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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
    Region Örebro län. 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 pneumonia2013Ingår i: Diagnostic microbiology and infectious disease, ISSN 0732-8893, E-ISSN 1879-0070, Vol. 76, nr 2, s. 141-146Artikel i tidskrift (Refereegranskat)
    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, Stockholm, Sweden.
    Barqasho, Babilonia
    Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Nowak, Piotr
    Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Cuong, Do Duy
    Infectious Diseases Department, Bach Mai Hospital, Hanoi, Viet Nam .
    Amogné, Wondwossen
    Department of Medicine, Faculty of Medicine, University, Addis Abeba, 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 University Hospital, Karolinska Institutet, Stockholm, 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, Stockholm, Sweden; Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Pattern of microbial translocation in patients living with HIV-1 from Vietnam, Ethiopia and Sweden2014Ingår i: Journal of the International AIDS Society, ISSN 1758-2652, E-ISSN 1758-2652, Vol. 17, s. 18841-Artikel i tidskrift (Refereegranskat)
    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, Helsinki, Finlan; Helsinki Univ Hosp, Helsinki, Finland.
    Galperine, T.
    Hop Claude Huriez, Lille, France.
    Goldenberg, S. D.
    Ctr Clin Infect & Diagnost Res, Guys & St Thomas NHS Fdn Trust, London, England; Kings Coll London, London, England.
    Gwynn, S.
    Triducive Ltd, St Albans, England.
    Jenkins, D.
    Univ Hosp Leicester NHS Trust, Leicester, England.
    Norén, Torbjörn
    Region Örebro län.
    Petrosillo, N.
    Natl Inst Infect Dis, Rome, Italy.
    Seifert, H.
    Inst Med Microbiol Immunol & Hyg, Univ Cologne, Cologne, Germany.
    Stallmach, A.
    Dept Internal Med 4, Univ Klinikum Jena, 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 line2015Ingår i: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 90, nr 2, s. 117-125Artikel i tidskrift (Refereegranskat)
    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 universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Medicine, Division of Hematology, Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Region Örebro län. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Svensson, Karolina
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Long-term molecular epidemiology of staphylococcus epidermidis blood culture isolates from patients with hematological malignancies2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 6, artikel-id e99045Artikel i tidskrift (Refereegranskat)
    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 universitet, Institutionen för hälsovetenskap och medicin. 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 universitet, Institutionen för läkarutbildning. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro universitet, Institutionen för läkarutbildning. 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 malignancy2012Ingår i: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 31, nr 7, s. 1679-1687Artikel i tidskrift (Refereegranskat)
    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, Nanjing, China; 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 SK, 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; 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 Hospital, 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 medicines2017Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, nr 7, artikel-id e1002366Artikel i tidskrift (Refereegranskat)
    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 universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Infectious Diseases.
    Mölling, Paula
    Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Norrby-Teglund, Anna
    Center for Infectious Medicine, 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.
    High HMGB1 levels in sputum are related to pneumococcal bacteraemia but not to disease severity in community-acquired pneumonia2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, nr 1, artikel-id 13428Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    During bacterial infections, damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) activate immune cells. Here, we investigated whether plasma and sputum levels of High Mobility Group Box 1 (HMGB1), a prototypic DAMP, are associated with disease severity and aetiology in community-acquired pneumonia (CAP). In addition, in patients with pneumococcal CAP, the impact of the level of sputum lytA DNA load, a PAMP, was investigated. We studied patients hospitalised for bacterial CAP (n = 111), and samples were collected at admission. HMGB1 was determined by enzyme-linked immunosorbent assays, and pneumococcal lytA DNA load was determined by quantitative polymerase chain reaction. Plasma and sputum HMGB1 levels did not correlate to disease severity (pneumonia severity index or presence of sepsis), but high sputum HMGB1 level was correlated to pneumococcal aetiology (p = 0.002). In pneumococcal pneumonia, high sputum lytA DNA load was associated with respiratory failure (low PaO2/FiO2 ratio; p = 0.019), and high sputum HMGB1 level was associated with bacteraemia (p = 0.006). To conclude, high sputum HMGB1 was not associated with severe disease, but with pneumococcal bacteraemia, indicating a potential role for HMGB1 in bacterial dissemination. High sputum lytA was associated with severe disease.

  • 8.
    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 universitet, Institutionen för hälsovetenskap och medicin. Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    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 Pneumonia2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 10, artikel-id e0140112Artikel i tidskrift (Refereegranskat)
    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.

  • 9.
    Alpkvist, Helena
    et al.
    Karolinska University Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Athlin, Simon
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    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 pneumoniaManuskript (preprint) (Övrigt vetenskapligt)
  • 10.
    Altun, O.
    et al.
    Division of Clinical Microbiology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Athlin, Simon
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Infectious Diseases, Örebro University, Örebro, Sweden.
    Almuhayawi, M.
    Division of Clinical Microbiology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Microbiology, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia.
    Strålin, K.
    Department of Infectious Diseases, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Özenci, V.
    Division of Clinical Microbiology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Rapid identification of Streptococcus pneumoniae in blood cultures by using the ImmuLex, Slidex and Wellcogen latex agglutination tests and the BinaxNOW antigen test2016Ingår i: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, nr 4, s. 579-585Artikel i tidskrift (Refereegranskat)
    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.

  • 11. Andersson, H.
    et al.
    Hartmanová, B.
    Bäck, Erik
    Örebro universitet, Institutionen för klinisk medicin.
    Eliasson, H.
    Örebro universitet, Institutionen för klinisk medicin.
    Landfors, M.
    Näslund, L.
    Rydén, P.
    Sjöstedt, A.
    Transcriptional profiling of the peripheral blood response during tularemia2006Ingår i: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 7, nr 6, s. 503-513Artikel i tidskrift (Refereegranskat)
    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.

  • 12.
    Andersson, Madelen
    et al.
    Dept Infect Dis, Blekinge Hosp, Karlskrona, Sweden.
    Resman, Fredrik
    Dept Translat Med Med Microbiol, Lund Univ, Malmö, Sweden.
    Eitrem, Rickard
    Dept Communicable Dis Control, County Blekinge, Karlskrona, Sweden.
    Drobni, Peter
    Dept Clin Microbiol, County Kronoberg, Växjö, Sweden; Dept Clin Microbiol, County Kronoberg, Karlskrona, Sweden.
    Riesbeck, Kristian
    Dept Translat Med Med Microbiol, Lund Univ, Malmö, Sweden.
    Kahlmeter, Gunnar
    Dept Clin Microbiol, County Kronoberg, Växjö, Sweden; Dept Clin Microbiol, County Kronoberg, Karlskrona, Sweden; Dept Med Sci, Div Clin Bacteriol, Uppsala Univ, Uppsala, Sweden.
    Sundqvist, Martin
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Örebro universitet, Institutionen för medicinska vetenskaper. Dept Clin Microbiol, County Kronoberg, Växjö, Sweden; Dept Clin Microbiol, County Kronoberg, Karlskrona, Sweden; Dept Lab Med Clin Microbiol, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Outbreak of a beta-lactam resistant non-typeable Haemophilus influenzae sequence type 14 associated with severe clinical outcomes2015Ingår i: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, artikel-id 581Artikel i tidskrift (Refereegranskat)
    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.

  • 13.
    Asghar, Naveed
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Gunaltay, Sezin
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Tran, Pham Tue Hung
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Melik, Wessam
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Höglund, Urban
    Adlego Biomedical AB, Uppsala, Sweden.
    Johansson, Christer
    Academy of Quality Pharm Science and BiQ Pharma AB, Södertälje, Sweden.
    Frelin, Lars
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Sällberg, Matti
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper.
    DNA launched suicidal flaviviruses as therapeutic vaccine candidates2018Konferensbidrag (Refereegranskat)
    Abstract [en]

    Chronic liver disease, resulting from Hepatitis B virus (HBV), Hepatitis D virus (HDV), or Hepatitis C virus (HCV) infections, contributes to a major health burden worldwide. The relativelyhigh cost of the HCV treatment brings concerns about the accessibility, especially in the developing countries. Hence, there exists a need for cost effect interventions with high efficiency. We aim to develop therapeutic vaccine candidates against HBV, HCV and HDV using DNA based subgenomic flavivirus replicons as a delivery system. Tick-borne encephalitis virus (TBEV), Langat virus (LGTV), West-Nile virus (WNV), or Kunjinvirus (KUNV) replicon with firefly luciferase geneas a reporter were expressed and characterized in cell culture studies. WNV and KUNV replicons showed significantly higher replication compared to their respective negative controls with unfunctional viral RNA dependent RNA polymerase. KUNV and WNV replicons were chosen for cloning the HCV or HB/DV vaccine candidate gene by replacing luciferasegene. Owing to the self-replicating trait of the flavivirus subgenomic replicons, Western blotting demonstrated that the antigen expression by KUNV and WNV replicons was several folds higher than the positive control. These results suggest that DNA based KUNV and WNV replicons may function as carriers for the hepatitis vaccine candidate genes, and these replicons are currently used for in vivostudies in animal models.

  • 14.
    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 universitet, Institutionen för läkarutbildning. 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 Variance2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 7, artikel-id e103264Artikel i tidskrift (Refereegranskat)
    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.

  • 15.
    Asghar, Naveed
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Maravelia, Panagiota
    aboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Caro-Perez, Noelia
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Tarn, Hung
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Melik, Wessam
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Pasetto, Anna
    aboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ahlen, Gustaf
    aboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Frelin, Lars
    aboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Höglund, Urban
    Johansson, Christer
    Sällberg, Matti
    aboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Immunogenicity of DNA launched suicidal flavivirus replicons for protective vaccination against hepatitis viruses2019Konferensbidrag (Refereegranskat)
    Abstract [en]

    Chronic liver disease, resulting from Hepatitis B virus (HBV), Hepatitis D virus (HDV), or Hepatitis C virus (HCV) infections, contributes to a major health burden worldwide. Chronic infections with the hepatitis C virus (HCV) can be effectively cured by antivirals. However, as cured patients can be re-infected they lack protective immune responses. In addition, the relativelyhigh cost of the HCV treatment brings concerns about the accessibility, especially in the developing countries. Hence, there exists a need for cost effect vaccines with high efficiency to control and possibly eradicate Hepatitis viruses globally. The vaccine should induce either, or both, neutralizing antibodies and protective T cell responses. We therefore have developed DNA based flavivirus replicons as a potent delivery system that effectively prime HCV-specific T cell responses. We generated suicidal subgenomic DNA replicons of Tick-borne encephalitis virus (TBEV), Langat virus (LGTV), West-Nile virus (WNV), and Kunjinvirus (KUNV) expressing either a fusion protein between the HCV NS3/4A and a stork hepatitis B virus core or a vaccine candidate gene of HB/DV. Transfection experiments showed that the antigen expression by KUNV and WNV replicons was several folds higher than the antigen expression by standard DNA plasmid with CMV promoter. The immunogenicity of three suicidal flaviviral DNA replicons expressing HCV NS3/4A was tested in mice and compared to HCV NS3/4A expression by the standard DNA plasmid. The KUNV-HCV replicon was the best replicon-based immunogen with respect to priming of HCV NS3/4A-specific T cells as determined by ELISpot, dextramer staining, and polyfunctionality. Importantly, a mutant KUNV-HCV immunogen lacking replication failed to induce immune responses. Thus, the newly developed KUNV-based suicidal DNA launched replicon vaccine for HCV is a highly attractive candidate as a prophylactic vaccine against chronic hepatitis C. In addition, we are currently testing the immunogenicity of KUNV-HB/DV replicon in mice.

  • 16.
    Asghar, Naveed
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Maravelia, Panagiota
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Caro-Perez, Noelia
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Tran, Pham Tue Hung
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Melik, Wessam
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Pasetto, Anna
    aboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Ahlen, Gustaf
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Frelin, Lars
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Höglund, Urban
    Adlego Biomedical AB, Uppsala, Sweden.
    Johansson, Christer
    Academy of Quality Pharm Science and BiQ Pharma AB, Södertälje, Sweden.
    Sällberg, Matti
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Immunogenicity of DNA launched suicidal flavivirus replicons for protective vaccination against hepatitis viruses2019Konferensbidrag (Refereegranskat)
    Abstract [en]

    Chronic liver disease, resulting from Hepatitis B virus (HBV), Hepatitis D virus (HDV), or Hepatitis C virus (HCV) infections, contributes to a major health burden worldwide. Chronic infections with the hepatitis C virus (HCV) can be effectively cured by antivirals. However, as cured patients can be re-infected they lack protective immune responses. In addition, the relativelyhigh cost of the HCV treatment brings concerns about the accessibility, especially in the developing countries. Hence, there exists a need for cost effect vaccines with high efficiency to control and possibly eradicate Hepatitis viruses globally. The vaccine should induce either, or both, neutralizing antibodies and protective T cell responses. We therefore have developed DNA based flavivirus replicons as a potent delivery system that effectively prime HCV-specific T cell responses. We generated suicidal subgenomic DNA replicons of Tick-borne encephalitis virus (TBEV), Langat virus (LGTV), West-Nile virus (WNV), and Kunjinvirus (KUNV) expressing either a fusion protein between the HCV NS3/4A and a stork hepatitis B virus core or a vaccine candidate gene of HB/DV. Transfection experiments showed that the antigen expression by KUNV and WNV replicons was several folds higher than the antigen expression by standard DNA plasmid with CMV promoter. The immunogenicity of three suicidal flaviviral DNA replicons expressing HCV NS3/4A was tested in mice and compared to HCV NS3/4A expression by the standard DNA plasmid. The KUNV-HCV replicon was the best replicon-based immunogen with respect to priming of HCV NS3/4A-specific T cells as determined by ELISpot, dextramer staining, and polyfunctionality. Importantly, a mutant KUNV-HCV immunogen lacking replication failed to induce immune responses. Thus, the newly developed KUNV-based suicidal DNA launched replicon vaccine for HCV is a highly attractive candidate as a prophylactic vaccine against chronic hepatitis C. In addition, we are currently testing the immunogenicity of KUNV-HB/DV replicon in mice.

  • 17.
    Asghar, Naveed
    et al.
    School of Natural Sciences,Technology and Environmental Studies, Södertörn University, Huddinge, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden; 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, Sweden.
    Johansson, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. School of Natural Sciences, Technology and Environmental Studies, Södertörn University, Huddinge, Sweden.
    Dinnetz, Patrik
    School of Natural Sciences, Technology and Environmental Studies, Södertörn University, Huddinge, Sweden.
    Local landscape effects on population dynamics of Ixodes ricinus2016Ingår i: Geospatial health, ISSN 1827-1987, Vol. 11, nr 3, s. 283-289, artikel-id 487Artikel i tidskrift (Refereegranskat)
    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.

  • 18.
    Athlin, Simon
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    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 bacteremia2015Ingår i: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 34, nr 8, s. 1583-1588Artikel i tidskrift (Refereegranskat)
    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.

  • 19.
    Athlin, Simon
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    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 bacteremiaManuskript (preprint) (Övrigt vetenskapligt)
  • 20.
    Athlin, Simon
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Granath, F.
    Strålin, K.
    Hedlund, J.
    Spindler, C.
    Naucler, P.
    Usefulness of pneumococcal urinary antigen detection for antimicrobial guidance in community-acquired pneumonia2018Konferensbidrag (Refereegranskat)
  • 21.
    Athlin, Simon
    et al.
    Region Örebro län. Örebro universitet, Institutionen för medicinska vetenskaper. Dept Infect Dis, Örebro University Hospital, Örebro, 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, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Comparison of the ImmuView and the BinaxNOW antigen tests in detection of Streptococcus pneumoniae and Legionella pneumophila in urine2017Ingår i: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, nr 10, s. 1933-1938Artikel i tidskrift (Refereegranskat)
    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.

  • 22.
    Athlin, Simon
    et al.
    Region Örebro län.
    Kaltoft, Margit
    Statens Serum Institut, Copenhagen, Denmark.
    Slotved, Hans-Christian
    Statens Serum Institut, Copenhagen, Denmark.
    Herrmann, Björn
    Uppsala University, Uppsala, Sweden.
    Holmberg, Hans
    Region Örebro län.
    Konradsen, Helle Bossen
    Statens Serum Institut, Copenhagen, Denmark.
    Strålin, Kristoffer
    Örebro University Hospital, Örebro, Sweden; Karolinska University Hospital, 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 potential2014Ingår i: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, nr 11, s. 1541-1549Artikel i tidskrift (Refereegranskat)
    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.

  • 23.
    Athlin, Simon
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Larsson, Emelie
    Nordenskjöld, Anna M.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Fröbert, Ole
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Evaluation of the novel IMMUVIEW RSV antigen test for detection of respiratory syncytial virus in adults and children2019Konferensbidrag (Övrigt vetenskapligt)
  • 24.
    Athlin, Simon
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Lidman, Christer
    Unit of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
    Lundqvist, Anders
    Department of Infectious Diseases, Södra Älvsborgs Hospital, Borås, Sweden.
    Naucler, Pontus
    Unit of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
    Nilsson, Anna C.
    Infectious Disease Research Unit, Department of Translational Medicine, Lund University, Malmö, Sweden.
    Spindler, Carl
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
    Strålin, Kristoffer
    Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Hedlund, Jonas
    Unit of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
    Management of community-acquired pneumonia in immunocompetent adults: updated Swedish guidelines 20172018Ingår i: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 50, nr 4, s. 247-272Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Based on expert group work, Swedish recommendations for the management of community-acquired pneumonia in adults are here updated. The management of sepsis-induced hypotension is addressed in detail, including monitoring and parenteral therapy. The importance of respiratory support in cases of acute respiratory failure is emphasized. Treatment with high-flow oxygen and non-invasive ventilation is recommended. The use of statins or steroids in general therapy is not found to be fully supported by evidence. In the management of pleural infection, new data show favourable effects of tissue plasminogen activator and deoxyribonuclease installation. Detailed recommendations for the vaccination of risk groups are afforded.

  • 25.
    Athlin, Simon
    et al.
    Region Örebro län.
    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.2013Ingår i: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, nr 6, s. 425-31Artikel i tidskrift (Refereegranskat)
    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.

  • 26.
    Athlin, Simon
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Ziegler, Ingrid
    Källgren, Magdalena
    Strålin, Kristoffer
    Mölling, Paula
    Rapid elimination of pneumococcal lytA DNA in the bloodstream of patients with invasive pneumococcal diseasae treated with beta-lactam antibiotics2016Konferensbidrag (Refereegranskat)
  • 27.
    Attram, Naiki
    et al.
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
    Agbodzi, Bright
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
    Dela, Helena
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
    Behene, Eric
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana; Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
    Nyarko, Edward O.
    Department of Public Health, Military Hospital, Accra, Ghana.
    Kyei, Nicholas N. A.
    Department of Public Health, Military Hospital, Accra, Ghana.
    Larbi, John A.
    Department of Theoretical and Applied Biology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
    Lawson, Bernard W. L.
    Department of Theoretical and Applied Biology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
    Addo, Kennedy K.
    Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana.
    Newman, Mercy J.
    Department of Medical Microbiology, School of Biomedical and Allied Health Science, College of Health Sciences, University of Ghana, Accra, Ghana.
    Duplessis, Christopher A.
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana.
    Adams, Nehkonti
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Letizia, Andrew G.
    US Naval Medical Research Unit Number Three, Ghana Laboratory, Legon, Ghana.
    Antimicrobial resistance (AMR) and molecular characterization of Neisseria gonorrhoeae in Ghana, 2012-20152019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 10, artikel-id e0223598Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance is essential for tracking the emergence and spread of AMR strains in local, national and international populations. This is crucial for developing or refining treatment guidelines. N. gonorrhoeae multiantigen sequence typing (NG-MAST) is beneficial for describing the molecular epidemiology of gonococci at national and international levels. Elucidation of AMR determinants to β-lactam drugs, is a means of monitoring the development of resistance. In Ghana, little is known about the current gonococcal AMR prevalence and no characterization of gonococcal isolates has been previously performed. In this study, gonococcal isolates (n = 44) collected from five health facilities in Ghana from 2012 to 2015, were examined using AMR testing, NG-MAST and sequencing of penA. High rates of resistance were identified to tetracycline (100%), benzylpenicillin (90.9%), and ciprofloxacin (81.8%). One isolate had a high cefixime MIC (0.75 μg/ml). Twenty-eight NG-MAST sequence types (STs) were identified, seventeen of which were novel. The isolate with the high cefixime MIC contained a mosaic penA-34 allele and belonged to NG-MAST ST1407, an internationally spreading multidrug-resistant clone that has accounted for most cefixime resistance in many countries. In conclusion, AMR testing, NG-MAST, and sequencing of the AMR determinant penA, revealed high rates of resistance to tetracycline, benzylpenicillin, and ciprofloxacin; as well as a highly diverse population of N. gonorrhoeae in Ghana. It is imperative to continue with enhanced AMR surveillance and to understand the molecular epidemiology of gonococcal strains circulating in Ghana and other African countries.

  • 28.
    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, Örebro University Hospital, 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 universitet, Institutionen för hälsovetenskaper. WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Gentamicin in vitro activity and tentative gentamicin interpretation criteria for the CLSI and calibrated dichotomous sensitivity disc diffusion methods for Neisseria gonorrhoeae2016Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, nr 7, s. 1856-1859Artikel i tidskrift (Refereegranskat)
    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.

  • 29.
    Bark, Tor
    et al.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Katouli, Mohammad
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Möllby, R.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Svenberg, Torgny E.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Bacterial translocation after non-lethal hemorrhage in the rat1993Ingår i: Circulatory Shock, ISSN 0092-6213, Vol. 41, nr 1, s. 60-65Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Translocation of enteric bacteria has been suggested to compromise patients in severe catabolic stress. Mechanisms for this route of infection are not known. In this study, ratswere subjected to hemorrhage without reinfusion during 60 min, total blood loss was 3.28 +/- 0.14 ml/100 g BW. Control groups consisted of sham-operated animals without bleeding, and rats not operated at all. The mean number of viable bacteria found in mesenteric lymph nodes (MLN) of bled animals was 168 +/- 45 colony forming units (c.f.u./MLN), significantly higher compared to sham operated (5 +/- 3 c.f.u./MLN) and not operated (0 +/- 0 c.f.u./MLN) controls (P < 0.01). Cultures from MLN were positive in 7/9 rats after bleeding, in 3/9 of sham operated, and in 0/6 of non-instrumented control animals. No positive blood cultures were isolated. Escherichia coli was the dominant species found in MLN. A biochemical fingerprinting method (the PhP system) was used to identify translocating strains of E. coli among strains found in cecum. The method was also used to compare translocating strains between different animals. Our findings reveal that bacteria translocate to MLN after hemorrhage. Some phenotypes of E. coli strains translocate more frequently than others, suggesting that they have properties facilitating translocation.

  • 30.
    Barmparas, Galinos
    et al.
    Cedars-Sinai Medical Center, Department of Surgery, Division of Acute Care Surgery and Surgical Critical Care, Los Angeles California, USA.
    Harada, Megan Y.
    Cedars-Sinai Medical Center, Department of Surgery, Division of Acute Care Surgery and Surgical Critical Care, Los Angeles California, USA.
    Ko, Ara
    Cedars-Sinai Medical Center, Department of Surgery, Division of Acute Care Surgery and Surgical Critical Care, Los Angeles California, USA.
    Dhillon, Navpreet K.
    Cedars-Sinai Medical Center, Department of Surgery, Division of Acute Care Surgery and Surgical Critical Care, Los Angeles California, USA.
    Smith, Eric J. T.
    Cedars-Sinai Medical Center, Department of Surgery, Division of Acute Care Surgery and Surgical Critical Care, Los Angeles California, USA.
    Li, Tong
    Cedars-Sinai Medical Center, Department of Surgery, Division of Acute Care Surgery and Surgical Critical Care, Los Angeles California, USA.
    Mohseni, Shahin
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Surgery, Division of Trauma and Emergency Surgery.
    Ley, Eric J.
    Cedars-Sinai Medical Center, Department of Surgery, Division of Acute Care Surgery and Surgical Critical Care, Los Angeles California, USA.
    The Effect of Early Positive Cultures on Mortality in Ventilated Trauma Patients2018Ingår i: Surgical Infections, ISSN 1096-2964, E-ISSN 1557-8674, Vol. 19, nr 4, s. 410-416Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The purpose was to examine the incidence of positive cultures in a highly susceptible subset of trauma patients admitted to the surgical intensive care unit (SICU) for mechanical ventilation and to examine the impact of their timing on outcomes.

    Patients and Methods: A retrospective review was conducted of blunt trauma patients admitted to the SICU for mechanical ventilation at a level I trauma center over a five-year period. All urine, blood, and sputum cultures were abstracted. Patients with at least one positive culture were compared with those with negative or no cultures. The primary outcome was mortality. A Cox regression model with a time-dependent variable was utilized to calculate the adjusted hazard ratio (AHR).

    Results: The median age of 635 patients meeting inclusion criteria was 46 and 74.2% were male. A total of 298 patients (46.9%) had at least one positive culture, with 28.9% occurring within two days of admission. Patients with positive cultures were more likely to be severely injured with an injury severity score (ISS) 16 (68.5% vs. 45.1%, p<0.001). Overall mortality was 22%. Patients who had their first positive culture within two and three days from admission had a significantly higher AHR for mortality (AHR: 14.46, p<0.001 and AHR: 10.59, p=0.028, respectively) compared to patients with a positive culture at day six or later.

    Conclusions: Early positive cultures are common among trauma patients requiring mechanical ventilation and are associated with higher mortality. Early identification with damage control cultures obtained on admission to aid with early targeted treatment might be justified.

  • 31.
    Bazzo, M. L.
    et al.
    Molecular Biology, Microbiology and Serology Laboratory, Federal University of Santa Catarina, Florianópolis, Brazil.
    Golfetto, L.
    Molecular Biology, Microbiology and Serology Laboratory, Federal University of Santa Catarina, Florianópolis, Brazil.
    Gaspar, P. C.
    Department of Surveillance, Prevention and Control of Sexually Transmitted Infections, HIV/AIDS and Viral Hepatitis, Ministry of Health, Brasilia, Brazil.
    Pires, A. F.
    Department of Surveillance, Prevention and Control of Sexually Transmitted Infections, HIV/AIDS and Viral Hepatitis, Ministry of Health, Brasilia, Brazil; University of Brasilia Postgraduate Program in Collective Health, Brasilia, Brazil.
    Ramos, M. C.
    Brazilian STD Society, Porto Alegre, Brazil.
    Franchini, M.
    Laboratory Consultant, Brasília, Brazil.
    Ferreira, W. A.
    Alfredo da Mata Foundation, Manaus, Brazil.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Benzaken, A. S.
    Department of Surveillance, Prevention and Control of Sexually Transmitted Infections, HIV/AIDS and Viral Hepatitis, Ministry of Health, Brasilia, Brazil.
    First nationwide antimicrobial susceptibility surveillance for Neisseria gonorrhoeae in Brazil, 2015-162018Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 73, nr 7, s. 1854-1861Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major public health concerns globally. Enhanced AMR surveillance for gonococci is essential worldwide; however, recent quality-assured gonococcal AMR surveillance in Latin America, including Brazil, has been limited. Our aims were to (i) establish the first nationwide gonococcal AMR surveillance, quality assured according to WHO standards, in Brazil, and (ii) describe the antimicrobial susceptibility of clinical gonococcal isolates collected from 2015 to 2016 in all five main regions (seven sentinel sites) of Brazil.

    Methods: Gonococcal isolates from 550 men with urethral discharge were examined for susceptibility to ceftriaxone, cefixime, azithromycin, ciprofloxacin, benzylpenicillin and tetracycline using the agar dilution method, according to CLSI recommendations and quality assured according to WHO standards.

    Results: The levels of resistance (intermediate susceptibility) to tetracycline, ciprofloxacin, benzylpenicillin and azithromycin were 61.6%(34.2%), 55.6%(0.5%), 37.1% (60.4%) and 6.9% (8.9%), respectively. All isolates were susceptible to ceftriaxone and cefixime using the US CLSI breakpoints. However, according to the European EUCAST cefixime breakpoints, 0.2% (n= 1) of isolates were cefixime resistant and 6.9% (n = 38) of isolates had a cefixime MIC bordering on resistance.

    Conclusions: This study describes the first national surveillance of gonococcal AMR in Brazil, which was quality assured according to WHO standards. The high resistance to ciprofloxacin (which promptly informed a revision of the Brazilian sexually transmitted infection treatment guideline), emerging resistance to azithromycin and decreasing susceptibility to extended-spectrum cephalosporins necessitate continuous surveillance of gonococcal AMR and ideally treatment failures, and increased awareness when prescribing treatment in Brazil.

  • 32.
    Bengtsson, Torbjörn
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Zhang, Boxi
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Selegård, Robert
    Örebro universitet, Institutionen för medicinska vetenskaper. 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 universitet, Institutionen för medicinska vetenskaper.
    Dual action of bacteriocin PLNC8 alpha beta through inhibition of Porphyromonas gingivalis infection and promotion of cell proliferation2017Ingår i: Pathogens and Disease, E-ISSN 2049-632X, Vol. 75, nr 5, artikel-id ftx064Artikel i tidskrift (Refereegranskat)
    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.

  • 33. Bereczky, S.
    et al.
    Dolo, A.
    Maiga, B.
    Hayano, M.
    Granath, F.
    Montgomery, Scott M.
    Örebro universitet, Hälsoakademin.
    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 Africa2006Ingår i: Transactions of the Royal Society of Tropical Medicine and Hygiene, ISSN 0035-9203, E-ISSN 1878-3503, Vol. 100, nr 3, s. 248-257Artikel i tidskrift (Refereegranskat)
    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.

  • 34. Bereczky, Sándor
    et al.
    Liljander, Anne
    Rooth, Ingegerd
    Faraja, Lea
    Granath, Fredrik
    Montgomery, Scott M.
    Örebro universitet, Hälsoakademin.
    Färnert, Anna
    Multiclonal asymptomatic Plasmodium falciparum infections predict a reduced risk of malaria disease in a Tanzanian population2007Ingår i: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 9, nr 1, s. 103-110Artikel i tidskrift (Refereegranskat)
    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.

  • 35. 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 universitet, Hälsoakademin.
    Kaneko, Akira
    Björkman, Anders
    Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar2007Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 4, nr 11, s. e309-Artikel i tidskrift (Refereegranskat)
    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.

  • 36.
    Bignell, Chris J.
    et al.
    City Hospital Campus, Nottingham University Hospitals NHS Trust, Nottingham, 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 adults2013Ingår i: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 24, nr 2, s. 85-92Artikel i tidskrift (Refereegranskat)
    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.

  • 37.
    Björk, Helena
    et al.
    Dept Otorhinolaryngol, Cent Hosp Växjö, Växjö, Sweden.
    Bieber, Lena
    Dept Clin Microbiol, Cent Hosp Växjö, Växjö, Sweden.
    Hedin, Katarina
    Dept Clin Sci Family Med, Lund Univ, Malmö, Sweden; Unit Res & Dev, Kronoberg County Council, Växjö, Sweden.
    Sundqvist, Martin
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Dept Clin Microbiol, Cent Hosp Växjö, Växjö, Sweden.
    Tonsillar colonisation of Fusobacterium necrophorum in patients subjected to tonsillectomy2015Ingår i: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, artikel-id 264Artikel i tidskrift (Refereegranskat)
    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.

  • 38.
    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 universitet. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro universitet, Hälsoakademin. Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Colonization pattern of coagulase-negative staphylococci in preterm neonates and the relation to bacteremia2010Ingår i: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 29, nr 9, s. 1085-1093Artikel i tidskrift (Refereegranskat)
    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.

  • 39.
    Boiko, Iryna
    et al.
    Ternopil Regional Clinical Dermatovenerologic Dispensary, Clinical Laboratory Department, Ternopil, Ukraine; Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil State Medical University, Ternopil, Ukraine; WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Golparian, Daniel
    Örebro universitet, Institutionen för medicinska vetenskaper. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Krynsytska, Inna
    Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil State Medical University, Ternopil, Ukraine.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    High prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae and particularly Trichomonas vaginalis diagnosed using US FDA-approved Aptima molecular tests and evaluation of conventional routine diagnostic tests in Ternopil, Ukraine2019Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, nr 9, s. 627-634Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sexually transmitted infections (STIs) remain major public health problems globally. Appropriate laboratory diagnosis of STIs is rare in Ukraine. We investigated the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) using the US FDA-approved Aptima Combo 2 and Aptima TV assays and compared the results with the conventional routine diagnostic tests (CDTs) in Ukraine. Urogenital swabs from consecutive mostly symptomatic females (n = 296) and males (n = 159) were examined. The prevalences were as follows: 10% (n = 47) of TV, 5.3% (n = 24) of CT and 1.5% (n = 7) of NG. The specificity of some CDTs was high, for example, 100% for NG culture, TV IgG ELISA, CT IgM ELISA and CT microscopy, but lower for other CDTs, that is, from 44% to 99.8%. The sensitivity of all CDTs was suboptimal, that is, 71% (n = 5) for NG microscopy, 57% (n = 4) for NG culture, 53% (n = 8) for CT IgG ELISA, 33% (n = 1) for TV IgG ELISA, 28% (n = 13) for TV microscopy, 25% (n = 1) for CT IgA ELISA, 20% (n = 3) for CT IgM ELISA and 0% (n = 0) for CT microscopy. The prevalences of particularly TV and CT were high, but substantial also for NG, in Ternopil, Ukraine. The sensitivities of all CDTs were low, and widespread implementation of validated, quality-assured and cost-effective molecular diagnostic STI tests in Ukraine is imperative.

  • 40.
    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, Stockholm, Sweden; 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 universitet, Institutionen för medicinska vetenskaper. 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 study2016Ingår i: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 16, artikel-id 419Artikel i tidskrift (Refereegranskat)
    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.

  • 41.
    Brehony, Carina
    et al.
    Dept Zool, Univ Oxford, Oxford, England..
    Trotter, Caroline L.
    Dept Vet Med, Univ Cambridge, Cambridge, England.
    Ramsay, Mary E.
    Publ Hlth England, London, England.
    Chandra, Manosree
    Publ Hlth England, London, England.
    Jolley, Keith A.
    Dept Zool, Univ Oxford, Oxford, England.
    van der Ende, Arie
    Dept Med Microbiol, Netherlands Reference Lab Bacterial Meningitis, Acad Med Ctr, Univ Amsterdam, Amsterdam, Netherlands.
    Carion, Francoise
    Meningococcal Reference Lab, Sci Inst Publ Hlth, Brussels, Belgium.
    Berthelsen, Lene
    Neisseria & Streptococcus Reference Lab, Statens Serum Inst, Copenhagen, Denmark.
    Hoffmann, Steen
    Neisseria & Streptococcus Reference Lab, Statens Serum Inst, Copenhagen, Denmark.
    Hardardottir, Hjordis
    Dept Microbiol, Landspitali Univ Hosp, 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
    Dept Infect Dis, Lab Antimicrobial Resistance, Natl Inst Hlth Dr Ricardo Jorge, Lisbon, Portugal.
    Ferreira, Eugenia
    Dept Infect Dis, Lab Antimicrobial Resistance, Natl Inst Hlth Dr Ricardo Jorge, Lisbon, Portugal.
    Diggle, Mathew
    Scottish Haemophilus Legionella Meningococcus & P, Glasgow, UK.
    Edwards, Giles F.
    Scottish Haemophilus Legionella Meningococcus & P, Glasgow, UK.
    Taha, Muhamed-Kheir
    Inst Pasteur, Natl Reference Ctr Meningococci, Institut Pasteur, Paris, France.
    Stefanelli, Paola
    Dept Infect Parasit & Immune Mediated Dis, Ist Super Sanita, Rome, Italy.
    Kriz, Paula
    Natl Reference Lab Meningococcal Infect, Natl Inst Publ Hlth, Prague, Czech Republic.
    Gray, Steve J.
    Meningococcal Reference Unit, Manchester Royal Infirm, Manchester, England.
    Fox, Andrew J.
    Meningococcal Reference Unit, Manchester Royal Infirm, Manchester, England.
    Jacobsson, Susanne
    Region Örebro län. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Claus, Heike
    Inst Hyg & Mikrobiol, Wurzburg, Germany.
    Vogel, Ulrich
    Inst Hyg & Mikrobiol, Wurzburg, Germany.
    Tzanakaki, Georgina
    Natl Meningococcal Reference Lab, Natl Sch Publ Hlth, Athens, Greece.
    Heuberger, Sigrid
    Natl Reference Ctr Meningococci, Inst Med Microbiol & Hyg, Graz, Austria.
    Caugant, Dominique A.
    Dept Bacteriol & Immunol, Norwegian Inst Publ Hlth, Oslo, Norway.
    Frosch, Matthias
    Inst Hyg & Mikrobiol, Wurzburg, Germany.
    Maiden, Martin C. J.
    Dept Zool, Univ Oxford, Oxford, England.
    Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development2014Ingår i: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, nr 6, s. 847-853Artikel i tidskrift (Refereegranskat)
    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.

  • 42.
    Bruggmann, P.
    et al.
    Arud Ctr Addict Med, Zurich, Switzerland.
    Berg, T.
    Univ Leipzig, Leipzig, Germany.
    Ovrehus, A. L. H.
    Dept Infect Dis, Odense Univ Hosp, Odense, Denmark.
    Moreno, C.
    Erasme Univ Hosp, Univ Libre Brussels, Brussels, Belgium.
    Brandao Mello, C. E.
    Dept Gastroenterol, Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil.
    Roudot-Thoraval, F.
    Dept Sante Publ, Hop Henri Mondor, Creteil, France.
    Marinho, R. T.
    Ctr Hosp Lisboa Norte, Dept Gastroenterol, Hosp Santa Maria,Lisbon, Portugal.
    Sherman, M.
    Toronto Gen Hosp, Univ Hlth Network, Univ Toronto, Toronto, Canada.
    Ryder, S. D.
    Nottingham Univ Hosp NHS Trust, Nottingham, England; Biomed Res Unit, Nottingham, England.
    Sperl, J.
    Dept Hepatogastroenterol, Inst Clin & Expt Med, Prague, Czech Republic.
    Akarca, U.
    Ege Univ, Izmir, Turkey.
    Balik, I.
    Ankara Univ, Ankara, Turkey.
    Bihl, F.
    Dept Gastroenterol, Osped Cantonale, Bellinzona, Switzerland.
    Bilodeau, M.
    Dept Med, Liver Unit, Univ Montreal, Montreal, Canada.
    Blasco, A. J.
    Adv Tech Hlth Serv Res TAISS, Madrid, Spain.
    Buti, M.
    Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Hosp Valle De Hebron, Barcelona, Spain.
    Calinas, F.
    Dept Gastroenterol, Ctr Hosp Lisboa Cent, Hosp Santo Antonio Capuchos, Lisbon, Portugal.
    Calleja, J. L.
    Hosp Puerta Hierro, Madrid, Spain.
    Cheinquer, H.
    Hosp Clin, Univ Fed Rio Grande do Sul, Porto Alegre RS, Brazil.
    Christensen, P. B.
    Dept Infect Dis, Odense Univ Hosp, Odense, Denmark.
    Clausen, M.
    Region Hosp Hovedstaden, Region Hovedstaden, Hillerød, Denmark.
    Coelho, H. S. M.
    Dept Clin Med, Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil.
    Cornberg, M.
    Dept Gastroenterol Hepatol & Endocrinol,Hannover Med Sch, Hannover, Germany; German Liver Fdn, Hannover, Germany.
    Cramp, M. E.
    Peninsula Schools Med & Dent, Univ Plymouth, Plymouth, England.
    Dore, G. J.
    Kirby Inst, Univ New S Wales, Sydney NSW, Australia.
    Doss, W.
    Cairo Univ, Cairo, Egypt.
    Duberg, Ann-Sofi
    Örebro universitet, Institutionen för läkarutbildning. Region Örebro län. Dept Infect Dis, Örebro University Hospital, Örebro, Sweden.
    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.
    Infect Dis Unit, Dept Med Huddinge, Karolinska Inst, Stockholm, Sweden.
    Felix, J.
    Exigo Consultores, Alhos Vedros, Portugal.
    Ferraz, M. L. G.
    Div Gastroenterol, Univ Fed Sao Paulo, Sao Paulo, Brazil.
    Ferreira, P. R.
    Div Infect Dis, Univ Fed Sao Paulo, Sao Paulo, Brazil.
    Frankova, S.
    Dept Hepatogastroenterol, Inst Clin & Expt Med, Prague, Czech Republic.
    Garcia-Samaniego, J.
    Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Hosp Carlos III, Madrid, Spain.
    Gerstoft, J.
    Univ Copenhagen, Copenhagen, Denmark.
    Giria, J. A.
    Direccao Geral Saude, Lisbon, Portugal.
    Goncales, F. L., Jr.
    Fac Ciencias Med, UNICAMP,Dept Clin Med, Grp Estudo Hepatites,Disciplina Doencas Infeccios, Univ Estadual Campinas, Sao Paulo, Brazil.
    Gower, E.
    Ctr Dis Anal CDA, Louisville CO, USA.
    Gschwantler, M.
    Dept Internal Med 4, Wilhelminenspital Stadt Wien, Vienna, Austria.
    Guimaraes Pessoa, M.
    Sch Med, Div Gastroenterol & Hepatol, Univ Sao Paulo, Sao Paulo, Brazil.
    Hezode, C.
    Serv Hepatogastroenterol, Hop Henri Mondor, Creteil, France.
    Hofer, H.
    Dept Internal Med 3, Div Gastroenterol & Hepatol, Med Univ Vienna, Vienna, Austria.
    Husa, P.
    Clin Infect Dis, Univ Hosp Brno, Masaryk Univ, Brno, Czech Republic.
    Idilman, R.
    Dept Gastroenterol, Sch Med, Ankara Univ, Ankara, Turkey.
    Kåberg, M.
    Infect Dis Unit, Dept Med Huddinge, Karolinska Inst, Stockholm, Sweden.
    Kaita, K. D. E.
    Dept Internal Med, Sect Hepatol, Univ Manitoba, Winnipeg MB, Canada; Viral Hepatitis Invest Unit, Hlth Sci Ctr, Winnipeg MB, Canada.
    Kautz, A.
    European Liver Patients Assoc, St Truiden, Belgium.
    Kaymakoglu, S.
    Istanbul Univ, Istanbul, Turkey.
    Krajden, M.
    British Columbia Ctr Dis Control, Univ British Columbia, Vancouver, Canada.
    Krarup, H.
    Dept Med Gastroenterol, Aalborg Univ Hosp, Aalborg, Denmark; Sect Mol Diagnost, Aalborg Univ Hosp, Aalborg, Denmark.
    Laleman, W.
    Univ Hosp Leuven, Katholieke Univ Leuven, Louvain, Belgium.
    Lavanchy, D.
    Lazaro, P.
    Adv Tech Hlth Serv Res TAISS, Madrid, Spain.
    Marotta, P.
    Div Gastroenterol, Univ Western Ontario, London ON, Canada.
    Mauss, S.
    Univ Dusseldorf, Dusseldorf, Germany.
    Mendes Correa, M. C.
    Sch Med, Univ Sao Paulo, Sao Paulo, Brazil.
    Muellhaupt, B.
    Swiss HPB Hepatopancreatobiliary Ctr, Univ Zurich Hosp, Zurich, Switzerland; Dept Gastroenterol & Hepatol, Univ Zurich Hosp, Zurich, Switzerland.
    Myers, R. P.
    Liver Unit, Div Gastroenterol & Hepatol, Univ Calgary, Calgary AB, Canada.
    Negro, F.
    Div Gastroenterol & Hepatol, Univ Hosp, Geneva, Switzerland; Div Clin Pathol,Univ Hosp, Geneva, Switzerland.
    Nemecek, V.
    Natl Reference Lab Hepatitis, Natl Inst Publ Hlth, Prague, Czech Republic.
    Ormeci, N.
    Ankara Univ, Ankara, Turkey.
    Parkes, J.
    Univ Southhampton, Southampton, England.
    Peltekian, K. M.
    Dept Med, Halifax, NS, Canada; Dept Surg, Dalhousie Univ, Halifax, Canada; Serv Hepatol, Queen Elizabeth II Hlth Sci Ctr, Capital Dist Hlth Author, Halifax NS, Canada.
    Ramji, A.
    Dept Gastroenterol, Univ British Columbia, 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.
    Inst Liver & Digest Hlth, Div Med, University College London (UCL), London, England.
    Sarmento-Castro, R.
    Dept Infect Dis, Ctr Hosp Porto, Oporto, Portugal.
    Sarrazin, C.
    JW Goethe Univ Hosp, Frankfurt, Germany.
    Semela, D.
    Div Gastroenterol & Hepatol, Cantonal Hosp St Gallen, 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.
    Clin Univ St Luc, Catholic Univ Louvain, Brussels, Belgium.
    Stauber, R. E.
    Dept Internal Med, Div Gastroenterol & Hepatol, Med Univ Graz, Graz, Austria.
    Thompson, A. J.
    Dept Gastroenterol, St Vincents Hosp, Melbourne Vic, Australia; Univ Melbourne, Melbourne Vic, Australia.
    Urbanek, P.
    Dept Internal Med, Fac Med 1, Charles Univ Prague, Prague, Czech Republic; Cent Mil Hosp, Prague, Czech Republic.
    van Thiel, I.
    St Truiden, Belgium; Deutsch Leberhilfe eV, European Liver Patients Assoc, Cologne, Germany.
    Van Vlierberghe, H.
    Ghent Univ Hosp, Ghent, Belgium.
    Vandijck, D.
    Ghent Univ Hosp, Ghent, Belgium; Univ Ghent, Ghent, Belgium; Dept Hlth Econ & Patient Safety, Hasselt Univ, Diepenbeek, Belgium.
    Vogel, W.
    Med Univ Innsbruck, Innsbruck, Austria.
    Waked, I.
    Natl Liver Inst, Menoufia, Egypt.
    Wedemeyer, H.
    Dept Gastroenterol Hepatol & Endocrinol, Hannover Med Sch, 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.
    St George Hosp Clin Sch Med, Univ New S Wales, Sydney NSW, Australia; Sch Med Sci, Univ New S Wales, Sydney NSW, Australia.
    Van Damme, P.
    Univ Antwerp, Antwerp, Belgium.
    Aleman, S.
    Dept Med Huddinge, Karolinska Inst, Stockholm, Sweden; Dept Gastroenterol & Hepatol Infect Dis, Karolinska Univ Hosp, Stockholm, Sweden.
    Hindman, S. J.
    Ctr Dis Anal CDA, Louisville CO, USA.
    Historical epidemiology of hepatitis C virus (HCV) in selected countries2014Ingår i: Journal of Viral Hepatitis, ISSN 1352-0504, E-ISSN 1365-2893, Vol. 21, s. 5-33Artikel i tidskrift (Refereegranskat)
    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.

  • 43.
    Bruni, Mirian Pinheiro
    et al.
    Biology Institute, Federal University of Pelotas (UFPel), Pelotas, Brazil.
    Freitas da Silveira, Mariangela
    School of Medicine, Federal University of Pelotas (UFPel), Pelotas, Brazil.
    Stauffert, Dulce
    School of Medicine, Federal University of Pelotas (UFPel), Pelotas, Brazil.
    Bicca, Guilherme Lucas de Oliveira
    School of Medicine, Federal University of Pelotas (UFPel), Pelotas, Brazil.
    Caetano Dos Santos, Carolina
    Biology Institute, Federal University of Pelotas (UFPel), Pelotas, Brazil.
    da Rosa Farias, Nara Amélia
    Biology Institute, Federal University of Pelotas (UFPel), Pelotas, Brazil.
    Golparian, Daniel
    Örebro universitet, Institutionen för medicinska vetenskaper. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine.
    Unemo, Magnus
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine.
    Aptima Trichomonas vaginalis assay elucidates significant underdiagnosis of trichomoniasis among women in Brazil according to an observational study2019Ingår i: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 95, nr 2, s. 129-132Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Trichomonas vaginalis (TV) infection is the most common non-viral STI globally and can result in adverse pregnancy outcomes and exacerbated HIV acquisition/transmission. Nucleic acid amplification tests (NAATs) are the most sensitive diagnostic tests, with high specificity, but TV NAATs are rarely used in Brazil. We investigated the TV prevalence and compared the performance of the US Food and Drug Association-cleared Aptima TV assay with microscopy (wet mount and Gram-stained) and culture for TV detection in women in Pelotas, Brazil in an observational study.

    METHODS: From August 2015 to December 2016, 499 consecutive asymptomatic and symptomatic sexually active women attending a Gynaecology and Obstetrics Outpatient Clinic were enrolled. Vaginal fluid and swab specimens were collected and wet mount microscopy, Gram-stained microscopy, culture and the Aptima TV assay performed.

    RESULTS: The median age of enrolled women was 36.5 years (range: 15-77). The majority were white, had a steady sexual partner and low levels of education. The TV detection rate was 4.2%, 2.4%, 1.2% and 0% using the Aptima TV assay, culture, wet mount microscopy and Gram-stained microscopy, respectively. The sensitivity of culture and wet mount microscopy was only 57.1% (95% CI 36.5 to 75.5) and 28.6% (95% CI 13.8 to 50.0), respectively.

    CONCLUSIONS: was found among women in Pelotas, Brazil and the routine diagnostic test (wet mount microscopy) and culture had low sensitivities. More sensitive diagnostic tests (NAATs) and enhanced testing of symptomatic and asymptomatic at-risk women are crucial to mitigate the transmission of TV infection, TV-associated sequelae and enhanced HIV acquisition and transmission.

  • 44.
    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; Dept Med Biosci, Umeå Univ, Umeå, 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
    Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Danielsson, Dan
    Region Örebro län. 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, Sahlgrenska University Hospital, University of Gothenburg, 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 adherence2017Ingår i: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 21, nr 3, s. 376-389, artikel-id S1931-3128(17)30075-6Artikel i tidskrift (Refereegranskat)
    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.

  • 45.
    Büsch, Katharina
    et al.
    AbbVie AB, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Waldenström, Jesper
    Department of Infectious Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Lagging, Martin
    Department of Infectious Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Aleman, Soo
    Department of Infectious Diseases, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Weiland, Ola
    Department of Medicine Huddinge, Division of Infectious Diseases, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Kövamees, Jan
    AbbVie AB, Stockholm, Sweden.
    Duberg, Ann-Sofi
    Örebro universitet, Institutionen för hälsovetenskaper. Department of Infectious Diseases, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Söderholm, Jonas
    AbbVie AB, Stockholm, Sweden; Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Prevalence and comorbidities of chronic hepatitis C: a nationwide population-based register study in Sweden2017Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, nr 1, s. 61-68Artikel i tidskrift (Refereegranskat)
    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.

  • 46.
    Cajander, Sara
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Infektionskliniken, Universitetssjukhuset i Örebro, Örebro, Sweden.
    Eliasson, Henrik
    Infektionskliniken, Örebro University Hospital, Region Örebro län, Örebro, Sweden.
    Mb Osler: ökad risk för infektioner och livshotande komplikationer: Fyra fall av invasiv infektionssjukdom under samma tidsperiod beskrivs2012Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 37, s. 1613-1615Artikel i tidskrift (Refereegranskat)
    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.

  • 47.
    Cajander, Sara
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Rasmussen, Gunlög
    Department of Infectious Diseases, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Tina, Elisabet
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Clinical Research Laboratory, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Magnuson, Anders
    Söderquist, Bo
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Källman, Jan
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Infectious Diseases, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Strålin, Kristoffer
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Dynamics of monocytic HLA-DR expression differs between bacterial etiologies during the course of bloodstream infection2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 2, artikel-id e0192883Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: In the pathogenesis of sepsis, activation of both pro- and anti-inflammatory responses are key components, but knowledge is lacking on the association between bacterial etiology and development of dysregulated responses with sustained immunosuppression. The aim of this study was to evaluate how the immunosupression marker HLA-DR on monocytes (mHLA-DR) is associated with bacterial etiology and markers of inflammation during the clinical trajectory of bloodstream infection (BSI).

    METHODS: Ninety-one adults, predominantly non-ICU patients, with BSI caused by Streptococcus pneumoniae (n = 27), Staphylococcus aureus (n = 22), Escherichia coli/Klebsiella pneumoniae (n = 23), and other species (n = 19) were prospectively included, and sampled on admission (day 0) and on days 1-2, 3, 7±1, 14±2, and 28±4.

    RESULTS: The dynamics of mHLA-DR, measured by flow cytometry, differed significantly between etiology groups (p<0.001). Patients with S. pneumoniae and S. aureus BSI demonstrated low initial mHLA-DR, with the S. aureus group showing delayed recovery over time. Eleven patients (55% S. aureus) had negative outcome (secondary bacteremia or death) and they demonstrated sustained C-reactive protein elevation, neutrophilia, lymphocytopenia, and loss of mHLA-DR.

    CONCLUSIONS: Dynamics of mHLA-DR varied according to the bacterial etiology of infection, with delayed recovery in patients with S. aureus BSI. Patients with negative outcome showed sustained CRP elevation, neutrophilia, lymphocytopenia, and low levels of mHLA-DR, supporting the theory of a dysregulated host response with persistent inflammation and immunosuppression in late stages of deleterious sepsis.

  • 48.
    Cajander, Sara
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län.
    Stammler Jaliff, B.
    Karolinska University Hospital, Stockholm, Sweden.
    Somell, A.
    Karolinska University Hospital, Stockholm, Sweden.
    Bäckman, Anders
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Alpkvist, H.
    Karolinska University Hospital, Stockholm, Sweden.
    Özenci, V.
    Karolinska University Hospital, Stockholm, Sweden.
    Wernerman, J.
    Karolinska University Hospital, Stockholm, Sweden.
    Strålin, K.
    Karolinska University Hospital, Stockholm, Sweden.
    HLA-DRA and CD74 on intensive care unit admission related to outcome in sepsis2018Ingår i: Critical Care, E-ISSN 1466-609X, Vol. 22, nr Suppl. 1, artikel-id 82Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: mRNA expressions of the major histocompatibility complex class II-related genes HLA-DRA and CD74 have been found to be promising markers for sepsis-induced immunosuppression. In the present study we aimed to study how expression of HLA-DRA and CD74 on intensive care unit (ICU) admission were related to death and/or secondary infections in patients with sepsis.

    Methods: During a full year adult patients admitted to the ICU of Karolinska University Hospital Huddinge were consecutively subjected to blood sampling within 1 hour from ICU admission. Patients treated with antibiotic therapy were eligible for inclusion. The plausibility of infection (definite, probable, possible, none) was determined based on the Centers for Diseases Control (CDC) criteria. Patients with sepsis (definite/probable/possible infection and a SOFA score increase of >=2) were screened for death within 60 days and secondary infections 48 h to 60 days after ICU admission, using the CDC criteria. HLA-DRA and CD74 mRNA expressions were determined by reverse transcription quantitative PCR.

    Results: Among 579 ICU admissions, a blood sample for RNA analysis was collected in 551 cases. Two hundred fifty-seven patients met the inclusion criteria and provided written informed consent. Sepsis was noted in 134 patients. The sepsis patients experienced death in 36 cases (27%), secondary infection in 32 cases (24%), and death and/or secondary infection in 60 cases (45%). Table 1 shows the results of HLA-DRA and CD74 expression related to death and secondary infections.

    Conclusions: The mRNA expression of HLA-DRA on ICU admission was significantly decreased in patients with sepsis who died or contracted secondary infections within 60 days. CD74 expression was not significantly decreased in patients with negative outcome.

  • 49.
    Cajander, Sara
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Tina, Elisabet
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Clinical Research Laboratory, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Clinical Research Laboratory, Örebro University Hospital, Örebro, Sweden.
    Magnuson, Anders
    Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Strålin, Kristoffer
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden .
    Söderquist, Bo
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Källman, Jan
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    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 Sepsis2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 5, artikel-id e0154690Artikel i tidskrift (Refereegranskat)
    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.

  • 50.
    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 universitet, Institutionen för hälsovetenskaper. WHO Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    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 China2016Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, nr 1, s. 92-99Artikel i tidskrift (Refereegranskat)
    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.

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