Refereed)
    Abstract [en]

    Mismatches between template sequences and reverse transcription (RT) or polymerase chain reaction (PCR) primers can lead to underestimation or false negative results during detection and quantification of sequence-diverse viruses. We performed an in silico inclusivity analysis of a widely used RT-PCR assay for detection of hepatitis A virus (HAV) in food, described in ISO 15216-1. One of the most common mismatches found was a single G (primer) to U (template) mismatch located at the terminal 3 '-end of the reverse primer region. This mismatch was present in all genotype III sequences available in GenBank. Partial HAV genomes with common or potentially severe mismatches were produced by in vitro transcription and analysed using RT-ddPCR and RT-qPCR. When using standard conditions for RT-qPCR, the mismatch identified resulted in underestimation of the template concentration by a factor of 1.7-1.8 and an increase in 95% limit of detection from 8.6 to 19 copies/reaction. The effect of this mismatch was verified using full-length viral genomes. Here, the same mismatch resulted in underestimation of the template concentration by a factor of 2.8. For the partial genomes, the presence of additional mismatches resulted in underestimation of the template concentration by up to a factor of 232. Quantification by RT-ddPCR and RT-qPCR was equally affected during analysis of RNA templates with mismatches within the reverse primer region. However, on analysing DNA templates with the same mismatches, we found that ddPCR quantification was less affected by mismatches than qPCR due to the end-point detection technique.

  • 42.
    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.

  • 43.
    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.

  • 44.
    Sidebottom, David
    et al.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
    Ekstrom, Anna Mia
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden; Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.
    Strömdahl, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
    A systematic review of adherence to oral pre-exposure prophylaxis for HIV - how can we improve uptake and adherence?2018In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 18, article id 581Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Oral pre-exposure prophylaxis (PrEP) is an effective strategy to reduce the risk of HIV transmission in high risk individuals. However, the effectiveness of oral pre-exposure prophylaxis is highly dependent on user adherence, which some previous trials have struggled to optimise particularly in low and middle income settings. This systematic review aims to ascertain the reasons for non-adherence to pre-exposure prophylaxis to guide future implementation.

    Methods: We performed structured literature searches of online databases and conference archives between August 8, 2016 and September 16, 2017. In total, 18 prospective randomized control trials and implementation studies investigating oral pre-exposure prophylaxis were reviewed. A structured form was used for data extraction and findings summarized regarding efficacy, effectiveness, adherence and possible reasons for non-adherence.

    Results: Adherence varied between differing populations both geographically and socioeconomically. Common reasons for non-adherence reported over multiple studies were; social factors such as stigma, low risk perception, low decision making power, an unacceptable dosing regimen, side effects, and the logistics of daily life. Oral pre-exposure prophylaxis with included antiviral regimens was not associated with a high risk of antiviral resistance development in the reviewed studies.

    Conclusion: Our findings indicate that oral pre-exposure prophylaxis should be delivered within a holistic intervention, acknowledging the other needs of the targeted demographic in order to maximise acceptability. Socioeconomic factors and poor governmental policy remain major barriers to widespread implementation of pre-exposure prophylaxis.

  • 45.
    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.

  • 46. 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.

  • 47.
    Strand, Tanja M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Department of Microbiology, National Veterinary Institute (SVA), Uppsala, Sweden.
    Pineda, Sebastian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Backhans, Annette
    Jakobsen, Frida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Råsbäck, Therese
    Lõhmus, Mare
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Institute for Environmental Medicine, Karolinska Institute, Stockholm, Sweden;Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden.
    Järhult, Josef D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Lundkvist, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Detection of Leptospira in Urban Swedish Rats: Pest Control Interventions as a Promising Source of Rats Used for Surveillance2019In: Vector Borne and Zoonotic Diseases, ISSN 1530-3667, E-ISSN 1557-7759, Vol. 19, no 6, p. 414-420Article in journal (Refereed)
    Abstract [en]

    Rat carcasses obtained from pest control interventions can potentially be used for an efficient surveillance of zoonotic diseases such as leptospirosis. To evaluate the performance of different laboratory methods for detection of pathogenic Leptospira spp., heart and kidney samples from wild Norway rats were analyzed by microscopic agglutination test (MAT, the gold standard), a commercial IgG enzyme-linked immunosorbent assay, and by an optimized quantitative PCR (secY qPCR, followed by sequencing). We found secY qPCR to be as sensitive as MAT for screening of Leptospira infection in pest control rats and selected secY qPCR for a larger screening of rats from urban and rural areas in central and southern Sweden. We identified secY qPCR positive rats from the cities Stockholm, Gothenburg, and Malmö, which were further confirmed by sequencing.

  • 48.
    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)
  • 49.
    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.

  • 50.
    Thorsted, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Bouchene, Salim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Tano, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine. Uppsala Univ Hosp, Sect Clin Microbiol & Infect Med, Dept Med Sci, Uppsala, Sweden.
    Castegren, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Karolinska Univ Hosp, Div Perioperat Med & Intens Care, Stockholm, Sweden;Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Lipcsey, Miklós
    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 Surgical Sciences, Hedenstierna laboratory. Uppsala Univ Hosp, Dept Surg Sci, Sect Anesthesiol & Intens Care, Hedenstierna Lab, Uppsala, Sweden.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala Univ Hosp, Infect Dis Sect, Dept Med Sci, Uppsala, Sweden.
    Karlsson, Mats O
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Friberg, Lena E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Nielsen, Elisabet I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    A non-linear mixed effect model for innate immune response: In vivo kinetics of endotoxin and its induction of the cytokines tumor necrosis factor alpha and interleukin-62019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 2, article id e0211981Article in journal (Refereed)
    Abstract [en]

    Endotoxin, a component of the outer membrane of Gram-negative bacteria, has been extensively studied as a stimulator of the innate immune response. However, the temporal aspects and exposure-response relationship of endotoxin and resulting cytokine induction and tolerance development is less well defined. The aim of this work was to establish an in silico model that simultaneously captures and connects the in vivo time-courses of endotoxin, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and associated tolerance development. Data from six studies of porcine endotoxemia in anesthetized piglets (n = 116) were combined and used in the analysis, with purified endotoxin (Escherichia coli O111: B4) being infused intravenously for 1-30 h in rates of 0.063-16.0 mu g/kg/h across studies. All data were modelled simultaneously by means of importance sampling in the non-linear mixed effects modelling software NONMEM. The infused endotoxin followed one-compartment disposition and non-linear elimination, and stimulated the production of TNF-alpha to describe the rapid increase in plasma concentration. Tolerance development, observed as declining TNF-alpha concentration with continued infusion of endotoxin, was also driven by endotoxin as a concentration-dependent increase in the potency parameter related to TNF-alpha production (EC50). Production of IL-6 was stimulated by both endotoxin and TNF-a, and four consecutive transit compartments described delayed increase in plasma IL-6. A model which simultaneously account for the time-courses of endotoxin and two immune response markers, the cytokines TNF-alpha and IL-6, as well as the development of endotoxin tolerance, was successfully established. This model-based approach is unique in its description of the time-courses and their interrelation and may be applied within research on immune response to bacterial endotoxin, or in pre-clinical pharmaceutical research when dealing with study design or translational aspects.

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