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  • 301. Warvsten, Anna
    et al.
    Bjornfors, Martin
    Arvidsson, Michael
    Vaziri-Sani, Fariba
    Jonsson, Ida
    Olsson, Gert E.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Larsson, Helena Elding
    Lernmark, Ake
    Nilsson, Anna-Lena
    Islet autoantibodies present in association with Ljungan virus infection in bank voles (Myodes glareolus) in northern Sweden2017In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 89, no 1, p. 24-31Article in journal (Refereed)
    Abstract [en]

    Bank voles are known reservoirs for Puumala hantavirus and probably also for Ljungan virus (LV), a suggested candidate parechovirus in type 1 diabetes etiology and pathogenesis. The aim of this study was to determine whether wild bank voles had been exposed to LV and if exposure associated to autoantibodies against insulin (IAA), glutamic acid decarboxylase 65 (GADA), or islet autoantigen-2 (IA-2A). Serum samples from bank voles (Myodes glareolus) captured in early summer or early winter of 1997 and 1998, respectively, were analyzed in radio binding assays for antibodies against Ljungan virus (LVA) and Puumala virus (PUUVA) as well as for IAA, GADA, and IA-2A. LVA was found in 25% (189/752), IAA in 2.5% (18/723), GADA in 2.6% (15/615), and IA-2A in 2.5% (11/461) of available bank vole samples. LVA correlated with both IAA (P=0.007) and GADA (P<0.001), but not with IA-2A (P=0.999). There were no correlations with PUUVA, detected in 17% of the bank voles. Compared to LVA negative bank voles, LVA positive animals had higher levels of both IAA (P=0.002) and GADA (P<0.001), but not of IA-2A (P=0.205). Levels of LVA as well as IAA and GADA were higher in samples from bank voles captured in early summer. In conclusion, LVA was detected in bank voles and correlated with both IAA and GADA but not with IA-2A. These observations suggest that exposure to LV may be associated with islet autoimmunity. It remains to be determined if islet autoantibody positive bank voles may develop diabetes in the wild.

  • 302. Watanabe, Yasuyoshi
    et al.
    Evengård, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Natelson, Benjamin H
    Jason, Leonard A
    Kuratsune, Hirohiko
    Fatigue Science for Human Health2008 (ed. 1)Book (Other (popular science, discussion, etc.))
    Abstract [en]

    Fatigue is quite a familiar sensation, one that everyone is likely to have experienced. Its moleuclar and neural mechanisms have not yet been elucidated, however, probably because of the complicated nature of its causes. To provide a broad forum for discussion, the International Conference on Fatigue Science was organiszed, the first being held in 2002 in Sandhamn, Sweden, and the second in 2005 in Karuizawa, Japan. Subsequently it was decided that the papers presented at the two conferences should be collected and incorporated in this pioneering work, Fatique Science for Human Health. The book summarizes fatigue researchers' achievements, explains the status of the reserch on fatigue, and presents perspectives on remedies for chonic fatigue and chronic fatigue syndrome. The result is an authoritative guide to recent progress in the molucular and neural mechanisms of fatigue and in the development of the ways to prevent and overcome fatigue and in the development of the ways to prevent and overcome fatigue and chronic fatigue. This book provides a valuable resource not only for physicians but for all who work in public health.

  • 303. Wertheim, Herman
    et al.
    Chuc, Nguyen Thi Kim
    Punpuing, Sureeporn
    Khan, Wasif Ali
    Gyapong, Margaret
    Asante, Kwaku Poku
    Munguambe, Khatia
    Gómez-Olivé, Xavier
    Ariana, Proochista
    John-Langba, Johannes
    Sigauque, Betuel
    Toan, Tran Khanh
    Tollman, Stephen
    Cremers, Amelieke
    Do, Nga
    Nadjm, Behzad
    van Doorn, Rogier
    Kinsman, John
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Sankoh, Osman
    Community-level antibiotic access and use (ABACUS) in low- and middle-income countries: Finding targets for social interventions to improve appropriate antimicrobial use: an observational multi-centre study2017In: Wellcome Open Research, ISSN 2398-502X, Vol. 2, article id 58Article in journal (Refereed)
    Abstract [en]

    In many low- and middle-income countries (LMICs), a poor link between antibiotic policies and practices exists. Numerous contextual factors may influence the degree of antibiotic access, appropriateness of antibiotic provision, and actual use in communities. Therefore, improving appropriateness of antibiotic use in different communities in LMICs probably requires interventions tailored to the setting of interest, accounting for cultural context. Here we present the ABACUS study (AntiBiotic ACcess and USe), which employs a unique approach and infrastructure, enabling quantitative validation, contextualization of determinants, and cross-continent comparisons of antibiotic access and use. The community infrastructure for this study is the INDEPTH-Network (International Network for the Demographic Evaluation of Populations and Their Health in Developing Countries), which facilitates health and population research through an established health and demographic surveillance system. After an initial round of formative qualitative research with community members and antibiotic suppliers in three African and three Asian countries, household surveys will assess the appropriateness of antibiotic access, provision and use. Results from this sample will be validated against a systematically conducted inventory of suppliers. All potential antibiotic suppliers will be mapped and characterized. Subsequently, their supply of antibiotics to the community will be measured through customer exit interviews, which tend to be more reliable than bulk purchase or sales data. Discrepancies identified between reported and observed antibiotic practices will be investigated in further qualitative interviews. Amartya Sen’s Capability Approach will be employed to identify the conversion factors that determine whether or not, and the extent to which appropriate provision of antibiotics may lead to appropriate access and use of antibiotics. Currently, the study is ongoing and expected to conclude by 2019. ABACUS will provide important new insights into antibiotic practices in LMICs to inform social interventions aimed at promoting optimal antibiotic use, thereby preserving antibiotic effectiveness.

  • 304. Westin, Johan
    et al.
    Aleman, Soo
    Castedal, Maria
    Duberg, Ann-Sofi
    Eilard, Anders
    Fischlere, Björn
    Kampmann, Christian
    Lindahl, Karin
    Lindh, Magnus
    Norkrans, Gunnar
    Stenmark, Stephan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Weiland, Ola
    Wejstål, Rune
    Management of hepatitis B virus infection, updated Swedish guidelines2019In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243Article in journal (Refereed)
    Abstract [en]

    Despite access to effective antiviral drugs and vaccines, hepatitis B virus (HBV) infection remains a major health issue worldwide. HBV is highly infectious and may cause chronic infection, progressive liver damage, hepatocellular cancer (HCC) and death. Early diagnosis, proper management and timing of treatment are crucial. The Swedish Reference group for Antiviral Treatment (RAV) here provides updated evidence-based guidelines for treatment and management of HBV infection which may be applicable also in other countries. Tenofovir alafenamide (TAF) has been introduced as a novel treatment option and new principles regarding indication and duration of treatment and characterization of hepatitis B have been gradually introduced which justifies an update of the previous guidelines from 2007. Updated guidelines on HCC surveillance in HBV-infected patients, treatment and prophylaxis for patients undergoing liver transplantation as well as management of pregnant women and children with HBV infection are also provided.

  • 305. Westling, Katarina
    et al.
    Jorup-Rönström, Christina
    Evengård, Birgitta
    Department of Laboratory Medicine, Division of Clinical Bacteriology, Karolinska University Hospital/Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Toxoplasmosis not transmitted by cat bite, but high prevalence of antibodies to toxoplasma gondii in patients bitten by their own cat2010In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 42, no 9, p. 687-690Article in journal (Refereed)
    Abstract [en]

    The aims of the study were to investigate the prevalence of antibodies to Toxoplasma gondii in a group of patients bitten by cats, and also to determine if toxoplasmosis can be transferred by cat bite. Seventy-two patients who attended the emergency wards at 3 hospitals in Stockholm, Sweden, due to infection by cat bite, were investigated for specific IgM and IgG antibodies to T. gondii in the acute phase, as well as in the convalescent phase about 2 weeks later. Specific IgG antibodies to T. gondii (> or =8 IU/ml) were found in 17/72 patients (24%) in the acute phase. No case of seroconversion occurred. Patients who were bitten by their own cat had positive antibody titres to T. gondii significantly more often than those bitten by a foreign cat; 30% and 5%, respectively (p = 0.02). This suggests that regular contact with cats may contribute to the transmission of the parasite.

  • 306. Westman, G.
    et al.
    Studahl, M.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Eriksson, B. M.
    Persson, B.
    Rönnelid, J.
    Schliamser, S.
    Aurelius, E.
    N-methyl-D-aspartate receptor autoimmunity affects cognitive performance in herpes simplex encephalitis2016In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 22, no 11, p. 934-940Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate the prevalence and temporal development of N-methyl-D-aspartate receptor (NMDAR) autoantibodies in relation to neurocognitive performance in patients with herpes simplex encephalitis (HSE).

    Methods: This prospective observational study enrolled a total of 49 HSE patients within a randomized controlled trial of valacyclovir. Cerebrospinal fluid and serum samples were drawn in the initial stage of disease, after 2 to 3 weeks and after 3 months. Anti-NMDAR IgG was detected with HEK293 cells transfected with plasmids encoding the NMDA NR1 type glutamate receptor. A batch of neurocognitive tests, including the Mattis Dementia Rating Scale (MDRS), Glasgow Coma Scale (GCS), Reaction Level Scale (RLS85), Mini-Mental State Examination (MMSE) and National Institutes of Health (NIH) stroke scale, was performed during 24 months' follow-up.

    Results: Anti-NMDAR IgG was detected in 12 of 49 participants. None were antibody positive in the initial stage of disease. In ten of 12 positive cases, specific antibodies were detectable only after 3 months. Notably, the development of NMDAR autoantibodies was associated with significantly impaired recovery of neurocognitive performance. After 24 months' follow-up, the median increase in MDRS total score was 1.5 vs. 10 points in antibody-positive and -negative participants (p = 0.018).

    Conclusions: Anti-NMDAR autoimmunity is a common complication to HSE that develops within 3 months after onset of disease. The association to impaired neurocognitive recovery could have therapeutical implications, as central nervous system autoimmunity is potentially responsive to immunotherapy. 

  • 307. Westman, Gabriel
    et al.
    Sohrabian, Azita
    Aurelius, Elisabeth
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Schliamser, Silvia
    Sund, Fredrik
    Studahl, Marie
    Rönnelid, Johan
    Clinical significance of IgM and IgA class anti-NMDAR antibodies in herpes simplex encephalitis2018In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 103, p. 75-80Article in journal (Refereed)
    Abstract [en]

    Background: Herpes simplex encephalitis (HSE) is a devastating disease, often leaving patients with severe disabilities. It has been shown that IgG anti-N-methyl-o-aspartate receptor (NMDAR) antibodies appear in approximately 25% of HSE patients and could be associated with impaired recovery of cognitive performance. Objectives: To characterize the prevalence of IgM and IgA anti-NMDAR antibodies in HSE patients, in relation to subsequent development of IgG anti-NMDAR and correlation to cognitive performance. Study design: A total of 48 subjects were included from a previously described cohort of patients with HSE verified by HSV-1 PCR. Cerebrospinal fluid (CSF) and serum samples drawn close to onset of disease, after 14-21 days of iv aciclovir treatment and after 90 days of follow-up, were analyzed for the presence of IgM and IgA anti-NMDAR, and related to IgG anti-NMDAR. Antibody levels were correlated to the recovery of cognitive performance, as estimated by the Mattis Dementia Rating Scale (MDRS), for a total of 24 months. Results: In total, 27 of 48 (56%) study subjects were anti-NMDAR positive, defined as the presence of IgG (12/ 48, 25%), IgM (14/48, 29%) or IgA (13/48, 27%) antibodies in CSF and/or serum. IgM or IgA anti-NMDAR did not predict subsequent IgG autoimmunization and did not correlate to cognitive outcome. IgG anti-NMDAR serostatus, but not antibody titers, correlated to impaired recovery of cognitive performance. Conclusions: A majority of HSE patients develop IgG, IgM or IgA anti-NMDAR antibodies. However, the predictive value and clinical relevance of non-IgG isotypes remains to be shown in this setting.

  • 308.
    Widerström, Micael
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Molecular epidemiology of coagulase-negative staphylococci in hospitals and in the community2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Coagulase-negative staphylococci (CoNS) and in particular Staphylococcus epidermidis have emerged as major pathogens primarily causing nosocomial infections in patients with indwelling medical devices. These infections are often caused by multidrug-resistant strains of S. epidermidis (MDRSE). Other clinical entities due to CoNS are lower urinary tract infections (UTI) in women and native valve endocarditis. The purpose of this work was to investigate the frequency of antibiotic resistance and the molecular epidemiology of both hospital and community-associated isolates of S. epidermidis in order to examine if certain clones are related to MDRSE infections. Furthermore, we aimed to explore if specific clones of S. saprophyticus are associated with UTI in women.

    Methods

    A total of 359 hospital-associated methicillin-resistant isolates of CoNS obtained from 11 hospitals in northern Europe and 223 community-associated staphylococcal isolates were examined. Furthermore, 126 isolates of S. saprophyticus isolated from women with uncomplicated UTI from five different locations in northern Europe were analyzed. Pulsed-field gel electrophoresis (PFGE) was used for genotyping. Additionally, some of the S. epidermidis isolates were analyzed with multilocus sequence typing (MLST). Antibiotic susceptibility was determined for all isolates by the disc diffusion test.

    Results

    293 of the 359 (82%) hospital-associated and 124 of the 223 (56%) community-associated isolates belonged to the species S. epidermidis. Among the hospital-associated S. epidermidis isolates, two dominating PFGE types (type A and B) were distinguished, comprising 78 (27%) and 51 (17%) isolates, respectively. Type A, which was detected in a Norwegian and eight Swedish hospitals, corresponded with a novel sequence type (ST215). Type B was discovered in a German, a Danish and seven Swedish hospitals and corresponded with ST2. In contrast, community-associated isolates of S. epidermidis were genetically extremely diverse with no predominating genotype, and showed a low rate of antibiotic resistance; only two (1.6%) methicillin-resistant strains were detected.

    Among 126 analyzed isolates of S. saprophyticus, 47 different PFGE profiles were identified. Several clusters of genetically highly related isolates were detected among isolates obtained from different locations and periods of time.

    Conclusion

    We have demonstrated the occurrence, persistence and potential dissemination of two multidrug-resistant S. epidermidis (MDRSE) genotypes, including a novel sequence type (ST215), within hospitals in northern Europe. Community-associated isolates of S. epidermidis showed a low rate of methicillin-resistance and were genetically heterogeneous. These results indicate that MDRSE by large are confined to the hospital setting in our region. Moreover, although the S. saprophyticus population was quite heterogeneous, indistinguishable isolates of S. saprophyticus causing lower UTI in women were identified in different countries 11 years apart, indicating the persistence and geographical spread of some clones of S. saprophyticus.

  • 309.
    Widerström, Micael
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Monsen, Tor
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Karlsson, Carina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Edebro, Helén
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Wiström, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Clonality among multidrug-resistant hospital-associated Staphylococcus epidermidis in northern Europe2009In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 41, no 9, p. 642-649Article in journal (Refereed)
    Abstract [en]

    Using pulsed-field gel electrophoresis (PFGE) we have previously described the occurrence and possible dissemination of a clone of multidrug-resistant Staphylococcus epidermidis (MDRSE) in 2 hospitals in northern Sweden during 2001-2003. The aims of the present study were to investigate if this clone still persisted, 7 y later, in these 2 hospitals and whether this specific clone was detectable among clinical isolates from 9 other hospitals, 6 Swedish as well as a Norwegian, Danish and a German hospital. In total, 173 clinical isolates of MDRSE isolated during 2003 to 2008 were analysed using PFGE, of which 22 isolates were also characterized by multilocus sequence typing (MLST). Two dominating PFGE types (types A and B) were identified, consisting of 56 (32%) and 38 (22%) isolates, respectively. Type A, which was detected in the Norwegian and all Swedish hospitals, proved indistinguishable to the clone previously identified in 2001-2003 and corresponded with a novel sequence type (ST215). Type B was discovered in the German, Danish and in 7 Swedish hospitals and corresponded with ST2. In conclusion, we have demonstrated the occurrence, persistence and potential dissemination of 2 MDRSE genotypes, including a novel sequence type (ST215), within hospitals in northern Europe.

  • 310.
    Widerström, Micael
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Jämtland Cty Council, Östersund, Sweden.
    Schönning, Caroline
    Lilja, Mikael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Lebbad, Marianne
    Ljung, Thomas
    Allestam, Görel
    Ferm, Martin
    Björkholm, Britta
    Hansen, Anette
    Hiltula, Jan I.
    Långmark, Jonas
    Löfdahl, Margareta
    Omberg, Maria
    Reuterwall, Christina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Samuelsson, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Widgren, Katarina
    Wallensten, Anders
    Lindh, Johan
    Large outbreak of cryptosporidium hominis infection transmitted through the public water supply, Sweden2014In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 20, no 4, p. 581-589Article in journal (Refereed)
    Abstract [en]

    In November 2010, approximate to 27,000 (approximate to 45%) inhabitants of Östersund, Sweden, were affected by a waterborne outbreak of cryptosporidiosis. The outbreak was characterized by a rapid onset and high attack rate, especially among young and middle-aged persons. Young age, number of infected family members, amount of water consumed daily, and gluten intolerance were identified as risk factors for acquiring cryptosporidiosis. Also, chronic intestinal disease and young age were significantly associated with prolonged diarrhea. Identification of Ctyptosporidium hominis subtype lbA10G2 in human and environmental samples and consistently low numbers of oocysts in drinking water confirmed insufficient reduction of parasites by the municipal water treatment plant. The current outbreak shows that use of inadequate microbial barriers at water treatment plants can have serious consequences for public health. This risk can be minimized by optimizing control of raw water quality and employing multiple barriers that remove or inactivate all groups of pathogens.

  • 311.
    Widerström, Micael
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Wiström, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Edebro, Helén
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Marklund, Elisabeth
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Backman, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Monsen, Tor
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Colonization of patients, healthcare workers, and the environment with healthcare-associated Staphylococcus epidermidis genotypes in an intensive care unit: a prospective observational cohort study2016In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 16, article id 743Article in journal (Refereed)
    Abstract [en]

    Background: During the last decades, healthcare-associated genotypes of methicillin-resistant Staphylococcus epidermidis (HA-MRSE) have been established as important opportunistic pathogens. However, data on potential reservoirs on HA-MRSE is limited. The aim of the present study was to investigate the dynamics and to which extent HA-MRSE genotypes colonize patients, healthcare workers (HCWs) and the environment in an intensive care unit (ICU).

    Methods: Over 12 months in 2006-2007, swab samples were obtained from patients admitted directly from the community to the ICU and patients transferred from a referral hospital, as well as from HCWs, and the ICU environment. Patients were sampled every third day during hospitalization. Antibiotic susceptibility testing was performed according to EUCAST guidelines. Pulsed-field gel electrophoresis and multilocus sequence typing were used to determine the genetic relatedness of a subset of MRSE isolates.

    Results: We identified 620 MRSE isolates from 570 cultures obtained from 37 HCWs, 14 patients, and 14 environmental surfaces in the ICU. HA-MRSE genotypes were identified at admission in only one of the nine patients admitted directly from the community, of which the majority subsequently were colonized by HA-MRSE genotypes within 3 days during hospitalization. Almost all (89%) of HCWs were nasal carriers of HA-MRSE genotypes. Similarly, a significant proportion of patients transferred from the referral hospital and fomites in the ICU were widely colonized with HA-MRSE genotypes.

    Conclusions: Patients transferred from a referral hospital, HCWs, and the hospital environment serve as important reservoirs for HA-MRSE. These observations highlight the need for implementation of effective infection prevention and control measures aiming at reducing HA-MRSE transmission in the healthcare setting.

  • 312.
    Widerström, Micael
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Wiström, Johan
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Ek, Elin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Edebro, Helen
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Monsen, Tor
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Near absence of methicillin-resistance and pronounced genetic diversity among Staphylococcus epidermidis isolated from healthy persons in northern Sweden2011In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 119, no 8, p. 505-512Article in journal (Refereed)
    Abstract [en]

    The main aim of the study was to examine if hospital-associated clones of multidrug-resistant Staphylococcus epidermidis (MDRSE), commonly identified in hospitals in our region, also are spread among healthy persons in the community. A total of 124 isolates of S. epidermidis sampled from subjects attending a Travel health clinic, Umeå, Sweden during 2008 were examined with antibiotic susceptibility testing and pulsed field gel electrophoresis (PFGE) analysis.

    Resistance to methicillin or any antibiotic was detected in two and 26 of the isolates, respectively. PFGE analysis showed an extensive genetic diversity with 86 different PFGE types, of whom 62 were singletons. No isolates belonged to the previously described hospital-associated MDRSE genotypes, indicating that MDRSE by large are confined to the hospital setting in our region. In conclusion, community-associated isolates of S. epidermidis showed a low level of methicillin-resistance and were genetically extremely diverse with no predominating genotype.

  • 313. Wielkoszynski, Tomasz
    et al.
    Moghaddam, Aliyeh
    Backman, Assar
    Broden, Jessica
    Piotrowski, Rafal
    Mond-Paszek, Renata
    Kozarenko, Alexander
    Ny, Tor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Wilczynska, Malgorzata
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Omnio AB, Umeå, Sweden.
    Novel diagnostic ELISA test for discrimination between infections with Yersinia enterocolitica and Yersinia pseudotuberculosis2018In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 37, no 12, p. 2301-2306Article in journal (Refereed)
    Abstract [en]

    Yersiniosis is a foodborne infection caused by Yersinia enterocolitica or Yersinia pseudotuberculosis. Although yersiniosis is most often self-limiting, some patients develop chronic infections, such as reactive arthritis, glomerulonephritis, or myocarditis, which require an antibiotic treatment. Whereas early infections can be diagnosed by direct detection of bacteria, chronic infections can only be identified by serological tests. At this point, a serological method for differentiation between infections with the two Yersinia species is important since antibiotic susceptibility of these bacteria is different. Traditional immunoassays do not distinguish between infections with Y. enterocolitica and Y. pseudotuberculosis. The only test that allows for this differentiation is Mikrogen's strip test where discrimination between the two types of infection is based on two recombinant bacterial proteins, MyfA and PsaA (specific for Y. enterocolitica and Y. pseudotuberculosis, respectively). Here, we show that Y. enterocolitica and Y. pseudotuberculosis, cultured under the conditions that mimic the natural rout of infection, express surface antigens different from MyfA and PsaA that can also be used in a discrimination test. Further, we describe a new ELISA that is based on the whole bacteria and recombinant MyfA and PsaA as antigens, and that allows the differentiation between infections with Y. enterocolitica and Y. pseudotuberculosis and simultaneous detection of yersiniosis.

  • 314.
    Wilder-Smith, Annelies
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; London School of Hygiene and Tropical Medicine, Department of Disease Control, London, UK.
    Chang, Chui Rhong
    Leong, Wei Yee
    Zika in travellers 1947-2017: a systematic review2018In: Journal of Travel Medicine, ISSN 1195-1982, E-ISSN 1708-8305, Vol. 25, article id tay044Article in journal (Refereed)
    Abstract [en]

    Introduction: Travellers contributed substantially to the rapid spread of Zika virus (ZIKV). They act as sentinel and may unmask ongoing ZIKV transmission in countries where outbreaks have not yet been reported. Our objectives were to (i) describe the burden of ZIKV infections in international travellers over time; (ii) estimate the proportion of birth defects as a result of maternal ZIKV infection in travellers; (iii) track the extent of sexual transmission; (iv) summarize ZIKV infections in returning travellers as reported by the GeoSentinel network; and (v) identify countries without reports on local ZIKV transmission where travellers served as sentinel.

    Methods: We performed a systematic review from 1947 to April 2017 on travel-associated ZIKV infections. We also compared published reports on autochthonous ZIKV transmission in Asia with published reports on exportations from travellers in Asia.

    Results: Of 314 papers that fit the inclusion criteria, 61 were eligible for final analysis. There was an exponential increase in the number of reported ZIKV infected travellers from the years 2013 to 2016, which declined in 2017. Amongst pregnant women with ZIKV infection, (5%) resulted in a fetus or infant with ZIKV-associated birth defects. An estimated 1% of the total number of ZIKV cases reported in the USA and Europe were acquired through sexual transmission. Through the GeoSentinel network, five countries (Indonesia, Philippines, Thailand, Vietnam, Cameroon) were identified as sentinel markers where ZIKV was exported despite the absence of reported local transmission.

    Conclusions: Mobility patterns and travel volumes can help to identify the most likely origin of importation, and also in predicting further propagation. Studies on pregnant returning travellers have contributed to a better understanding of the risk estimates of congenital Zika syndrome/microcephaly as a result of maternal ZIKV infection, and the relative contribution of sexual transmission.

  • 315.
    Wilder-Smith, Annelies
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
    Quam, Mikkel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Sessions, O.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Liu-Helmersson, Jing
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Franco, L.
    Khan, K.
    The 2012 dengue outbreak in Madeira: exploring the origins2014In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 19, no 8, p. 20718-Article in journal (Refereed)
    Abstract [en]

    In 2012, Madeira reported its first major outbreak of dengue. To identify the origin of the imported dengue virus, we investigated the interconnectivity via air travel between dengue-endemic countries and Madeira, and compared available sequences against GenBank. There were 22,948 air travellers to Madeira in 2012, originating from twenty-nine dengue-endemic countries; 89.6% of these international travellers originated from Venezuela and Brazil. We developed an importation index that takes into account both travel volume and the extent of dengue incidence in the country of origin. Venezuela and Brazil had by far the highest importation indices compared with all other dengue-endemic countries. The importation index for Venezuela was twice as high as that for Brazil. When taking into account seasonality in the months preceding the onset of the Madeira outbreak, this index was even seven times higher for Venezuela than for Brazil during this time. Dengue sequencing shows that the virus responsible for the Madeira outbreak was most closely related to viruses circulating in Venezuela, Brazil and Columbia. Applying the importation index, Venezuela was identified as the most likely origin of importation of dengue virus via travellers to Madeira. We propose that the importation index is a new additional tool that can help to identify and anticipate the most probable country of origin for importation of dengue into currently non-endemic countries.

  • 316.
    Wilder-Smith, Annelies
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Immunization, Vaccines & Biologicals, World Health Organization, Geneva, Switzerland; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
    Vannice, Kirsten
    Durbin, Anna
    Hombach, Joachim
    Thomas, Stephen J.
    Thevarjan, Irani
    Simmons, Cameron P.
    Zika vaccines and therapeutics: landscape analysis and challenges ahead2018In: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 16, article id 84Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Various Zika virus (ZIKV) vaccine candidates are currently in development. Nevertheless, unique challenges in clinical development and regulatory pathways may hinder the licensure of high-quality, safe, and effective ZIKV vaccines.

    DISCUSSION: Implementing phase 3 efficacy trials will be difficult given the challenges of the spatio-temporal heterogeneity of ZIKV transmission, the unpredictability of ZIKV epidemics, the broad spectrum of clinical manifestations making a single definite endpoint difficult, a lack of sensitive and specific diagnostic assays, and the need for inclusion of vulnerable target populations. In addition to a vaccine, drugs for primary prophylaxis, post-exposure prophylaxis, or treatment should also be developed to prevent or mitigate the severity of congenital Zika syndrome.

    CONCLUSION: Establishing the feasibility of immune correlates and/or surrogates are a priority. Given the challenges in conducting phase 3 trials at a time of waning incidence, human challenge trials should be considered to evaluate efficacy. Continued financial support and engagement of industry partners will be essential to the successful development, licensure, and accessibility of Zika vaccines or therapeutics.

  • 317. Wilhelmsson, Peter
    et al.
    Fryland, Linda
    Lindblom, Pontus
    Sjöwall, Johanna
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Berglund, Johan
    Haglund, Mats
    Henningsson, Anna J
    Nolskog, Peter
    Nordberg, Marika
    Nyberg, Clara
    Ornstein, Katharina
    Nyman, Dag
    Ekerfelt, Christina
    Forsberg, Pia
    Lindgren, Per-Eric
    A prospective study on the incidence of Borrelia burgdorferi sensu lato infection after a tick bite in Sweden and On the Åland Islands, Finland (2008-2009)2016In: Ticks and Tick-borne Diseases, ISSN 1877-959X, E-ISSN 1877-9603, Vol. 7, no 1, p. 71-79Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis (LB) is a common and increasing tick-borne disease in Europe. The risk of acquiring a Borrelia infection after a tick bite is not fully known. Therefore, we investigated the incidence of Borrelia infection after a bite by a Borrelia-infected tick and if the Borrelia load and/or the duration of tick-feeding influenced the risk of infection. During 2008-2009, ticks and blood samples were collected from 1546 tick-bitten persons from Sweden and the Åland Islands, Finland. Follow-up blood samples were taken 3 months after the tick bite. The duration of tick feeding was microscopically estimated and Borrelia was detected and quantified in ticks by real-time PCR. Anti-Borrelia antibodies were detected in sera using ELISA tests and immunoblot. Five percent (78/1546) of the study participants developed Borrelia infection (LB diagnosis and/or seroconversion) after a tick bite (45% bitten by Borrelia-infected ticks and 55% bitten by uninfected ticks). Of these, 33 developed LB (whereof 9 also seroconverted) while 45 participants seroconverted only. Experience of non-specific symptoms was more frequently reported by Borrelia-infected participants compared to uninfected participants. All who seroconverted removed "their" ticks significantly later than those who did not. The Borrelia load in the ticks did not explain the risk of seroconversion. Regional and sex differences in the Borrelia seroprevalence were found. The risk of developing a Borrelia infection after a bite by a Borrelia-infected tick is small but increases with the duration of tick feeding.

  • 318.
    Winblad, Bengt
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Experimental studies on the pathogenesis of infections of the male uro-genital tract caused by Mycobacterium tuberculosis var. hominis and Candida albicans1975Doctoral thesis, comprehensive summary (Other academic)
  • 319. Wolter, Nicole
    et al.
    Cohen, Cheryl
    Tempia, Stefano
    Madhi, Shabir A.
    Venter, Marietjie
    Moyes, Jocelyn
    Walaza, Sibongile
    Kgokong, Babatyi Malope
    Groome, Michelle
    du Plessis, Mignon
    Pretorius, Marthi
    Dawood, Halima
    Kahn, Kathleen
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Center for Global Health Research.
    Variava, Ebrahim
    Klugman, Keith P.
    von Gottberg, Anne
    HIV and Influenza Virus Infections Are Associated With Increased Blood Pneumococcal Load: A Prospective, Hospital-Based Observational Study in South Africa, 2009-20112014In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 209, no 1, p. 56-65Article in journal (Refereed)
    Abstract [en]

    Background. Increased pneumococcal loads are associated with severe outcomes. We determined the prevalence of pneumococcal DNA in blood specimens from patients hospitalized with acute lower respiratory tract infection and identified factors associated with invasive pneumococcal pneumonia, bacterial loads, and death. Methods. A total of 8523 patients were enrolled as part of prospective hospital-based surveillance. Blood was collected for quantitative pneumococcal (tytA) detection, and nasopharyngeal specimens were collected for detection of influenza virus and other respiratory viruses by real-time polymerase chain reaction. Results. Of 6396 cases (75%) with /ytA results, 422 (7%) were positive for pneumococcal DNA. The prevalences of human immunodeficiency virus (HIV) and influenza virus were 51% (2965/5855) and 8% (485/6358), respectively. On multivariable analysis, HIV infection (adjusted odds ratio [aOR], 2.4; 95% confidence interval [CI], 1.6-3.6), influenza virus coinfection (aOR, 1.4; 95% CI, 1.2-2.1), oxygen therapy during admission (a0R, 1.6; 95% CI, 1.1-2.3) and in-hospital death (aOR, 2.1; 95% CI, 1.1-4.0) were significantly associated with increased pneumococcal load. Among /ytA-positive patients, after adjustment for length of hospitalization, duration of symptoms, and oxygen therapy during admission, pneumococcal loads >= 10,000 DNA copies/mi. (a0R, 3.6; 95% CI, 1.8-7.2) were associated with increased risk of death. Conclusions. HIV and influenza virus infections were associated with elevated pneumococcal loads, which, in turn, were associated with increased risk of death.

  • 320. Wolter, Nicole
    et al.
    Tempia, Stefano
    Cohen, Cheryl
    Madhi, Shabir A.
    Venter, Marietjie
    Moyes, Jocelyn
    Walaza, Sibongile
    Malope-Kgokong, Babatyi
    Groome, Michelle
    du Plessis, Mignon
    Magomani, Victoria
    Pretorius, Marthi
    Hellferscee, Orienka
    Dawood, Halima
    Kahn, Kathleen
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. MRC/Wits Rural Public Health and Health Transition Research Unit Research Unit (Agincourt), Faculty of Health Sciences, University of the Witwatersrand, Johannesburg ; INDEPTH Network, Accra, Ghana.
    Variava, Ebrahim
    Klugman, Keith P.
    von Gottberg, Anne
    High nasopharyngeal pneumococcal density, increased by viral coinfection, is associated with invasive pneumococcal pneumonia2014In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 210, no 10, p. 1649-1657Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We identified factors associated with pneumococcal colonization, high colonization density, and invasive pneumococcal pneumonia among patients hospitalized with acute lower respiratory tract infections (ALRTIs). METHODS: In 2010, 4025 cases were enrolled in surveillance in South Africa. A total of 969 of 4025 systematically selected nasopharyngeal-oropharyngeal specimens (24%) were tested for respiratory viruses and Streptococcus pneumoniae by real-time polymerase chain reaction. Of these, 749 (77%) had blood tested for S. pneumoniae. RESULTS: Pneumococcal colonization was detected in 55% of cases (534 of 969). On multivariable analysis that controlled for age and tuberculosis treatment, infection with influenza virus (adjusted odds ratio [OR], 2.2; 95% confidence interval [CI], 1.1-4.5), adenovirus (adjusted OR, 1.7; 95% CI, 1.1-2.7), rhinovirus (adjusted OR, 1.6; 95% CI, 1.1-2.3), and human immunodeficiency virus (HIV; adjusted OR, 1.6; 95% CI, 1.1-2.4) were associated with pneumococcal colonization. High colonization density was associated with respiratory virus coinfection (adjusted OR, 1.7; 95% CI, 1.1-2.6) and invasive pneumococcal pneumonia (adjusted OR, 2.3; 95% CI, 1.3-4.0), after adjustment for age and sex. Seven percent (52 of 749) had pneumococci detected in blood. On multivariable analysis among colonized cases, invasive pneumococcal pneumonia was associated with HIV (adjusted OR, 3.2; 95% CI, 1.4-7.5), influenza virus (adjusted OR, 8.2; 95% CI, 2.7-25.0), high colonization density (adjusted OR, 18.7; 95% CI, 2.3-155.1), and >= 5 days of hospitalization (adjusted OR, 3.7; 95% CI, 1.7-8.2). CONCLUSIONS: Respiratory virus infection was associated with elevated colonization density and, in turn, invasive pneumococcal pneumonia.

  • 321. Zeimes, Caroline B.
    et al.
    Olsson, Gert E.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Vanwambeke, Sophie O.
    Modelling zoonotic diseases in humans: comparison of methods for hantavirus in Sweden2012In: International Journal of Health Geographics, ISSN 1476-072X, E-ISSN 1476-072X, no 11, p. 39-Article in journal (Refereed)
    Abstract [en]

    Because their distribution usually depends on the presence of more than one species, modelling zoonotic diseases in humans differs from modelling individual species distribution even though the data are similar in nature. Three approaches can be used to model spatial distributions recorded by points: based on presence/absence, presence/available or presence data. Here, we compared one or two of several existing methods for each of these approaches. Human cases of hantavirus infection reported by place of infection between 1991 and 1998 in Sweden were used as a case study. Puumala virus (PUUV), the most common hantavirus in Europe, circulates among bank voles (Myodes glareolus). In northern Sweden, it causes nephropathia epidemica (NE) in humans, a mild form of hemorrhagic fever with renal syndrome. Logistic binomial regression and boosted regression trees were used to model presence and absence data. Presence and available sites (where the disease may occur) were modelled using cross-validated logistic regression. Finally, the ecological niche model MaxEnt, based on presence-only data, was used. In our study, logistic regression had the best predictive power, followed by boosted regression trees, MaxEnt and cross-validated logistic regression. It is also the most statistically reliable but requires absence data. The cross-validated method partly avoids the issue of absence data but requires fastidious calculations. MaxEnt accounts for non-linear responses but the estimators can be complex. The advantages and disadvantages of each method are reviewed.

  • 322.
    Zettervall, Carl-Johan
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Anderl, Ines
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Williams, Michael
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Palmer, Ruth
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Kurucz, Eva
    Ando, Istvan
    Hultmark, Dan
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    A directed screen for genes involved in Drosophila blood cell activation2004In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 101, no 39, p. 14192-14197Article in journal (Refereed)
    Abstract [en]

    An attack by a parasitic wasp activates a vigorous cellular immune response in Drosophila larvae. This response is manifested by an increased number of circulating cells, the hemocytes, and by the appearance of a specialized class of hemocyte, the lamellocytes, which participate in the encapsulation and killing of the parasite. To study the molecular mechanisms of this response, we have overexpressed different genes in the hemocytes, by using the GAL4-upstream activating sequence system and a hemocyte-specific Hemese-GAL4 driver. Multiple transgenes were tested, representing several important signaling pathways. We found that the proliferation response and the activation of lamellocyte formation are independent phenomena. A drastic increase in the number of circulating hemocytes is caused by receptor tyrosine kinases, such as Egfr, Pvr, and Alk, as well as by the downstream signaling components Ras85D and pointed, supporting the notion that the Ras-mitogen-activated protein kinase pathway regulates hemocyte numbers. In the case of Pvr and Alk, this phenotype also is accompanied by lamellocyte formation. By contrast, constitutively active hopscotch and hemipterous give massive activation of lamellocyte formation with little or no increase in total hemocyte numbers. This finding indicates that both the Jak/Stat and the Jun kinase pathways affect lamellocyte formation. Still other signals, mediated by aop(ACT), Toll(10b), and Rac1 expression, cause a simultaneous increase in lamellocyte and total cell numbers, and the same effect is seen when WNT signaling is suppressed. We conclude that the activation of a cellular response is complex and affected by multiple signaling pathways.

  • 323. Zhang, Zhong-Wei
    et al.
    Liu, Ting
    Zeng, Jian
    Chen, Yang-Er
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Bioinformatic Study Centre, College of Life Sciences, Sichuan Agricultural University, Ya’an 625014, China.
    Yuan, Ming
    Zhang, Da-Wei
    Zhu, Feng
    Yuan, Shu
    Prediction of the next highly pathogenic avian influenza pandemic that can cause illness in humans2015In: Infectious diseases of poverty, ISSN 2049-9957, Vol. 4, article id 50Article in journal (Refereed)
    Abstract [en]

    Background: In recent years, avian influenza viruses (AIVs) have seriously threatened human health. Questions such as: why do AIVs infect humans?, how quickly can an AIV become pandemic?, and which virus is the most dangerous? cannot be sufficiently answered using current bioinformatic studies. Method: Secondary structures and energies of representative 5'-untranslated region (UTR) of the HA gene were calculated. Then their secondary structures and energies were re-calculated after one or two nucleotide substitutions were introduced into the HA 5'-UTR. Phylogenetic trees on the basis of hemagglutinin (HA) and polymerase basic protein 2 (PB2) amino acid sequences and HA 5'-UTR nucleotide sequences were constructed. The connection between the energy and translation efficiency of 5'-UTR was confirmed by in vitro coupled transcription/translation assay. Results: The simplicity of the secondary structure of the 5'-UTR of the HA gene determines the overall virus replication rate and transmission potential. Point mutation assays show that the 5'-UTR sequences of the HA gene in the influenza subtypes H2N2, H3N2, and H7N9 have greater variation potentials than other virus subtypes. Conclusion: Some high-virulent strains of avian influenza might emerge in the next two to three years. The H2N2 subtype, once disappeared in humans, may stage a comeback. The current outbreak of H7N9 may become pandemic and cause even more deaths, if one or two bases are substituted in the 5'-UTR sequence of the HA gene.

  • 324. Zhao, Linshu
    et al.
    Vahlquist, Anders
    Virtanen, Marie
    Wennerstrand, Lena
    Lind, Lisbet K.
    Lundström, Anita
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Pigg, Maritta Hellström
    Palmoplantar Keratoderma of the Gamborg-Nielsen Type is Caused by Mutations in the SLURP1 Gene and Represents a Variant of Mal de Meleda2014In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 94, no 6, p. 707-710Article in journal (Refereed)
    Abstract [en]

    Palmoplantar keratoderma of the Gamborg-Nielsen type (PPK-GN) is a rare autosomal recessive skin disorder described in patients from Sweden. Mal de Meleda (MDM) is also a rare autosomal recessive inherited PPK first reported in 5 families from the island of Meleda. The 2 conditions phenotypically overlap and are characterised by palmoplantar erythematous hyperkeratotic plaques. The genetic background giving rise to PPK-GN has hitherto been unknown, whereas MDM is known to be caused by mutations in the gene encoding secreted Ly-6/uPAR-related protein 1, SLURP-1. In the present study we scrutinised individuals affected by PPK-GN for mutations in the SLURP1 gene and identified 2 different mutations. Fourteen Swedish patients were homozygous for a previously described mutation, c.43T>C, while one individual was a compound heterozygote with one copy of a novel mutation, c.280T>A, in addition to one copy of the c.43T>C mutation. Hereby we confirm that PPK-GN is an allelic variant of MDM.

  • 325. Åberg, Emma
    et al.
    Ottosson, Ann
    Granlund, Margareta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Saeedi, Baharak
    Stamm, Christina
    Brune, Thomas
    Tammelin, Ann
    Johansson, Stefan
    Harbouring group B streptococci in a neonatal intensive care unit led to an outbreak among preterm infants2019In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, no 1, p. 58-61Article in journal (Refereed)
    Abstract [en]

    We report a nosocomial outbreak with group B streptococci (GBS) in a level two neonatal intensive care unit (NICU) at Sachs' Children and Youth Hospital, Stockholm, Sweden, in 2014. There were five very preterm infants with severe late-onset septicaemia, and 10 further infants were colonised. Pulsed-field gel electrophoresis and multilocus sequence typing genetic characterisation showed that one GBS strain was the cause: serotype Ia, sequence type 23, clonal complex 23. The NICU environment cultures revealed GBS reservoirs on surfaces near sick and colonised patients. We identified workflows and guidelines that could increase the risks of nosocomial infections. Conclusion: This nosocomial GBS outbreak among preterm infants demonstrates that GBS can be harboured in the NICU environment.

  • 326.
    Åhlund, Monika K
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Stöven, Svenja
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Directed screen of Francisella novicida virulence determinants using Drosophila melanogaster2010In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 78, no 7, p. 3118-3128Article in journal (Refereed)
    Abstract [en]

    Francisella tularensis is a highly virulent, facultative intracellular human pathogen whose virulence mechanisms are not well understood. Occasional outbreaks of tularemia and the potential use of F. tularensis as a bioterrorist agent warrant better knowledge about the pathogenicity of this bacterium. Thus far, genome-wide in vivo screens for virulence factors have been performed in mice, all however restricted by the necessity to apply competition-based, negative-selection assays. We wanted to individually evaluate putative virulence determinants suggested by such assays and performed directed screening of 249 F. novicida transposon insertion mutants by using survival of infected fruit flies as a measure of bacterial virulence. Some 20% of the genes tested were required for normal virulence in flies; most of these had not previously been investigated in detail in vitro or in vivo. We further characterized their involvement in bacterial proliferation and pathogenicity in flies and in mouse macrophages. Hierarchical cluster analysis of mutant phenotypes indicated a functional linkage between clustered genes. One cluster grouped all but four genes of the Francisella pathogenicity island and other loci required for intracellular survival. We also identified genes involved in adaptation to oxidative stress and genes which might induce host energy wasting. Several genes related to type IV pilus formation demonstrated hypervirulent mutant phenotypes. Collectively, the data demonstrate that the bacteria in part use similar virulence mechanisms in mammals as in Drosophila melanogaster but that a considerable proportion of the virulence factors active in mammals are dispensable for pathogenicity in the insect model.

  • 327. Åkesson, Per
    et al.
    Moritz, Linnea
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Truedsson, Mikael
    Christensson, Bertil
    von Pawel-Rammingen, Ulrich
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    IdeS, a highly specific immunoglobulin G (IgG)-cleaving enzyme from Streptococcus pyogenes, is inhibited by specific IgG antibodies generated during infection2006In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 74, no 1, p. 497-503Article in journal (Refereed)
    Abstract [en]

    IdeS, a recently discovered cysteine proteinase secreted by the important human pathogen Streptococcus pyogenes, interferes with phagocytic killing by specifically cleaving the heavy chain of immunoglobulin G. The fact that the enzyme targets one of the key molecules of the adapted immune response raised the question of whether an antibody response against IdeS could inhibit, i.e., neutralize, enzyme activity. Paired acute- and convalescent-phase serum samples from patients with pharyngotonsillitis (n = 10), bacteremia (n = 7), and erysipelas (n = 4) were analyzed. Antibodies with the ability to neutralize IdeS enzymatic activity were already found in two-thirds of acute-phase sera. However, patients who seroconverted to IdeS, in particular patients with pharyngotonsillitis and erysipelas, developed specific antibodies during convalescence with an increased capability to efficiently neutralize the enzymatic activity of IdeS. Also, the presence of neutralizing antibodies decreased the ability of IdeS to mediate bacterial survival in human immune blood. In patients with bacteremia, several acute-phase sera contained neutralizing antibodies, but no correlation was found to severity or outcome of invasive infections. Still, the fact that the human immune response targets the enzymatic activity of IdeS supports the view that the enzyme plays an important role during streptococcal infection.

  • 328.
    Åström, Morgan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Using 2-pyridones as molecular tools to understand chlamydiae genetics2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
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