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  • 1.
    Abdeldaim, Guma M. K.
    et al.
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Department of Clinical Mycobacteriology, National Center for Diseases Control, Benghazi, Libyan Arab Jamahiriya.
    Strålin, Kristoffer
    Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
    Olcén, Per
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Blomberg, Jonas
    Section of Clinical Virology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Mölling, Paula
    Orebro University Hospital. Department of Laboratory Medicine.
    Herrmann, Björn
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Quantitative fucK gene polymerase chain reaction on sputum and nasopharyngeal secretions to detect Haemophilus influenzae pneumonia2013In: Diagnostic microbiology and infectious disease, ISSN 0732-8893, E-ISSN 1879-0070, Vol. 76, no 2, 141-146 p.Article in journal (Refereed)
    Abstract [en]

    A quantitative polymerase chain reaction (PCR) for the fucK gene was developed for specific detection of Haemophilus influenzae. The method was tested on sputum and nasopharyngeal aspirate (NPA) from 78 patients with community-acquired pneumonia (CAP). With a reference standard of sputum culture and/or serology against the patient's own nasopharyngeal isolate, H. influenzae etiology was detected in 20 patients. Compared with the reference standard, fucK PCR (using the detection limit 10(5) DNA copies/mL) on sputum and NPA showed a sensitivity of 95.0% (19/20) in both cases, and specificities of 87.9% (51/58) and 89.5% (52/58), respectively. In a receiver operating characteristic curve analysis, sputum fucK PCR was found to be significantly superior to sputum P6 PCR for detection of H. influenzae CAP. NPA fucK PCR was positive in 3 of 54 adult controls without respiratory symptoms. In conclusion, quantitative fucK real-time PCR provides a sensitive and specific identification of H. influenzae in respiratory secretions.

  • 2.
    Abdulla, Salim
    et al.
    Ifakara Hlth Inst, Dar Es Salaam, Tanzania..
    Adam, Ishag
    Univ Khartoum, Fac Med, Khartoum, Sudan..
    Adjei, George O.
    Univ Ghana, Sch Med, Ctr Trop Clin Pharmacol & Therapeut, Accra, Ghana..
    Adjuik, Martin A.
    INDEPTH Network Secretariat, Accra, Ghana..
    Alemayehu, Bereket
    Int Ctr AIDS Care & Treatment Programs, Addis Ababa, Ethiopia..
    Allan, Richard
    MENTOR Initiat, Crawley, England..
    Arinaitwe, Emmanuel
    Infect Dis Res Collaborat, Kampala, Uganda..
    Ashley, Elizabeth A.
    Epictr, Paris, France..
    Ba, Mamadou S.
    Univ Cheikh Anta Diop, Dept Parasitol & Mycol, Fac Med, Dakar, Senegal..
    Barennes, Hubert
    Ctr Muraz, Bobo Dioulasso, Burkina Faso.;French Foreign Affairs, Biarritz, France..
    Barnes, Karen I.
    WorldWide Antimalarial Resistance Network WWARN, Cape Town, South Africa.;Univ Cape Town, Dept Med, Div Clin Pharmacol, ZA-7925 Cape Town, South Africa..
    Bassat, Quique
    Ctr Invest Saude Manhica, Manhica, Mozambique.;Univ Barcelona, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Hosp Clin, Barcelona, Spain..
    Baudin, Elisabeth
    MENTOR Initiat, Crawley, England..
    Berens-Riha, Nicole
    Univ Munich LMU, Med Ctr, Div Infect Dis & Trop Med, Munich, Germany.;LMU, German Ctr Infect Res DZIF, Munich, Germany..
    Bjoerkman, Anders
    Karolinska Inst, Dept Microbiol Tumour & Cell Biol, Stockholm, Sweden..
    Bompart, Francois
    Sanofi Aventis, Direct Acces Med Access Med, Gentilly, France..
    Bonnet, Maryline
    Epictr, Geneva, Switzerland..
    Borrmann, Steffen
    Wellcome Trust Res Programme, Kenya Med Res Inst, Kilifi, Kenya.;Univ Tubingen, Inst Trop Med, Tubingen, Germany.;German Ctr Infect Res, Tubingen, Germany..
    Bousema, Teun
    London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Infect & Immun, London WC1, England.;Radboud Univ Nijmegen, Med Ctr, Dept Med Microbiol, Njimegen, Netherlands..
    Brasseur, Philippe
    IRD, Dakar, Senegal..
    Bukirwa, Hasifa
    Uganda Malaria Surveillance Project, Kampala, Uganda..
    Checchi, Francesco
    Epictr, Paris, France..
    Dahal, Prabin
    WorldWide Antimalarial Resistance Network WWARN, Oxford, England.;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England..
    D'Alessandro, Umberto
    Inst Trop Med, Unit Malariol, B-2000 Antwerp, Belgium.;MRC Unit, Fajara, Gambia.;London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Dis Control, London WC1, England..
    Desai, Meghna
    Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Malaria Branch, Atlanta, GA USA..
    Dicko, Alassane
    Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali.;Univ Bamako, Fac Med Pharm & Dent, Dept Publ Hlth, Bamako, Mali..
    Djimde, Abdoulaye A.
    Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali..
    Dorsey, Grant
    Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA..
    Doumbo, Ogobara K.
    Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali..
    Drakeley, Chris J.
    German Ctr Infect Res, Tubingen, Germany..
    Duparc, Stephan
    Med Malaria Venture, Geneva, Switzerland..
    Eshetu, Teferi
    Univ Barcelona, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Hosp Clin, Barcelona, Spain.;Jimma Univ, Dept Med Lab Sci & Pathol, Jimma, Ethiopia..
    Espie, Emmanuelle
    Epictr, Paris, France..
    Etard, Jean-Francois
    Epictr, Paris, France.;IRD, Montpellier, France..
    Faiz, Abul M.
    Mahidol Univ, Fac Trop Med, Bangkok, Thailand..
    Falade, Catherine O.
    Univ Ibadan, Coll Med, Dept Pharmacol & Therapeut, Ibadan, Nigeria..
    Fanello, Caterina I.
    Mahidol Univ, Fac Trop Med, Mahidol Oxford Res Unit, Bangkok, Thailand..
    Faucher, Jean-Francois
    IRD, Mother & Child Hlth Trop Res Unit, Paris, France.;Univ Paris 05, PRES Sorbonne Paris Cite, Paris, France.;Univ Besancon, Med Ctr, Dept Infect Dis, F-25030 Besancon, France..
    Faye, Babacar
    Univ Cheikh Anta Diop, Dept Parasitol & Mycol, Fac Med, Dakar, Senegal..
    Faye, Oumar
    Univ Cheikh Anta Diop, Dept Parasitol & Mycol, Fac Med, Dakar, Senegal..
    Filler, Scott
    Global Fund Fight AIDS TB & Malaria, Geneva, Switzerland..
    Flegg, Jennifer A.
    WorldWide Antimalarial Resistance Network WWARN, Oxford, England.;Monash Univ, Sch Math Sci, Melbourne, Vic 3004, Australia.;Monash Univ, Monash Acad Cross & Interdisciplinary Math Applic, Melbourne, Vic 3004, Australia..
    Fofana, Bakary
    Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali..
    Fogg, Carole
    Univ Portsmouth, Portsmouth Hosp NHS Trust, Portsmouth, Hants, England..
    Gadalla, Nahla B.
    London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Infect & Immun, London WC1, England.;Natl Res Ctr, Res Inst Trop Med, Dept Epidemiol, Khartoum, Sudan.;NIAID, Rockville, MD USA..
    Gaye, Oumar
    Univ Cheikh Anta Diop, Dept Parasitol & Mycol, Fac Med, Dakar, Senegal..
    Genton, Blaise
    Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.;Univ Lausanne Hosp, Div Infect Dis, Lausanne, Switzerland.;Univ Lausanne Hosp, Dept Ambulatory Care & Community Med, Lausanne, Switzerland..
    Gething, Peter W.
    Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford OX1 3PS, England..
    Gil, Jose P.
    Karolinska Inst, Pharmacogenet Sect, Drug Resistance Unit, Dept Physiol & Pharmacol, Stockholm, Sweden.;Univ Lisbon, Fac Sci, Biosyst & Integrat Sci Inst BioISI, P-1699 Lisbon, Portugal.;SUNY Binghamton, Harpur Coll Arts & Sci, Binghamton, NY USA..
    Gonzalez, Raquel
    Ctr Invest Saude Manhica, Manhica, Mozambique.;Univ Barcelona, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Hosp Clin, Barcelona, Spain..
    Grandesso, Francesco
    Epictr, Paris, France..
    Greenhouse, Bryan
    Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA..
    Greenwood, Brian
    London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Dis Control, London WC1, England..
    Grivoyannis, Anastasia
    Univ Washington, Div Emergency Med, Seattle, WA 98195 USA..
    Guerin, Philippe J.
    WorldWide Antimalarial Resistance Network WWARN, Oxford, England.;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England..
    Guthmann, Jean-Paul
    Inst Veille Sanit, Dept Malad Infect, St Maurice, France..
    Hamed, Kamal
    Novartis Pharmaceut, E Hanover, NJ USA..
    Hamour, Sally
    Royal Free Hosp, UCL Ctr Nephrol, London NW3 2QG, England..
    Hay, Simon I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.;NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA..
    Hodel, Eva Maria
    Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.;Univ Liverpool, Liverpool Sch Trop Med, Dept Parasitol, Liverpool L3 5QA, Merseyside, England..
    Humphreys, Georgina S.
    WorldWide Antimalarial Resistance Network WWARN, Oxford, England.;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England..
    Hwang, Jimee
    Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Malaria Branch, Atlanta, GA USA.;Univ Calif San Francisco, Global Hlth Grp, San Francisco, CA 94143 USA..
    Ibrahim, Maman L.
    Ctr Rech Med & Sanit, Niamey, Niger..
    Jima, Daddi
    Fed Minist Hlth, Addis Ababa, Ethiopia..
    Jones, Joel J.
    Minist Hlth & Social Welf, Natl Malaria Control Programme, Monrovia, Liberia..
    Jullien, Vincent
    Univ Paris 05, AP HP, Paris, France..
    Juma, Elizabeth
    Kenya Govt Med Res Ctr, Nairobi, Kenya..
    Kachur, Patrick S.
    Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Malaria Branch, Atlanta, GA USA..
    Kager, Piet A.
    Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam CINIMA, Div Infect Dis Trop Med & AIDS, NL-1105 AZ Amsterdam, Netherlands..
    Kamugisha, Erasmus
    Catholic Univ Hlth & Allied Sci, Mwanza, Tanzania..
    Kamya, Moses R.
    Makerere Univ, Coll Hlth Sci, Kampala, Uganda..
    Karema, Corine
    Minist Hlth, Malaria & Other Parasit Dis Div RBC, Kigali, Rwanda..
    Kayentao, Kassoum
    Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali..
    Kiechel, Jean-Rene
    Drugs Neglected Dis initiat, Geneva, Switzerland..
    Kironde, Fred
    Makerere Univ, Dept Biochem, Kampala, Uganda..
    Kofoed, Poul-Erik
    Projecto Saude Bandim, Bissau, Guinea Bissau.;Kolding Cty Hosp, Dept Paediat, Kolding, Denmark..
    Kremsner, Peter G.
    Univ Tubingen, Inst Trop Med, Tubingen, Germany.;Ctr Rech Med Lambarene, Lambarene, Gabon..
    Krishna, Sanjeev
    Univ London, Inst Infect & Immun, London, England. Operat Ctr Barcelona Athens, Med Sans Frontieres, Barcelona, Spain..
    Lameyre, Valerie
    Sanofi Aventis, Direct Acces Med Access Med, Gentilly, France..
    Lell, Bertrand
    Univ Tubingen, Inst Trop Med, Tubingen, Germany.;Ctr Rech Med Lambarene, Lambarene, Gabon..
    Lima, Angeles
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Makanga, Michael
    European & Dev Countries Clin Trials Partnership, Cape Town, South Africa..
    Malik, ElFatih M.
    Fed Minist Hlth, Khartoum, Sudan..
    Marsh, Kevin
    Wellcome Trust Res Programme, Kenya Med Res Inst, Kilifi, Kenya.;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England..
    Mårtensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Karolinska Inst, Dept Microbiol Tumour & Cell Biol, Stockholm, Sweden.;Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden..
    Massougbodji, Achille
    Univ Abomey Calavi, FSS, CERPAGE, Cotonou, Benin..
    Menan, Herve
    Univ Cocody, Fac Pharm, Dept Parasitol, Abidjan, Cote Ivoire..
    Menard, Didier
    Inst Pasteur Cambodia, Malaria Mol Epidemiol Unit, Phnom Penh, Cambodia..
    Menendez, Clara
    Ctr Invest Saude Manhica, Manhica, Mozambique.;Univ Barcelona, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Hosp Clin, Barcelona, Spain..
    Mens, Petra F.
    Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam CINIMA, Div Infect Dis Trop Med & AIDS, NL-1105 AZ Amsterdam, Netherlands.;KIT Biomed Res, Royal Trop Inst, Amsterdam, Netherlands..
    Meremikwu, Martin
    Univ Calabar, Dept Paediat, Calabar, Nigeria.;Inst Trop Dis Res & Prevent, Calabar, Nigeria..
    Moreira, Clarissa
    WorldWide Antimalarial Resistance Network WWARN, Oxford, England.;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England..
    Nabasumba, Carolyn
    Epictr, Paris, France.;Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda..
    Nambozi, Michael
    Trop Dis Res Ctr, Ndola, Zambia..
    Ndiaye, Jean-Louis
    Univ Cheikh Anta Diop, Dept Parasitol & Mycol, Fac Med, Dakar, Senegal..
    Ngasala, Billy E.
    Muhimbili Univ Hlth & Allied Sci, Dept Parasitol, Dar Es Salaam, Tanzania.;Karolinska Inst, Dept Med Solna, Infect Dis Unit, Malaria Res, Stockholm, Sweden..
    Nikiema, Frederic
    Inst Rech Sci Sante, Bobo Dioulasso, Burkina Faso..
    Nsanzabana, Christian
    WorldWide Antimalarial Resistance Network WWARN, Oxford, England.;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England..
    Ntoumi, Francine
    Univ Tubingen, Inst Trop Med, Tubingen, Germany.;Univ Marien Ngouabi, FCRM, Fac Sci Sante, Brazzaville, Congo..
    Oguike, Mary
    London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Infect & Immun, London WC1, England..
    Ogutu, Bernhards R.
    United States Army Med Res Unit, Kenya Med Res Inst, Kisumu, Kenya..
    Olliaro, Piero
    Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England.;UNICEF UNDP World Bank WHO Special Programme Res, Geneva, Switzerland..
    Omar, Sabah A.
    Kenya Govt Med Res Ctr, Ctr Biotechnol Res & Dev, Nairobi, Kenya..
    Ouedraogo, Jean-Bosco
    Ctr Muraz, Bobo Dioulasso, Burkina Faso.;Inst Rech Sci Sante, Bobo Dioulasso, Burkina Faso..
    Owusu-Agyei, Seth
    Kintampo Hlth Res Ctr, Kintampo, Ghana..
    Penali, Louis K.
    WorldWide Antimalarial Resistance Network WWARN W, Dakar, Senegal..
    Pene, Mbaye
    Univ Cheikh Anta Diop, Dept Parasitol & Mycol, Fac Med, Dakar, Senegal..
    Peshu, Judy
    Wellcome Trust Res Programme, Kenya Med Res Inst, Kilifi, Kenya..
    Piola, Patrice
    Inst Pasteur Madagascar, Epidemiol Unit, Antananarivo, Madagascar..
    Plowe, Christopher V.
    Univ Maryland, Sch Med, Howard Hughes Med Inst, Ctr Vaccine Dev, Baltimore, MD 21201 USA..
    Premji, Zul
    Muhimbili Univ Hlth & Allied Sci, Dept Parasitol, Dar Es Salaam, Tanzania..
    Price, Ric N.
    WorldWide Antimalarial Resistance Network WWARN, Oxford, England.;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England.;Menzies Sch Hlth Res, Darwin, NT, Australia.;Charles Darwin Univ, Darwin, NT 0909, Australia..
    Randrianarivelojosia, Milijaona
    Inst Pasteur Madagascar, Malaria Res Unit, Antananarivo, Madagascar..
    Rombo, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Karolinska Inst, Karolinska Univ Hosp, Infect Dis Unit, Malaria Res Lab,Dept Med, Stockholm, Sweden.;Malarsjukhuset, Dept Infect Dis, S-63188 Eskilstuna, Sweden..
    Roper, Cally
    London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Pathogen Mol Biol, London WC1, England..
    Rosenthal, Philip J.
    Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA..
    Sagara, Issaka
    Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali..
    Same-Ekobo, Albert
    Ctr Hosp Univ Yaounde, Fac Med & Sci Biomed, Yaounde, Cameroon..
    Sawa, Patrick
    Int Ctr Insect Physiol & Ecol, Human Hlth Div, Mbita, Kenya..
    Schallig, Henk D. F. H.
    KIT Biomed Res, Royal Trop Inst, Amsterdam, Netherlands..
    Schramm, Birgit
    Epictr, Paris, France..
    Seck, Amadou
    WorldWide Antimalarial Resistance Network WWARN W, Dakar, Senegal..
    Shekalaghe, Seif A.
    Ifakara Hlth Inst, Dar Es Salaam, Tanzania.;Kilimanjaro Christian Med Ctr, Kilimanjaro Clin Med Res Inst, Moshi, Tanzania..
    Sibley, Carol H.
    WorldWide Antimalarial Resistance Network WWARN, Oxford, England.;Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA..
    Sinou, Vronique
    Aix Marseille Univ, Fac Pharm, UMR MD3, Marseille, France..
    Sirima, Sodiomon B.
    CNRFP, Ouagadougou, Burkina Faso..
    Som, Fabrice A.
    Inst Rech Sci Sante, Bobo Dioulasso, Burkina Faso..
    Sow, Doudou
    Univ Cheikh Anta Diop, Dept Parasitol & Mycol, Fac Med, Dakar, Senegal..
    Staedke, Sarah G.
    Infect Dis Res Collaborat, Kampala, Uganda.;London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Clin Res, London WC1, England..
    Stepniewska, Kasia
    WorldWide Antimalarial Resistance Network WWARN, Oxford, England.;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England..
    Sutherland, Colin J.
    London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Infect & Immun, London WC1, England..
    Swarthout, Todd D.
    Med Sans Frontieres, London, England..
    Sylla, Khadime
    Univ Cheikh Anta Diop, Dept Parasitol & Mycol, Fac Med, Dakar, Senegal..
    Talisuna, Ambrose O.
    East Africa Reg Ctr, WorldWide Antimalarial Resistance Network WWARN, Nairobi, Kenya.;Univ Oxford, KEMRI, Wellcome Trust Res Programme, Nairobi, Kenya..
    Taylor, Walter R. J.
    UNICEF UNDP World Bank WHO Special Programme Res, Geneva, Switzerland.;Hop Cantonal Univ Geneva, Serv Med Int & Humanitaire, Geneva, Switzerland..
    Temu, Emmanuel A.
    MENTOR Initiat, Crawley, England.;Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland.;Univ Basel, Basel, Switzerland..
    Thwing, Julie I.
    Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Malaria Branch, Atlanta, GA USA..
    Tine, Roger C. K.
    Univ Cheikh Anta Diop, Dept Parasitol & Mycol, Fac Med, Dakar, Senegal..
    Tinto, Halidou
    Ctr Muraz, Bobo Dioulasso, Burkina Faso.;Inst Rech Sci Sante, Bobo Dioulasso, Burkina Faso..
    Tommasini, Silva
    Sigma Tau Ind Farmaceut Riunite SpA, Rome, Italy..
    Toure, Offianan A.
    Inst Pasteur Cote Ivoire, Malariol Dept, Abidjan, Cote Ivoire..
    Ursing, Johan
    Projecto Saude Bandim, Bissau, Guinea Bissau.;Karolinska Inst, Dept Med Solna, Infect Dis Unit, Malaria Res, Stockholm, Sweden..
    Vaillant, Michel T.
    CRP Sante, Ctr Hlth Studies, Methodol & Stat Unit, Luxembourg, Luxembourg.;Univ Bordeaux 2, Unite Bases Therapeut Inflammat & Infect 3677, F-33076 Bordeaux, France..
    Valentini, Giovanni
    Sigma Tau Ind Farmaceut Riunite SpA, Rome, Italy..
    Van den Broek, Ingrid
    Med Sans Frontieres, London, England.;Natl Inst Publ Hlth & Environm, Ctr Infect Dis Control, NL-3720 BA Bilthoven, Netherlands..
    Van Vugt, Michele
    Univ Amsterdam, Acad Med Ctr, Ctr Trop Med & Travel Med, Div Infect Dis, NL-1012 WX Amsterdam, Netherlands..
    Ward, Stephen A.
    Univ Liverpool, Liverpool Sch Trop Med, Dept Parasitol, Liverpool L3 5QA, Merseyside, England..
    Winstanley, Peter A.
    Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England..
    Yavo, William
    Univ Cocody, Fac Pharmaceut & Biol Sci, Dept Parasitol & Mycol, Abidjan, Cote Ivoire.;Natl Inst Publ Hlth, Malaria Res & Control Ctr, Abidjan, Cote Ivoire..
    Yeka, Adoke
    Uganda Malaria Surveillance Project, Kampala, Uganda..
    Zolia, Yah M.
    Minist Hlth & Social Welf, Natl Malaria Control Programme, Monrovia, Liberia..
    Zongo, Issaka
    Inst Rech Sci Sante, Bobo Dioulasso, Burkina Faso..
    Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data2015In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 13, 212Article, review/survey (Refereed)
    Abstract [en]

    Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). Methods: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. Results: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 degrees C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). Conclusions: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

  • 3.
    Abdurahman, Samir
    et al.
    Division of Clinical Microbiology, Department of Laboratory Medicine, F68, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Barqasho, Babilonia
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Sweden.
    Nowak, Piotr
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Sweden.
    Cuong, Do Duy
    Infectious Diseases Department, Bach Mai Hospital, Hanoi, Viet Nam .
    Amogné, Wondwossen
    Department of Medicine, Faculty of Medicine, Addis Ababa University, Ethiopia .
    Larsson, Mattias
    Division of Global Health (IHCAR), Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden; Oxford University Clinical Research Unit (OUCRU), Hanoi, Viet Nam .
    Lindquist, Lars
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Sweden .
    Marrone, Gaetano
    Division of Global Health (IHCAR), Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden .
    Sönnerborg, Anders
    Division of Clinical Microbiology, Department of Laboratory Medicine, F68, Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Sweden.
    Pattern of microbial translocation in patients living with HIV-1 from Vietnam, Ethiopia and Sweden2014In: Journal of the International AIDS Society, ISSN 1758-2652, Vol. 17, 18841- p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The role of microbial translocation (MT) in HIV patients living with HIV from low- and middle-income countries (LMICs) is not fully known. The aim of this study is to investigate and compare the patterns of MT in patients from Vietnam, Ethiopia and Sweden.

    METHODS: Cross-sectional samples were obtained from treatment-naïve patients living with HIV-1 and healthy controls from Vietnam (n=83; n=46), Ethiopia (n=9492; n=50) and Sweden (n=51; n=19). Longitudinal samples were obtained from a subset of the Vietnamese (n=24) in whom antiretroviral therapy (ART) and tuberculostatics were given. Plasma lipopolysaccharide (LPS), sCD14 and anti-flagellin IgG were determined by the endpoint chromogenic Limulus Amebocyte Assay and enzyme-linked immunosorbent assay.

    RESULTS: All three biomarkers were significantly increased in patients living with HIV-1 from all countries as compared to controls. No differences were found between males and females. Vietnamese and Ethiopian patients had significantly higher levels of anti-flagellin IgG and LPS, as compared to Swedes. ART reduced these levels for the Vietnamese. Vietnamese patients given tuberculostatics at initiation of ART had significantly lower levels of anti-flagellin IgG and higher sCD14. The biomarkers were lower in Vietnamese who did not develop opportunistic infection.

    CONCLUSIONS: Higher MT is common in patients living with HIV compared to healthy individuals, and in patients from LMICs compared to patients from a high-income country. Treatment with tuberculostatics decreased MT while higher levels of MT are associated with a poorer clinical outcome.

  • 4.
    Abrahamsson, Daria
    et al.
    Linnaeus University, Faculty of Health, Social Work and Behavioural Sciences, School of Health and Caring Sciences.
    Miller, Sofi
    Linnaeus University, Faculty of Health, Social Work and Behavioural Sciences, School of Health and Caring Sciences.
    MRSA – EN FÖLJETONG UTAN SLUT: Effekter av olika åtgärder i smittskyddsarbete mot MRSA 2010Independent thesis Basic level (degree of Bachelor), 15 credits / 22,5 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Multiresistenta bakterier, däribland MRSA, är idag ett globalt samhällsproblem. Infektioner förorsakade av MRSA skapar ett onödigt lidande för patienter med utdragen vårdtid som i värsta fall kan resultera i ökad dödlighet. Enligt Smittskyddsinstitutet (2010) drabbades 1479 patienter förra året i Sverige. Med få verksamma antibiotika måste andra åtgärder tillämpas, så som basala hygienrutiner, screening, isoleringsvård och utökad städning av sjukhusmiljön. Det är dock viktigt att utvärdera åtgärdernas effekter för att kunna utföra smittskyddsarbete på bästa möjliga sätt.

    Syfte: Syftet var att undersöka effekterna av olika åtgärder i smittskyddsarbetet mot MRSA.

    Metod: Litteraturstudie med kvantitativ ansats baserad på tio vetenskapliga original artiklar. Analysen gjordes enligt Forsberg och Wengströms (2008) riktlinjer för meta-analys.

    Resultat: Studien visar att MRSA förekommer i kliniska miljöer samt förutom hos patienten även hos vårdpersonal. Förebyggande åtgärder som bland annat noggrann städning, basala hygienrutiner och screening hade varierande effekt och reducerade MRSA- förekomsten bäst i kombination. I vissa fall kunde brister i vårdpersonalens följsamhet (compliance) av hygienrutiner ses.

    Slutsats: För att reducera MRSA- förekomst och spridning är det viktigt att implementera de åtgärder som finns idag och som visat sig har effekt. För att genomföra detta krävs det att vårdpersonalens följsamhet blir bättre.

     

     

  • 5. Adjuik, Martin A.
    et al.
    Allan, Richard
    Anvikar, Anupkumar R.
    Ashley, Elizabeth A.
    Ba, Mamadou S.
    Barennes, Hubert
    Barnes, Karen I.
    Bassat, Quique
    Baudin, Elisabeth
    Bjorkman, Anders
    Bompart, Francois
    Bonnet, Maryline
    Borrmann, Steffen
    Brasseur, Philippe
    Bukirwa, Hasifa
    Checchi, Francesco
    Cot, Michel
    Dahal, Prabin
    D'Alessandro, Umberto
    Deloron, Philippe
    Desai, Meghna
    Diap, Graciela
    Djimde, Abdoulaye A.
    Dorsey, Grant
    Doumbo, Ogobara K.
    Espie, Emmanuelle
    Etard, Jean-Francois
    Fanello, Caterina I.
    Faucher, Jean-Francois
    Faye, Babacar
    Flegg, Jennifer A.
    Gaye, Oumar
    Gething, Peter W.
    Gonzalez, Raquel
    Grandesso, Francesco
    Guerin, Philippe J.
    Guthmann, Jean-Paul
    Hamour, Sally
    Hasugian, Armedy Ronny
    Hay, Simon I.
    Humphreys, Georgina S.
    Jullien, Vincent
    Juma, Elizabeth
    Kamya, Moses R.
    Karema, Corine
    Kiechel, Jean R.
    Kremsner, Peter G.
    Krishna, Sanjeev
    Lameyre, Valerie
    Ibrahim, Laminou M.
    Lee, Sue J.
    Lell, Bertrand
    Martensson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Massougbodji, Achille
    Menan, Herve
    Menard, Didier
    Menendez, Clara
    Meremikwu, Martin
    Moreira, Clarissa
    Nabasumba, Carolyn
    Nambozi, Michael
    Ndiaye, Jean-Louis
    Nikiema, Frederic
    Nsanzabana, Christian
    Ntoumi, Francine
    Ogutu, Bernhards R.
    Olliaro, Piero
    Osorio, Lyda
    Ouedraogo, Jean-Bosco
    Penali, Louis K.
    Pene, Mbaye
    Pinoges, Loretxu
    Piola, Patrice
    Price, Ric N.
    Roper, Cally
    Rosenthal, Philip J.
    Rwagacondo, Claude Emile
    Same-Ekobo, Albert
    Schramm, Birgit
    Seck, Amadou
    Sharma, Bhawna
    Sibley, Carol Hopkins
    Sinou, Veronique
    Sirima, Sodiomon B.
    Smith, Jeffery J.
    Smithuis, Frank
    Some, Fabrice A.
    Sow, Doudou
    Staedke, Sarah G.
    Stepniewska, Kasia
    Swarthout, Todd D.
    Sylla, Khadime
    Talisuna, Ambrose O.
    Tarning, Joel
    Taylor, Walter R. J.
    Temu, Emmanuel A.
    Thwing, Julie I.
    Tjitra, Emiliana
    Tine, Roger C. K.
    Tinto, Halidou
    Vaillant, Michel T.
    Valecha, Neena
    Van den Broek, Ingrid
    White, Nicholas J.
    Yeka, Adoke
    Zongo, Issaka
    The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data2015In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 13, 66Article in journal (Refereed)
    Abstract [en]

    Background: Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods: Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results: Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P < 0.001 for all comparisons). After controlling for age, AQ dose, baseline parasitemia and region; treatment with loose NFDC-25 was associated with a 3.5-fold greater risk of recrudescence by day 28 (adjusted hazard ratio, AHR = 3.51 [95% CI: 2.02-6.12], P < 0.001) compared to FDC, and treatment with loose NFDC-30 was associated with a higher risk of recrudescence at only three sites. Conclusions: There was substantial variation in the total dose of amodiaquine administered in different AS-AQ combination regimens. Fixed dose AS-AQ combinations ensure optimal dosing and provide higher antimalarial treatment efficacy than the loose individual tablets in all age categories.

  • 6. Affognon, H.
    et al.
    Mburu, P.
    Hassan, Osama Ahmed
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kingori, S.
    Ahlm, C.
    Sang, R.
    Evander, M.
    Sociocultural differences affect Rift Valley fever exposureManuscript (preprint) (Other academic)
  • 7. Affognon, Hippolyte
    et al.
    Mburu, Peter
    Hassan, Osama Ahmed
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Kingori, Sarah
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Sang, Rosemary
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ethnic groups' knowledge, attitude and practices and Rift Valley fever exposure in Isiolo County of Kenya2017In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, no 3, e0005405Article in journal (Refereed)
    Abstract [en]

    Rift Valley fever (RVF) is an emerging mosquito-borne viral hemorrhagic fever in Africa and the Arabian Peninsula, affecting humans and livestock. For spread of infectious diseases, including RVF, knowledge, attitude and practices play an important role, and the understanding of the influence of behavior is crucial to improve prevention and control efforts. The objective of the study was to assess RVF exposure, in a multiethnic region in Kenya known to experience RVF outbreaks, from the behavior perspective. We investigated how communities in Isiolo County, Kenya were affected, in relation to their knowledge, attitude and practices, by the RVF outbreak of 2006/2007. A cross-sectional study was conducted involving 698 households selected randomly from three different ethnic communities. Data were collected using a structured questionnaire regarding knowledge, attitudes and practices that could affect the spread of RVF. In addition, information was collected from the communities regarding the number of humans and livestock affected during the RVF outbreak. This study found that better knowledge about a specific disease does not always translate to better practices to avoid exposure to the disease. However, the high knowledge, attitude and practice score measured as a single index of the Maasai community may explain why they were less affected, compared to other investigated communities (Borana and Turkana), by RVF during the 2006/2007 outbreak. We conclude that RVF exposure in Isiolo County, Kenya during the outbreak was likely determined by the behavioral differences of different resident community groups. We then recommend that strategies to combat RVF should take into consideration behavioral differences among communities.

  • 8. Afset, J. E.
    et al.
    Larssen, K. W.
    Bergh, K.
    Larkeryd, A.
    Sjodin, A.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Forsman, M.
    Phylogeographical pattern of Francisella tularensis in a nationwide outbreak of tularaemia in Norway, 20112015In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 20, no 19, 9-14 p., 21125Article in journal (Refereed)
    Abstract [en]

    In 2011, a nationwide outbreak of tularaemia occurred in Norway with 180 recorded cases. It was associated with the largest peak in lemming density seen in 40 years. Francisella tularensis was isolated from 18 patients. To study the geographical distribution of F. tularensis genotypes in Norway and correlate genotype with epidemiology and clinical presentation, we performed whole genome sequencing of patient isolates. All 18 genomes from the outbreak carried genetic signatures of F. tularensis subsp. holarctica and were assigned to genetic clades using canonical single nucleotide polymorphisms. Ten isolates were assigned to major genetic clade B.6 (subclade B.7), seven to clade B.12, and one to clade B.4. The B.6 subclade B.7 was most common in southern and central Norway, while clade B.12 was evenly distributed between the southern, central and northern parts of the country. There was no association between genotype and clinical presentation of tularaemia, time of year or specimen type. We found extensive sequence similarity with F. tularensis subsp. holarctica genomes from high-endemic tularaemia areas in Sweden. Finding nearly identical genomes across large geographical distances in Norway and Sweden imply a life cycle of the bacterium without replication between the outbreaks and raise new questions about long-range migration mechanisms.

  • 9.
    Aguado, J. M.
    et al.
    Univ Hosp 12 Octubre, Madrid, Spain..
    Anttila, V. J.
    Univ Helsinki, FIN-00014 Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
    Galperine, T.
    Hop Claude Huriez, Lille, France..
    Goldenberg, S. D.
    Guys & St Thomas NHS Fdn Trust, Ctr Clin Infect & Diagnost Res, London SE1 7EH, England.;Kings Coll London, London WC2R 2LS, England..
    Gwynn, S.
    Triducive Ltd, St Albans, England..
    Jenkins, D.
    Univ Hosp Leicester NHS Trust, Leicester, Leics, England..
    Norén, Torbjörn
    Orebro University Hospital.
    Petrosillo, N.
    Natl Inst Infect Dis, Rome, Italy..
    Seifert, H.
    Univ Cologne, Inst Med Microbiol Immunol & Hyg, D-50931 Cologne, Germany..
    Stallmach, A.
    Univ Klinikum Jena, Dept Internal Med 4, Jena, Germany..
    Warren, T.
    Triducive Ltd, St Albans, England..
    Wenisch, C.
    Sud Kaiser Franz Josef Spital, Vienna, Austria..
    Highlighting clinical needs in Clostridium difficile infection: the views of European healthcare professionals at the front line2015In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 90, no 2, 117-125 p.Article in journal (Refereed)
    Abstract [en]

    Background: Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea in Europe. Despite increased focus, its incidence and severity are increasing in many European countries. Aim: We developed a series of consensus statements to identify unmet clinical needs in the recognition and management of CDI. Methods: A consortium of European experts prepared a series of 29 statements representing their collective views on the diagnosis and management of CDI in Europe. The statements were grouped into the following six broad themes: diagnosis; definitions of severity; treatment failure, recurrence and its consequences; infection prevention and control interventions; education and antimicrobial stewardship; and National CDI clinical guidance and policy. These statements were reviewed using questionnaires by 1047 clinicians involved in managing CDI, who indicated their level of agreement with each statement. Findings: Levels of agreement exceeded the 66% threshold for consensus for 27 out of 29 statements (93.1%), indicating strong support. Variance between countries and specialties was analysed and showed strong alignment with the overall consensus scores. Conclusion: Based on the consensus scores of the respondent group, recommendations are suggested for the further development of CDI services in order to reduce transmission and recurrence and to ensure that appropriate diagnosis and treatment strategies are applied across all healthcare settings.

  • 10.
    Ahlm, Clas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Vapalahti, O.
    University of Helsinki and Helsinki University Central Hospital Laboratory, Finland.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Seroprevalence of Sindbis virus and associated risk factors in northern Sweden2014In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 142, no 7, 1559-1565 p.Article in journal (Refereed)
    Abstract [en]

    Mosquito-borne Sindbis virus (SINV) cause disease characterized by rash, fever and arthritis which often leads to long-lasting arthralgia. To determine the seroprevalence of SINV and associated risk factors in northern Sweden, a randomly selected population aged between 25 and 74 years were invited to join the MONICA study. Serum from 1611 samples were analysed for specific IgG antibodies. Overall, 2·9% had IgG against SINV. More men (3·7%) than women (2·0%) were SINV seropositive (P = 0·047) and it was more common in subjects with a lower educational level (P = 0·013) and living in small, rural communities (P < 0·001). Seropositivity was associated with higher waist circumference (P = 0·1), elevated diastolic blood pressure (P = 0·037), and history of a previous stroke (P = 0·011). In a multiple logistic regression analysis, adjusting for known risk factors for stroke, seropositivity for SINV was an independent predictor of having had a stroke (odds ratio 4·3, 95% confidence interval 1·4–13·0,P = 0·011).

  • 11.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Orebro University Hospital. Department of Medicine, Division of Hematology.
    Hellmark, Bengt
    Orebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Svensson, Karolina
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Orebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Long-term molecular epidemiology of staphylococcus epidermidis blood culture isolates from patients with hematological malignancies2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, e99045Article in journal (Refereed)
    Abstract [en]

    Staphylococcus epidermidis is an important cause of bloodstream infections in patients with hematological malignancies. Knowledge of the long-term epidemiology of these infections is limited. We surveyed all S. epidermidis blood culture isolates from patients treated for hematological malignancies at the University Hospital of Orebro, Sweden from 1980 to 2009. A total of 373 S. epidermidis isolates were identified and multilocus sequence typing, staphylococcal chromosome cassette mec (SCCmec) typing and standard antibiotic susceptibility testing were employed to characterize these isolates. The majority of the isolates 361/373 (97%) belonged to clonal complex 2, and the 373 isolates were divided into 45 sequence types (STs); Simpson's Diversity Index was 0.56. The most prevalent STs were ST2 (243/373, 65%) and ST215 (28/373, 8%). Ninety three percent (226/243) of the ST2 isolates displayed either SCCmec type III or IV. ST2 and 215 were isolated during the entire study period, and together these STs caused temporal peaks in the number of positive blood cultures of S. epidermidis. Methicillin resistance was detected in 213/273 (78%) of all isolates. In the two predominating STs, ST2 and ST215, methicillin resistance was detected in 256/271 isolates (95%), compared with 34/100 (34%) in other STs (p<0.001). In conclusion, in this long-term study of patients with hematological malignancies, we demonstrate a predominance of methicillin-resistant ST2 among S. epidermidis blood culture isolates.

  • 12.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Hematology, Department of Medicine,Örebro University Hospital, Örebro, Sweden.
    Persson, Lennart
    Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Clinical Microbiology, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Alteration of the colonization pattern of coagulase-negative staphylococci in patients undergoing treatment for hematological malignancy2012In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 31, no 7, 1679-1687 p.Article in journal (Refereed)
    Abstract [en]

    The aim was to prospectively describe the colonization pattern of coagulase-negative staphylococci (CoNS) and the relationship between colonizing and invasive CoNS isolates among patients undergoing treatment for hematological malignancy. Fourteen newly diagnosed patients were included with either multiple myeloma or acute leukemia. Patients were repeatedly sampled from nares, throat, axillae, and perineum, and the CoNS isolates obtained were phenotypically characterized together with blood isolates of CoNS using the PhenePlate system (PhP). During the treatment a gradual reduction in the heterogeneity of colonizing CoNS was observed as well as an inter-patient accumulation of phenotypically related and multi-drug-resistant CoNS. These clusters of CoNS persisted for 2–3 months after the end of therapy. Ten positive blood cultures of CoNS were obtained and in the majority of these cases CoNS of the same PhP type were found in superficial cultures collected prior to the blood culture sampling. In conclusion, the study shows that therapy for hematological malignancy is associated with a homogenization of colonizing CoNS isolates and that this acquired flora of CoNS is persistent several months after the end of therapy. Furthermore, the results suggest that the source of bloodstream infections of CoNS in hematological patients is colonizing CoNS of the skin and mucosa.

  • 13. Albrecht, Letusa
    et al.
    Moll, Kirsten
    Blomqvist, Karin
    Normark, Johan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Chen, Qijun
    Wahlgren, Mats
    var gene transcription and PfEMP1 expression in the rosetting and cytoadhesive Plasmodium falciparum clone FCR3S1.22011In: Malaria Journal, ISSN 1475-2875, Vol. 10, 17Article in journal (Refereed)
    Abstract [en]

    Background: The pathogenicity of Plasmodium falciparum is in part due to the ability of the parasitized red blood cell (pRBC) to adhere to intra- vascular host cell receptors and serum-proteins. Binding of the pRBC is mediated by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large multi-variant molecule encoded by a family of approximate to 60 var genes. Methods: The study of var gene transcription in the parasite clone FCR3S1.2 was performed by semi-quantitative PCR and quantitative PCR (qPCR). The expression of the major PfEMP1 in FCR3S1.2 pRBC was analysed with polyclonal sera in rosette disruption assays and immunofluorecence. Results: Transcripts from var1 (FCR3S1.2(var1); IT4var21) and other var genes were detected by semi-quantitative PCR but results from qPCR showed that one var gene transcript dominated over the others (FCR3S1.2var2; IT4var60). Antibodies raised in rats to the recombinant NTS-DBL1a of var2 produced in E. coli completely and dosedependently disrupted rosettes (approximate to 95% at a dilution of 1/5). The sera reacted with the Maurer's clefts in trophozoite stages (IFA) and to the infected erythrocyte surface (FACS) indicating that FCR3S1.2var2 encodes the dominant PfEMP1 expressed in this parasite. Conclusion: The major transcript in the rosetting model parasite FCR3S1.2 is FCR3S1.2var2 (IT4var60). The results suggest that this gene encodes the PfEMP1-species responsible for the rosetting phenotype of this parasite. The activity of previously raised antibodies to the NTS-DBL1a of FCR3S1.2var1 is likely due to cross-reactivity with NTS-DBL1 alpha of the var2 encoded PfEMP1.

  • 14.
    Alpkvist, Helena
    et al.
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med Huddinge, Infect Dis Unit, Stockholm, Sweden..
    Athlin, Simon
    Univ Orebro, Dept Infect Dis, Fac Med & Hlth, SE-70182 Orebro, Sweden..
    Naucler, Pontus
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Infect Dis Unit, Stockholm, Sweden..
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Abdeldaim, Guma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. Benghazi Univ, Dept Med Microbiol & Parasitol, Fac Med, Benghazi, Libya..
    Slotved, Hans-Christian
    Statens Serum Inst, Dept Microbiol & Infect Control, DK-2300 Copenhagen, Denmark..
    Hedlund, Jonas
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Infect Dis Unit, Stockholm, Sweden..
    Stralin, Kristoffer
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med Huddinge, Infect Dis Unit, Stockholm, Sweden.;Univ Orebro, Dept Infect Dis, Fac Med & Hlth, SE-70182 Orebro, Sweden..
    Clinical and Microbiological Factors Associated with High Nasopharyngeal Pneumococcal Density in Patients with Pneumococcal Pneumonia2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, e0140112Article in journal (Refereed)
    Abstract [en]

    Background We aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia. Methods Adult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/ or culture of respiratory secretions and/or urinary antigen test. Results Of 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p<0.0001). The median NP pneumococcal density of DNA positive patients with pneumococcal etiology was 6.83 log(10) DNA copies/mL (range 1.79-9.50). In a multivariate analysis of patients with pneumococcal etiology, a high pneumococcal density was independently associated with severe pneumonia (Pneumonia Severity Index risk class IV-V), symptom duration >= 2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient's own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54-82% and positive predictive values of 37-56%, indicating suboptimal performance. Conclusions Pneumonia severity, symptom duration similar to 2 days, and a medium/high serum immunoglobulin titer against the patient's own serotype were independently associated with a high NP pneumococcal density. NP pneumococcal density has limited value for detection of severe pneumococcal pneumonia.

  • 15.
    Alpkvist, Helena
    et al.
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Athlin, Simon
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious Diseases.
    Naucler, Pontus
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Herrmann, Björn
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Abdeldaim, Guma
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Department of Medical Microbiology and Parasitology, Faculty of Medicine, Benghazi University, Benghazi, Libya.
    Slotved, Hans-Christian
    Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Hedlund, Jonas
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Strålin, Kristoffer
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Clinical and Microbiological Factors Associated with High Nasopharyngeal Pneumococcal Density in Patients with Pneumococcal Pneumonia2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, e0140112Article in journal (Refereed)
    Abstract [en]

    Background: We aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia.

    Methods: Adult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/ or culture of respiratory secretions and/or urinary antigen test.

    Results: Of 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p<0.0001). The median NP pneumococcal density of DNA positive patients with pneumococcal etiology was 6.83 log(10) DNA copies/mL (range 1.79-9.50). In a multivariate analysis of patients with pneumococcal etiology, a high pneumococcal density was independently associated with severe pneumonia (Pneumonia Severity Index risk class IV-V), symptom duration >= 2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient's own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54-82% and positive predictive values of 37-56%, indicating suboptimal performance.

    Conclusions: Pneumonia severity, symptom duration similar to 2 days, and a medium/high serum immunoglobulin titer against the patient's own serotype were independently associated with a high NP pneumococcal density. NP pneumococcal density has limited value for detection of severe pneumococcal pneumonia.

  • 16.
    Alpkvist, Helena
    et al.
    Karolinska University Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Athlin, Simon
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nauclér, Pontus
    Karolinska University Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Herrmann, Björn
    Uppsala University, Uppsala, Sweden.
    Abdeldaim, Guma
    Uppsala University, Uppsala, Sweden; Benghazi University, Benghazi, Libya.
    Slotved, Hans-Christian
    Statens Serum Institut, Copenhagen, Denmark.
    Hedlund, Jonas
    Karolinska University Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden .
    Strålin, Kristoffer
    Karolinska University Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden; Örebro University, Örebro, Sweden.
    Clinical and microbiological factors associated with high pneumococcal colonization density in pneumococcal pneumoniaManuscript (preprint) (Other academic)
  • 17.
    Alsterlund, Rolf
    et al.
    Department of Infectious Diseases, Central Hospital, Kristianstad.
    Axelsson, Carolina
    Kristianstad University, School of Education and Environment, Avdelningen för Naturvetenskap. Kristianstad University, Forskningsmiljön PRO-CARE.
    Olsson-Liliequist, Barbro
    Unit of Antibiotics and Infection Control, Swedish Institute for Communicable Disease Control, Solna.
    Long-term carriage of extended-spectrum beta-lactamase-producing Escherichia Coli2012In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, Vol. 44, no 1, 51-54 p.Article in journal (Refereed)
    Abstract [en]

    In 2009 we described an outbreak caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in southern Sweden that occurred during 2005–2006. An important finding from the investigation was the long carriage times of the ESBL-producing E. coli in several of the patients, which in some cases exceeded 30 months. Here we report findings from the continued follow-up of bacterial carriage. In September 2010, 5 of the 42 patients still carried the bacteria after a median of 58 months (range 41–59 months), 18 had had repeatedly negative cultures after shedding bacteria for a median of 7.5 months (range 0–39 months), 16 had died while still shedding the bacteria for a median of 9 months (range 0–38 months), and 3 had been lost to follow-up.

  • 18.
    Altun, O.
    et al.
    Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Athlin, Simon
    Örebro University, School of Health Sciences. Department of Infectious Diseases.
    Almuhayawi, M.
    Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden; Department of Microbiology, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia.
    Strålin, K.
    Department of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Özenci, V.
    Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Rapid identification of Streptococcus pneumoniae in blood cultures by using the ImmuLex, Slidex and Wellcogen latex agglutination tests and the BinaxNOW antigen test2016In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, no 4, 579-585 p.Article in journal (Refereed)
    Abstract [en]

    Rapid identification of Streptococcus pneumoniae in blood culture (BC) bottles is important for early directed antimicrobial therapy in pneumococcal bacteraemia. We evaluated a new latex agglutination (LA) test on BC bottles, the ImmuLex™ S. pneumoniae Omni (Statens Serum Institut, Denmark), and compared the performance with the Slidex® pneumo-Kit (bioMérieux, France) and the Wellcogen™ S. pneumoniae (Remel, UK) LA tests, as well as the BinaxNOW® S. pneumoniae (Alere, USA) antigen test. The four tests were directly applied on 358 positive BC bottles with Gram-positive cocci in pairs or chains and on 15 negative bottles. Valid test results were recorded in all cases for ImmuLex and BinaxNOW and in 88.5 % (330/373) and 94.1 % (351/373) of cases for Slidex and Wellcogen, respectively. Based on bottles positive for S. pneumoniae by conventional methods, the sensitivity of ImmuLex was 99.6 %, similar to the other tests (range, 99.6-100 %). Based on bottles positive for non-pneumococcal pathogens, the specificity of ImmuLex was 82.6 %, in comparison to 97.6 % for Slidex (p < 0.01) and 85.4 % for Wellcogen (p = ns). The BinaxNOW test had a lower specificity (64.1 %) than any LA test (p < 0.01). On BC bottles positive for α-haemolytic streptococci, ImmuLex was positive in 12/67 (17.9 %) cases, Slidex in 2/59 (3.4 %) cases, Wellcogen in 11/64 (17.2 %) cases and BinaxNOW in 25/67 (37.3 %) cases. In conclusion, the ImmuLex test provides a valid and sensitive technique for the rapid detection of S. pneumoniae in BC bottles, similar to the other compared methods. However, the specificity was sub-optimal, since the test may cross-react with other Gram-positive bacteria.

  • 19. Amada, Takako
    et al.
    Yoshimatsu, Kumiko
    Koma, Takaaki
    Shimizu, Kenta
    Gamage, Chandika D.
    Shiokawa, Kanae
    Nishio, Sanae
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Arikawa, Jiro
    Development of an immunochromatography strip test based on truncated nucleocapsid antigens of three representative hantaviruses2014In: Virology Journal, ISSN 1743-422X, E-ISSN 1743-422X, Vol. 11, 87- p.Article in journal (Refereed)
    Abstract [en]

    Background: Hantaviruses are causative agents of hemorrhagic fever with renal syndrome (HFRS) and nephropathia epidemica (NE) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. There is a need for time-saving diagnostic methods. In the present study, recombinant N antigens were used as antigens in an immunochromatography strip (ICG) test to detect specific IgG antibodies. Methods: The N-terminal 103 amino acids (aa) of Hantaan virus (HTNV), Puumala virus (PUUV) and Andes virus (ANDV) nucleocapsid (N) protein were expressed in E. coli as representative antigens of three groups (HFRS, NE and HPS-causing viruses) of hantavirus. Five different types of ICG test strips, one antigen line on one strip for each of the three selected hantaviruses (HTNV, PUUV and ANDV), three antigen lines on one strip and a mixed antigen line on one strip, were developed and sensitivities were compared. Results: A total of 87 convalescent-phase patient sera, including sera from 35 HFRS patients, 36 NE patients and 16 HPS patients, and 25 sera from healthy seronegative people as negative controls were used to evaluate the ICG test. Sensitivities of the three-line strip and mixed-line strip were similar to those of the single antigen strip (97.2 to 100%). On the other hand, all of the ICG test strips showed high specificities to healthy donors. Conclusion: These results indicated that the ICG test with the three representative antigens is an effective serodiagnostic tool for screening and typing of hantavirus infection in humans.

  • 20. Ambjörnsson, Joakim
    et al.
    Jonsson, Anders
    University of Borås, Faculty of Caring Science, Work Life and Social Welfare.
    Strömsöe, Annelie
    Andersson, Henrik
    University of Borås, Faculty of Caring Science, Work Life and Social Welfare.
    Bång, Angela
    University of Borås, Faculty of Caring Science, Work Life and Social Welfare.
    Bremer, Anders
    University of Borås, Faculty of Caring Science, Work Life and Social Welfare.
    Prehospital suspicion and identification of adult septic patients: Experiences of a screening tool2016Conference paper (Refereed)
    Abstract [en]

    Introduction: Sepsis is life threatening and requires urgent healthcare to reduce suffering and death. Therefore it is important that septic patients are identified early to enable treatment.

    Aim: To investigate to what extent EMS personnel identified patients with sepsis using the “BAS 90-30-90” model, and to describe assessments and medical procedures that were undertaken by the personnel.

    Methods: This was a retrospective study where 185 EMS medical records were reviewed. The inclusion was based on patients who were later diagnosed with sepsis in the hospital.

    Results: A physician assessed the patients in 74 of the EMS cases, which lead to exclusion of these records in regard to the EMS personnel’s ability to identify sepsis. The personnel documented suspicion of severe sepsis in eight (n=8) of the remaining 111 records (7.2%). The proportion of patients ˃65 years of age was 73% (n=135) of which 37% (n=50) were over 80 years old. Thirty-nine percent (39%, n=72) were females. The personnel documented blood pressure in 91% (n=168), respiratory rate in 76% (n=140), saturation in 100% (n=185), temperature in 76% (n=141), and heart rate in 94% (n=174) of the records. Systolic blood pressure <90 mmHg was documented in 14,2% (n=24), respiratory rate ˃30 in 36% (n=50), saturation <90 in 49%  (n=91), temperature >38°C in 37.6% (n=53), and heart rate ˃90 in 70% (n=121) of the records. Documented medical procedures and treatments were intravenous lines (70%, n=130), intravenous fluids (10%, n=19) and administration of oxygen (72%, n=133).

    Conclusion: The EMS personnel identified only a few septic patients with the help of the BAS 90-30-90 model when all three criteria would be met for severe sepsis. Either advanced age (>65 years), fever (>38°C) or tachypnea (˃20 breaths/min) appeared to increase the personnel’s suspicion of sepsis. Oxygen, but not intravenous fluids, was given in an adequate way.

  • 21. Ambjörnsson, Joakim
    et al.
    Jonsson, Anders
    Högskolan i Borås.
    Strömsöe, Annelie
    Andersson, Henrik
    Högskolan i Borås.
    Bång, Angela
    Högskolan i Borås.
    Bremer, Anders
    Högskolan i Borås.
    Prehospital suspicion and identification of adult septic patients: Experiences of a screening tool2016In: 2nd Global Conference on Emergency Nursing and Trauma Care, Melia Sitges, September 22-24, 2016, 2016Conference paper (Refereed)
    Abstract [en]

    Introduction: Sepsis is life threatening and requires urgent healthcare to reduce suffering and death. Therefore it is important that septic patients are identified early to enable treatment. Aim: To investigate to what extent EMS personnel identified patients with sepsis using the “BAS 90-30-90” model, and to describe assessments and medical procedures that were undertaken by the personnel.

    Methods: This was a retrospective study where 185 EMS medical records were reviewed. The inclusion was based on patients who were later diagnosed with sepsis in the hospital.

    Results: A physician assessed the patients in 74 of the EMS cases, which lead to exclusion of these records in regard to the EMS personnel’s ability to identify sepsis. The personnel documented suspicion of severe sepsis in eight (n=8) of the remaining 111 records (7.2%). The proportion of patients ˃65 years of age was 73% (n=135) of which 37% (n=50) were over 80 years old. Thirty-nine percent (39%, n=72) were females. The personnel documented blood pressure in 91% (n=168), respiratory rate in 76% (n=140), saturation in 100% (n=185), temperature in 76% (n=141), and heart rate in 94% (n=174) of the records. Systolic blood pressure &lt;90 mmHg was documented in 14,2% (n=24), respiratory rate ˃30 in 36% (n=50), saturation &lt;90 in 49%  (n=91), temperature &gt;38°C in 37.6% (n=53), and heart rate ˃90 in 70% (n=121) of the records. Documented medical procedures and treatments were intravenous lines (70%, n=130), intravenous fluids (10%, n=19) and administration of oxygen (72%, n=133).

    Conclusion: The EMS personnel identified only a few septic patients with the help of the BAS 90-30-90 model when all three criteria would be met for severe sepsis. Either advanced age (&gt;65 years), fever (&gt;38°C) or tachypnea (˃20 breaths/min) appeared to increase the personnel’s suspicion of sepsis. Oxygen, but not intravenous fluids, was given in an adequate way.

  • 22.
    Amin, Kawa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Beillevaire, Didier
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mahmoud, Elgaali
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Hammar, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mard, Per-Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Froman, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Binding of Galanthus nivalis lectin to Chlamydia trachomatis and inhibition of in vitro infection1995In: APMIS: Acta pathologica, microbiologica et immunologica Scandinavica. Supplementum, ISSN 0903-465X, E-ISSN 1600-5503, ISSN 0903-4641, Vol. 103, no 10, 714-720 p., 8534430Article in journal (Refereed)
  • 23.
    Anagandula, Mahesh
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Richardson, Sarah J.
    University of Exeter Medical School, Institute of Biomedical and Clinical Science, Exeter, UK.
    Oberste, M. Steven
    Centers for Disease Control and Prevention, Atlanta, Georgia.
    Sioofy-Khojine, Amir-Babak
    School of Medicine, University of Tampere, Tampere, Finland.
    Hyoty, Heikki
    School of Medicine, University of Tampere, Tampere, Finland ,Fimlab Ltd, Pirkanmaa Hospital District, Finland.
    Morgan, Noel G.
    University of Exeter Medical School, Institute of Biomedical and Clinical Science, Exeter, UK.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Frisk, Gun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Infection of Human Islets of Langerhans With Two Strains of Coxsackie B Virus Serotype 1: Assessment of Virus Replication, Degree of Cell Death and Induction of Genes Involved in the Innate Immunity Pathway2014In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 86, no 8, 1402-1411 p.Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes mellitus is believed to be triggered, in part, by one or more environmental factors and human enteroviruses (HEVs) are among the candidates. Therefore, this study has examined whether two strains of HEV may differentially affect the induction of genes involved in pathways leading to the synthesis of islet hormones, chemokines and cytokines in isolated, highly purified, human islets. Isolated, purified human pancreatic islets were infected with strains of Coxsackievirus B1. Viral replication and the degree of CPE/islet dissociation were monitored. The expression of insulin, glucagon, CXCL10, TLR3, IF1H1, CCL5, OAS-1, IFN beta, and DDX58 was analyzed. Both strains replicated in islets but only one of strain caused rapid islet dissociation/CPE. Expression of the insulin gene was reduced during infection of islets with either viral strain but the gene encoding glucagon was unaffected. All genes analyzed which are involved in viral sensing and the development of innate immunity were induced by Coxsackie B viruses, with the notable exception of TLR3. There was no qualitative difference in the expression pattern between each strain but the magnitude of the response varied between donors. The lack of virus induced expression of TLR3, together with the differential regulation of IF1H1, OAS1 and IFN beta, (each of which has polymorphic variants influence the predisposition to type 1 diabetes), that might result in defective clearance of virus from islet cells. The reduced expression of the insulin gene and the unaffected expression of the gene encoding glucagon by Coxsackie B1 infection is consistent with the preferential beta-cell tropism of the virus.

  • 24. Anantharajah, Ahalieyah
    et al.
    Faure, Emmanuel
    Buyck, Julien M.
    Sundin, Charlotta
    Creative Antibiotics, Umeå, Sweden .
    Lindmark, Tuulikki
    Mecsas, Joan
    Yahr, Timothy L.
    Tulkens, Paul M.
    Mingeot-Leclercq, Marie-Paule
    Guery, Benoît
    Van Bambeke, Françoise
    Inhibition of the Injectisome and Flagellar Type III Secretion Systems by INP1855 Impairs Pseudomonas aeruginosa Pathogenicity and Inflammasome Activation2016In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 214, no 7, 1105-1116 p.Article in journal (Refereed)
    Abstract [en]

    With the rise of multidrug resistance, Pseudomonas aeruginosa infections require alternative therapeutics. The injectisome (iT3SS) and flagellar (fT3SS) type III secretion systems are 2 virulence factors associated with poor clinical outcomes. iT3SS translocates toxins, rod, needle, or regulator proteins, and flagellin into the host cell cytoplasm and causes cytotoxicity and NLRC4-dependent inflammasome activation, which induces interleukin 1 beta (IL-1 beta) release and reduces interleukin 17 (IL-17) production and bacterial clearance. fT3SS ensures bacterial motility, attachment to the host cells, and triggers inflammation. INP1855 is an iT3SS inhibitor identified by in vitro screening, using Yersinia pseudotuberculosis. Using a mouse model of P. aeruginosa pulmonary infection, we show that INP1855 improves survival after infection with an iT3SS-positive strain, reduces bacterial pathogenicity and dissemination and IL-1 beta secretion, and increases IL-17 secretion. INP1855 also modified the cytokine balance in mice infected with an iT3SS-negative, fT3SS-positive strain. In vitro, INP1855 impaired iT3SS and fT3SS functionality, as evidenced by a reduction in secretory activity and flagellar motility and an increase in adenosine triphosphate levels. As a result, INP1855 decreased cytotoxicity mediated by toxins and by inflammasome activation induced by both laboratory strains and clinical isolates. We conclude that INP1855 acts by dual inhibition of iT3SS and fT3SS and represents a promising therapeutic approach.

  • 25. Anchang-Kimbi, Judith K.
    et al.
    Achidi, Eric A.
    Apinjoh, Tobias O.
    Mugri, Regina N.
    Chi, Hanesh Fru
    Tata, Rolland B.
    Nkegoum, Blaise
    Mendimi, Joseph-Marie N.
    Sverremark-Ekström, Eva
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Troye Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Antenatal care visit attendance, intermittent preventive treatment during pregnancy (IPTp) and malaria parasitaemia at delivery2014In: Malaria Journal, ISSN 1475-2875, Vol. 13, 162- p.Article in journal (Refereed)
    Abstract [en]

    Background: The determinants and barriers for delivery and uptake of IPTp vary with different regions in sub-Saharan Africa. This study evaluated the determinants of ANC clinic attendance and IPTp-SP uptake among parturient women from Mount Cameroon Area and hypothesized that time of first ANC clinic attendance could influence uptake of IPTp-SP/dosage and consequently malaria parasite infection status at delivery. Methods: Two cross sectional surveys were carried out at the Government Medical Centre in the Mutengene Health Area, Mt Cameroon Area from March to October 2007 and June 2008 to April 2009. Consented parturient women were consecutively enrolled in both surveys. In 2007, socio-demographic data, ANC clinic attendance, gestational age, fever history and reported use/dosage of IPTp-SP were documented using a structured questionnaire. In the second survey only IPT-SP usage/dosage was recorded. Malaria parasitaemia at delivery was determined by blood smear microscopy and placental histology. Results and discussion: In 2007, among the 287 women interviewed, 2.2%, 59.7%, and 38.1% enrolled in the first, second and third trimester respectively. About 90% of women received at least one dose SP but only 53% received the two doses in 2007 and by 2009 IPTp-two doses coverage increased to 64%. Early clinic attendance was associated (P = 0.016) with fever history while being unmarried (OR = 2.2; 95% CI: 1.3-3.8) was significantly associated with fewer clinic visits (<4visits). Women who received one SP dose (OR = 3.7; 95% CI: 2.0-6.8) were more likely not to have attended >= 4visits. A higher proportion (P < 0.001) of women with first visit during the third trimester received only one dose, meanwhile, those who had an early first ANC attendance were more likely (OR = 0.4; 95% CI = 0.2 - 0.7) to receive two or more doses. Microscopic parasitaemia at delivery was frequent (P = 0.007) among women who enrolled in the third trimester and had received only one SP dose than in those with two doses. Conclusion: In the study area, late first ANC clinic enrolment and fewer clinic visits may prevent the uptake of two SP doses and education on early and regular ANC clinic visits can increase IPTp coverage.

  • 26.
    Andersson, Anna-Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Andersson, Blanka
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lorell, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Raffetseder, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Blomgran, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Autophagy induction targeting mTORC1 enhances Mycobacterium tuberculosis replication in HIV co-infected human macrophages2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 28171Article in journal (Refereed)
    Abstract [en]

    To survive and replicate in macrophages Mycobacterium tuberculosis (Mtb) has developed strategies to subvert host defence mechanisms, including autophagy. Autophagy induction has the potential to clear Mtb, but little is known about its effect during controlled tuberculosis and HIV co-infection. Mammalian target of rapamycin complex1 (mTORC1) inhibitors were used to induce autophagy in human macrophages pre-infected with HIV-1(BaL) and infected with a low dose of Mtb (co-infected), or single Mtb infected (single infected). The controlled Mtb infection was disrupted upon mTOR inhibition resulting in increased Mtb replication in a dose-dependent manner which was more pronounced during co-infection. The increased Mtb replication could be explained by the marked reduction in phagosome acidification upon mTOR inhibition. Autophagy stimulation targeting mTORC1 clearly induced a basal autophagy with flux that was unlinked to the subcellular environment of the Mtb vacuoles, which showed a concurrent suppression in acidification and maturation/flux. Overall our findings indicate that mTOR inhibition during Mtb or HIV/Mtb co-infection interferes with phagosomal maturation, thereby supporting mycobacterial growth during low-dose and controlled infection. Therefore pharmacological induction of autophagy through targeting of the canonical mTORC1-pathway should be handled with caution during controlled tuberculosis, since this could have serious consequences for patients with HIV/Mtb co-infection.

  • 27. Andersson, H.
    et al.
    Hartmanová, B.
    Bäck, Erik
    Örebro University, Department of Clinical Medicine.
    Eliasson, H.
    Örebro University, Department of Clinical Medicine.
    Landfors, M.
    Näslund, L.
    Rydén, P.
    Sjöstedt, A.
    Transcriptional profiling of the peripheral blood response during tularemia2006In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 7, no 6, 503-513 p.Article in journal (Refereed)
    Abstract [en]

    Tularemia is a febrile disease caused by the highly contagious bacterium Francisella tularensis. We undertook an analysis of the transcriptional response in peripheral blood during the course of ulceroglandular tularemia by use of Affymetrix microarrays comprising 14,500 genes. Samples were obtained from seven individuals at five occasions during 2 weeks after the first hospital visit and convalescent samples 3 months later. In total, 265 genes were differentially expressed, 95 of which at more than one time point. The differential expression was verified with real-time quantitative polymerase chain reaction for 36 genes (R(2)=0.590). The most prominent changes were noted in samples drawn on days 2-3 and a considerable proportion of the upregulated genes appeared to represent an interferon-gamma-induced response and also a proapoptotic response. Genes involved in the generation of innate and acquired immune responses were found to be downregulated, presumably a pathogen-induced event. A logistic regression analysis revealed that seven genes were good predictors of the early phase of tularemia. This is the first description of the transcriptional host response to ulceroglandular tularemia and the study has identified gene subsets relevant to the pathogenesis of the disease and subsets that may serve as early diagnostic biomarkers.

  • 28.
    Andersson, Helene
    et al.
    Sophiahemmet University.
    Kalin, Mats
    Fossum, Bjöörn
    Sophiahemmet University.
    Lindholm, Christina
    Ortqvist, Ake
    Är MRSA-patienter olika smittsamma i olika län?2009In: Läkartidningen, ISSN 0023-7205, Vol. 106, no 7, 412-3 p.Article in journal (Other academic)
  • 29.
    Andersson, Madelen
    et al.
    Blekinge Hosp, Dept Infect Dis, Karlskrona, Sweden..
    Resman, Fredrik
    Lund Univ, Dept Translat Med Med Microbiol, Malmo, Sweden..
    Eitrem, Rickard
    Dept Communicable Dis Control Cty Blekinge, Karlskrona, Sweden..
    Drobni, Peter
    Dept Clin Microbiol Cty Kronoberg, Vaxjo Karlskrona, Sweden..
    Riesbeck, Kristian
    Lund Univ, Dept Translat Med Med Microbiol, Malmo, Sweden..
    Kahlmeter, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology. Dept Clin Microbiol Cty Kronoberg, Vaxjo Karlskrona, Sweden..
    Sundqvist, Martin
    Dept Clin Microbiol Cty Kronoberg, Vaxjo Karlskrona, Sweden.;Univ Orebro, Fac Med & Hlth, Dept Lab Med Clin Microbiol, SE-70182 Orebro, Sweden..
    Outbreak of a beta-lactam resistant non-typeable Haemophilus influenzae sequence type 14 associated with severe clinical outcomes2015In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, 581Article in journal (Refereed)
    Abstract [en]

    Background: During October 2011 several residents and staff members at a long-term care facility (LTCF) for elderly fell ill with respiratory symptoms. Several of the residents required hospitalization and one died. Non-typeable Haemophilus influenzae (NTHi) was identified as the causative pathogen. Methods: A descriptive analysis of the outbreak and countermeasures was performed. For each identified bacterial isolate implied in the outbreak, standard laboratory resistance testing was performed, as well as molecular typing and phylogenetic analysis. Results: The identified H. influenzae was beta-lactamase negative but had strikingly high MIC-values of ampicillin, cefuroxime and cefotaxime. All isolates displayed the same mutation in the ftsI gene encoding penicillin-binding protein (PBP) 3, and all but one were identified as sequence type 14 by Multilocus Sequence Typing (MLST). In total 15 individuals in connection to the LTCF; 8 residents, 6 staff members and one partner to a staff member were colonized with the strain. Conclusion: This report illustrates the existence of non-typeable H. influenzae with high virulence, and furthermore emphasizes the importance of continuous surveillance of possible outbreaks in health care facilities and prompt measures when outbreaks occur.

  • 30.
    Andersson, Madelen
    et al.
    Blekinge Hosp, Dept Infect Dis, Karlskrona, Sweden..
    Resman, Fredrik
    Lund Univ, Dept Translat Med Med Microbiol, Malmo, Sweden..
    Eitrem, Rickard
    Dept Communicable Dis Control Cty Blekinge, Karlskrona, Sweden..
    Drobni, Peter
    Dept Clin Microbiol Cty Kronoberg, Vaxjo Karlskrona, Sweden..
    Riesbeck, Kristian
    Lund Univ, Dept Translat Med Med Microbiol, Malmo, Sweden..
    Kahlmeter, Gunnar
    Dept Clin Microbiol Cty Kronoberg, Vaxjo Karlskrona, Sweden.;Uppsala Univ, Dept Med Sci, Div Clin Bacteriol, Uppsala, Sweden..
    Sundqvist, Martin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Dept Clin Microbiol Cty Kronoberg, Vaxjo Karlskrona, Sweden.; Univ Orebro, Dept Lab Med Clin Microbiol.
    Outbreak of a beta-lactam resistant non-typeable Haemophilus influenzae sequence type 14 associated with severe clinical outcomes2015In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, 581Article in journal (Refereed)
    Abstract [en]

    Background: During October 2011 several residents and staff members at a long-term care facility (LTCF) for elderly fell ill with respiratory symptoms. Several of the residents required hospitalization and one died. Non-typeable Haemophilus influenzae (NTHi) was identified as the causative pathogen. Methods: A descriptive analysis of the outbreak and countermeasures was performed. For each identified bacterial isolate implied in the outbreak, standard laboratory resistance testing was performed, as well as molecular typing and phylogenetic analysis. Results: The identified H. influenzae was beta-lactamase negative but had strikingly high MIC-values of ampicillin, cefuroxime and cefotaxime. All isolates displayed the same mutation in the ftsI gene encoding penicillin-binding protein (PBP) 3, and all but one were identified as sequence type 14 by Multilocus Sequence Typing (MLST). In total 15 individuals in connection to the LTCF; 8 residents, 6 staff members and one partner to a staff member were colonized with the strain. Conclusion: This report illustrates the existence of non-typeable H. influenzae with high virulence, and furthermore emphasizes the importance of continuous surveillance of possible outbreaks in health care facilities and prompt measures when outbreaks occur.

  • 31.
    Andersson, T
    et al.
    Department of Mathematics, Stockholm University, Sweden and Swedish Institute for National Food Agency (SLV), Sweden and Communicable Disease Control (SMI), Solna, Sweden.
    Bjelkmar, P
    Swedish Institute for Communicable Disease Control (SMI), Solna, Sweden, and Inera AB, Sweden.
    Hulth, A
    Swedish Institute for Communicable Disease Control (SMI), Solna, Sweden.
    Lindh, J
    Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Sweden and Swedish Institute for Communicable Disease Control (SMI), Solna, Sweden.
    Stenmark, Stephan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. County Medical Officer, Västerbotten, Sweden.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Syndromic surveillance for local outbreak detection and awareness: evaluating outbreak signals of acute gastroenteritis in telephone triage, web-based queries and over-the-counter pharmacy sales2014In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 142, no 2, 303-313 p.Article in journal (Refereed)
    Abstract [en]

    For the purpose of developing a national system for outbreak surveillance, local outbreak signals were compared in three sources of syndromic data - telephone triage of acute gastroenteritis, web queries about symptoms of gastrointestinal illness, and over-the-counter (OTC) pharmacy sales of antidiarrhoeal medication. The data sources were compared against nine known waterborne and foodborne outbreaks in Sweden in 2007-2011. Outbreak signals were identified for the four largest outbreaks in the telephone triage data and the two largest outbreaks in the data on OTC sales of antidiarrhoeal medication. No signals could be identified in the data on web queries. The signal magnitude for the fourth largest outbreak indicated a tenfold larger outbreak than officially reported, supporting the use of telephone triage data for situational awareness. For the two largest outbreaks, telephone triage data on adult diarrhoea provided outbreak signals at an early stage, weeks and months in advance, respectively, potentially serving the purpose of early event detection. In conclusion, telephone triage data provided the most promising source for surveillance of point-source outbreaks.

  • 32.
    Andresen, Liis
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Varik, Vallo
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
    Tozawa, Yuzuru
    Jimmy, Steffi
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Lindberg, Stina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Tenson, Tanel
    Hauryliuk, Vasili
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
    Auxotrophy-based High Throughput Screening assay for the identification of Bacillus subtilis stringent response inhibitors2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 35824Article in journal (Refereed)
    Abstract [en]

    The stringent response is a central adaptation mechanism that allows bacteria to adjust their growth and metabolism according to environmental conditions. The functionality of the stringent response is crucial for bacterial virulence, survival during host invasion as well as antibiotic resistance and tolerance. Therefore, specific inhibitors of the stringent response hold great promise as molecular tools for disarming and pacifying bacterial pathogens. By taking advantage of the valine amino acid auxotrophy of the Bacillus subtilis stringent response-deficient strain, we have set up a High Throughput Screening assay for the identification of stringent response inhibitors. By screening 17,500 compounds, we have identified a novel class of antibacterials based on the 4-(6-(phenoxy) alkyl)-3,5-dimethyl-1H-pyrazole core. Detailed characterization of the hit compounds as well as two previously identified promising stringent response inhibitors-a ppGpp-mimic nucleotide Relacin and cationic peptide 1018 - showed that neither of the compounds is sufficiently specific, thus motivating future application of our screening assay to larger and more diverse molecular libraries.

  • 33.
    Angelin, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Travel – a risk factor for disease and spread of antibiotic resistance2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    As international travel is rapidly increasing, more people are being exposed to potentially more antibiotic resistant bacteria, a changed infectious disease epidemiology, and an increased risk of accidents and crime. Research-based advice is needed to adequately inform travellers about these risks. We studied travellers who sought advice from the Travel Medicine Clinic at the Department of Infectious Diseases, Umeå University Hospital, as well as university students from Umeå, Stockholm, and Gothenburg travelling abroad for study, research, and clinical exchange programs.

    From retrospective data at the Travel Medicine Clinic, we found that pre-existing health problems were rare among travellers from Umeå seeking pre- travel health advice and vaccinations. In addition, we found that the travel destination and the sex of the traveller affected vaccination levels. Although hepatitis A is endemic to both Thailand and Turkey, compared to travellers to Thailand few travellers to Turkey visited the clinic for hepatitis A vaccination. The data also revealed that more women than men were vaccinated against Japanese encephalitis despite comparable trips.

    A prospective survey study showed that travellers felt that the pre-travel health advice they received was helpful. Two-thirds of the travellers followed the advice given although they still fell ill to the same extent as those who were not compliant with the advice. Factors outside the control of travellers likely affect the travel-related morbidity. Compared to older travellers, younger travellers were less compliant with advice, fell ill to a greater extent, and took greater risks during travel.

    In a prospective survey study, we found that healthcare students had higher illness rates and risk exposure when abroad compared to students from other disciplines. This difference was mainly due to the fact that healthcare students more often travelled to developing regions during their study period abroad. When abroad, half of all students increased their alcohol consumption and this was linked to an increased risk of theft and higher likelihood of meeting a new sex partner.

    The healthcare students participating in the survey study also submitted stool samples before and after travel. These samples were tested for the presence of antibiotic resistance, both by selective culturing for ESBL-PE (Extended-Spectrum Beta-Lactamase Producing Enterobacteriaceae) as well as by metagenomic sequencing. About one-third (35%) of the students became colonised by ESBL-PE following their study abroad. The strongest risk factor for colonisation was travel destination; for example, 70% of students who had travelled to India became colonised. Antibiotic treatment during travel was also a significant risk factor for colonisation.

    The stool samples from a subset of study subjects were analysed using metagenomic sequencing. From this we learned that although the majority of resistance genes in the gut microbiome remained unchanged following travel, several clinically important resistance genes increased, most prominently genes encoding resistance to sulphonamide, trimethoprim, and beta-lactams. Overall, taxonomic changes associated with travel were small but the proportion of Proteobacteria, which includes several clinically important bacteria (e.g., Enterobacteriaceae), increased in a majority of the study subjects.

    Clearly, there are risks associated with international travel and these risks include outside factors as well as the personal behaviour of travellers. We believe our results can be used to develop better pre-travel advice for tourists as well as university students studying abroad resulting in safer travel.

  • 34.
    Angelin, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evengård, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Palmgren, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Travel and vaccination patterns: a report from a travel medicine clinic in northern Sweden2011In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 43, no 9, 714-720 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Travel Medicine Clinic in Umeå is one of Sweden's largest public providers of vaccination and counselling prior to international travel. During the study period it was the only travel medicine clinic in Umeå. This study describes the demography of the visitors to the clinic and travel destinations and durations, as well as vaccinations administered. METHODS: This was a retrospective study for the period January 2005 to April 2008 based on pre-travel consultation questionnaires and on vaccine expenditure data. A 10% sample of 16,735 first visits prior to international travel was consecutively selected according to the chronology of the visits. RESULTS: Data on 1698 travellers were included in the study. Thailand was the most common destination among visitors, accounting for one third of all destinations. Medical problems affecting pre-travel health planning were rare. Four out of 5 visitors (79%) received only 1 vaccination, mainly for hepatitis A. Travellers to Thailand more often sought travel health advice compared to travellers to Turkey, despite the fact that the 2 destinations were almost equally distributed among travellers from Umeå. We found differences between men and women in money spent on vaccines and in particular in vaccination against Japanese encephalitis. CONCLUSIONS: To assess the optimal vaccination level at a travel medicine clinic is difficult. Decisions are affected by general recommendations and the risk perception of the travel medicine practitioner, as well as the risk perception of the traveller. The sex difference found in this study might be due to gender differences in risk perception and should be further investigated.

  • 35.
    Angelin, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evengård, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Palmgren, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Travel health advice: Benefits, compliance, and outcome2014In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 46, no 6, 447-453 p.Article in journal (Refereed)
    Abstract [en]

    Background: Travel health advice is an important and difficult part of a pre-travel consultation. The aim of this study was to determine whether the travel health advice given is followed by the traveller and whether it affects disease and injury experienced during travel. Methods: A prospective survey study was carried out from October 2009 to April 2012 at the Travel Medicine Clinic of the Department of Infectious Diseases, Umea University Hospital, Umea, Sweden. The Travel Medicine Clinic in Umea is the largest travel clinic in northern Sweden. Results: We included 1277 individuals in the study; 1059 (83%) responded to the post-travel questionnaire. Most visitors (88%) remembered having received travel health advice; among these, 95% found some of the health advice useful. Two-thirds (67%) claimed to have followed the advice, but fell ill during travel to the same extent as those who did not. Younger travellers (< 31 y) found our travel health advice less beneficial, were less compliant with the advice, took more risks during travel, and fell ill during travel to a greater extent than older travellers. Conclusions: Helping travellers stay healthy during travel is the main goal of travel medicine. Younger travellers are a risk group for illness during travel and there is a need to find new methods to help them avoid illness. Travellers find travel health advice useful, but it does not protect them from travel-related illness. Factors not easily influenced by the traveller play a role, but a comprehensive analysis of the benefits of travel health advice is needed.

  • 36.
    Angelin, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Forsell, Joakim
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Granlund, Margareta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Evengård, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Palmgren, Helena
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Risk factors for colonization with extended-spectrum beta-lactamase producing Enterobacteriaceae in healthcare students on clinical assignment abroad: A prospective study2015In: Travel Medicine and Infectious Disease, ISSN 1477-8939, E-ISSN 1873-0442, Vol. 13, no 3, 223-229 p.Article in journal (Refereed)
    Abstract [en]

    Background: The increase of antibiotic resistance in clinically important bacteria is a worldwide threat, especially in healthcare environments. International travel is a risk factor for gut colonization with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). The risk for healthcare students of being colonized with ESBL-PE when participating in patient-related work abroad has not been previously investigated. Methods: Swedish healthcare students travelling for pre-clinical and clinical courses outside Scandinavia submitted faecal samples and survey data before and after travel. The faecal samples were screened for ESBL-PE and carbapenemase-producing Enterobacteriaceae (CPE). Screening results and survey data were analysed to identify risk factors for colonization. Results: In the 99 subjects who submitted a full set of samples, 35% were colonized with a new ESBL-PE strain during travel. No CPE was found. The most important risk factor for ESBL-PE colonization was travel destination, and the highest colonization rate was found in the South East Asia region. Antibiotic treatment during travel was an independent risk factor for ESBL-PE colonization but patient-related work was not significantly associated with an increased risk. Conclusions: Patient-related work abroad was not a risk factor for ESBL-PE suggesting that transmission from patients is uncommon. Pre-travel advice on avoiding unnecessary antibiotic treatment during travel is recommended.

  • 37.
    Ansell, Brendan R. E.
    et al.
    Univ Melbourne, Fac Vet & Agr Sci, Parkville, Vic 3052, Australia..
    McConville, Malcolm J.
    Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Parkville, Vic 3052, Australia..
    Baker, Louise
    Univ Melbourne, Fac Vet & Agr Sci, Parkville, Vic 3052, Australia..
    Korhonen, Pasi K.
    Univ Melbourne, Fac Vet & Agr Sci, Parkville, Vic 3052, Australia..
    Young, Neil D.
    Univ Melbourne, Fac Vet & Agr Sci, Parkville, Vic 3052, Australia..
    Hall, Ross S.
    Univ Melbourne, Fac Vet & Agr Sci, Parkville, Vic 3052, Australia..
    Rojas, Cristian A. A.
    Univ Melbourne, Fac Vet & Agr Sci, Parkville, Vic 3052, Australia..
    Svärd, Staffan G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Gasser, Robin B.
    Univ Melbourne, Fac Vet & Agr Sci, Parkville, Vic 3052, Australia..
    Jex, Aaron R.
    Univ Melbourne, Fac Vet & Agr Sci, Parkville, Vic 3052, Australia..
    Time-Dependent Transcriptional Changes in Axenic Giardia duodenalis Trophozoites2015In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 9, no 12, e0004261Article in journal (Refereed)
    Abstract [en]

    Giardia duodenalis is the most common gastrointestinal protozoan parasite of humans and a significant contributor to the global burden of both diarrheal disease and post-infectious chronic disorders. Although G. duodenalis can be cultured axenically, significant gaps exist in our understanding of the molecular biology and metabolism of this pathogen. The present study employed RNA sequencing to characterize the mRNA transcriptome of G. duodenalis trophozoites in axenic culture, at log (48 h of growth), stationary (60 h), and declining (96 h) growth phases. Using similar to 400-times coverage of the transcriptome, we identified 754 differentially transcribed genes (DTGs), mainly representing two large DTG groups: 438 that were down-regulated in the declining phase relative to log and stationary phases, and 281 that were up-regulated. Differential transcription of prominent antioxidant and glycolytic enzymes implicated oxygen tension as a key factor influencing the transcriptional program of axenic trophozoites. Systematic bioinformatic characterization of numerous DTGs encoding hypothetical proteins of unknown function was achieved using structural homology searching. This powerful approach greatly informed the differential transcription analysis and revealed putative novel antioxidant-coding genes, and the presence of a nearcomplete two-component-like signaling system that may link cytosolic redox or metabolite sensing to the observed transcriptional changes. Motif searching applied to promoter regions of the two large DTG groups identified different putative transcription factor-binding motifs that may underpin global transcriptional regulation. This study provides new insights into the drivers and potential mediators of transcriptional variation in axenic G. duodenalis and provides context for static transcriptional studies.

  • 38. Aoki, Koki
    et al.
    Benkö, Mária
    Davison, Andrew J
    De Jong, Jan C
    Echavarria, Marcela
    Erdman, Dean D
    Harrach, Balázs
    Kajon, Adriana E
    Schnurr, David
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Towards an integrated human adenovirus designation system that utilizes molecular and serological data and serves both clinical and fundamental virology2011In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 85, no 11, 5703-5704 p.Article in journal (Refereed)
  • 39. Arama, Charles
    et al.
    Skinner, Jeff
    Doumtabe, Didier
    Portugal, Silvia
    Tran, Tuan M.
    Jain, Aarti
    Traore, Boubacar
    Doumbo, Ogobara K.
    Davies, David Huw
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Dolo, Amagana
    Felgner, Philip L.
    Crompton, Peter D.
    Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens2015In: Open forum infectious diseases, ISSN 2328-8957, Vol. 2, no 3Article in journal (Refereed)
    Abstract [en]

    Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to < 0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig) M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection.

  • 40. Artursson, Karin
    et al.
    Järhult, Josef D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Berg, Charlotte
    Varför är det så svårt att förstå betydelsen av One Health?2014In: Svensk veterinärtidning, ISSN 0346-2250, Vol. Feb, no 2, 35-39 p.Article in journal (Refereed)
  • 41. Asghar, Naveed
    et al.
    Lee, Yi-Ping
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Nilsson, Emma
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Lindqvist, Richard
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Melik, Wessam
    Kröger, Andrea
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Johansson, Magnus
    The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 39265Article in journal (Refereed)
    Abstract [en]

    The tick-borne encephalitis virus (TBEV) is a flavivirus transmitted to humans, usually via tick bites. The virus causes tick-borne encephalitis (TBE) in humans, and symptoms range from mild flu-like symptoms to severe and long-lasting sequelae, including permanent brain damage. It has been suggested that within the population of viruses transmitted to the mammalian host, quasispecies with neurotropic properties might become dominant in the host resulting in neurological symptoms. We previously demonstrated the existence of TBEV variants with variable poly(A) tracts within a single blood-fed tick. To characterize the role of the poly(A) tract in TBEV replication and virulence, we generated infectious clones of Toro-2003 with the wild-type (A)(3)C(A)(6) sequence (Toro-6A) or with a modified (A)(3)C(A)(38) sequence (Toro-38A). Toro-38A replicated poorly compared to Toro-6A in cell culture, but Toro-38A was more virulent than Toro-6A in a mouse model of TBE. Next-generation sequencing of TBEV genomes after passaging in cell culture and/or mouse brain revealed mutations in specific genomic regions and the presence of quasispecies that might contribute to the observed differences in virulence. These data suggest a role for quasispecies development within the poly(A) tract as a virulence determinant for TBEV in mice.

  • 42. Asghar, Naveed
    et al.
    Lindblom, Pontus
    Melik, Wessam
    Lindqvist, Richard
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Haglund, Mats
    Forsberg, Pia
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Andreassen, Åshild
    Lindgren, Per-Eric
    Johansson, Magnus
    Tick-borne encephalitis virus sequenced directly from questing and blood-feeding ticks reveals quasispecies variance2014In: PLoS ONE, ISSN 1932-6203, Vol. 9, no 7, e103264- p.Article in journal (Refereed)
    Abstract [en]

    The increased distribution of the tick-borne encephalitis virus (TBEV) in Scandinavia highlights the importance of characterizing novel sequences within the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009 (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. Interestingly, the sequence of Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly virulent Hypr strain, within the 3' non-coding region (3'NCR). A different genomic structure was found in the 3'NCR of Saringe 2009, as in-depth analysis demonstrated TBEV variants with different lengths within the poly(A) tract. This shows that TBEV quasispecies exists in nature and indicates a putative shift in the quasispecies pool when the virus switches between invertebrate and vertebrate environments. This prompted us to further sequence and analyze the 3'NCRs of additional Scandinavian TBEV strains and control strains, Hypr and Neudoerfl. Toro 2003 and Habo 2011 contained mainly a short (A) 3C(A)6 poly(A) tract. A similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944; however, one clone of 1991/4944 contained an (A) 3C(A)11 poly(A) sequence, demonstrating that quasispecies with longer poly(A) could be present in human isolates. Neudoerfl has previously been reported to contain a poly(A) region, but to our surprise the resequenced genome contained two major quasispecies variants, both lacking the poly(A) tract. We speculate that the observed differences are important factors for the understanding of virulence, spread, and control of the TBEV.

  • 43.
    Asghar, Naveed
    et al.
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden.
    Lindblom, Pontus
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Melik, Wessam
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden.
    Lindqvist, Richard
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden.
    Haglund, Mats
    Department of Infectious Diseases, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Clinic of Infectious Diseases, Linköping University Hospital, Linköping, Sweden.
    Överby, Anna K.
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden.
    Andreassen, Åshild
    Division of Infectious Disease Control, Department of Virology, Norwegian Institute of Public Health, Oslo, Norway.
    Lindgren, Per-Eric
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Division of Medical Services, Department of Microbiology, County Hospital Ryhov, Jönköping, Sweden.
    Johansson, Magnus
    Örebro University, School of Medicine, Örebro University, Sweden. School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden; RiSC - Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Tick-Borne Encephalitis Virus Sequenced Directly from Questing and Blood-Feeding Ticks Reveals Quasispecies Variance2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 7, e103264Article in journal (Refereed)
    Abstract [en]

    The increased distribution of the tick-borne encephalitis virus (TBEV) in Scandinavia highlights the importance of characterizing novel sequences within the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009 (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. Interestingly, the sequence of Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly virulent Hypr strain, within the 3' non-coding region (3'NCR). A different genomic structure was found in the 3'NCR of Saringe 2009, as in-depth analysis demonstrated TBEV variants with different lengths within the poly(A) tract. This shows that TBEV quasispecies exists in nature and indicates a putative shift in the quasispecies pool when the virus switches between invertebrate and vertebrate environments. This prompted us to further sequence and analyze the 3'NCRs of additional Scandinavian TBEV strains and control strains, Hypr and Neudoerfl. Toro 2003 and Habo 2011 contained mainly a short (A) 3C(A)6 poly(A) tract. A similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944; however, one clone of 1991/4944 contained an (A) 3C(A)11 poly(A) sequence, demonstrating that quasispecies with longer poly(A) could be present in human isolates. Neudoerfl has previously been reported to contain a poly(A) region, but to our surprise the resequenced genome contained two major quasispecies variants, both lacking the poly(A) tract. We speculate that the observed differences are important factors for the understanding of virulence, spread, and control of the TBEV.

  • 44.
    Asghar, Naveed
    et al.
    School of Natural Sciences, Technology and Environmental Studies, Södertörn University, Huddinge; Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Petersson, Mona
    School of Natural Sciences, Technology and Environmental Studies, Södertörn University, Huddinge.
    Johansson, Magnus
    Örebro University, School of Medical Sciences. School of Natural Sciences, Technology and Environmental Studies, Södertörn University, Huddinge; 3Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Dinnetz, Patrik
    School of Natural Sciences, Technology and Environmental Studies, Södertörn University, Huddinge.
    Local landscape effects on population dynamics of Ixodes ricinus2016In: Geospatial health, ISSN 1827-1987, Vol. 11, no 3, 283-289 p., 487Article in journal (Refereed)
    Abstract [en]

    Ixodes ricinus, a common tick in Europe, transmits severe tickborne pathogens (TBPs). In Sweden, both prevalence and incidence of tick-borne infections have increased during the last few decades, and a majority of the cases is reported from the area around Stockholm. Among ticks, transmission of TBPs involves co-feeding of susceptible larvae or nymphs with infected ticks on the same host. Seasonal synchrony of immature stages and total tick abundance are important factors for the probability of horizontal transmission of TBPs. We have studied the association between local landscape characteristics and population dynamics and the probability of co-occurrence of different life cycle stages of I. ricinus at different locations south of Stockholm, Sweden. We found significant spatiotemporal variation in tick activity patterns. Mean tick abundance varied with a tenfold difference among study sites. The probability of co-occurrence of larvae, nymphs and female adults was highest in June and decreased significantly with vegetation height. In addition, the amount of forest habitat and open water in the surrounding landscape of the study sites expressed significant negative effects on tick abundance and co-occurrence, indicating that environmental heterogeneity may increase the likelihood of good rodent habitats, which in turn, are suitable hosts for immature ticks.

  • 45.
    Askling, Helena H
    et al.
    Karolinska Institute, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Lesko, Birgitta
    Swedish National Board of Health & Welfare, Stockholm, Sweden; Swedish Institute for Infectious Disease Control, Stockholm.
    Vene, Sirkka
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Berndtson, Angerd
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Björkman, Per
    Malmö University Hospital, Malmö, Sweden.
    Bläckberg, Jonas
    Lund University Hospital, Lund, Sweden.
    Bronner, Ulf
    Karolinska University Hospital, Stockholm, Sweden.
    Follin, Per
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Hellgren, Urban
    Karolinska University Hospital, Stockholm, Sweden.
    Palmerus, Maria
    County Hospital Ryhov, Jönköping, Sweden.
    Ekdahl, Karl
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Tegnell, Anders
    Swedish National Board of Health & Welfare, Stockholm, Sweden.
    Struwe, Johan
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Serologic Analysis of Returned Travelers with Fever, Sweden2009In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 15, no 11, 1805-1808 p.Article in journal (Refereed)
    Abstract [en]

    We studied 1,432 febrile travelers from Sweden who had returned from malaria-endemic areas during March 2005-March 2008. In 383 patients, paired serum samples were blindly analyzed for influenza and 7 other agents. For 21% of 115 patients with fever of unknown origin, serologic analysis showed that influenza was the major cause.

  • 46.
    Askling, Helena H.
    et al.
    Karolinska Inst, Dept Med Solna, Infect Dis Unit, SE-17176 Stockholm, Sweden; Dept Communicable Dis Control & Prevent, SE-11891 Stockholm, Sweden.
    Rombo, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Karolinska Inst, Dept Med Solna, Infect Dis Unit, SE-17176 Stockholm, Sweden.
    van Vollenhoven, Ronald
    Karolinska Inst, Unit Clin Therapy Res Inflammatory Dis ClinTRID, SE-17176 Stockholm, Sweden.
    Hallén, Ingemar
    Karlstad Cty Hosp, Dept Infect Dis, SE-65185 Karlstad, Sweden.
    Thörner, Åke
    Malar Hosp, Dept Rheumatol, SE-63188 Eskilstuna, Sweden.
    Nordin, Margareta
    Karolinska Univ Hosp, Dept Clin Microbiol, SE-17176 Stockholm, Sweden.
    Herzog, Christian
    Swiss Trop & Publ Hlth Inst, CH-4051 Basel, Switzerland.
    Kantele, Anu
    Univ Helsinki, Cent Hosp, Dept Med, Div Infect Dis, FI-00029 Huch Helsinki, Finland; Univ Helsinki, Dept Med, FI-00014 Helsinki, Finland.
    Hepatitis A vaccine for immunosuppressed patients with rheumatoid arthritis: a prospective, open-label, multi-centre study2014In: Travel Medicine and Infectious Disease, ISSN 1477-8939, E-ISSN 1873-0442, Vol. 12, no 2, 134-42 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hepatitis A vaccine is the most frequently used travel vaccine, yet data are scarce about its ability to induce protection in patients with concurrent immunosuppressive treatment. We assessed the immunogenicity of this vaccine in rheumatoid arthritis (RA) patients treated with tumour necrosis factor-inhibitors (TNFi) and/or methotrexate (MTX).

    METHODS: Hepatitis A vaccine was administered to non-immune RA patients at 0 and 6 months. Hepatitis A virus (HAV) antibodies were assessed at 0, 1, 6, 7, 12, and 24 months with a quantitative Chemiluminescent Microparticle Immuno Assay (CMIA) for HAV-IgG. Samples from month 1, 6, and 7 were, in addition, analysed with a microparticle EIA (MEIA) for anti-HAV IgM + IgG.

    RESULTS: The final study population consisted of 53 patients treated with TNFi (n = 15), TNFi + MTX (n = 21) or MTX (n = 17). One and six months after the first dose, 10% and 33% of the patients had attained seroprotection. One and six months after the second dose 83% and 72% were seroprotected. At month 24, 86% of the vaccinees showed protective levels.

    CONCLUSIONS: Two doses of hepatitis A vaccine at a 6-month interval provided protection for most immunosuppressed RA patients. A single dose does not seem to afford sufficient protection to this group of patients.

  • 47.
    Athlin, Simon
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious Diseases.
    Altun, O.
    Department of Clinical Microbiology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Eriksen, H. B.
    Department of Clinical Microbiology, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark.
    Özenci, V.
    Department of Clinical Microbiology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Strålin, K.
    Department of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    The UniGold(TM) Streptococcus pneumoniae urinary antigen test: an interassay comparison with the BinaxNOW (R) Streptococcus pneumoniae test on consecutive urine samples and evaluation on patients with bacteremia2015In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 34, no 8, 1583-1588 p.Article in journal (Refereed)
    Abstract [en]

    The performance of the recently commercialized UniGoldTM Streptococc-us pneurnonfac test for the detection of pneumococcal antigen in urine was studied in a multicenter study. First, we studied the interassay agreement between UniGoldTm and the BinaxNOVs," S. pneumoniae urinary antigen test on 337 consecutive urine samples sent to the laboratory for the detection of pneumococcal antigen. The two tests performed similarly (K-0.82): both tests positive in 27 cases, both tests negative in 299 cases, and with divergent test results in 11 cases. Secondly, the tests were run on urine samples from 203 patients with bacteremia, including 51 patients with pneumococcal bacteremia. The sensitivities and specificities were 67 and 86 A for Uni-GoldTm, and 57 % and 94 % for BinaxNOW, respectively. The false-positivity rate was significantly higher for Uni-GoldTm compared with BinaxNOW in patients with Escherichia colt bacteremia (15 vs. 2.1 %. p=0.04), and tended to be higher in patients with bacteremia with alpha-hemolytic streptococci (32 vs. 11 %, p=0.13). When cases with E. coli and alphahemolytic streptococci were excluded from the analysis, the overall false-positivity rate was 9/85 (11 A) for Uni-GoldTm and 6/85 (7.1 %) for BinaxNOW. In conclusion, the study showed that UniGold(TM) was not inferior to BinaxNOW (R) for the detection of pneumococcal urinary antigen in patients with pneumococcal bacteremia. The specificity of UniGold(TM) was suboptimal due to false-positive results in cases with E. colt and alpha-hemolytic streptococci bacteremia. However, in patient populations usually subjected to testing for pneumococcal urinary antigen, such as pneumonia and meningitis patients, bacteremia with these pathogens is uncommon. The diagnostic usefulness of the UniGoldTM test should be further evaluated.

  • 48.
    Athlin, Simon
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Altun, Osman
    Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Brander Eriksen, Helle
    Copenhagen University Hospital Hvidovre, Copenhagen, Denmark.
    Özenci, Volkan
    Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Strålin, Kristoffer
    Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    The Uni-Gold™ Streptococcus pneumoniae urinary antigen test: an inter-assay comparison with the BinaxNOW® Streptococcus pneumoniae test on consecutive urine samples and evaluation on patients with bacteremiaManuscript (preprint) (Other academic)
  • 49.
    Athlin, Simon
    et al.
    Orebro University Hospital.
    Kaltoft, Margit
    Statens Serum Institut, Copenhagen, Denmark.
    Slotved, Hans-Christian
    Statens Serum Institut, Copenhagen, Denmark.
    Herrmann, Björn
    Uppsala University, Uppsala, Sweden.
    Holmberg, Hans
    Orebro University Hospital.
    Konradsen, Helle Bossen
    Statens Serum Institut, Copenhagen, Denmark.
    Strålin, Kristoffer
    Örebro University Hospital, Örebro, Sweden; Karolinska University Hospital, Huddinge, Stockholm, Sweden .
    Association between serotype-specific antibody response and serotype characteristics in patients with pneumococcal pneumonia, with special reference to degree of encapsulation and invasive potential2014In: Clinical and Laboratory Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 11, 1541-1549 p.Article in journal (Refereed)
    Abstract [en]

    We studied the immunoglobulin (Ig) response to causative serotype-specific capsular polysaccharides in adult pneumococcal pneumonia patients. The serotypes were grouped according to their degree of encapsulation and invasive potential. Seventy patients with pneumococcal pneumonia, 20 of whom were bacteremic, were prospectively studied. All pneumococcal isolates from the patients were serotyped, and the Ig titers to the homologous serotype were determined in acute- and convalescent-phase sera using a serotype-specific enzyme-linked immunosorbent assay. The Ig titers were lower in bacteremic cases than in nonbacteremic cases (P < 0.042). The Ig titer ratio (convalescent/acute titer) was ≥2 in 33 patients, 1 to 1.99 in 20 patients, and <1 in 17 patients. Patients ≥65 years old had a lower median Ig titer ratio than did younger patients (P < 0.031). The patients with serotypes with a thin capsule (1, 4, 7F, 9N, 9V, and 14) and medium/high invasive potential (1, 4, 7F, 9N, 9V, 14, and 18C) had higher Ig titer ratios than did patients with serotypes with a thick capsule (3, 6B, 11A, 18C, 19A, 19F, and 23F) and low invasive potential (3, 6B, 19A, 19F, and 23F) (P < 0.05 for both comparisons after adjustment for age). Ig titer ratios of <1 were predominantly noted in patients with serotypes with a thick capsule. In 8 patients with pneumococcal DNA detected in plasma, the three patients with the highest DNA load had the lowest Ig titer ratios. In conclusion, a high antibody response was associated with serotypes with a thin capsule and medium/high invasive potential, although a low antibody response was associated with serotypes with a thick capsule and a high pneumococcal plasma load.

  • 50.
    Athlin, Simon
    et al.
    Orebro University Hospital.
    Strålin, Kristoffer
    Örebro University Hospital, Örebro, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    The Binax NOW Streptococcus pneumoniae test applied on nasopharyngeal aspirates to support pneumococcal aetiology in community-acquired pneumonia.2013In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, no 6, 425-31 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The use of nasopharyngeal secretions to enhance diagnostic yields of pneumococcal aetiology in community-acquired pneumonia (CAP) is of interest. We evaluated the Binax NOW Streptococcus pneumoniae immunochromatographic test (ICT) on nasopharyngeal aspirates (NPA) in order to support pneumococcal aetiology in CAP.

    METHODS: The NPA ICT was applied on 180 adult CAP patients and 64 healthy controls. The rate of pneumococcal detection in the nasopharynx was compared to rates for lytA polymerase chain reaction (PCR) and culture on NPA.

    RESULTS: According to blood and sputum culture and urine ICT, the test sensitivity in 59 patients with a pneumococcal aetiology was 81%. The specificity was suboptimal, with 72% negative tests among CAP patients without a pneumococcal aetiology. However, the test was positive in only 11% of patients with atypical pneumonia and in 4.7% of healthy controls. The positivity rate was higher for NPA ICT compared to culture on NPA in all CAP patients, and to both PCR and culture on NPA in non-pneumococcal non-atypical CAP patients. In 113 (63%) patients with β-lactam monotherapy, cure without treatment alteration was noted more often in cases with positive compared to negative NPA ICT at admission (91% vs 69%; p < 0.01).

    CONCLUSIONS: The high sensitivity and the low positivity rates in patients with atypical pneumonia and healthy controls, in combination with the correlation between positive test results and clinical cure with β-lactam therapy, may support a pneumococcal aetiology in CAP in populations with low pneumococcal carriage rates.

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