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

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

  • 2.
    Abdurahman, Samir
    et al.
    Division of Clinical Microbiology, Department of Laboratory Medicine F68, Karolinska University Hospital, 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 Sweden2014In: Journal of the International AIDS Society, E-ISSN 1758-2652, Vol. 17, p. 18841-Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 3.
    Aguado, J. M.
    et al.
    Univ Hosp 12 Octubre, Madrid, Spain.
    Anttila, V. J.
    Univ Helsinki, 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
    Örebro University Hospital.
    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 line2015In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 90, no 2, p. 117-125Article in journal (Refereed)
    Abstract [en]

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

  • 4.
    Ahlstrand, Erik
    et al.
    Örebro University Hospital. Örebro University, School of Medical Sciences. Department of Medicine.
    Cajander, Sara
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Infectious Diseases.
    Cajander, Per
    Örebro University, School of Medical Sciences. Department of Anesthesiology and Intensive Care.
    Ingberg, Edvin
    Faculty of Medicine and Health, Department of Infectious Diseases, Örebro University, Örebro, Sweden.
    Löf, Erika
    Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Wegener, Matthias
    Department of Radiology, Örebro University Hospital, Örebro, Sweden.
    Lidén, Mats
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Radiology.
    Visual scoring of chest CT at hospital admission predicts hospitalization time and intensive care admission in Covid-192021In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 53, no 8, p. 622-632Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Chest CT is prognostic in Covid-19 but there is a lack of consensus on how to report the CT findings. A chest CT scoring system, ÖCoS, was implemented in clinical routine on 1 April 2020, in Örebro Region, Sweden. The ÖCoS-severity score measures the extent of lung involvement. The objective of the study was to evaluate the ÖCoS scores as predictors of the clinical course of Covid-19.

    METHODS: Population based study including data from all hospitalized patients with Covid-19 in Örebro Region during March to July 2020. We evaluated the correlations between CT scores at the time of admission to hospital and intensive care in relation to hospital and intensive care length of stay (LoS), intensive care admission and death. C-reactive protein and lymphocyte count were included as covariates in multivariate regression analyses.

    RESULTS: In 381 included patients, the ÖCoS-severity score at admission closely correlated to hospital length of stay, and intensive care admission or death. At admission to intensive care, the ÖCoS-severity score correlated with intensive care length of stay. The ÖCoS-severity score was superior to basic inflammatory biomarkers in predicting clinical outcomes.

    CONCLUSION: Chest CT visual scoring at admission to hospital predicted the clinical course of Covid-19 pneumonia.

  • 5.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Hematology, Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University Hospital. 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 University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. 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 malignancies2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 6, article id e99045Article in journal (Refereed)
    Abstract [en]

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

  • 6.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Hematology, Department of Medicine,Örebro University Hospital, Örebro, Sweden.
    Persson, Lennart
    Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Clinical Microbiology, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Alteration of the colonization pattern of coagulase-negative staphylococci in patients undergoing treatment for hematological malignancy2012In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 31, no 7, p. 1679-1687Article in journal (Refereed)
    Abstract [en]

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

  • 7.
    Akhtar, Zubair
    et al.
    Infectious Diseases Division, ICDDRB, Dhaka, Dhaka District, Bangladesh.
    Chowdhury, Fahmida
    Infectious Diseases Division, ICDDRB, Dhaka, Dhaka District, Bangladesh.
    Aleem, Mohammad Abdul
    Infectious Diseases Division, ICDDRB, Dhaka, Dhaka District, Bangladesh; Biosecurity Research Program, Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
    Ghosh, Probir Kumar
    Infectious Diseases Division, ICDDRB, Dhaka, Dhaka District, Bangladesh.
    Rahman, Mahmudur
    Infectious Diseases Division, ICDDRB, Dhaka, Dhaka District, Bangladesh.
    Rahman, Mustafizur
    Infectious Diseases Division, ICDDRB, Dhaka, Dhaka District, Bangladesh.
    Hossain, Mohammad Enayet
    Infectious Diseases Division, ICDDRB, Dhaka, Dhaka District, Bangladesh.
    Sumiya, Mariya Kibtiya
    Infectious Diseases Division, ICDDRB, Dhaka, Dhaka District, Bangladesh.
    Islam, A. K. M. Monwarul
    Department of Cardiology, National Institute of Cardiovascular Diseases Dhaka (NICVD), Dhaka, Bangladesh.
    Uddin, Mir Jamal
    Department of Cardiology, National Institute of Cardiovascular Diseases Dhaka (NICVD), Dhaka, Bangladesh.
    MacIntyre, C. Raina
    Biosecurity Research Program, Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
    Cajander, Sara
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Infectious Diseases.
    Fröbert, Ole
    Department of Cardiology, Örebro University Hospital, Orebro, Swede.
    Undiagnosed SARS-CoV-2 infection and outcome in patients with acute MI and no COVID-19 symptoms2021In: Open heart, E-ISSN 2053-3624, Vol. 8, no 1, article id e001617Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We aimed to determine the prevalence and outcome of occult infection with SARS-CoV-2 and influenza in patients presenting with myocardial infarction (MI) without COVID-19 symptoms.

    METHODS: We conducted an observational study from 28 June to 11 August 2020, enrolling patients admitted to the National Institute of Cardiovascular Disease Hospital, Dhaka, Bangladesh, with ST-segment elevation MI (STEMI) or non-ST-segment elevation MI who did not meet WHO criteria for suspected COVID-19. Samples were collected by nasopharyngeal swab to test for SARS-CoV-2 and influenza virus by real-time reverse transcriptase PCR. We followed up patients at 3 months (13 weeks) postadmission to record adverse cardiovascular outcomes: all-cause death, new MI, heart failure and new percutaneous coronary intervention or stent thrombosis. Survival analysis was performed using the Kaplan-Meier method.

    RESULTS: We enrolled 280 patients with MI, 79% male, mean age 54.5±11.8 years, 140 of whom were diagnosed with STEMI. We found 36 (13%) to be infected with SARS-CoV-2 and 1 with influenza. There was no significant difference between mortality rate observed among SARS-CoV-2 infected patients compared with non-infected (5 (14%) vs 26 (11%); p=0.564). A numerically shorter median time to a recurrent cardiovascular event was recorded among SARS-CoV-2 infected compared with non-infected patients (21 days, IQR: 8-46 vs 27 days, IQR: 7-44; p=0.378).

    CONCLUSION: We found a substantial rate of occult SARS-CoV-2 infection in the studied cohort, suggesting SARS-CoV-2 may precipitate MI. Asymptomatic patients with COVID-19 admitted with MI may contribute to disease transmission and warrants widespread testing of hospital admissions.

  • 8.
    Aleman, Soo
    et al.
    Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
    Söderholm, Jonas
    AbbVie AB, Stockholm, Sweden; Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Büsch, Katharina
    AbbVie AB, Stockholm, Sweden; Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Kövamees, Jan
    AbbVie AB, Stockholm, Sweden.
    Duberg, Ann-Sofi
    Örebro University, School of Health Sciences. partment of Infectious Diseases.
    Frequent loss to follow-up after diagnosis of hepatitis C virus infection: A barrier towards the elimination of hepatitis C virus2020In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 40, no 8, p. 1832-1840Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous studies on hepatitis C cascade of care have been mainly focused on diagnosis and treatment rate, while less attention has been given to patients lost to follow-up (LTFU) after diagnosis. Analyses of this latter issue on population level are missing.

    AIMS: In this nationwide study of people with HCV, we aimed to estimate the proportion LTFU after HCV diagnosis, characterize them, and analyze their other healthcare contacts.

    METHODS: Patients diagnosed with chronic HCV in the Swedish National Patient register during 2001-2011 and still alive December 31, 2013, were included. The number of cured patients without need of follow-up was estimated. Visits to HCV specialist care during 2012-2013 were analysed. For those LTFU, other specialist care contacts were studied.

    RESULTS: In total 29,217 patients were included, with 24,733 with need of HCV care. 61% (n=15,007) of them were LTFU from HCV care in 2012-2013 and 58% did not attend HCV care during the second year after HCV diagnosis. The departments of surgery/orthopedic or psychiatry/dependency were the most common other non-primary healthcare contacts. Predictors for LTFU were young age, male sex, low education, presence of psychiatric/dependency diagnosis, unmarried, and longer duration since diagnosis of HCV.

    CONCLUSIONS: This study showed that almost two-thirds of patients were LTFU after HCV diagnosis, with frequent occurrence early after diagnosis. Efforts to link patients back to HCV care, in combination with early and easy access to HCV treatment and harm reduction, are necessary to reach the HCV elimination goal.

  • 9.
    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 medicines2017In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, no 7, article id e1002366Article in journal (Refereed)
    Abstract [en]

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

  • 10.
    Al-Maslamani, Muna
    et al.
    Hamad Medical Corporation, Doha, Qatar.
    Elmagboul, Emad Bashier Ibrahim
    Hamad Medical Corporation, Doha, Qatar; Infectious Diseases Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar.
    Puthiyottil, Aslam
    Hamad Medical Corporation, Doha, Qatar.
    Chemaitelly, Hiam
    Infectious Diseases Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar; World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar.
    Varghese, Manoj Kizhakkepeedikayil
    Hamad Medical Corporation, Doha, Qatar.
    Al Romaihi, Hamad Eid
    Ministry of Public Health, Doha, Qatar.
    Al-Thani, Mohamed H.
    Ministry of Public Health, Doha, Qatar.
    Al Khal, Abdullatif
    Hamad Medical Corporation, Doha, Qatar.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. Faculty of Medicine and Health, WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Örebro University, Örebro, Sweden; Institute for Global Health, University College London, London, United Kingdom.
    Abu-Raddad, Laith J.
    Infectious Diseases Epidemiology Group, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar; World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine-Qatar, Cornell University, Qatar Foundation-Education City, Doha, Qatar; Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York City, New York, United States of America; Department of Public Health, College of Health Sciences, Member of QU Health, Qatar University, Doha, Qatar.
    First characterisation of antimicrobial susceptibility and resistance of Neisseria gonorrhoeae isolates in Qatar, 2017-20202022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 3, article id e0264737Article in journal (Refereed)
    Abstract [en]

    Limited data are available regarding antimicrobial resistance in Neisseria gonorrhoeae strains circulating in WHO Eastern Mediterranean Region (EMR). We investigated the antimicrobial susceptibility/resistance of N. gonorrhoeae isolates to five antimicrobials (ceftriaxone, azithromycin, ciprofloxacin, tetracycline, and benzylpenicillin) currently or previously used for gonorrhoea treatment in Qatar, 2017-2020. Minimum inhibitory concentrations (MICs; mg/L) of antimicrobials were determined using Etest on gonococcal isolates collected during January 1, 2017-August 30, 2020 at Hamad Medical Corporation, a national public healthcare provider. During 2017-2020, resistance in isolates from urogenital sites of 433 patients was 64.7% (95% CI: 59.5-69.6%; range: 43.9-78.7%) for ciprofloxacin, 50.7% (95% CI: 45.3-56.1%; range: 41.3-70.4%) for tetracycline, and 30.8% (95% CI: 26.3-35.6%; range: 26.7-35.8%) for benzylpenicillin. Percentage of isolates non-susceptible to azithromycin was 4.1% (95% CI: 2.0-7.4%; range: 2.7-4.8%) and all (100%) isolates were susceptible to ceftriaxone. Two (1.6%) isolates from 2019 and one (2.2%) isolate from 2020 had high-level resistance to azithromycin (MIC≥256 mg/L). Overall, 1.0% (4/418) of isolates had a ceftriaxone MIC of 0.25 mg/L, which is at the ceftriaxone susceptibility breakpoint (MIC≤0.25 mg/L). Treatment with ceftriaxone 250 mg plus azithromycin 1 g can continuously be recommended for gonorrhoea therapy in Qatar. Continued quality-assured gonococcal AMR surveillance is warranted in EMR.

  • 11.
    Alpkvist, Helena
    et al.
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Athlin, Simon
    Örebro University, School of Medical Sciences. Örebro University Hospital. 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 pneumonia2018In: Scientific Reports, E-ISSN 2045-2322, Vol. 8, no 1, article id 13428Article in journal (Refereed)
    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.

  • 12.
    Alpkvist, Helena
    et al.
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Athlin, Simon
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious Diseases, 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 Pneumonia2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 10, article id e0140112Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 13.
    Alpkvist, Helena
    et al.
    Karolinska University Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Athlin, Simon
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nauclér, Pontus
    Karolinska University Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Herrmann, Björn
    Uppsala University, Uppsala, Sweden.
    Abdeldaim, Guma
    Uppsala University, Uppsala, Sweden; Benghazi University, Benghazi, Libya.
    Slotved, Hans-Christian
    Statens Serum Institut, Copenhagen, Denmark.
    Hedlund, Jonas
    Karolinska University Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden .
    Strålin, Kristoffer
    Karolinska University Hospital, Stockholm, Sweden; Karolinska Institutet, Stockholm, Sweden; Örebro University, Örebro, Sweden.
    Clinical and microbiological factors associated with high pneumococcal colonization density in pneumococcal pneumoniaManuscript (preprint) (Other academic)
  • 14.
    Altun, O.
    et al.
    Division of Clinical Microbiology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Athlin, Simon
    Örebro University, School of Medical Sciences. 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 test2016In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, no 4, p. 579-585Article in journal (Refereed)
    Abstract [en]

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

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

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

  • 16.
    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 University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University, School of Medical Sciences. 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 outcomes2015In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 15, article id 581Article in journal (Refereed)
    Abstract [en]

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

  • 17.
    Andersson, Martin
    et al.
    Department of Research and Development, Region Kronoberg, Växjö, Sweden.
    Pallon, Jon
    Department of Research and Development, Region Kronoberg, Växjö, Sweden; Department of Clinical Sciences in Malmö, Family Medicine, Lund University, Malmö, Sweden.
    Cronberg, Olof
    Department of Research and Development, Region Kronoberg, Växjö, Sweden; Department of Clinical Sciences in Malmö, Family Medicine, Lund University, Malmö, Sweden.
    Sundqvist, Martin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology.
    Hedin, Katarina
    Department of Clinical Sciences in Malmö, Family Medicine, Lund University, Malmö, Sweden; Futurum, Region Jönköping County, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Seasonal variations in use and outcome of rapid antigen detection tests and cultures in pharyngotonsillitis: a register study in primary care2021In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 21, no 1, article id 1104Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Diagnosis and treatment of pharyngotonsillitis are commonly focused on group A streptococci (GAS), although the disease is often associated with other pathogens. While the incidence of pharyngotonsillitis is known to vary with season, seasonal variations in the prevalence of potential pathogens are sparsely explored. The aim of this study was to explore any seasonal variations in the use and outcome of rapid antigen detection tests (RADTs) for GAS and throat cultures among patients diagnosed with pharyngotonsillitis in primary care.

    METHODS: We retrieved and combined retrospective data from the electronic medical record system and the laboratory information system in Kronoberg County, Sweden. Primary care visits resulting in a diagnosis of tonsillitis or pharyngitis were included, covering the period 2013-2016. The monthly rate of visits was measured, along with the use and outcome of RADTs for GAS and throat cultures obtained on the date of diagnosis. The variations between calendar months were then analysed.

    RESULTS: We found variations between calendar months, not only in the mean rate of visits resulting in a diagnosis of pharyngotonsillitis (p < 0.001), but in the mean proportion of RADTs being positive for GAS among the diagnosed (p < 0.001), and in the mean proportion of visits associated with a throat culture (p < 0.001). A lower mean rate of visits in August and September coincided with a lower proportion of RADTs being positive for GAS among them, which correlated with a higher proportion of visits associated with a throat culture.

    CONCLUSIONS: This study suggests that the role of GAS in pharyngotonsillitis in Sweden is less prominent in August and September than during the rest of the year.

  • 18.
    Aniskevich, Aliaksandra
    et al.
    Belarusian Medical Academy of Postgraduate Education, Minsk, Belarus.
    Shimanskaya, Iryna
    Belarusian Medical Academy of Postgraduate Education, Minsk, Belarus.
    Boiko, Iryna
    Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine; World Health Organization Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections (STIs), National Reference Laboratory for STIs, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Golubovskaya, Tatyana
    Mogilev Regional Skin and Venereal Diseases Dispensary, Mogilev, Belarus.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. World Health Organization Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections (STIs), National Reference Laboratory for STIs, Department of Laboratory Medicine, Clinical Microbiology.
    Stanislavova, Iryna
    Mogilev Regional Skin and Venereal Diseases Dispensary, Mogilev, Belarus.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections (STIs), National Reference Laboratory for STIs, Department of Laboratory Medicine, Clinical Microbiology.
    Adaskevich, Aliaksandr
    Mogilev Regional Skin and Venereal Diseases Dispensary, Mogilev, Belarus.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections (STIs), National Reference Laboratory for STIs, Department of Laboratory Medicine, Clinical Microbiology.
    Antimicrobial resistance in Neisseria gonorrhoeae isolates and gonorrhoea treatment in the Republic of Belarus, Eastern Europe, 2009-20192021In: BMC Infectious Diseases, E-ISSN 1471-2334, Vol. 21, no 1, article id 520Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Limited antimicrobial resistance (AMR) data for Neisseria gonorrhoeae are available in Eastern Europe. We investigated AMR in N. gonorrhoeae isolates in the Republic of Belarus from 2009 to 2019, antimicrobial treatment recommended nationally, and treatment given to patients with gonorrhoea.

    METHODS: N. gonorrhoeae isolates (n = 522) cultured in three regions of Belarus in 2009-2019 were examined. Determination of minimum inhibitory concentrations (MICs) of eight antimicrobials was performed using Etest. Resistance breakpoints from the European Committee on Antimicrobial Susceptibility Testing were applied where available. A Nitrocefin test identified β-lactamase production. Gonorrhoea treatment for 1652 patients was also analysed. Statistical significance was determined by the Z-test, Fisher's exact test, or Mann-Whitney U test with p-values of < 0.05 indicating significance.

    RESULTS: In total, 27.8% of the N. gonorrhoeae isolates were resistant to tetracycline, 24.7% to ciprofloxacin, 7.0% to benzylpenicillin, 2.7% to cefixime, and 0.8% to azithromycin. No isolates were resistant to ceftriaxone, spectinomycin, or gentamicin. However, 14 (2.7%) isolates had a ceftriaxone MIC of 0.125 mg/L, exactly at the resistance breakpoint (MIC > 0.125 mg/L). Only one (0.2%) isolate, from 2013, produced β-lactamase. From 2009 to 2019, the levels of resistance to ciprofloxacin and tetracycline were relatively high and stable. Resistance to cefixime was not identified before 2013 but peaked at 22.2% in 2017. Only sporadic isolates with resistance to azithromycin were found in 2009 (n = 1), 2012 (n = 1), and 2018-2019 (n = 2). Overall, 862 (52.2%) patients received first-line treatment according to national guidelines (ceftriaxone 1 g). However, 154 (9.3%) patients received a nationally recommended alternative treatment (cefixime 400 mg or ofloxacin 400 mg), and 636 (38.5%) were given non-recommended treatment.

    CONCLUSIONS: The gonococcal resistance to ciprofloxacin and tetracycline was high, however, the resistance to azithromycin was low and no resistance to ceftriaxone was identified. Ceftriaxone 1 g can continuously be recommended as empiric first-line gonorrhoea therapy in Belarus. Fluoroquinolones should not be prescribed for treatment if susceptibility has not been confirmed by testing. Timely updating and high compliance with national evidence-based gonorrhoea treatment guidelines based on quality-assured AMR data are imperative. The need for continued, improved and enhanced surveillance of gonococcal AMR in Belarus is evident.

  • 19.
    Ariel Gianecini, Ricardo
    et al.
    Instituto Nacional de Enfermedades Infecciosas—Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
    Poklepovich, Tomas
    Instituto Nacional de Enfermedades Infecciosas—Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. World Health Organization Collaborating Centre for Gonorrhoea and Other STIs.
    Cuenca, Noelia
    Instituto Nacional de Enfermedades Infecciosas—Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
    Tuduri, Ezequiel
    Instituto Nacional de Enfermedades Infecciosas—Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization Collaborating Centre for Gonorrhoea and Other STIs.
    Campos, Josefina
    Instituto Nacional de Enfermedades Infecciosas—Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
    Galarza, Patricia
    Instituto Nacional de Enfermedades Infecciosas—Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
    Genomic Epidemiology of Azithromycin-Nonsusceptible Neisseria gonorrhoeae, Argentina, 2005-20192021In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 27, no 9, p. 2369-2378Article in journal (Refereed)
    Abstract [en]

    Azithromycin-nonsusceptible Neisseria gonorrhoeae strains are an emerging global public health threat. During 2015-2018, the prevalence of azithromycin-nonsusceptible gonococcal infection increased significantly in Argentina. To investigate the genomic epidemiology and resistance mechanisms of these strains, we sequenced 96 nonsusceptible isolates collected in Argentina during 2005-2019. Phylogenomic analysis revealed 2 main clades, which were characterized by a limited geographic distribution, circulating during January 2015-November 2019. These clades included the internationally spreading multilocus sequence types (STs) 1580 and 9363. The ST1580 isolates, which had MICs of 2-4 mu g/mL, had mutations in the 23S rRNA. The ST9363 isolates, which had MICs of 2-4 or >256 mu g/mL, had mutations in the 23S rRNA, a mosaic mtr locus, or both. Identifying the geographic dissemination and characteristics of these predominant clones will guide public health policies to control the spread of azithromycin-nonsusceptible N. gonorrhoeae in Argentina.

  • 20.
    Arnason, Sigurdur
    et al.
    Department of Clinical Science, Intervention and Technology – CLINTEC, Huddinge, Stockholm, Sweden; Department of Pediatric Infectious Diseases, Astrid Lindgren’s Children’s Hospital, Solna, Stockholm, Sweden.
    Molewijk, Kesia
    Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Henningsson, Anna J.
    Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linköping University, Linköping, Sweden; National Reference Laboratory for Borrelia and Other Tick-Borne Bacteria, Division of Clinical Microbiology, Laboratory Medicine, Region Jönköping County, Linköping University, Linköping, Sweden; Department of Clinical Microbiology in Linköping, Linköping University, Linköping, Sweden.
    Tjernberg, Ivar
    Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linköping University, Linköping, Sweden; Department of Clinical Chemistry and Transfusion Medicine, Region Kalmar County, Kalmar, Sweden.
    Skogman, Barbro H
    Örebro University, School of Medical Sciences. Center for Clinical Research Dalarna – Uppsala University, Falun, Sweden; Department of Clinical Science, Intervention and Technology – CLINTEC, Karolinska Institutet, Huddinge, Stockholm, Sweden.
    Brain damage markers neuron-specific enolase (NSE) and S100B in serum in children with Lyme neuroborreliosis-detection and evaluation as prognostic biomarkers for clinical outcome2022In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 41, no 7, p. 1051-1057Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis (LB) is the most common tick-borne infection in Europe, with Lyme neuroborreliosis (LNB) its second most frequent clinical manifestation. Prognostic factors for clinical outcomes in LNB have not been identified. Elevated serum levels of the brain damage markers neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) have been associated with poor clinical outcomes in other disorders of the central nervous system. The aim of this study is to assess NSE and S100B in serum as prognostic biomarkers for clinical outcomes in paediatric LNB patients. Children evaluated for LNB (n= 121) in Sweden were prospectively included during 2010-2014, serum samples were collected on admission, and all children underwent a 2-month follow-up. Patients with pleocytosis and anti-Borrelia antibodies in cerebrospinal fluid (CSF) were classified as having LNB (n= 61). Controls were age- and gender-matched non-LNB patients (n= 60). NSE was elevated in 38/61 (62%) LNB patients and in 31/60 (52%) controls. S100B was elevated in 3/60 (5%) LNB patients and 0/59 (0%) controls. NSE and S100B concentrations did not differ significantly when comparing LNB patients with controls. No differences were found in the concentrations when comparing the clinical recovery of LNB patients at the 2-month follow-up. NSE was detectable in the majority of LNB patients and controls, whereas S100B was detectable in only a few LNB patients and no controls. NSE and S100B in serum cannot be recommended as prognostic biomarkers for clinical outcomes in children with LNB.

  • 21.
    Arnason, Sigurdur
    et al.
    Department of Clinical Science, Intervention and Technology - CLINTEC, Huddinge, Sweden; Department of Pediatric Infectious Diseases, Astrid Lindgren's Children's Hospital, Solna, Stockholm, Sweden.
    Skogman, Barbro H.
    Örebro University, School of Medical Sciences. Center for Clinical Research Dalarna - Uppsala University, Falun, Sweden; Department of Clinical Science, Intervention and Technology - CLINTEC, Karolinska Institutet, Huddinge, Sweden.
    Effectiveness of antibiotic treatment in children with Lyme neuroborreliosis: a retrospective study2022In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 22, no 1, article id 332Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Lyme neuroborreliosis (LNB) is a tick-borne infection caused by the spirochete Borrelia burgdorferi sensu lato complex with various neurological manifestations. The recommended treatment for LNB in Swedish children has been intravenous ceftriaxone 50-100 mg/kg × 1 (< 8 years of age) or oral doxycycline 4 mg/kg × 1 (≥ 8 years of age) for 10-14 days. Studies on adult LNB patients have shown equal efficacy for ceftriaxone and doxycycline, but no such studies have been conducted on pediatric LNB patients. The aim of this study is to retrospectively evaluate clinical outcome in children with LNB who have received intravenous ceftriaxone or oral doxycycline.

    RESULTS: Clinical and laboratory data from three previously conducted prospective studies on children with LNB (1998-2014) were retrospectively analyzed. A total of 321 children (1-19 years of age), who received antibiotic treatment for definite LNB or possible LNB, were included. Clinical outcome at the 2-month follow-up (recovery/non-recovery) was evaluated using Chi2 test and logistic multivariate regression analysis. Out of 321 LNB patients, 194 children (60%) had received ceftriaxone and 127 children (40%) had received doxycycline. When comparing clinical outcome between treatment groups, no difference was found (p = 0,217). Results did not change when incorporating relevant clinical and laboratory data into the logistic multivariate regression analysis.

    CONCLUSION: In this large retrospective study, no difference in clinical outcome was found, independent of age, when comparing children who received ceftriaxone with those who received doxycycline, supporting an equal effectiveness for treatment of LNB pediatric patients. However, future randomized comparative treatment studies are warranted for evaluation of efficacy of antibiotic treatment in pediatric LNB patients.

  • 22.
    Asghar, Naveed
    et al.
    Örebro University, School of Medical Sciences.
    Gunaltay, Sezin
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Tran, Pham Tue Hung
    Örebro University, School of Medical Sciences.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    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 University, School of Medical Sciences.
    DNA launched suicidal flaviviruses as therapeutic vaccine candidates2018Conference paper (Refereed)
    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.

  • 23.
    Asghar, Naveed
    et al.
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden.
    Lindblom, Pontus
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Melik, Wessam
    School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden.
    Lindqvist, Richard
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden.
    Haglund, Mats
    Department of Infectious Diseases, County Hospital, Kalmar, Sweden.
    Forsberg, Pia
    Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Clinic of Infectious Diseases, Linköping University Hospital, Linköping, Sweden.
    Överby, Anna K.
    Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden.
    Andreassen, Åshild
    Division of Infectious Disease Control, Department of Virology, Norwegian Institute of Public Health, Oslo, Norway.
    Lindgren, Per-Eric
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Division of Medical Services, Department of Microbiology, County Hospital Ryhov, Jönköping, Sweden.
    Johansson, Magnus
    Örebro University, School of Medicine, Örebro University, Sweden. School of Natural Science, Technology & Environmental Studies, Södertörn University, Huddinge, Sweden; RiSC - Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Tick-Borne Encephalitis Virus Sequenced Directly from Questing and Blood-Feeding Ticks Reveals Quasispecies Variance2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 7, article id e103264Article in journal (Refereed)
    Abstract [en]

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

  • 24.
    Asghar, Naveed
    et al.
    Örebro University, School of Medical Sciences.
    Maravelia, Panagiota
    aboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Caro-Perez, Noelia
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Tran, Hung
    Örebro University, School of Medical Sciences.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    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 University, School of Medical Sciences.
    Immunogenicity of DNA launched suicidal flavivirus replicons for protective vaccination against hepatitis viruses2019Conference paper (Refereed)
    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.

  • 25.
    Asghar, Naveed
    et al.
    Örebro University, School of Medical Sciences.
    Maravelia, Panagiota
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Caro-Perez, Noelia
    Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
    Tran, Pham Tue Hung
    Örebro University, School of Medical Sciences.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    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 University, School of Medical Sciences.
    Immunogenicity of DNA launched suicidal flavivirus replicons for protective vaccination against hepatitis viruses2019Conference paper (Refereed)
    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.

  • 26.
    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 University, School of Medical Sciences. 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 ricinus2016In: Geospatial health, ISSN 1827-1987, Vol. 11, no 3, p. 283-289, article id 487Article in journal (Refereed)
    Abstract [en]

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

  • 27.
    Athlin, Simon
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. 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 bacteremia2015In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 34, no 8, p. 1583-1588Article in journal (Refereed)
    Abstract [en]

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

  • 28.
    Athlin, Simon
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Altun, Osman
    Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Brander Eriksen, Helle
    Copenhagen University Hospital Hvidovre, Copenhagen, Denmark.
    Özenci, Volkan
    Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Strålin, Kristoffer
    Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    The Uni-Gold™ Streptococcus pneumoniae urinary antigen test: an inter-assay comparison with the BinaxNOW® Streptococcus pneumoniae test on consecutive urine samples and evaluation on patients with bacteremiaManuscript (preprint) (Other academic)
  • 29.
    Athlin, Simon
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Granath, F.
    Strålin, K.
    Hedlund, J.
    Spindler, C.
    Naucler, P.
    Usefulness of pneumococcal urinary antigen detection for antimicrobial guidance in community-acquired pneumonia2018Conference paper (Refereed)
  • 30.
    Athlin, Simon
    et al.
    Örebro University Hospital. Örebro University, School of Medical Sciences. 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 urine2017In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, no 10, p. 1933-1938Article in journal (Refereed)
    Abstract [en]

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

  • 31.
    Athlin, Simon
    et al.
    Örebro University Hospital.
    Kaltoft, Margit
    Statens Serum Institut, Copenhagen, Denmark.
    Slotved, Hans-Christian
    Statens Serum Institut, Copenhagen, Denmark.
    Herrmann, Björn
    Uppsala University, Uppsala, Sweden.
    Holmberg, Hans
    Örebro University Hospital.
    Konradsen, Helle Bossen
    Statens Serum Institut, Copenhagen, Denmark.
    Strålin, Kristoffer
    Örebro University Hospital, Örebro, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Association between serotype-specific antibody response and serotype characteristics in patients with pneumococcal pneumonia, with special reference to degree of encapsulation and invasive potential2014In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 11, p. 1541-1549Article in journal (Refereed)
    Abstract [en]

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

  • 32.
    Athlin, Simon
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Larsson, Emelie
    Nordenskjöld, Anna M.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Fröbert, Ole
    Örebro University, School of Medical Sciences.
    Evaluation of the novel IMMUVIEW RSV antigen test for detection of respiratory syncytial virus in adults and children2019Conference paper (Other academic)
  • 33.
    Athlin, Simon
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. 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 20172018In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 50, no 4, p. 247-272Article, review/survey (Refereed)
    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.

  • 34.
    Athlin, Simon
    et al.
    Örebro University Hospital.
    Strålin, Kristoffer
    Örebro University Hospital, Örebro, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    The Binax NOW Streptococcus pneumoniae test applied on nasopharyngeal aspirates to support pneumococcal aetiology in community-acquired pneumonia.2013In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, no 6, p. 425-31Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 35.
    Athlin, Simon
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    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 antibiotics2016Conference paper (Refereed)
  • 36.
    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 University, School of Medical Sciences. Örebro University Hospital. 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, 2012-20152019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 10, article id e0223598Article in journal (Refereed)
    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.

  • 37.
    Ayala, Julio C.
    et al.
    Department of Microbiology and Immunology, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA.
    Schmerer, Matthew W.
    STD Laboratory Reference and Research Branch, Division of STD Prevention, NCHHSTP, Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
    Kersh, Ellen N.
    STD Laboratory Reference and Research Branch, Division of STD Prevention, NCHHSTP, Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, Department of Laboratory Medicine, Microbiology.
    Shafer, William M.
    Department of Microbiology and Immunology, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA; Emory Antibiotic Resistance Center, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA; Laboratories of Bacterial Pathogenesis, Veterans Affairs Medical Center, Decatur, Georgia, USA.
    Gonococcal Clinical Strains Bearing a Common gdhR Single Nucleotide Polymorphism That Results in Enhanced Expression of the Virulence Gene lctP Frequently Possess a mtrR Promoter Mutation That Decreases Antibiotic Susceptibility2022In: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 13, no 2, article id e0027622Article in journal (Refereed)
    Abstract [en]

    GdhR is a transcriptional repressor of the virulence factor gene lctP, which encodes a unique l-lactate permease that has been linked to pathogenesis of Neisseria gonorrhoeae, and loss of gdhR can confer increased fitness of gonococci in a female mouse model of lower genital tract infection. In this work, we identified a single nucleotide polymorphism (SNP) in gdhR, which is often present in both recent and historical gonococcal clinical strains and results in a proline (P)-to-serine (S) change at amino acid position 6 (P6S) of GdhR. This mutation (gdhR6) was found to reduce GdhR transcriptional repression at lctP in gonococcal strains containing the mutant protein compared to wild-type GdhR. By using purified recombinant proteins and in vitro DNA-binding and cross-linking experiments, we found that gdhR6 impairs the DNA-binding activity of GdhR at lctP without an apparent effect on protein oligomerization. By analyzing a panel of U.S. (from 2017 to 2018) and Danish (1928 to 2013) clinical isolates, we observed a statistical association between gdhR6 and the previously described adenine deletion in the promoter of mtrR (mtrR-P A-del), encoding the repressor (MtrR) of the mtrCDE operon that encodes the MtrCDE multidrug efflux pump that can export antibiotics, host antimicrobials, and biocides. The frequent association of gdhR6 with the mtrR promoter mutation in these clinical isolates suggests that it has persisted in this genetic background to enhance lctP expression, thereby promoting virulence. IMPORTANCE We report the frequent appearance of a novel SNP in the gdhR gene (gdhR6) possessed by Neisseria gonorrhoeae. The resulting amino acid change in the GdhR protein resulted in enhanced expression of a virulence gene (lctP) that has been suggested to promote gonococcal survival during infection. The mutant GdhR protein expressed by gdhR6 had a reduced ability to bind to its target DNA sequence upstream of lctP. Interestingly, gdhR6 was found in clinical gonococcal strains isolated in the United States and Denmark at a high frequency and was frequently associated with a mutation in the promoter of the gene encoding a repressor (MtrR) of both the mtrCDE antimicrobial efflux pump operon and gdhR. Given this frequent association and the known impact of these regulatory mutations, we propose that virulence and antibiotic resistance properties are often phenotypically linked in contemporary gonococcal strains.

  • 38.
    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 University, School of Health Sciences. 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 gonorrhoeae2016In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 7, p. 1856-1859Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 39.
    Banhart, Sebastian
    et al.
    Unit 'Sexually Transmitted Bacterial Infections', Department for Infectious Diseases, Robert Koch Institute, Berlin, Germany.
    Jansen, Klaus
    Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Buder, Susanne
    German Reference Laboratory for Gonococci, Department of Dermatology and Venerology, Vivantes Hospital Berlin, Berlin, Germany.
    Tamminga, Thalea
    Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Calvignac-Spencer, Sébastien
    Project Group 'Epidemiology of Highly Pathogenic Microorganisms', Robert Koch Institute, Berlin, Germany.
    Pilz, Tanja
    Unit 'Sexually Transmitted Bacterial Infections', Department for Infectious Diseases, Robert Koch Institute, Berlin, Germany.
    Martini, Andrea
    Unit 'Sexually Transmitted Bacterial Infections', Department for Infectious Diseases, Robert Koch Institute, Berlin, Germany.
    Dudareva, Sandra
    Charité Universitätsmedizin Berlin, Berlin, Germany; Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Nikisins, Sergejs
    Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Dehmel, Kerstin
    Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Zuelsdorf, Gabriele
    Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Guhl, Eva
    German Reference Laboratory for Gonococci, Department of Dermatology and Venerology, Vivantes Hospital Berlin, Berlin, Germany.
    Graeber, Ingeborg
    German Reference Laboratory for Gonococci, Department of Dermatology and Venerology, Vivantes Hospital Berlin, Berlin, Germany.
    Kohl, Peter K.
    German Reference Laboratory for Gonococci, Department of Dermatology and Venerology, Vivantes Hospital Berlin, Berlin, Germany.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs.
    Bremer, Viviane
    Unit 'HIV/AIDS, STI and Blood-borne Infections', Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
    Heuer, Dagmar
    Unit 'Sexually Transmitted Bacterial Infections', Department for Infectious Diseases, Robert Koch Institute, Berlin, Germany.
    GORENET, Study Group
    Molecular epidemiological typing of Neisseria gonorrhoeae isolates identifies a novel association between genogroup G10557 (G7072) and decreased susceptibility to cefixime, Germany, 2014 to 20172020In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 25, no 41, article id 1900648Article in journal (Refereed)
    Abstract [en]

    Background: Emerging antimicrobial resistance (AMR) challenges gonorrhoea treatment and requires surveillance.AimThis observational study describes the genetic diversity of Neisseria gonorrhoeae isolates in Germany from 2014 to 2017 and identifies N. gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroups associated with AMR or some patient demographics.

    Methods: 1,220 gonococcal isolates underwent AMR testing and NG-MAST. Associations between genogroups and AMR or sex/age of patients were statistically assessed.

    Results: Patients' median age was 32 years (interquartile range: 25-44); 1,078 isolates (88.4%) originated from men. In total, 432 NG-MAST sequence types including 156 novel ones were identified, resulting in 17 major genogroups covering 59.1% (721/1,220) of all isolates. Genogroups G1407 and G10557 (G7072) were significantly associated with decreased susceptibility to cefixime (Kruskal-Wallis chi-squared: 549.3442, df: 16, p < 0.001). Their prevalences appeared to decline during the study period from 14.2% (15/106) to 6.2% (30/481) and from 6.6% (7/106) to 3.1% (15/481) respectively. Meanwhile, several cefixime susceptible genogroups' prevalence seemed to increase. Proportions of isolates from men differed among genogroups (Fisher's exact test, p < 0.001), being e.g. lower for G25 (G51) and G387, and higher for G5441 and G2992. Some genogroups differed relative to each other in affected patients' median age (Kruskal-Wallis chi-squared: 47.5358, df: 16, p < 0.001), with e.g. G25 (G51) and G387 more frequent among ≤ 30 year olds and G359 and G17420 among ≥ 40 year olds.

    Conclusion: AMR monitoring with molecular typing is important. Dual therapy (ceftriaxone plus azithromycin) recommended in 2014 in Germany, or only the ceftriaxone dose of this therapy, might have contributed to cefixime-resistant genogroups decreasing.

  • 40.
    Bark, Tor
    et al.
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Katouli, Mohammad
    Department of Surgery, Karolinska Hospital, Stockholm, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. 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 rat1993In: Circulatory Shock, ISSN 0092-6213, Vol. 41, no 1, p. 60-65Article in journal (Refereed)
    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.

  • 41.
    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 University, School of Medical Sciences. Örebro University Hospital. 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 Patients2018In: Surgical Infections, ISSN 1096-2964, E-ISSN 1557-8674, Vol. 19, no 4, p. 410-416Article in journal (Refereed)
    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.

  • 42.
    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 University, School of Medical Sciences. Örebro University Hospital. 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, 2015-162018In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 73, no 7, p. 1854-1861Article in journal (Refereed)
    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.

  • 43.
    Beale, M.
    et al.
    Wellcome Sanger Institute, Cambridge, UK.
    Marks, M.
    London School of Hygiene and Tropical Medicine, London, UK.
    Cole, M.
    National Infection Service, Public Health England, London, UK.
    Lee, M.
    British Columbia Centre for Disease Control, Vancouver, Canada.
    Pitt, R.
    National Infection Service, Public Health England, London, UK.
    Ruis, C.
    University of Cambridge Department of Medicine, Cambridge, UK.
    Naidu, P.
    Alberta Precision Laboratories, Edmonton, Canada.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for STI.
    Krajden, M.
    British Columbia Centre for Disease Control, Vancouver, Canada.
    Lukehart, S.
    University of Washington, Seattle, USA.
    Morshed, M.
    British Columbia Centre for Disease Control, Vancouver, Canada.
    Fifer, H.
    National Infection Service, Public Health England, London, UK.
    Thomson, N.
    Wellcome Sanger Institute, Cambridge, UK; London School of Hygiene and Tropical Medicine, London, UK.
    CONTEMPORARY SYPHILIS IS CHARACTERISED BY RAPID GLOBAL SPREAD OF PANDEMIC TREPONEMA PALLIDUM LINEAGES2021In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 97, no Suppl. 1, p. A17-A17, article id O01.8Article in journal (Other academic)
    Abstract [en]

    Background: Syphilis is an important sexually transmitted infection caused by the bacterium Treponema pallidum subspecies pallidum. The last two decades have seen syphilis incidence rise in many high-income countries, yet the evolutionary and epidemiological relationships that underpin this are poorly understood, as is the global T. pallidum population structure.

    Methods: We assembled a geographically and temporally diverse collection of clinical and laboratory samples, performing direct sequencing on the majority, and combining these with 133 publicly available sequences to compile a dataset comprising 726 T. pallidum genomes. We analysed the resulting genomes using detailed phylogenetic analysis and clustering.

    Results: We show that syphilis globally can be described by only two deeply branching lineages, Nichols and SS14. We show that both of these lineages can be found circulatingcon currently in 12 of the 23 countries sampled. To provide further phylodynamic resolution we subdivided Treponema pallidum subspecies pallidum into 17 distinct sublineages. Importantly, like SS14, we provide evidence that two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analysis showed that recent isolates circulating in 14 different countries were genetically identical in their core genome to those from other countries, suggesting frequent exchange through international transmission pathways. This contrasts with the majority of samples collected prior to 1983, which are phylogenetically distinct from these more recently isolated sublineages. Bayesian temporal analysis provided evidence of a population bottleneck and decline occurring during the late 1990s, followed by a rapid population expansion a decade later. This was driven by the dominant T. pallidum sublineages circulating today, many of which are resistant to macrolides.

    Conclusion: Combined we show that the population of contemporary syphilis in high-income countries has undergone a recent and rapid global expansion. This dataset will provide a framework for future characterisation and epidemiological investigation of syphilis populations.

  • 44.
    Beale, Mathew A.
    et al.
    Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton, UK.
    Marks, Michael
    Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK; Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, UK.
    Cole, Michelle J.
    HCAI, Fungal, AMR, AMU and Sepsis Division, UK Health Security Agency, London, UK.
    Lee, Min-Kuang
    British Columbia Centre for Disease Control, Public Health Laboratory, Vancouver, British Columbia, Canada.
    Pitt, Rachel
    HCAI, Fungal, AMR, AMU and Sepsis Division, UK Health Security Agency, London, UK.
    Ruis, Christopher
    Molecular Immunity Unit, MRC-Laboratory of Molecular Biology, Department of Medicine, University of Cambridge, Cambridge, UK; Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
    Balla, Eszter
    Bacterial STIs Reference Laboratory, Department of Bacteriology, National Public Health Centre, Budapest, Hungary.
    Crucitti, Tania
    Department of Clinical Sciences, Institute of Tropical Medicine, Antwerpen, Belgium.
    Ewens, Michael
    Brotherton Wing, Leeds General Infirmary, Leeds, UK.
    Fernández-Naval, Candela
    Microbiology Department, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
    Grankvist, Anna
    National Reference Laboratory for STIs, Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Guiver, Malcolm
    Laboratory Network, Manchester, UK Health Security Agency, Manchester Royal Infirmary, Manchester, UK.
    Kenyon, Chris R.
    Department of Clinical Sciences, Institute of Tropical Medicine, Antwerpen, Belgium.
    Khairullin, Rafil
    Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
    Kularatne, Ranmini
    Centre for HIV and STI, National Institute for Communicable Diseases, Johannesburg, South Africa.
    Arando, Maider
    STI Unit Vall d'Hebron-Drassanes, Infectious Diseases Department, Hospital Vall d'Hebron, Barcelona, Spain.
    Molini, Barbara J.
    Department of Medicine, University of Washington, Seattle, WA, USA.
    Obukhov, Andrey
    Tuvan Republican Skin and Venereal Diseases Dispensary, Ministry of Health of Tuva Republic, Kyzyl, Russia.
    Page, Emma E.
    Virology Department, Old Medical School, Leeds Teaching Hospitals Trust, Leeds, UK.
    Petrovay, Fruzsina
    Bacterial STIs Reference Laboratory, Department of Bacteriology, National Public Health Centre, Budapest, Hungary.
    Rietmeijer, Cornelis
    Colorado School of Public Health, University of Colorado, Denver, CO, USA.
    Rowley, Dominic
    Midlands Regional Hospital Portlaoise, Laois, Ireland.
    Shokoples, Sandy
    Alberta Precision Laboratories, Edmonton, Alberta, Canada.
    Smit, Erasmus
    Clinical Microbiology Department, Queen Elizabeth Hospital, Birmingham, UK; Institute of Environmental Science and Research, Wellington, New Zealand.
    Sweeney, Emma L.
    The University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
    Taiaroa, George
    Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
    Vera, Jaime H.
    Department of Global Health and Infection, Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
    Wennerås, Christine
    National Reference Laboratory for STIs, Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
    Whiley, David M.
    The University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia; Pathology Queensland Central Laboratory, Brisbane, Queensland, Australia .
    Williamson, Deborah A.
    Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
    Hughes, Gwenda
    Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
    Naidu, Prenilla
    Alberta Precision Laboratories, Edmonton, Alberta, Canada; Department of Laboratory Medicine and Pathology, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada .
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for STIs, Faculty of Medicine and Health.
    Krajden, Mel
    British Columbia Centre for Disease Control, Public Health Laboratory, Vancouver, British Columbia, Canada; Clinical Microbiology Department, Queen Elizabeth Hospital, Birmingham, UK.
    Lukehart, Sheila A.
    Departments of Medicine/Infectious Diseases and Global Health, University of Washington, Seattle, WA, USA.
    Morshed, Muhammad G.
    British Columbia Centre for Disease Control, Public Health Laboratory, Vancouver, British Columbia, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
    Fifer, Helen
    Blood Safety, Hepatitis, STI and HIV Division, UK Health Security Agency, London, UK.
    Thomson, Nicholas R.
    Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton; Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
    Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis2021In: Nature Microbiology, E-ISSN 2058-5276, Vol. 6, no 12, p. 1549-1560Article in journal (Refereed)
    Abstract [en]

    Syphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p. pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides.

  • 45.
    Behzadi, Payam
    et al.
    Department of Microbiology, College of Basic Sciences, Shahr-e-Qods Branch, Islamic Azad University, Tehran, Iran.
    Sameer, Aga Syed
    Molecular Disease & Diagnosis Division, Infinity Biochemistry Pvt. Ltd, Sajjad Abad, Chattabal, Srinagar, Kashmir, India; Department of Biochemistry, Government Medical College, Karan Nagar, Srinagar, Kashmir, India.
    Nissar, Saniya
    Molecular Disease & Diagnosis Division, Infinity Biochemistry Pvt. Ltd, Sajjad Abad, Chattabal, Srinagar, Kashmir, India; Department of Biochemistry, Government Medical College, Karan Nagar, Srinagar, Kashmir, India.
    Banday, Mujeeb Zafar
    Molecular Disease & Diagnosis Division, Infinity Biochemistry Pvt. Ltd, Sajjad Abad, Chattabal, Srinagar, Kashmir, India; Department of Biochemistry, Government Medical College, Karan Nagar, Srinagar, Kashmir, India.
    Gajdács, Márió
    Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, Szeged, Hungary.
    García-Perdomo, Herney Andrés
    Division of Urology, Department of Surgery, School of Medicine, UROGIV Research Group, Universidad del Valle, Cali, Colombia.
    Akhtar, Kulsum
    Department of Clinical Biochemistry, Sher I Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India.
    Pinheiro, Marina
    Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, Porto, Portugal; CHUP, Centro Hospitalar Universitário do Porto, Largo do Prof. Abel Salazar, Porto, Portugal.
    Magnusson, Peter
    Örebro University, School of Medical Sciences. Cardiology Research Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Sarshar, Meysam
    Research Laboratories, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
    Ambrosi, Cecilia
    IRCCS San Raffaele Roma, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Rome, Italy.
    The Interleukin-1 (IL-1) Superfamily Cytokines and Their Single Nucleotide Polymorphisms (SNPs)2022In: Journal of Immunology Research, ISSN 2314-8861, E-ISSN 2314-7156, Vol. 2022, article id 2054431Article, review/survey (Refereed)
    Abstract [en]

    Interleukins (ILs)-which are important members of cytokines-consist of a vast group of molecules, including a wide range of immune mediators that contribute to the immunological responses of many cells and tissues. ILs are immune-glycoproteins, which directly contribute to the growth, activation, adhesion, differentiation, migration, proliferation, and maturation of immune cells; and subsequently, they are involved in the pro and anti-inflammatory responses of the body, by their interaction with a wide range of receptors. Due to the importance of immune system in different organisms, the genes belonging to immune elements, such as ILs, have been studied vigorously. The results of recent investigations showed that the genes pertaining to the immune system undergo progressive evolution with a constant rate. The occurrence of any mutation or polymorphism in IL genes may result in substantial changes in their biology and function and may be associated with a wide range of diseases and disorders. Among these abnormalities, single nucleotide polymorphisms (SNPs) can represent as important disruptive factors. The present review aims at concisely summarizing the current knowledge available on the occurrence, properties, role, and biological consequences of SNPs within the IL-1 family members.

  • 46.
    Bengtsson, Torbjörn
    et al.
    Örebro University, School of Medical Sciences.
    Selegård, Robert
    School of Medical Sciences, Örebro University, Örebro, Sweden; Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Musa, Amani
    Örebro University, School of Medical Sciences.
    Hultenby, Kjell
    Department of Laboratory Medicine, Division of Clinical Research Centre, Karolinska Institutet, Stockholm, Sweden.
    Utterström, Johanna
    Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Sivlér, Petter
    S2Medical AB, Linköping, Sweden.
    Skog, Mårten
    S2Medical AB, Linköping, Sweden.
    Nayeri, Fariba
    PEAS Research Institute, Department of Infection Control, Linköping, Sweden.
    Hellmark, Bengt
    Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Aili, Daniel
    Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    Plantaricin NC8 αβ exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 3580Article in journal (Refereed)
    Abstract [en]

    The use of conventional antibiotics has substantial clinical efficacy, however these vital antimicrobial agents are becoming less effective due to the dramatic increase in antibiotic-resistant bacteria. Novel approaches to combat bacterial infections are urgently needed and bacteriocins represent a promising alternative. In this study, the activities of the two-peptide bacteriocin PLNC8 αβ were investigated against different Staphylococcus spp. The peptide sequences of PLNC8 α and β were modified, either through truncation or replacement of all L-amino acids with D-amino acids. Both L- and D-PLNC8 αβ caused rapid disruption of lipid membrane integrity and were effective against both susceptible and antibiotic resistant strains. The D-enantiomer was stable against proteolytic degradation by trypsin compared to the L-enantiomer. Of the truncated peptides, β1-22, β7-34 and β1-20 retained an inhibitory activity. The peptides diffused rapidly (2 min) through the bacterial cell wall and permeabilized the cell membrane, causing swelling with a disorganized peptidoglycan layer. Interestingly, sub-MIC concentrations of PLNC8 αβ substantially enhanced the effects of different antibiotics in an additive or synergistic manner. This study shows that PLNC8 αβ is active against Staphylococcus spp. and may be developed as adjuvant in combination therapy to potentiate the effects of antibiotics and reduce their overall use.

  • 47.
    Bengtsson, Torbjörn
    et al.
    Örebro University, School of Medical Sciences.
    Zhang, Boxi
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Selegård, Robert
    Örebro University, School of Medical Sciences. Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Wiman, Emanuel
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Aili, Daniel
    Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    Dual action of bacteriocin PLNC8 alpha beta through inhibition of Porphyromonas gingivalis infection and promotion of cell proliferation2017In: Pathogens and Disease, E-ISSN 2049-632X, Vol. 75, no 5, article id ftx064Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 50.
    Berçot, Béatrice
    et al.
    Université Paris Cité, INSERM, IAME, Paris, France; APHP, Infectious Agents Department, Saint Louis Hospital, Paris, France; French National Reference Centre for bacterial STIs, Associated Laboratory for Gonococci, Paris, France.
    Caméléna, François
    Université Paris Cité, INSERM, IAME, Paris, France; APHP, Infectious Agents Department, Saint Louis Hospital, Paris, France; French National Reference Centre for bacterial STIs, Associated Laboratory for Gonococci, Paris, France.
    Mérimèche, Manel
    Université Paris Cité, INSERM, IAME, Paris, France; APHP, Infectious Agents Department, Saint Louis Hospital, Paris, France; French National Reference Centre for bacterial STIs, Associated Laboratory for Gonococci, Paris, France.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Ӧrebro University, Ӧrebro, Sweden.
    Sbaa, Ghalia
    APHP, Infectious Agents Department, Saint Louis Hospital, Paris, France; French National Reference Centre for bacterial STIs, Associated Laboratory for Gonococci, Paris, France.
    Mainardis, Mary
    APHP, Infectious Agents Department, Saint Louis Hospital, Paris, France; French National Reference Centre for bacterial STIs, Associated Laboratory for Gonococci, Paris, France.
    Valin, Cyrille
    Laboratoire Anse, Biogroup, Lyon, France.
    Molina, Jean-Michel
    AP-HP, Hôpital Saint-Louis, Lariboisière, Département de Maladies Infectieuses et Tropicales, Paris, France; Université Paris Cité, UMR S976, INSERM, Paris, France.
    Bébéar, Cécile
    University of Bordeaux, USC EA 3671, Mycoplasmal and Chlamydial Infections in Humans, Bordeaux University Hospital, French National Reference Centre for Bacterial STIs, Bordeaux, France.
    Chazelle, Emilie
    Santé Publique France, French National Public Health Agency, Saint-Maurice, France.
    Lot, Florence
    Santé Publique France, French National Public Health Agency, Saint-Maurice, France.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Ӧrebro University, Ӧrebro, Sweden.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Ӧrebro University, Ӧrebro, Sweden; Institute for Global Health, University College London, London, United Kingdom .
    Ceftriaxone-resistant, multidrug-resistant Neisseria gonorrhoeae with a novel mosaic penA-237.001 gene, France, June 20222022In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 27, no 50, p. 17-22Article in journal (Refereed)
    Abstract [en]

    We report a ceftriaxone-resistant, multidrug-resistant urogenital gonorrhoea case in a heterosexual woman in France, June 2022. The woman was successfully treated with azithromycin 2 g. She had unprotected sex with her regular partner, who developed urethritis following travel to Vietnam and Switzerland. Whole genome sequencing of the gonococcal isolate (F92) identified MLST ST1901, NG-STAR CC- 199, and the novel mosaic penA-237.001, which caused ceftriaxone resistance. penA-237.001 is 98.7% identical to penA-60.001, reported in various ceftriaxone-resistant strains, including the internationally spreading FC428 clone.

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