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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
    Örebro 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.
    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.

  • 3.
    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
    Örebro 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.

  • 4.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Hematology.
    Hellmark, Bengt
    Örebro 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. Örebro 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.

  • 5.
    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.

  • 6.
    Alirol, Emilie
    et al.
    Global Antibiotics Research and Development Partnership (GARDP), Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
    Wi, Teodora E.
    World Health Organization (WHO), Geneva, Switzerland.
    Bala, Manju
    Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Bazzo, Maria Luiza
    Federal University of Santa Catarina, Florianópolis, Brazil.
    Chen, Xiang-Sheng
    National Center for STD Control, Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Dermatology, Nanjing, China.
    Deal, Carolyn
    STD Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), Rockville MD, United States of America.
    Dillon, Jo-Anne R.
    University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
    Kularatne, Ranmini
    Centre for HIV & Sexually Transmitted Infections, National Institute for Communicable Diseases, Johannesburg, South Africa.
    Heim, Jutta
    Global Antibiotics Research and Development Partnership (GARDP), Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
    Hooft van Huijsduijnen, Rob
    Global Antibiotics Research and Development Partnership (GARDP), Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
    Hook, Edward W.
    University of Alabama, Birmingham AL, United States of America.
    Lahra, Monica M.
    World Health Organization Collaborating Centre for Sexually Transmitted Diseases, South Eastern Area Laboratory Services, The Prince of Wales Hospital, Sydney, Australia.
    Lewis, David A.
    Western Sydney Sexual Health Centre, Parramatta, NSW, Australia, and Marie Bashir Institute for Infectious Diseases and Biosecurity & Sydney Medical School-Westmead, University of Sydney, Westmead, Australia.
    Ndowa, Francis
    Skin & GU Medicine Clinic, Harare, Zimbabwe.
    Shafer, William M.
    Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta GA, United States of America; Laboratories of Bacterial Pathogenesis, VA Medical Center, Decatur GA, United States of America.
    Tayler, Liz
    World Health Organization (WHO), Geneva, Switzerland.
    Workowski, Kimberly
    Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta GA, United States of America.
    Unemo, Magnus
    World Health Organization Collaborating Centre for Gonorrhoea and other STIs, Örebro University, Örebro, Sweden.
    Balasegaram, Manica
    Global Antibiotics Research and Development Partnership (GARDP), Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland.
    Multidrug-resistant gonorrhea: A research and development roadmap to discover new medicines2017In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, no 7, e1002366Article in journal (Refereed)
    Abstract [en]

    Emilie Alirol and colleagues discuss the development of new treatments for gonorrhea.

  • 7.
    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.

  • 8.
    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)
  • 9.
    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.

  • 10. 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.

  • 11.
    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.

  • 12.
    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.

  • 13.
    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.

  • 14.
    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.

  • 15.
    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)
  • 16.
    Athlin, Simon
    et al.
    Örebro University Hospital. Örebro University, School of Medical Sciences. Orebro Univ, Fac Med & Hlth, Dept Infect Dis, S-70185 Orebro, Sweden..
    Iversen, A.
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Microbiology, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Özenci, V.
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Microbiology F 72, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Comparison of the ImmuView and the BinaxNOW antigen tests in detection of Streptococcus pneumoniae and Legionella pneumophila in urine2017In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, no 10, 1933-1938 p.Article in journal (Refereed)
    Abstract [en]

    The use of urinary antigen tests (UATs) may provide early etiology in pneumonia, and facilitates rapid and directed antibiotic treatment. In this study, we evaluated the novel lateral flow ImmuView Streptococcus pneumoniae and Legionella pneumophila UAT, which detects pneumococcal and L. pneumophila serogroup 1 antigens in a combined test. We compared the ImmuView UAT with the BinaxNOW S. pneumoniae UAT and the BinaxNOW L. pneumophila UAT in 147 patients with pneumococcal bacteremia (n = 48), non-pneumococcal non-Legionella bacteremia (n = 93) and Legionella infections in the lower airways (L. pneumophila, n = 5; L. bozemanii, n = 1). In three cases, the ImmuView test was invalid before and after boiling while the BinaxNOW tests were valid in all cases. In 144 cases, the three UATs demonstrated a very good inter-assay agreement for detection of pneumococcal antigen (kappa = 0.86) and L. pneumophila antigen (kappa = 1.00). The ImmuView and BinaxNOW S. pneumoniae tests had similar sensitivities (62% vs 60%; p = ns) in 48 cases with pneumococcal bacteremia and both tests had specificities of 97% in 96 cases with non-pneumococcal infections. Furthermore, the ImmuView and BinaxNOW L. pneumophila tests were positive for Legionella antigen in five patients with confirmed L. pneumophila serogroup 1 infections, and negative in all non-L. pneumophila cases. The ImmuView and BinaxNOW tests performed similarly when evaluated on urine samples from bacteremic and non-bacteremic patients with identified etiology.

  • 17.
    Athlin, Simon
    et al.
    Örebro University, School of Medical Sciences. Department of Infectious Diseases.
    Iversen, A.
    Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Microbiology, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Özenci, Volkan
    Department of Clinical Microbiology F 72, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Comparison of the ImmuView and the BinaxNOW antigen tests in detection of Streptococcus pneumoniae and Legionella pneumophila in urine2017In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, no 10, 1933-1938 p.Article in journal (Refereed)
    Abstract [en]

    The use of urinary antigen tests (UATs) may provide early etiology in pneumonia, and facilitates rapid and directed antibiotic treatment. In this study, we evaluated the novel lateral flow ImmuView Streptococcus pneumoniae and Legionella pneumophila UAT, which detects pneumococcal and L. pneumophila serogroup 1 antigens in a combined test. We compared the ImmuView UAT with the BinaxNOW S. pneumoniae UAT and the BinaxNOW L. pneumophila UAT in 147 patients with pneumococcal bacteremia (n = 48), non-pneumococcal non-Legionella bacteremia (n = 93) and Legionella infections in the lower airways (L. pneumophila, n = 5; L. bozemanii, n = 1). In three cases, the ImmuView test was invalid before and after boiling while the BinaxNOW tests were valid in all cases. In 144 cases, the three UATs demonstrated a very good inter-assay agreement for detection of pneumococcal antigen (κ = 0.86) and L. pneumophila antigen (κ = 1.00). The ImmuView and BinaxNOW S. pneumoniae tests had similar sensitivities (62% vs 60%; p = ns) in 48 cases with pneumococcal bacteremia and both tests had specificities of 97% in 96 cases with non-pneumococcal infections. Furthermore, the ImmuView and BinaxNOW L. pneumophila tests were positive for Legionella antigen in five patients with confirmed L. pneumophila serogroup 1 infections, and negative in all non-L. pneumophila cases. The ImmuView and BinaxNOW tests performed similarly when evaluated on urine samples from bacteremic and non-bacteremic patients with identified etiology.

  • 18.
    Athlin, Simon
    et al.
    Örebro 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
    Örebro 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 Vaccine 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.

  • 19.
    Athlin, Simon
    et al.
    Örebro 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.

  • 20.
    Bala, Manju
    et al.
    Apex Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Singh, Vikram
    Apex Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Philipova, Ivva
    WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; National Reference Laboratory for Mycology and Sexually Transmitted Infections (STIs), National Center of Infections and Parasitic Diseases, Sofia, Bulgaria.
    Bhargava, Aradhana
    Apex Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Chandra Joshi, Naveen
    Apex Regional STD Teaching, Training & Research Centre, VMMC and Safdarjung Hospital, New Delhi, India.
    Unemo, Magnus
    Örebro University, School of Health Sciences. WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology.
    Gentamicin in vitro activity and tentative gentamicin interpretation criteria for the CLSI and calibrated dichotomous sensitivity disc diffusion methods for Neisseria gonorrhoeae2016In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 7, 1856-1859 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: XDR Neisseria gonorrhoeae imposes the threat of untreatable gonorrhoea. Gentamicin is considered for future treatment; however, no interpretation criteria for the CLSI and calibrated dichotomous sensitivity (CDS) disc diffusion (DD) techniques are available for N. gonorrhoeae. We investigated the in vitro gentamicin activity by MIC and DD methods, proposed DD breakpoints and determined DD ranges for 10 international quality control (QC) strains.

    Methods: Gentamicin susceptibility of 333 N. gonorrhoeae isolates, including 323 clinical isolates and 10 QC strains, was determined. MIC determination (Etest) and DD methods (CLSI and CDS) were performed. The relationship between MIC, inhibition zone diameter and annular radius was determined by linear regression analysis and the correlation coefficient (r) was calculated.

    Results: Gentamicin MICs for the QC strains were within published ranges. Of the 323 clinical isolates, according to published breakpoints 75.9%, 23.5% and 0.6% were susceptible, intermediately susceptible and resistant, respectively. Based on error minimization with MICs of ≤4, 8-16 and ≥32 mg/L, breakpoints proposed are susceptible ≥16 mm, intermediately susceptible 13-15 mm and resistant ≤12 mm for the CLSI method and susceptible ≥6 mm, less susceptible 3-5 mm and resistant ≤2 mm for the CDS technique.

    Conclusions: Low resistance to gentamicin was identified and gentamicin might be a future treatment option for gonorrhoea. Tentative gentamicin zone breakpoints were defined for two DD methods and QC ranges for 10 international reference strains were established. Our findings suggest that in resource-poor settings where MIC testing is not a feasible option, the DD methods can be used to indicate gentamicin resistance.

  • 21.
    Bengtsson, Torbjörn
    et al.
    Örebro University, School of Medical Sciences.
    Zhang, Boxi
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Selegård, Robert
    Örebro University, School of Medical Sciences. Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Wiman, Emanuel
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Aili, Daniel
    Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    Dual action of bacteriocin PLNC8 alpha beta through inhibition of Porphyromonas gingivalis infection and promotion of cell proliferation2017In: Pathogens and Disease, E-ISSN 2049-632X, Vol. 75, no 5, ftx064Article in journal (Refereed)
    Abstract [en]

    Periodontitis is a chronic inflammatory disease that is characterised by accumulation of pathogenic bacteria, including Porphyromonas gingivalis, in periodontal pockets. The lack of effective treatments has emphasised in an intense search for alternative methods to prevent bacterial colonisation and disease progression. Bacteriocins are bacterially produced antimicrobial peptides gaining increased consideration as alternatives to traditional antibiotics. We show rapid permeabilisation and aggregation of P. gingivalis by the two-peptide bacteriocin PLNC8 alpha beta. In a cell culture model, P. gingivalis was cytotoxic against gingival fibroblasts. The proteome profile of fibroblasts is severely affected by P. gingivalis, including induction of the ubiquitin-proteasome pathway. PLNC8 alpha beta enhanced the expression of growth factors and promoted cell proliferation, and suppressed proteins associated with apoptosis. PLNC8 alpha beta efficiently counteracted P. gingivalis-mediated cytotoxicity, increased expression of a large number of proteins and restored the levels of inflammatory mediators. In conclusion, we show that bacteriocin PLNC8 alpha beta displays dual effects by acting as a potent antimicrobial agent killing P. gingivalis and as a stimulatory factor promoting cell proliferation. We suggest preventive and therapeutical applications of PLNC8 alpha beta in periodontitis to supplement the host immune defence against P. gingivalis infection and support wound healing processes.

  • 22. Bereczky, S.
    et al.
    Dolo, A.
    Maiga, B.
    Hayano, M.
    Granath, F.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Daou, M.
    Arama, C.
    Troye-Blomberg, M.
    Doumbo, O. K.
    Färnert, A.
    Spleen enlargement and genetic diversity of Plasmodium falciparum infection in two ethnic groups with different malaria susceptibility in Mali, West Africa2006In: Transactions of the Royal Society of Tropical Medicine and Hygiene, ISSN 0035-9203, E-ISSN 1878-3503, Vol. 100, no 3, 248-257 p.Article in journal (Refereed)
    Abstract [en]

    The high resistance to malaria in the nomadic Fulani population needs further understanding. The ability to cope with multiclonal Plasmodium falciparum infections was assessed in a cross-sectional survey in the Fulani and the Dogon, their sympatric ethnic group in Mali. The Fulani had lower parasite prevalence and densities and more prominent spleen enlargement. Spleen rates in children aged 2–9 years were 75% in the Fulani and 44% in the Dogon (P < 0.001). There was no difference in number of P. falciparum genotypes, defined by merozoite surface protein 2 polymorphism, with mean values of 2.25 and 2.11 (P = 0.503) in the Dogon and Fulani, respectively. Spleen rate increased with parasite prevalence, density and number of co-infecting clones in asymptomatic Dogon. Moreover, splenomegaly was increased in individuals with clinical malaria in the Dogon, odds ratio 3.67 (95% CI 1.65–8.15, P = 0.003), but not found in the Fulani, 1.36 (95% CI 0.53–3.48, P = 0.633). The more susceptible Dogon population thus appear to respond with pronounced spleen enlargement to asymptomatic multiclonal infections and acute disease whereas the Fulani have generally enlarged spleens already functional for protection. The results emphasize the importance of spleen function in protective immunity to the polymorphic malaria parasite.

  • 23. Bereczky, Sándor
    et al.
    Liljander, Anne
    Rooth, Ingegerd
    Faraja, Lea
    Granath, Fredrik
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Färnert, Anna
    Multiclonal asymptomatic Plasmodium falciparum infections predict a reduced risk of malaria disease in a Tanzanian population2007In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 9, no 1, 103-110 p.Article in journal (Refereed)
    Abstract [en]

    Protective immunity to malaria is acquired after repeated exposure to the polymorphic Plasmodium falciparum parasite. Whether the number of concurrent antigenically diverse clones in asymptomatic infections predicts the risk of subsequent clinical malaria needs further understanding. We assessed the diversity of P. falciparum infections by merozoite surface protein 2 genotyping in a longitudinal population based study in Tanzania. The number of clones was highest in children 6–10 years and in individuals with long time to previous anti-malarial treatment. Individual exposure, analysed by circumsporozoite protein antibody levels, was associated with parasite prevalence but not with the number of clones. The risk of subsequent clinical malaria in children free of acute disease or recent treatment was, compared to one clone, reduced in individuals with multiclonal infections or without detectable parasites, with the lowest hazard ratio 0.28 (95% confidence interval 0.10–0.78 Cox regression) for 2–3 clones. The number of clones was not associated with haemoglobin levels. A reduced risk of malaria in asymptomatic individuals with multiclonal persistent P. falciparum infections suggests that controlled maintenance of diverse infections is important for clinical protection in continuously exposed individuals, and needs to be considered in the design and evaluation of new malaria control strategies.

  • 24. Bhattarai, Achuyt
    et al.
    Ali, Abdullah S.
    Kachur, S. Patrick
    Mårtensson, Andreas
    Abbas, Ali K.
    Khatib, Rashid
    Al-Mafazy, Abdul-Wahiyd
    Ramsan, Mahdi
    Rotllant, Guida
    Gerstenmaier, Jan F.
    Molteni, Fabrizio
    Abdulla, Salim
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Kaneko, Akira
    Björkman, Anders
    Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar2007In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 4, no 11, e309- p.Article in journal (Refereed)
    Abstract [en]

    Background

    The Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y (“under five”) and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar.

    Methods and Findings

    Cross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner's Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28–1.08), and for 2006, 0.03 (0.00–0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1–4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period.

    Conclusions

    Following deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions.

  • 25.
    Bignell, Chris J.
    et al.
    City Hospital Campus, Nottingham University Hospitals NHS Trust, Hucknall Road, Nottingham NG 1PB, UK.
    Unemo, Magnus
    WHO Collaborating Center for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    2012 European guideline on the diagnosis and treatment of gonorrhoea in adults2013In: International Journal of STD and AIDS (London), ISSN 0956-4624, Vol. 24, no 2, 85-92 p.Article in journal (Refereed)
    Abstract [en]

    Gonorrhoea is a major public health concern globally. Of particularly grave concern is that resistance to the extended-spectrum cephalosporins has emerged during the most recent years. This guideline provides recommendations regarding the diagnosis and treatment of gonorrhoea in Europe. Compared to the outdated 2009 European gonorrhoea guideline, this 2012 European gonorrhoea guideline provides up-to-date guidance on, broader indications for testing and treatment of gonorrhoea; the introduction of dual antimicrobial therapy (ceftriaxone 500 mg and azithromycin 2 g) for uncomplicated gonorrhoea when the antimicrobial sensitivity is unknown; recommendation of test of cure in all gonorrhoea cases to ensure eradication of infection and identify emerging resistance; and recommendations to identify, verify and report failures with recommended treatment regimens. Optimisations of the testing, diagnostics, antimicrobial treatment and follow-up of gonorrhoea patients are crucial in controlling the emergent spread of cephalosporin-resistant and multidrug-resistant gonorrhoea.

  • 26.
    Björk, Helena
    et al.
    Cent Hosp Vaxjo, Dept Otorhinolaryngol, SE-35185 Vaxjo, Sweden..
    Bieber, Lena
    Cent Hosp Vaxjo, Dept Clin Microbiol, SE-35185 Vaxjo, Sweden..
    Hedin, Katarina
    Lund Univ, Dept Clin Sci Family Med, SE-20502 Malmo, Sweden.;Kronoberg Cty Council, Unit Res & Dev, SE-35212 Vaxjo, Sweden..
    Sundqvist, Martin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Cent Hosp Vaxjo, Dept Clin Microbiol, SE-35185 Vaxjo, Sweden..
    Tonsillar colonisation of Fusobacterium necrophorum in patients subjected to tonsillectomy2015In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, 264Article in journal (Refereed)
    Abstract [en]

    Background: Fusobacterium necrophorum is a well-known cause of Lemirre's disease and accumulating evidence support its pathogenic role in peritonsillar abscess while its role in recurrent and chronic tonsillitis is uncertain. The objective of this study was to assess the prevalence of oropharyngeal colonisation with F. necrophorum and Beta-haemolytic streptococci in a cohort of patients scheduled for tonsillectomy due to recurrent or persistent throat pain, and to evaluate the dynamics of colonisation with repeated sampling during a follow-up time of 6 to 8 months. Methods: Fifty-seven (57) patients aged 15-52 years scheduled for tonsillectomy due to chronic/recurrent tonsillitis or recurrent peritonsillar abscess were included. Throat swabs for the detection of F. necrophorum and Beta-haemolytic streptococci and clinical data was collected at inclusion, at the time of surgery and 6 to 8 months after surgery. Statistical analysis was performed using the Chi-square, Fisher's exact and Mc Nemar tests. Results: Fusobacterium necrophorum was found in 28, 30 and 16 % of the patients at inclusion, surgery and follow up respectively. The corresponding results for beta-haemolytic streptococci were 5, 9 and 5 %. Patients colonised with F. necrophorum at follow-up, after tonsillectomy, were equally relieved from their previous throat pain as non-colonised patients. Looking at individual patients, the culture results for F. necrophorum varied over time, indicating a transient colonisation. Conclusion: Fusobacterium necrophorum was frequently found in throat cultures in this cohort of patients with recurrent or chronic throat pain leading to tonsillectomy. Colonisation was equally frequent in the asymptomatic cohort post-tonsillectomy, indicating that F. necrophorum is not alone causative of the symptoms. In an individual perspective, colonisation with F. necrophorum was transient over time.

  • 27.
    Björkqvist, Maria
    et al.
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Liljedahl, M.
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Zimmermann, J.
    Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Schollin, Jens
    Örebro University. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences. Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Colonization pattern of coagulase-negative staphylococci in preterm neonates and the relation to bacteremia2010In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 29, no 9, 1085-1093 p.Article in journal (Refereed)
    Abstract [en]

    Coagulase-negative staphylococci (CoNS) are the major cause of sepsis in extreme preterm (EPT) newborns, but data on the CoNS colonization in EPT newborns prior to invasive infection are limited. Our aim was to describe the early establishment of the CoNS microflora in EPT newborns and to compare the colonization pattern in neonates with and without positive CoNS blood cultures. From a cohort of 46 EPT neonates, newborns with positive CoNS blood culture were identified (n = 10) and compared with matched controls. Samples for bacterial cultures were obtained repetitively from nares, perineum, and umbilicus. All CoNS isolates were characterized using the PhenePlate system for biochemical fingerprinting. Persistent CoNS strains were found on day 2-3 after delivery in 7/20 newborns, and there was a tendency for earlier colonization in nares than in the perineum or umbilicus. The CoNS blood strains were prevalent in superficial sites prior to positive blood culture (11/14 blood strains), but no single invasive pathway was identified. Most CoNS blood strains (9/14) persisted on superficial sites after antibiotic treatment. We hypothesize that the invasive pathways in neonatal CoNS sepsis are complex and that the colonization of mucosal membranes and umbilical catheters might be of equal importance.

  • 28.
    Bond, Emily
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lu, Donghao
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Herweijer, Eva
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sundström, Karin
    Department of Laboratory Medicine, Karolinska Institutet, H5, Division of Pathology, Karolinska Universitetssjukhuset Huddinge, Stockholm, Sweden.
    Valdimarsdottir, Unnur
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA .
    Fall, Katja
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Arnheim-Dahlstrom, Lisen
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sparén, Par
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Fang, Fang
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sexually transmitted infections after bereavement - a population-based cohort study2016In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 16, 419Article in journal (Refereed)
    Abstract [en]

    Background: Loss of a loved one has consistently been associated with various health risks. Little is however known about its relation to sexually transmitted infections (STIs).

    Methods: We conducted a population-based cohort study during 1987-2012 using the Swedish Multi-Generation Register, including 3,002,209 women aged 10-44 years. Bereavement was defined as death of a child, parent, sibling or spouse (N = 979,579, 33 %). STIs were defined as hospital visits with an STI as main or secondary diagnosis. Poisson regression and negative binomial regression were used to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) of STIs, comparing incidence rates of women who had experienced loss to those who had not.

    Results: Bereaved women were at significantly higher risk of nearly all STIs studied. The relative risk of any STI was highest during the first year after loss (IRR: 1.45, 95 % CI: 1.27-1.65) and predominantly among women with subsequent onset of psychiatric disorders after bereavement (IRR: 2.61, 95 % CI: 2.00-3.34). Notably, a consistent excess risk, persisting for over five years, was observed for acute salpingitis (IRR: 1.28, 95 % CI: 1.13-1.44), a severe complication of bacterial STIs.

    Conclusion: These data suggest that women who have experienced bereavement are at increased risk of STIs.

  • 29.
    Brehony, Carina
    et al.
    Univ Oxford, Dept Zool, Oxford OX1 3PS, England..
    Trotter, Caroline L.
    Univ Cambridge, Dept Vet Med, Cambridge, England..
    Ramsay, Mary E.
    Publ Hlth England, London, England..
    Chandra, Manosree
    Publ Hlth England, London, England..
    Jolley, Keith A.
    Univ Oxford, Dept Zool, Oxford OX1 3PS, England..
    van der Ende, Arie
    Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, Netherlands Reference Lab Bacterial Meningitis, NL-1105 AZ Amsterdam, Netherlands..
    Carion, Francoise
    Sci Inst Publ Hlth, Meningococcal Reference Lab, Brussels, Belgium..
    Berthelsen, Lene
    Statens Serum Inst, Neisseria & Streptococcus Reference Lab, DK-2300 Copenhagen, Denmark..
    Hoffmann, Steen
    Statens Serum Inst, Neisseria & Streptococcus Reference Lab, DK-2300 Copenhagen, Denmark..
    Hardardottir, Hjordis
    Landspitali Univ Hosp, Dept Microbiol, Reykjavik, Iceland..
    Vazquez, Julio A.
    Meningococcal Reference Lab, Madrid, Spain..
    Murphy, Karen
    Irish Meningococcal & Meningitis Reference Lab, Dublin, Ireland..
    Toropainen, Maija
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Canica, Manuela
    Natl Inst Hlth Dr Ricardo Jorge, Dept Infect Dis, Lab Antimicrobial Resistance, Lisbon, Portugal..
    Ferreira, Eugenia
    Natl Inst Hlth Dr Ricardo Jorge, Dept Infect Dis, Lab Antimicrobial Resistance, Lisbon, Portugal..
    Diggle, Mathew
    Scottish Haemophilus Legionella Meningococcus & P, Glasgow, Lanark, Scotland..
    Edwards, Giles F.
    Scottish Haemophilus Legionella Meningococcus & P, Glasgow, Lanark, Scotland..
    Taha, Muhamed-Kheir
    Inst Pasteur, Natl Reference Ctr Meningococci, Paris, France..
    Stefanelli, Paola
    Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy..
    Kriz, Paula
    Natl Inst Publ Hlth, Natl Reference Lab Meningococcal Infect, Prague, Czech Republic..
    Gray, Steve J.
    Manchester Royal Infirm, Meningococcal Reference Unit, Manchester M13 9WL, Lancs, England..
    Fox, Andrew J.
    Manchester Royal Infirm, Meningococcal Reference Unit, Manchester M13 9WL, Lancs, England..
    Jacobsson, Susanne
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology.
    Claus, Heike
    Inst Hyg & Mikrobiol, Wurzburg, Germany..
    Vogel, Ulrich
    Inst Hyg & Mikrobiol, Wurzburg, Germany..
    Tzanakaki, Georgina
    Natl Sch Publ Hlth, Natl Meningococcal Reference Lab, Athens, Greece..
    Heuberger, Sigrid
    Inst Med Microbiol & Hyg, Natl Reference Ctr Meningococci, Graz, Austria..
    Caugant, Dominique A.
    Norwegian Inst Publ Hlth, Dept Bacteriol & Immunol, Oslo, Norway..
    Frosch, Matthias
    Inst Hyg & Mikrobiol, Wurzburg, Germany..
    Maiden, Martin C. J.
    Univ Oxford, Dept Zool, Oxford OX1 3PS, England..
    Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development2014In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 6, 847-853 p.Article in journal (Refereed)
    Abstract [en]

    New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and >= 25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.

  • 30.
    Bruggmann, P.
    et al.
    Arud Ctr Addict Med, Zurich, Switzerland.
    Berg, T.
    Univ Leipzig, Leipzig, Germany.
    Ovrehus, A. L. H.
    Odense Univ Hosp, Dept Infect Dis, Odense, Denmark.
    Moreno, C.
    Univ Libre Brussels, Erasme Univ Hosp, Brussels, Belgium.
    Brandao Mello, C. E.
    Univ Fed Rio de Janeiro, Dept Gastroenterol, Rio De Janeiro, Brazil.
    Roudot-Thoraval, F.
    Hop Henri Mondor, Dept Sante Publ, Creteil, France.
    Marinho, R. T.
    Hosp Santa Maria, Ctr Hosp Lisboa Norte, Dept Gastroenterol, Lisbon, Portugal.
    Sherman, M.
    Univ Toronto, Toronto Gen Hosp, Univ Hlth Network, Toronto, Canada.
    Ryder, S. D.
    Nottingham Univ Hosp NHS Trust, Nottingham, England; Biomed Res Unit, Nottingham, England.
    Sperl, J.
    Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic.
    Akarca, U.
    Ege Univ, Izmir, Turkey.
    Balik, I.
    Ankara Univ, Ankara, Turkey.
    Bihl, F.
    Osped Cantonale, Dept Gastroenterol, Bellinzona, Switzerland.
    Bilodeau, M.
    Univ Montreal, Dept Med, Liver Unit, Montreal, Canada.
    Blasco, A. J.
    Adv Tech Hlth Serv Res TAISS, Madrid, Spain.
    Buti, M.
    Hosp Valle De Hebron, CIBERehd, Barcelona, Spain.
    Calinas, F.
    Hosp Santo Antonio Capuchos, Dept Gastroenterol, Ctr Hosp Lisboa Cent, Lisbon, Portugal.
    Calleja, J. L.
    Hosp Puerta Hierro, Madrid, Spain.
    Cheinquer, H.
    Univ Fed Rio Grande do Sul, Hosp Clin, Porto Alegre, RS, Brazil.
    Christensen, P. B.
    Odense Univ Hosp, Dept Infect Dis, Odense, Denmark.
    Clausen, M.
    Region Hosp Hovedstaden, Region Hovedstaden, Denmark.
    Coelho, H. S. M.
    Univ Fed Rio de Janeiro, Dept Clin Med, Rio De Janeiro, Brazil.
    Cornberg, M.
    Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany; German Liver Fdn, Hannover, Germany.
    Cramp, M. E.
    Univ Plymouth, Peninsula Schools Med & Dent, Plymouth, Devon, England.
    Dore, G. J.
    Univ New S Wales, Kirby Inst, Sydney, NSW, Australia.
    Doss, W.
    Cairo Univ, Cairo, Egypt.
    Duberg, Ann-Sofi
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Dept Infect Dis.
    El-Sayed, M. H.
    Ain Shams Univ, Cairo, Egypt.
    Ergor, G.
    Dokuz Eylul Univ, Izmir, Turkey.
    Esmat, G.
    Cairo Univ, Cairo, Egypt.
    Estes, C.
    Ctr Dis Anal CDA, Louisville, CO USA.
    Falconer, K.
    Karolinska Inst, Infect Dis Unit, Dept Med Huddinge, Stockholm, Sweden.
    Felix, J.
    Exigo Consultores, Alhos Vedros, Portugal.
    Ferraz, M. L. G.
    Univ Fed Sao Paulo, Div Gastroenterol, Sao Paulo, Brazil.
    Ferreira, P. R.
    Univ Fed Sao Paulo, Div Infect Dis, Sao Paulo, Brazil.
    Frankova, S.
    Inst Clin & Expt Med, Dept Hepatogastroenterol, Prague, Czech Republic.
    Garcia-Samaniego, J.
    Hosp Carlos III, CIBERehd, Madrid, Spain.
    Gerstoft, J.
    Univ Copenhagen, Copenhagen, Denmark.
    Giria, J. A.
    Direccao Geral Saude, Lisbon, Portugal.
    Goncales, F. L., Jr.
    Univ Estadual Campinas, Fac Ciencias Med, UNICAMP,Dept Clin Med, Grp Estudo Hepatites,Disciplina Doencas Infeccios, Sao Paulo, Brazil.
    Gower, E.
    Ctr Dis Anal CDA, Louisville, CO USA.
    Gschwantler, M.
    Wilhelminenspital Stadt Wien, Dept Internal Med 4, Vienna, Austria.
    Guimaraes Pessoa, M.
    Univ Sao Paulo, Sch Med, Div Gastroenterol & Hepatol, Sao Paulo, Brazil.
    Hezode, C.
    Hop Henri Mondor, Serv Hepatogastroenterol, Creteil, France.
    Hofer, H.
    Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, Vienna, Austria.
    Husa, P.
    Masaryk Univ, Univ Hosp Brno, Clin Infect Dis, Brno, Czech Republic.
    Idilman, R.
    Ankara Univ, Dept Gastroenterol, Sch Med, Ankara, Turkey.
    Kåberg, M.
    Karolinska Inst, Infect Dis Unit, Dept Med Huddinge, Stockholm, Sweden.
    Kaita, K. D. E.
    Univ Manitoba, Dept Internal Med, Sect Hepatol, Winnipeg, MB, Canada; Hlth Sci Ctr, Viral Hepatitis Invest Unit, Winnipeg, MB, Canada.
    Kautz, A.
    European Liver Patients Assoc, St Truiden, Belgium.
    Kaymakoglu, S.
    Istanbul Univ, Istanbul, Turkey.
    Krajden, M.
    Univ British Columbia, British Columbia Ctr Dis Control, Vancouver, Canada.
    Krarup, H.
    Aalborg Univ Hosp, Dept Med Gastroenterol, Aalborg, Denmark; Aalborg Univ Hosp, Sect Mol Diagnost, Aalborg, Denmark.
    Laleman, W.
    Katholieke Univ Leuven, Univ Hosp Leuven, Louvain, Belgium.
    Lavanchy, D.
    Lazaro, P.
    Adv Tech Hlth Serv Res TAISS, Madrid, Spain.
    Marotta, P.
    Univ Western Ontario, Div Gastroenterol, London, ON, Canada.
    Mauss, S.
    Univ Dusseldorf, Dusseldorf, Germany.
    Mendes Correa, M. C.
    Univ Sao Paulo, Sch Med, Sao Paulo, Brazil.
    Muellhaupt, B.
    Univ Zurich Hosp, Swiss HPB Hepatopancreatobiliary Ctr, Zurich, Switzerland; Univ Zurich Hosp, Dept Gastroenterol & Hepatol, Zurich, Switzerland.
    Myers, R. P.
    Univ Calgary, Liver Unit, Div Gastroenterol & Hepatol, Calgary, AB, Canada.
    Negro, F.
    Univ Hosp, Div Gastroenterol & Hepatol, Geneva, Switzerland; Univ Hosp, Div Clin Pathol, Geneva, Switzerland.
    Nemecek, V.
    Natl Inst Publ Hlth, Natl Reference Lab Hepatitis, Prague, Czech Republic.
    Ormeci, N.
    Ankara Univ, Ankara, Turkey.
    Parkes, J.
    Univ Southhampton, Southampton, England.
    Peltekian, K. M.
    Dalhousie Univ, Dept Med, Halifax, NS, Canada; Dalhousie Univ, Dept Surg, Halifax, Canada; Capital Dist Hlth Author, Serv Hepatol, Queen Elizabeth II Hlth Sci Ctr, Halifax, NS, Canada.
    Ramji, A.
    Univ British Columbia, Dept Gastroenterol, Vancouver, Canada.
    Razavi, H.
    Ctr Dis Anal CDA, Louisville, CO USA.
    Reis, N.
    Assembleia Republ, Lisbon, Portugal.
    Roberts, S. K.
    Alfred Hosp, Melbourne, Vic, Australia; Monash Univ, Melbourne, Australia.
    Rosenberg, W. M.
    UCL, UCL Inst Liver & Digest Hlth, Div Med, London, England.
    Sarmento-Castro, R.
    Ctr Hosp Porto, Dept Infect Dis, Oporto, Portugal.
    Sarrazin, C.
    JW Goethe Univ Hosp, Frankfurt, Germany.
    Semela, D.
    Cantonal Hosp St Gallen, Div Gastroenterol & Hepatol, St Gallen, Switzerland.
    Shiha, G. E.
    Egyptian Liver Res Inst & Hosp ELRIAH, Dakahliah, Egypt.
    Sievert, W.
    Monash Univ, Melbourne, Australia; Monash Hlth, Melbourne, Vic, Australia.
    Starkel, P.
    Catholic Univ Louvain, Clin Univ St Luc, Brussels, Belgium.
    Stauber, R. E.
    Med Univ Graz, Dept Internal Med, Div Gastroenterol & Hepatol, Graz, Austria.
    Thompson, A. J.
    St Vincents Hosp, Dept Gastroenterol, Melbourne, Vic, Australia; Univ Melbourne, Melbourne, Vic, Australia.
    Urbanek, P.
    Charles Univ Prague, Dept Internal Med, Fac Med 1, Prague, Czech Republic; Cent Mil Hosp, Prague, Czech Republic.
    van Thiel, I.
    European Liver Patients Assoc, St Truiden, Belgium; Deutsch Leberhilfe eV, Cologne, Germany.
    Van Vlierberghe, H.
    Ghent Univ Hosp, Ghent, Belgium.
    Vandijck, D.
    Ghent Univ Hosp, Ghent, Belgium; Univ Ghent, Ghent, Belgium; Hasselt Univ, Dept Hlth Econ & Patient Safety, Diepenbeek, Belgium.
    Vogel, W.
    Med Univ Innsbruck, Innsbruck, Austria.
    Waked, I.
    Natl Liver Inst, Menoufia, Egypt.
    Wedemeyer, H.
    Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany; German Liver Fdn, Hannover, Germany.
    Weis, N.
    Copenhagen Univ Hosp, Hvidovre, Denmark.
    Wiegand, J.
    Univ Leipzig, Leipzig, Germany.
    Yosry, A.
    Cairo Univ, Cairo, Egypt.
    Zekry, A.
    Univ New S Wales, St George Hosp Clin Sch Med, Sydney, NSW, Australia; Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia.
    Van Damme, P.
    Univ Antwerp, Antwerp, Belgium.
    Aleman, S.
    Karolinska Inst, Dept Med Huddinge, Stockholm, Sweden; Karolinska Univ Hosp, Dept Gastroenterol & Hepatol Infect Dis, Stockholm, Sweden.
    Hindman, S. J.
    Ctr Dis Anal CDA, Louisville, CO USA.
    Historical epidemiology of hepatitis C virus (HCV) in selected countries2014In: Journal of Viral Hepatitis, ISSN 1352-0504, E-ISSN 1365-2893, Vol. 21, 5-33 p.Article in journal (Refereed)
    Abstract [en]

    Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6358000 cases in 2008 and Brazil with 2106000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

  • 31.
    Bugaytsova, Jeanna A.
    et al.
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Björnham, Oscar
    Department of Applied Physics and Electronics, Umeå University, Umeå, Sweden; Swedish Defence Research Agency, Umeå, Sweden.
    Chernov, Yevgen A.
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Gideonsson, Pär
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Henriksson, Sara
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden: Umeå Core Facil Electron Microscopy UCEM, Umeå University, Umeå, Sweden.
    Mendez, Melissa
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Sjöström, Rolf
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Mahdavi, Jafar
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden; School of Life Sciences, CBS, University of Nottingham, Nottingham, United Kingdom.
    Shevtsova, Anna
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Ilver, Dag
    Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Acreo Swedish ICT AB, Gothenburg, Sweden.
    Moonens, Kristof
    Structural and Molecular Microbiology, VIB Department of Structural Biology, Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium .
    Quintana-Hayashi, Macarena P.
    Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Moskalenko, Roman
    Department of Pathology, Medical Institute, Sumy State University, Sumy, Ukraine.
    Aisenbrey, Christopher
    Department of Chemistry, Umeå University, Umeå, Sweden; Inst Chim, Univ Strasbourg, Strasbourg, France.
    Bylund, Göran
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Schmidt, Alexej
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden; Umea Univ, Dept Med Biosci, Umea, Sweden.
    Åberg, Anna
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Brännström, Kristoffer
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Königer, Verena
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany.
    Vikström, Susanne
    Department of Medical Biochemistry and Biophysics & Faculty Science and Technology, Umeå University, Umeå, Sweden.
    Rakhimova, Lena
    Department of Chemistry, Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Hofer, Anders
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Ögren, Johan
    Department of Odontology, Umeå University, Umeå, Sweden.
    Liu, Hui
    Department of Medicine, USUHS, Bethesda MD, United States.
    Goldman, Matthew D.
    Department of Pediatrics, USUHS, Bethesda MD, United States.
    Whitmire, Jeannette M.
    Department of Microbiology and Immunology, USUHS, Bethesda MD, United States.
    Ådén, Jörgen
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Younson, Justine
    Dental Institute, King's College London, London, United Kingdom.
    Kelly, Charles G.
    Dental Institute, King's College London, London, United Kingdom.
    Gilman, Robert H.
    Department of International Health, John Hopkins School of Public Health, Baltimore MD, United States.
    Chowdhury, Abhijit
    Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India.
    Mukhopadhyay, Asish K.
    Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
    Nair, G. Balakrish
    Translational Health Science and Technology Institute, Haryana, India; WHO Research Policy & Cooperation Unit, New Delhi, India.
    Papadakos, Konstantinos S.
    Hellenic Pasteur Institute, Athens, Greece; Department of Translational Medicine, Wallenberg Lab, Lund University, Malmö, Sweden.
    Martinez-Gonzalez, Beatriz
    Hellenic Pasteur Institute, Athens, Greece.
    Sgouras, Dionyssios N.
    Hellenic Pasteur Institute, Athens, Greece.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Sci Life Lab, Solna, Sweden.
    Unemo, Magnus
    Örebro University Hospital. Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Danielsson, Dan
    Örebro University Hospital. Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Suerbaum, Sebastian
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany ; Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Hannover, Germany; German Center for Infection Research (DZIF), Munich, Germany.
    Oscarson, Stefan
    Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Dublin, Ireland.
    Morozova-Roche, Ludmilla A.
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Olofsson, Anders
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Gröbner, Gerhard
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Holgersson, Jan
    Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Esberg, Anders
    Department of Odontology, Umeå University, Umeå, Sweden.
    Strömberg, Nicklas
    Department of Odontology, Umeå University, Umeå, Sweden.
    Landström, Maréne
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany.
    Eldridge, Angela M.
    Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento CA, United States; Genentech Inc, Vacaville CA, USA.
    Chromy, Brett A.
    Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento CA, United States ; Singulex Inc, Alameda CA, USA.
    Hansen, Lori M.
    Departments of Medical Microbiology and Immunology, Center for Comparative Medicine, University of California Davis, Davis CA, United States.
    Solnick, Jay V.
    Departments of Medical Microbiology and Immunology, Center for Comparative Medicine, University of California, Davis CA, United States; California National Primate Research Center, University of California, Davis CA, USA .
    Lindén, Sara K.
    Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Haas, Rainer
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany; German Center for Infection Research (DZIF), Munich, Germany .
    Dubois, Andre
    Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda MD, United States.
    Merrell, D. Scott
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda MD, United States.
    Schedin, Staffan
    Department of Applied Physics and Electronics, Umeå University, Umeå, Sweden.
    Remaut, Han
    Structural and Molecular Microbiology, VIB Department of Structural Biology, Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium .
    Arnqvist, Anna
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Berg, Douglas E.
    Department of Medicine, University of California San Diego, La Jolla, CA, United States.
    Borén, Thomas
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Helicobacter pylori adapts to chronic infection and gastric disease via ph-responsive baba-mediated adherence2017In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 21, no 3, 376-389 p., S1931-3128(17)30075-6Article in journal (Refereed)
    Abstract [en]

    The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.

  • 32.
    Büsch, Katharina
    et al.
    AbbVie AB, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Waldenström, Jesper
    Department of Infectious Medicine, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Lagging, Martin
    Department of Infectious Medicine, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
    Aleman, Soo
    Department of Infectious Diseases Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Gastroenterology and Hepatology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Weiland, Ola
    Department of Medicine Huddinge, Division of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Kövamees, Jan
    AbbVie AB, Stockholm, Sweden.
    Duberg, Ann-Sofi
    Örebro University, School of Health Sciences. Department of Infectious Diseases.
    Söderholm, Jonas
    AbbVie AB, Stockholm, Sweden; Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Prevalence and comorbidities of chronic hepatitis C: a nationwide population-based register study in Sweden2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 1, 61-68 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of this study was to estimate the prevalence of physician-diagnosed and registered chronic hepatitis C (CHC), and to estimate the reported frequencies of Charlson comorbidities compared with matched comparators from the general population.

    Materials and methods: Patients were identified according to ICD codes for CHC in the Swedish National Patient Register (1997-2013). Prevalence was estimated according to different patient identification algorithms and for different subgroups. Charlson comorbidities were ascertained from the same register and compared with age/sex/county of residence matched general population comparators.

    Results: A total of 34,633 individuals with physician-diagnosed CHC were alive in Sweden in 2013 (mean age, 49 years; 64% men), corresponding to a physician-diagnosed prevalence of 0.36%. The prevalence varied by case definition (0.22%-0.36%). The estimate dropped to 0.14% for monitored CHC disease (defined as ≥1 CHC-related visit in 2013). Overall, 41.3% of the CHC patients had ≥1 physician-registered Charlson comorbidity; the most common was liver diseases (22.1%). Compared with matched comparators from the general population (n = 171,338), patients with CHC had more physician-diagnosed and registered diseases such as chronic pulmonary disease (10.2% vs. 4.0%), diabetes (10.6% vs. 5.5%) and liver-related cancer (1.3% vs. 0.2%; all p < .01). No information on behavioural factors, such as smoking, alcohol consumption or on-going illicit drug use, was available.

    Conclusion: The physician-diagnosed prevalence of CHC was slightly lower than previously reported estimates, and varied by case definition. The additional comorbidities observed in the CHC group should be taken into consideration, as these comorbidities add to the disease burden.

  • 33.
    Cajander, Sara
    et al.
    Örebro University, School of Medical Sciences. Infektionskliniken, Universitetssjukhuset i Örebro, Sweden.
    Eliasson, Henrik
    Örebro University Hospital. Infektionskliniken.
    Mb Osler: ökad risk för infektioner och livshotande komplikationer: Fyra fall av invasiv infektionssjukdom under samma tidsperiod beskrivs2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 37, 1613-1615 p.Article in journal (Refereed)
    Abstract [sv]

    Mb Osler är internationellt mer känd under namnen heredi-tary hemorrhagic telangiectasia (HHT) eller Osler–Weber–Rendu syndrome. Sjukdomen beror på en nedärvd genetisk defekt, där den muterade genen påverkar TGF-superfamiljens signalering i kärlendotel. Detta leder till telangiektasier och ibland större arteriovenösa missbildningar [1]. Eftersom kärl-missbildningarna kan uppstå i olika organ varierar symtom-bilden mellan olika familjer och individer. En till två tredjede-lar av de drabbade söker någon gång medicinsk hjälp på grund av komplikationer till sjukdomen [2]. De vanligaste kliniska uttrycken är recidiverande näsblöd-ningar och järnbristanemi. Incidensen varierar geografiskt och finns rapporterad från 1/2351 till 1/39216 [3]. Diagnosen ställs med hjälp av de sk Curaçao-kriterierna [4] (Fakta 1). Hos en del patienter leder sjukdomen till svåra organkompli-kationer, och på senare tid har ökad risk för infektioner upp-märksammats. Vi beskriver fyra patienter med diagnosen Mb Osler som vårdades på grund av allvarlig infektionssjukdom under sam-ma tidsperiod.

  • 34.
    Cajander, Sara
    et al.
    Örebro University, School of Health Sciences. Department of Infectious Diseases.
    Tina, Elisabet
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory.
    Magnuson, Anders
    Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Strålin, Kristoffer
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden .
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Källman, Jan
    Örebro University, School of Medical Sciences. Department of Infectious Diseases.
    Quantitative Real-Time Polymerase Chain Reaction Measurement of HLA-DRA Gene Expression in Whole Blood Is Highly Reproducible and Shows Changes That Reflect Dynamic Shifts in Monocyte Surface HLA-DR Expression during the Course of Sepsis2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, e0154690Article in journal (Refereed)
    Abstract [en]

    Introduction: A decrease in the expression of monocyte surface protein HLA-DR (mHLA-DR), measured by flow cytometry (FCM), has been suggested as a marker of immunosuppression and negative outcome in severe sepsis. However, FCM is not always available due to sample preparation that limits its use to laboratory operational hours. In this prospective study we evaluated dynamic changes in mHLA-DR expression during sepsis in relation to changes in HLA-DRA gene expression and Class II transactivator (CIITA), measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).

    Aims: The aims of this study were: 1. to validate the robustness of qRT-PCR measurement of HLA-DRA- and CIITA-mRNA expression, in terms of reproducibility; and 2. to see if changes in expression of these genes reflect changes in mHLA-DR expression during the course of severe and non-severe bacteraemic sepsis.

    Methods and Findings: Blood samples were collected from 60 patients with bacteraemic sepsis on up to five occasions during Days 1-28 after hospital admission. We found the reproducibility of the qRT-PCR method to be high by demonstrating low threshold variations (<0.11 standard deviation (SD)) of the qRT-PCR system, low intra-assay variation of Ct-values within triplicates (≤0.15 SD) and low inter-assay variations (12%) of the calculated target gene ratios. Our results also revealed dynamic HLA-DRA expression patterns during the course of sepsis that reflected those of mHLA-DR measured by FCM. Furthermore, HLA-DRA and mHLA-DR recovery slopes in patients with non-severe sepsis differed from those in patients with severe sepsis, shown by mixed model for repeated measurements (p<0.05). However, during the first seven days of sepsis, PCR-measurements showed a higher magnitude of difference between the two sepsis groups. Mean differences (95% CI) between severe sepsis (n = 20) and non-severe sepsis (n = 40) were; on day 1-2, HLA-DRA 0.40 (0.28-0.59) p<0.001, CIITA 0.48 (0.32-0.72) p = 0.005, mHLA-DR 0.63 (0.45-1.00) p = 0.04, day 7 HLA-DRA 0.59 (0.46-0.77) p<0.001, CIITA 0.56 (0.41-0.76) p<0.001, mHLA-DR 0.81 (0.66-1.00) p = 0.28.

    Conclusion: We conclude that qRT-PCR measurement of HLA-DRA expression is robust, and that this method appears to be preferable to FCM in identifying patients with severe sepsis that may benefit from immunostimulation.

  • 35.
    Chen, Shao-Chun
    et al.
    National Center for STD Control, Chinese Center for Disease Control and Prevention, and Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, and Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.
    Yin, Yue-Ping
    National Center for STD Control, Chinese Center for Disease Control and Prevention, and Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, and Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.
    Dai, Xiu-Qin
    National Center for STD Control, Chinese Center for Disease Control and Prevention, and Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, and Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.
    Unemo, Magnus
    Örebro University, School of Health Sciences. WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology.
    Chen, Xiang-Sheng
    National Center for STD Control, Chinese Center for Disease Control and Prevention, and Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, and Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, China.
    First nationwide study regarding ceftriaxone resistance and molecular epidemiology of Neisseria gonorrhoeae in China2016In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 1, 92-99 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern worldwide. This is the first nationwide study, performed within the China Gonococcal Antimicrobial Susceptibility Programme (China-GASP), regarding AMR, including ceftriaxone genetic resistance determinants, and molecular epidemiology of gonococci in China.

    Methods: Gonococcal isolates (naEuroS=aEuroS1257) from consecutive patients were collected at 11 sentinel sites distributed across China during 2012-13. Susceptibility to ceftriaxone, spectinomycin, ciprofloxacin and tetracycline was determined using the agar dilution method. Ceftriaxone resistance determinants penA and penB were examined using sequencing. N. gonorrhoeae multiantigen sequence typing (NG-MAST) was performed for molecular epidemiology.

    Results: Among isolates, 0.2% were resistant to spectinomycin, 4.4% to ceftriaxone, 42.9% to tetracyclines (high-level resistance) and 99.8% to ciprofloxacin. Among 890 sequenced isolates, 16 (1.8%) possessed a penA mosaic allele; 4 of these isolates belonged to the MDR internationally spread NG-MAST genogroup G1407 (first description in China). Non-mosaic penA alleles with an A501T mutation and an A102D alteration in porB1b were statistically associated with decreased susceptibility/resistance to ceftriaxone. NG-MAST G10339, G1424 and G1053 were associated with decreased susceptibility/resistance to ceftriaxone.

    Conclusions: In China, ceftriaxone and spectinomycin can continue to be recommended for gonorrhoea treatment, with the possible exception of Hainan and Sichuan provinces where ceftriaxone resistance exceeded 5% and AMR surveillance needs to be strengthened. Molecular approaches including genotyping and AMR determinant analysis can be valuable to supplement and enhance conventional surveillance of gonococcal AMR in China.

  • 36.
    Chen, Shao-Chun
    et al.
    China CDC, Natl Ctr STD Control, Nanjing, Jiangsu, Peoples R China.;Chinese Acad Med Sci, Inst Dermatol, Nanjing, Jiangsu, Peoples R China.;Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China.;Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Jiangsu, Peoples R China..
    Yin, Yue-Ping
    China CDC, Natl Ctr STD Control, Nanjing, Jiangsu, Peoples R China.;Chinese Acad Med Sci, Inst Dermatol, Nanjing, Jiangsu, Peoples R China.;Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China.;Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Jiangsu, Peoples R China..
    Dai, Xiu-Qin
    China CDC, Natl Ctr STD Control, Nanjing, Jiangsu, Peoples R China.;Chinese Acad Med Sci, Inst Dermatol, Nanjing, Jiangsu, Peoples R China.;Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China.;Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Jiangsu, Peoples R China..
    Yu, Rui-Xing
    China CDC, Natl Ctr STD Control, Nanjing, Jiangsu, Peoples R China.;Chinese Acad Med Sci, Inst Dermatol, Nanjing, Jiangsu, Peoples R China.;Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China.;Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Jiangsu, Peoples R China..
    Han, Yan
    China CDC, Natl Ctr STD Control, Nanjing, Jiangsu, Peoples R China.;Chinese Acad Med Sci, Inst Dermatol, Nanjing, Jiangsu, Peoples R China.;Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China.;Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Jiangsu, Peoples R China..
    Sun, Hou-Hua
    China CDC, Natl Ctr STD Control, Nanjing, Jiangsu, Peoples R China.;Chinese Acad Med Sci, Inst Dermatol, Nanjing, Jiangsu, Peoples R China.;Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China.;Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Jiangsu, Peoples R China..
    Ohnishi, Makoto
    Natl Inst Infect Dis, Tokyo, Japan..
    Unemo, Magnus
    Örebro University Hospital. Dept Lab Med, WHO Collaborating Ctr Gonorrhoea & Other STIs.
    Chen, Xiang-Sheng
    China CDC, Natl Ctr STD Control, Nanjing, Jiangsu, Peoples R China.;Chinese Acad Med Sci, Inst Dermatol, Nanjing, Jiangsu, Peoples R China.;Peking Union Med Coll, Nanjing, Jiangsu, Peoples R China.;Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing, Jiangsu, Peoples R China..
    Prevalence and Molecular Epidemiological Typing of Penicillinase-Producing Neisseria gonorrhoeae and Their bla(TEM-135) Gene Variants in Nanjing, China2013In: Sexually Transmitted Diseases, ISSN 0148-5717, E-ISSN 1537-4521, Vol. 40, no 11, 872-876 p.Article in journal (Refereed)
    Abstract [en]

    Background: This study aimed to investigate the prevalence of penicillinase-producing Neisseria gonorrhoeae (PPNG) and their bla(TEM-135) gene variant in 2007 and 2012 in Nanjing, China. In addition, molecular epidemiological typing of all isolates was performed to elucidate the genetic relationships of the PPNG strains. Methods: A total of 199 and 77 N. gonorrhoeae isolates were collected at the National Center for STD Control in 2007 and 2012, respectively. Nitrocefin tests were performed to identify PPNG. Mismatch amplification mutation assay was used to identify bla(TEM-135). All isolates were genotyped using N. gonorrhoeae multiantigen sequence typing (NG-MAST), and additionally, porB-based phylogenetic analysis was performed for the PPNG isolates. Results: The total prevalence of PPNG isolates was 41% (114/276) and 58% (66/114) of these PPNG isolates possessed bla(TEM-135). In 2007, 45% (90/199) produced beta-lactamase, and of those PPNG, 58% (52/90) possessed bla(TEM-135). In 2012, 31% (24/77) were PPNG, and 58% (14/24) of those isolates contained bla(TEM-135). There were 162 NG-MAST STs among the 276 isolates, and 89 of those were novel STs. A strong association between specific NG-MAST STs and bla(TEM-135) was found, and the porB-based phylogenetic analysis showed a distant evolutionary relationship between isolates in 2007 and isolates in 2012. Conclusions: A high prevalence of PPNG and bla(TEM-135) was found in Nanjing, China. bla(TEM-135) might be a precursor in the evolution into an extended-spectrum beta-lactamase that can degrade ceftriaxone, which stresses the need to continuously monitor PPNG, bla(TEM-135), and additional evolving bla(TEM) gene variants.

  • 37.
    Chisholm, S. A.
    et al.
    Hlth Protect Agcy, Sexually Transmitted Bacteria Reference Lab, London, England..
    Unemo, Magnus
    Örebro University Hospital. Natl Reference Lab Pathogen Neisseria, Dept Lab Med.
    Quaye, N.
    Hlth Protect Agcy, Sexually Transmitted Bacteria Reference Lab, London, England..
    Johansson, E.
    Orebro Univ Hosp, Natl Reference Lab Pathogen Neisseria, Dept Lab Med, Orebro, Sweden..
    Cole, M. J.
    Hlth Protect Agcy, Sexually Transmitted Bacteria Reference Lab, London, England..
    Ison, C. A.
    Hlth Protect Agcy, Sexually Transmitted Bacteria Reference Lab, London, England..
    Van de Laar, M. Jw
    European Ctr Dis Prevent & Control, Stockholm, Sweden..
    Molecular epidemiological typing within the European Gonococcal Antimicrobial Resistance Surveillance Programme reveals predominance of a multidrug-resistant clone2013In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 18, no 3, 14-23 p., 20358Article in journal (Refereed)
    Abstract [en]

    Treatment of gonorrhoea is threatened by antimicrobial resistance, and decreased susceptibility and resistance to recommended therapies is emerging in Europe. Current associations between resistance and molecular type remain poorly understood. Gonococcal isolates (n=1,066) collected for the 2009 and 2010 European Gonococcal Antimicrobial Surveillance Programme were typed by Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST). A total of 406 sequence types (STs) were identified, 125 of which occurred in >= two isolates. Seven major genogroups of closely related STs (varying by <= 1% at just one of the two target loci) were defined. Genogroup 1407 (G1407), observed in 20/21 countries and predominant in 13/21 countries, accounted for 23% of all isolates and was associated with decreased susceptibility to cefixime and resistance to ciprofloxacin and raised minimum inhibitory concentrations for ceftriaxone and azithromycin. Genogroup 225 (G225), associated with ciprofloxacin resistance, was observed in 10% of isolates from 19/21 countries. None of the other genogroups were associated with antimicrobial resistance. The predominance of a multidrug-resistant clone (G1407) in Europe is worrying given the recent reports of recommended third generation cephalosporins failing to treat infections with this clone. Identifying associations between ST and antimicrobial resistance aids the understanding of the dissemination of resistant clones within a population and could facilitate development of targeted intervention strategies.

  • 38.
    Cole, Michelle J.
    et al.
    Public Health England, Sexually Transmitted Bacteria Reference Unit, Microbiological Services, London, England, United Kingdom.
    Spiteri, Gianfranco
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Pitt, Rachel
    Public Health England, Sexually Transmitted Bacteria Reference Unit, Microbiological Services, London, England, United Kingdom.
    Grigorjev, Vlad
    Public Health England, Sexually Transmitted Bacteria Reference Unit, Microbiological Services, London, England, United Kingdom.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Is the tide turning again for cephalosporin resistance in Neisseria gonorrhoeae in Europe?: Results from the 2013 European surveillance2015In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, 321Article in journal (Refereed)
    Abstract [en]

    Background: The emerging resistance to the extended-spectrum cephalosporins (ESCs) in Neisseria gonorrhoeae together with increasing incidence of gonorrhoea cases in many countries have been global public health concerns. However, in recent years the levels of ESC resistance have decreased in several regions worldwide. We describe the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) data from 2013, and compare them to corresponding data from 2009-2012.

    Methods: During 2013, N. gonorrhoeae isolates from 21 participating countries were examined. Antimicrobial susceptibility testing (Etest or agar dilution) was performed for cefixime, ceftriaxone, ciprofloxacin, azithromycin, spectinomycin and gentamicin. Statistical analyses were performed to identify significant changes in resistance between years and to investigate associations between patients with resistant gonococcal isolates and collected epidemiological variables.

    Results: In total, 93 (4.7 %) of 1994 isolates displayed resistance to cefixime, representing an increase compared to the 3.9 % detected in 2012 (p = 0.23). Cefixime resistance was detected in 13 (61.9 %) of the 21 countries. Cefixime resistance among men who have sex with men was only 1.2 %, compared to 5.6 % and 6.1 % in females and male heterosexuals, respectively. The univariate analysis confirmed that isolates resistant to cefixime were more likely to be from females (OR 4.87, p < 0.01) or male heterosexuals (OR 5.32, p < 0.01). Seven (0.4 %) isolates displayed ceftriaxone resistance (in addition to cefixime resistance) compared to three and 10 isolates in 2012 and 2011, respectively. All 93 isolates with cefixime resistance were additionally resistant to ciprofloxacin and 16 (17.2 %) were also resistant to azithromycin. Among all tested isolates (n = 1994), the ciprofloxacin resistance level (52.9 %) was higher than in 2012 (50.1 %; p = 0.08), and azithromycin resistance (5.4 %) increased since 2012 (4.5 %; p = 0.16).

    Conclusions: In 2013, the ESC resistance was again slightly increasing in Europe. This emphasises the importance of implementing the actions outlined in the European and additional response plans, particularly activities strengthening the surveillance of antimicrobial resistance. Ceftriaxone combined with azithromycin remains a satisfactory option for the first-line treatment of gonorrhoea. However novel antimicrobials (new derivatives of previously developed antimicrobials or newly developed antimicrobials) for effective monotherapy or at least inclusion in new dual antimicrobial therapy regimens (combined with previously developed antimicrobials or novel antimicrobials) will likely be required.

  • 39.
    Cole, Michelle J.
    et al.
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, Public Health England, London, United Kingdom.
    Spiteri, Gianfranco
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs.
    Woodford, Neil
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, Public Health England, London, United Kingdom.
    Tripodo, Francesco
    Antimicrobial Resistance and Healthcare Associated Infections (AMRHAI) Reference Unit, Public Health England, London, United Kingdom.
    Amato-Gauci, Andrew J.
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Unemo, Magnus
    Örebro University, WHO Collaborating Centre for Gonorrhoea and other STIs, Örebro, Sweden.
    Overall Low Extended-Spectrum Cephalosporin Resistance but high Azithromycin Resistance in Neisseria gonorrhoeae in 24 European Countries, 20152017In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 17, 617Article in journal (Refereed)
    Abstract [en]

    Background: Surveillance of Neisseria gonorrhoeae antimicrobial susceptibility in Europe is performed through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), which additionally provides data to inform the European gonorrhoea treatment guideline; currently recommending ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. We present antimicrobial susceptibility data from 24 European countries in 2015, linked to epidemiological data of patients, and compare the results to Euro-GASP data from previous years.

    Methods: Antimicrobial susceptibility testing by MIC gradient strips or agar dilution methodology was performed on 2134 N. gonorrhoeae isolates and interpreted using EUCAST breakpoints. Patient variables associated with resistance were established using logistic regression to estimate odds ratios (ORs).

    Results: In 2015, 1.7% of isolates were cefixime resistant compared to 2.0% in 2014. Ceftriaxone resistance was detected in only one (0.05%) isolate in 2015, compared with five (0.2%) in 2014. Azithromycin resistance was detected in 7.1% of isolates in 2015 (7.9% in 2014), and five (0.2%) isolates displayed high-level azithromycin resistance (MIC = 256 mg/L) compared with one (0.05%) in 2014. Ciprofloxacin resistance remained high (49.4%, vs. 50.7% in 2014). Cefixime resistance significantly increased among heterosexual males (4.1% vs. 1.7% in 2014), which was mainly attributable to data from two countries with high cefixime resistance (similar to 11%), however rates among men-who-have-sex-with-men (MSM) and females continued to decline to 0.5% and 1%, respectively. Azithromycin resistance in MSM and heterosexual males was higher (both 8.1%) than in females (4.9% vs. 2.2% in 2014). The association between azithromycin resistance and previous gonorrhoea infection, observed in 2014, continued in 2015 (OR 2.1, CI 1.2-3.5, p < 0.01).

    Conclusions: The 2015 Euro-GASP sentinel system revealed high, but stable azithromycin resistance and low overall resistance to ceftriaxone and cefixime. The low cephalosporin resistance may be attributable to the effectiveness of the currently recommended first-line dual antimicrobial therapy; however the high azithromycin resistance threatens the effectiveness of this therapeutic regimen. Whether the global use of azithromycin in mono-or dual antimicrobial therapy of gonorrhoea is contributing to the global increases in azithromycin resistance remains to be elucidated. The increasing cefixime resistance in heterosexual males also needs close monitoring.

  • 40.
    Cole, Michelle J.
    et al.
    Sexually Transmitted Bacteria Reference Unit, Public Health England, London, UK.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology.
    Grigorjev, Vlad
    Sexually Transmitted Bacteria Reference Unit, Public Health England, London, UK.
    Quaye, Nerteley
    National Mycobacterium Reference Laboratory, Public Health England, London, UK.
    Woodford, Neil
    Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, Public Health England, London, UK.
    Genetic diversity of bla(TEM) alleles, antimicrobial susceptibility and molecular epidemiological characteristics of penicillinase-producing Neisseria gonorrhoeae from England and Wales2015In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 70, no 12, 3238-3243 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: The objective of this study was to investigate the genetic diversity of bla(TEM) alleles, antimicrobial susceptibility and molecular epidemiological characteristics of penicillinase-producing Neisseria gonorrhoeae (PPNG) isolates collected in 2012 from England and Wales.

    Methods: PPNG isolates were from the 2012 Gonococcal Resistance to Antimicrobial Surveillance Programme (GRASP). Their susceptibility to seven antimicrobials was determined using agar dilution methodology. beta-Lactamase production was detected using a nitrocefin test. beta-Lactamase plasmid types were determined and bla(TEM) genes were sequenced. Isolates were also typed by N. gonorrhoeae multi-antigen sequence typing (NG-MAST).

    Results: Seventy-three PPNG isolates were identified in the 2012 GRASP collection (4.6%, 73/1603). Three different bla(TEM) alleles were identified, encoding three TEM amino acid sequences: TEM-1 (53%), TEM-1 with a P14S substitution (19%) and TEM-135 (27%). The bla(TEM-135) allele was present in nine different NG-MAST types and was found mostly on Asian (60%) and Toronto/Rio (35%) plasmids. By contrast, most TEM-1-encoding plasmids were African (98%). All the TEM-135 isolates displayed high-level ciprofloxacin and tetracycline resistance.

    Conclusions: The high proportion of bla(TEM-135) alleles (27%) demonstrates that this variant is circulating within several gonococcal lineages. Only a single specific mutation near the beta-lactamase active site could result in TEM-135 evolving into an ESBL. This is concerning particularly because the TEM-135 isolates were associated with high-level ciprofloxacin and tetracycline resistance. It is encouraging that no further TEM alleles were detected in this gonococcal population; however, vigilance is vital as an ESBL in N. gonorrhoeae would render the last remaining option for monotherapy, ceftriaxone, useless.

  • 41.
    Davey, Dvora Joseph
    et al.
    Ark, Maputo, Mozambique; †Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA.
    Nhavoto, José Antonio
    Örebro University, Örebro University School of Business. Department of Mathematics and Informatics, Eduardo Mondlane University, Maputo, Mozambique.
    Augusto, Orvalho
    Department of Community Health, Eduardo Mondlane University, Maputo, Mozambique.
    Ponce, Walter
    Ark, Maputo, Mozambique.
    Traca, Daila
    Ark, Maputo, Mozambique.
    Nguimfack, Alexandre
    Ark, Maputo, Mozambique.
    de Sousa, Cesar Palha
    Department of Community Health, Eduardo Mondlane University, Maputo, Mozambique.
    SMSaude: Evaluating Mobile Phone Text Reminders to Improve Retention in HIV Care for Patients on Antiretroviral Therapy in Mozambique2016In: Journal of Acquired Immune Deficiency Syndromes, ISSN 1525-4135, E-ISSN 1944-7884, Vol. 73, no 2, E23-E30 p.Article in journal (Refereed)
    Abstract [en]

    Objective: We evaluated whether regular mobile phone text reminders improved patients' retention in antiretroviral therapy (ART) care in Mozambique.

    Design: SMSaude was a randomized control trial of HIV-infected patients on ART who received regular text message reminder vs. standard of care at 3 public health facilities in Maputo Province, Mozambique. The primary outcome was retention in HIV care. Between November 2011 and March 2012, 830 eligible HIV-infected patients on ART were randomized 1: 1 to the text reminder intervention or standard of care.

    Methods: We used Kaplan-Meier estimators and log-rank tests to compare proportions of patients who received SMS reminders who were retained in HIV care compared to the control group who received standard of care. Post hoc analyses were performed using Cox proportional hazards models stratified by urban/rural facility and when initiated ART (<= 3 months vs. >3 months). Hazard ratios and confidence intervals (CIs) are reported. Analysis was with intention to treat.

    Results: Patients who received text messages had lower attrition from HIV care at 12 months, though the difference was nonsignificant (RR: 0.68, 95% CI: 0.41 to 1.13). Among urban patients, text messages improved retention in HIV care (RR: 0.54, 95% CI: 0.31 to 0.95). Intervention patients newly initiated on ART (<3 months) had lower attrition than control patients (HR: 0.54; 95% CI: 0.23 to 0.91), especially urban newly initiated patients (HR: 0.20, 95% CI: 0.06 to 0.64). Text messages had no effect on retention among rural patients.

    Conclusions: Text messages did not improve retention in HIV care for all patients on ART but improved retention in care of urban patients and those who recently started ART and received text reminders compared with standard of care.

  • 42.
    Davies, Kerrie A.
    et al.
    Univ Leeds, EUCLID European Coordinators, Leeds, W Yorkshire, England..
    Longshaw, Christopher M.
    Astellas Pharma Europe, Chertsey, England..
    Davis, Georgina L.
    Univ Leeds, EUCLID European Coordinators, Leeds, W Yorkshire, England..
    Bouza, Emilio
    Univ Gregorio Maranon, Gen Hosp, Microbiol Clin E Infecc, Catedrat Jefe Serv, Madrid, Spain..
    Barbut, Frederic
    Univ Paris 06, Natl Reference Lab Clostridium Difficile, Paris, France..
    Barna, Zsuzsanna
    Natl Ctr Epidemiol, Dept Bacteriol, Budapest, Hungary..
    Delmee, Michel
    Catholic Univ Louvain, IREC, B-1200 Brussels, Belgium..
    Fitzpatrick, Fidelma
    Hlth Protect Surveillance Ctr, Dublin, Ireland.;Beaumont Hosp, Dublin 9, Ireland..
    Ivanova, Kate
    Natl Ctr Infect & Parasit Dis, Sofia, Bulgaria..
    Kuijper, Ed
    Leiden Univ, Med Ctr, Dept Med Microbiol, Leiden, Netherlands..
    Macovei, Ioana S.
    Cantacuzino Natl Inst Res & Dev Microbiol & Immun, Bucharest, Romania..
    Mentula, Silja
    Natl Inst Hlth & Welf THL, Bacteriol Unit, Helsinki, Finland..
    Mastrantonio, Paola
    Ist Super Sanita, Dept Infect Dis, I-00161 Rome, Italy..
    von Mueller, Lutz
    Univ Saarland, Med Ctr, Inst Med Microbiol & Hyg, Homburg, Germany..
    Oleastro, Monica
    Natl Inst Hlth Dr Ricardo Jorge, Dept Infect Dis, Lisbon, Portugal..
    Petinaki, Efthymia
    Univ Thessalia, Univ Hosp, Sch Med, Larisa, Greece..
    Pituch, Hanna
    Med Univ Warsaw, Dept Med Microbiol, Warsaw, Poland..
    Norén, Torbjörn
    Örebro University Hospital.
    Novakova, Elena
    Comenius Univ, Jessenius Fac Med Martin, Martin, TN, Slovakia..
    Nyc, Otakar
    Univ Hosp Motol, Dept Med Microbiol, Prague, Czech Republic..
    Rupnik, Maja
    Univ Maribor, Fac Med, SLO-2000 Maribor, Slovenia.;Natl Lab Hlth Environm & Food NLZOH, Maribor, Slovenia..
    Schmid, Daniela
    Austrian Agcy Hlth & Food Safety, Inst Med Microbiol & Hyg, Vienna, Austria..
    Wilcox, Mark H.
    Univ Leeds, EUCLID European Coordinators, Leeds, W Yorkshire, England..
    Underdiagnosis of Clostridium difficile across Europe: the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID)2014In: Lancet. Infectious diseases (Print), ISSN 1473-3099, E-ISSN 1474-4457, Vol. 14, no 12, 1208-1219 p.Article in journal (Refereed)
    Abstract [en]

    Background: Variations in testing for Clostridium difficile infection can hinder patients' care, increase the risk of transmission, and skew epidemiological data. We aimed to measure the underdiagnosis of C difficile infection across Europe.

    Methods: We did a questionnaire-based study at 482 participating hospitals across 20 European countries. Hospitals were questioned about their methods and testing policy for C difficile infection during the periods September, 2011, to August, 2012, and September, 2012, to August, 2013. On one day in winter, 2012-13 (December, 2012, or January, 2013), and summer, 2013 (July or August), every hospital sent all diarrhoeal samples submitted to their microbiology laboratory to a national coordinating laboratory for standardised testing of C difficile infection. Our primary outcome measures were the rates of testing for and cases of C difficile infection per 10 000 patient bed-days. Results of local and national C difficile infection testing were compared with each other. If the result was positive at the national laboratory but negative at the local hospital, the result was classified as undiagnosed C difficile infection. We compared differences in proportions with the Mann-Whitney test, or McNemar's test if data were matched.

    Findings: During the study period, participating hospitals reported a mean of 65.8 tests (country range 4. 6-223.3) for C difficile infection per 10 000 patient-bed days and a mean of 7.0 cases (country range 0.7-28.7) of C difficile infection per 10 000 patient-bed days. Only two-fifths of hospitals reported using optimum methods for testing of C difficile infection (defined by European guidelines), although the number of participating hospitals using optimum methods increased during the study period, from 152 (32%) of 468 in 2011-12 to 205 (48%) of 428 in 2012-13. Across all 482 European hospitals on the two sampling days, 148 (23%) of 641 samples positive for C difficile infection (as determined by the national laboratory) were not diagnosed by participating hospitals because of an absence of clinical suspicion, equating to about 74 missed diagnoses per day.

    Interpretation: A wide variety of testing strategies for C difficile infection are used across Europe. Absence of clinical suspicion and suboptimum laboratory diagnostic methods mean that an estimated 40 000 inpatients with C difficile infection are potentially undiagnosed every year in 482 European hospitals.

  • 43.
    de Leon, Alex
    et al.
    Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Thörn, Sven-Egron
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden.
    Raoof, M.
    Lindesberg Hosp, Dept Surg, Lindesberg, Sweden.
    Ottosson, J.
    Lindesberg Hosp, Dept Surg, Lindesberg, Sweden; Örebro University Hospital, Örebro, Sweden.
    Wattwil, Magnus
    Örebro University, School of Health and Medical Sciences.
    Effects of different respiratory maneuvers on esophageal sphincters in obese patients before and during anesthesia2010In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 54, no 10, 1204-1209 p.Article in journal (Refereed)
    Abstract [en]

    Background: Data on esophageal sphincters in obese individuals during anesthesia are sparse. The aim of the present study was to evaluate the effects of different respiratory maneuvers on the pressures in the esophagus and esophageal sphincters before and during anesthesia in obese patients.

    Methods: Seventeen patients, aged 28-68 years, with a BMI >= 35 kg/m2, who were undergoing a laparoscopic gastric by-pass surgery, were studied, and pressures from the hypopharynx to the stomach were recorded using high-resolution solid-state manometry. Before anesthesia, recordings were performed during normal spontaneous breathing, Valsalva and forced inspiration. The effects of anesthesia induction with remifentanil and propofol were evaluated, and positive end-expiratory pressure (PEEP) 10 cmH(2)O was applied during anesthesia.

    Results: During spontaneous breathing, the lower esophageal sphincter (LES) pressure was significantly lower during end-expiration compared with end-inspiration (28.5 +/- 7.7 vs. 35.4 +/- 10.8 mmHg, P < 0.01), but barrier pressure (BrP) and intra-gastric pressure (IGP) were unchanged. LES, BrP (P < 0.05) and IGP (P < 0.01) decreased significantly during anesthesia. BrP remained positive in all patients. IGP increased during Valsalva (P < 0.01) but was unaffected by PEEP. Esophageal pressures were positive during both spontaneous breathing and mechanical ventilation. Esophageal pressures increased during PEEP from 9.4 +/- 3.8 to 11.3 +/- 3.3 mmHg (P < 0.01).

    Conclusion: During spontaneous breathing, the LES pressure was the lowest during end-expiration but there were no differences in BrP and IGP. LES, BrP and IGP decreased during anesthesia but BrP remained positive in all patients. During the application of PEEP, esophageal pressures increased and this may have a protective effect against regurgitation.

  • 44.
    Donà, Valentina
    et al.
    Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
    Low, Nicola
    Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea, Örebro University, Örebro, Sweden.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea, Örebro University, Örebro, Sweden.
    Recent advances in the development and use of molecular tests to predict antimicrobial resistance in Neisseria gonorrhoeae.2017In: Expert Review of Molecular Diagnostics, ISSN 1473-7159, E-ISSN 1744-8352, Vol. 17, no 9, 845-859 p.Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The number of genetic tests, mostly real-time PCRs, to detect antimicrobial resistance (AMR) determinants and predict AMR in Neisseria gonorrhoeae is increasing. Several of these assays are promising, but there are important shortcomings and few assays have been adequately validated and quality assured. Areas covered: Recent advances, focusing on publications since 2012, in the development and use of molecular tests to predict gonococcal AMR for surveillance and for clinical use, advantages and disadvantages of these tests and of molecular AMR prediction compared with phenotypic AMR testing, and future perspectives for effective use of molecular AMR tests for different purposes. Expert commentary: Several challenges for direct testing of clinical, especially extra-genital, specimens remain. The choice of molecular assay needs to consider the assay target, quality controls, sample types, limitations intrinsic to molecular technologies, and specific to the chosen methodology, and the intended use of the test. Improved molecular- and particularly genome-sequencing-based methods will supplement AMR testing for surveillance purposes, and translate into point-of-care tests that will lead to personalized treatments, while sparing the last available empiric treatment option (ceftriaxone). However, genetic AMR prediction will never completely replace phenotypic AMR testing, which detects also AMR due to unknown AMR determinants.

  • 45.
    Du, Juan
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Nordfors, Cecilia
    Karolinska Institutet, Stockholm, Sweden.
    Ährlund-Richter, Andreas
    Karolinska Institutet, Stockholm, Sweden.
    Sobkowiak, Michal
    Karolinska Institutet, Stockholm, Sweden.
    Romanitan, Mircea
    Karolinska Institutet, Stockholm, Sweden.
    Näsman, Anders
    Karolinska Institutet, Stockholm, Sweden.
    Andersson, Sören
    Örebro University Hospital. Örebro University, School of Medical Sciences. Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Ramqvist, Torbjörn
    Karolinska Institutet, Stockholm, Sweden.
    Dalianis, Tina
    Karolinska Institutet, Stockholm, Sweden.
    Prevalence of Oral Human Papillomavirus Infection among Youth, Sweden2012In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 18, no 9, 1468-1471 p.Article in journal (Refereed)
    Abstract [en]

    Human papillomavirus (HPV) causes cervical, head, and neck cancers. We studied 483 patients at a youth clinic in Stockholm, Sweden, and found oral HPV prevalence was 9.3% and significantly higher for female youth with than without cervical HPV infection (p = 0.043). Most oral HPV types matched the co-occurring cervical types.

  • 46.
    Duberg, Ann-Sofi
    et al.
    Örebro University, School of Health and Medical Sciences.
    Janzon, R.
    Bäck, Erik
    Örebro University, School of Health and Medical Sciences.
    Ekdahl, Karl
    Blaxhult, A.
    The epidemiology of hepatitis C virus infection in Sweden2008In: Eurosurveillance, ISSN 1560-7917, Vol. 13, no 21Article in journal (Refereed)
    Abstract [en]

    In Sweden, infection with hepatitis C virus (HCV) has been a notifiable disease since 1990, when diagnostic methods became available. Blood donor screening indicated that about 0.5% of the Swedish population (9 millions) had been HCV infected. Here we present the Swedish hepatitis C epidemic based on data from all the HCV notifications 1990-2006. During this time about 42,000 individuals (70% men) were diagnosed and reported as HCV infected. The majority (80%) were born in 1950 or later, with a high percentage (60%) born in the 1950s and 1960s. Younger people, 15-24 years old at notification, were reported on the same level each year. The main reported routes of HCV transmission were intravenous drug use in 65%, blood transfusions/products in 6%, and sexual in 2%, though unknown or not stated in 26%. Approximately 6,000 of all notified individuals have died during the study period. To conclude, the Swedish HCV epidemic is highly related to the increase of intravenous drug use in the late 1960s and 1970s, with a high proportion of people now chronically infected for more than 25 years, resulting in an increase of severe liver complications in form of cirrhosis and hepatocellular carcinoma. Furthermore the unchanged number of notifications of newly infected younger people indicates an ongoing HCV epidemic.

    PMID: 18761966 [PubMed - indexed for MEDLINE]

  • 47.
    Duberg, Ann-Sofi
    et al.
    Örebro University, School of Health and Medical Sciences.
    Pettersson, Helena
    Smittskyddsinstitutet.
    Aleman, Soo
    Karolinska Sjukhuset.
    Blaxhult, Anders
    Smittskyddsinstitutet.
    Davidsdottir, Loa
    Karolinska sjukhuset.
    Hultcrantz, Rolf
    Karolinska Institutet.
    Bäck, Erik
    Örebro University, School of Health and Medical Sciences.
    Ekdahl, Karl
    Karolinska Institutet.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    The burden of hepatitis C in Sweden: a national study of inpatient careManuscript (preprint) (Other academic)
  • 48.
    Duberg, Ann-Sofi
    et al.
    Örebro University, School of Health and Medical Sciences.
    Törner, Anna
    Davidsdóttir, Lóa
    Aleman, Soo
    Blaxhult, Anders
    Svensson, Åke
    Hultcrantz, Rolf
    Bäck, Erik
    Örebro University, School of Health and Medical Sciences.
    Ekdahl, Karl
    Cause of death in individuals with chronic HBV and/or HCV infection, a nationwide community-based register study2008In: Journal of Viral Hepatitis, ISSN 1352-0504, E-ISSN 1365-2893, Vol. 15, no 7, 538-550 p.Article in journal (Refereed)
    Abstract [en]

    Studies on chronic viral hepatitis and mortality have often been made on selected populations or in high-endemic countries. The aim of this study was to investigate the causes of death and the mortality rates in the nationwide cohorts of people chronically infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) in Sweden, a low-endemic country. All notifications on chronic HBV infection and HCV infection 1990-2003 were linked to the Cause of Death Register. A total of 9517 people with chronic HBV infection, 34 235 people with HCV infection and 1601 with chronic HBV-HCV co-infection were included, and the mean observation times were 6.4, 6.3 and 7.9 years, respectively. The mortality in the cohorts was compared with age- and gender-specific mortality in the general population and standardized mortality ratios (SMR) were calculated. All-cause mortality was significantly increased, SMR 2.3 (HBV), 5.8 (HCV) and 8.5 (HBV-HCV), with a great excess liver-related mortality in all cohorts, SMR 21.7, 35.5 and 46.2, respectively. In HCV and HBV-HCV infected there was an increased mortality due to drug-related psychiatric diagnoses (SMR: 20.7 and 27.6) and external causes (SMR: 12.4 and 11.4), predominantly at younger age. To conclude, this study demonstrated an increased all-cause mortality, with a great excess mortality from liver disease, in all cohorts. In people with HCV infection the highest excess mortality in younger ages was from drug-related and external reasons.

    PMID: 18397223 [PubMed - indexed for MEDLINE]

  • 49.
    Ehlersson, Gustaf
    et al.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Svartström, Olov
    Department of Clinical Microbiology, Linköping University Hospital, Linköping, Sweden.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Phenotypic characterisation of coagulase-negative staphylococci isolated from blood cultures in newborn infants, with a special focus on Staphylococcus capitis2017In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 106, no 10, 1576-1582 p.Article in journal (Refereed)
    Abstract [en]

    AIM: This Swedish study determined which species of coagulase-negative staphylococci (CoNS) were found in neonatal blood cultures and whether they included Staphylococcus capitis clones with decreased susceptibility to vancomycin.

    METHODS: CoNS isolates (n = 332) from neonatal blood cultures collected at Örebro University Hospital during 1987-2014 were identified to species level with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). The antibiotic susceptibility pattern of S. capitis isolates was determined by the disc diffusion test and Etest, and the presence of heterogeneous glycopeptide-intermediate S. capitis (hGISC) was evaluated.

    RESULTS: Staphylococcus epidermidis (67.4%), Staphylococcus haemolyticus (10.5%) and S. capitis (9.6%) were the most common CoNS species. Of the S. capitis isolates, 75% were methicillin-resistant and 44% were multidrug-resistant. No isolate showed decreased susceptibility to vancomycin, but at least 59% displayed the hGISC phenotype. Staphylococcus capitis isolates related to the strain CR01 displaying pulsotype NRCS-A were found.

    CONCLUSION: Staphylococcus epidermidis, S. haemolyticus and S. capitis were the predominant species detected in neonatal blood cultures by MALDI-TOF MS. The number of episodes caused by S. capitis increased during the study period, but no isolates with decreased susceptibility to vancomycin were identified. However, S. capitis isolates related to the strain CR01 displaying pulsotype NRCS-A were found.

  • 50.
    Eliasson, Henrik
    et al.
    Örebro University, School of Health and Medical Sciences.
    Broman, Tina
    Forsman, Mats
    Bäck, Erik
    Örebro University, School of Health and Medical Sciences.
    Tularemia: current epidemiology and disease management2006In: Infectious Disease Clinics of North America, ISSN 0891-5520, Vol. 20, no 2, 289-311, ix p.Article in journal (Refereed)
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