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  • 101. Goncalves, Adriana
    et al.
    Peeling, Rosanna W.
    Chu, May C.
    Gubler, Duane J.
    de Silva, Aravinda M.
    Harris, Eva
    Murtagh, Maurine
    Chua, Arlene
    Rodriguez, William
    Kelly, Cassandra
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Lee Kong Chian School of Medicine, Singapore; Institute of Public Health, University of Heidelberg, Germany.
    Innovative and New Approaches to Laboratory Diagnosis of Zika and Dengue: A Meeting Report2018In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 217, no 7, p. 1060-1068Article in journal (Refereed)
    Abstract [en]

    Epidemics of dengue, Zika, and other arboviral diseases are increasing in frequency and severity. Current efforts to rapidly identify and manage these epidemics are limited by the short diagnostic window in acute infection, the extensive serologic cross-reactivity among flaviviruses, and the lack of point-of-care diagnostic tools to detect these viral species in primary care settings. The Partnership for Dengue Control organized a workshop to review the current landscape of Flavivirus diagnostic tools, identified current gaps, and developed strategies to accelerate the adoption of promising novel technologies into national programs. The rate-limiting step to bringing new diagnostic tools to the market is access to reference materials and well-characterized clinical samples to facilitate performance evaluation. We suggest the creation of an international laboratory-response consortium for flaviviruses with a decentralized biobank of well-characterized samples to facilitate assay validation. Access to proficiency panels are needed to ensure quality control, in additional to in-country capacity building.

  • 102.
    Grahn, Eva
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Bacteriological aspects of treatment failures in streptococcal tonsillitis1986Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    ß-hemolytic streptococci persist in 10-25% of patients with acute streptococal tonsillitis (about 10.000-25.000 per year in Sweden) in spite of treatment with a recommended dosage and schedule of Phenoxymethylpenicillin. The aim of the study was to investigate different bacteriological factors involved in treatment failures of streptococcal tonsillitis. Patients included in the study were 33 patients who underwent tonsillectomy, 62 persons included in a tonsillitis epidemic outbreak, 267 tonsillitis patients contacting the ENT-clinic, Sahlgrenska Hospital, Göteborg, and 20 healthy volunteers taking Phenoxymethylpenicillin. It was found that the Steer's steel pin replicator was a useful tool to study interference between a- and ß-hemolytic streptococci and a guantitative differen ce in. the inhibitory capacity of the different a-strains was noted, a-streptococci with a strong inhibitory capacity on ß-streptococci were isolated mainly from individuals seemingly resistant to ß-streptococcal tonsillitis, while from patients with repeated tonsillitis no or low numbers of inhibiting a-streptococci were demonstrated. Patients with clinical treatment failure had less a-streptococci with inhibiting capacity on their own ß-streptococcal strain compared with the healthy carriers. These treatment failures also showed beta-lactamase activity in their saliva pellet significantly more often than patients in the control groups. In volunteers penicillin was released from ordinary sugar coated tablets already in the mouth resulting in a decrease of the a-strep- tococcal flora. A synergistic effect on ß-hemolytic killing by low concentration of penicillin and inhibition of a-streptococci was noted in vitro and in vivo. Penicillin tolerance was registered in most strains from the treatment failure group, but in none of the strains from the group of successfully treated patients. A co-operation between different bacteriological factors (bacterial interference, beta-lactamase production, penicillin tolerance) seems to be important in treatment failures of streptococcal tonsillitis.

  • 103.
    Granlund, Margareta
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Axemo, P
    Bremme, K
    Bryngelsson, A-L
    Carlsson Wallin, M
    Ekström, C-M
    Håkansson, Stellan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Jacobsson, B
    Källén, K
    Spetz, E
    Tessin, I
    Antimicrobial resistance in colonizing group B Streptococci before the implementation of a Swedish intrapartum antibiotic prophylaxis program2010In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 29, no 10, p. 1195-1201Article in journal (Refereed)
    Abstract [en]

    The prevalence of antibiotic resistance and their genetic determinants in colonizing group B streptococci (GBS) sampled in a Swedish nationwide survey was examined. In five GBS isolates (1.3%), kanamycin/amikacin resistance and the presence of the aphA-3 gene was identified. Three of these isolates carried the aad-6 gene and were streptomycin-resistant. Screening with kanamycin and streptomycin 1,000-μg disks enabled a rapid and easy detection of these isolates. In all, 312/396 (79%) GBS were tetracycline-resistant and 95% of the examined isolates harbored the tetM gene. Among the 22 (5.5%) GBS resistant to erythromycin and/or clindamycin, the ermB gene was detected in nine isolates (41%) and erm(A/TR) in ten isolates (45%). A high level of erythromycin and clindamycin resistance with minimum inhibitory concentrations (MICs) >256 mg/L was found in four serotype V isolates that harbored ermB. The erythromycin/clindamycin resistance was distributed among all of the common serotypes Ia, Ib, II, III, IV, and V, but was not present in any of the 44 serotype III isolates associated to clonal complex 17. Screening for penicillin resistance with 1-μg oxacillin disks showed a homogenous population with a mean inhibition zone of 20 mm. A change in the present oxacillin breakpoints for GBS is suggested.

  • 104. Grimm, Melissa J
    et al.
    Vethanayagam, R Robert
    Almyroudis, Nikolaos G
    Dennis, Carly G
    Khan, A Nazmul H
    D'Auria, Anthony C
    Singel, Kelly L
    Davidson, Bruce A
    Knight, Paul R
    Blackwell, Timothy S
    Hohl, Tobias M
    Mansour, Michael K
    Vyas, Jatin M
    Röhm, Marc
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Urban, Constantin F
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Kelkka, Tiina
    Holmdahl, Rikard
    Segal, Brahm H
    Monocyte- and macrophage-targeted NADPH oxidase mediates antifungal host defense and regulation of acute inflammation in mice2013In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 190, no 8, p. 4175-4184Article in journal (Refereed)
    Abstract [en]

    Chronic granulomatous disease, an inherited disorder of the NADPH oxidase in which phagocytes are defective in the generation of superoxide anion and downstream reactive oxidant species, is characterized by severe bacterial and fungal infections and excessive inflammation. Although NADPH oxidase isoforms exist in several lineages, reactive oxidant generation is greatest in neutrophils, where NADPH oxidase has been deemed vital for pathogen killing. In contrast, the function and importance of NADPH oxidase in macrophages are less clear. Therefore, we evaluated susceptibility to pulmonary aspergillosis in globally NADPH oxidase-deficient mice versus transgenic mice with monocyte/macrophage-targeted NADPH oxidase activity. We found that the lethal inoculum was >100-fold greater in transgenic versus globally NADPH oxidase-deficient mice. Consistent with these in vivo results, NADPH oxidase in mouse alveolar macrophages limited germination of phagocytosed Aspergillus fumigatus spores. Finally, globally NADPH oxidase-deficient mice developed exuberant neutrophilic lung inflammation and proinflammatory cytokine responses to zymosan, a fungal cell wall-derived product composed principally of particulate beta-glucans, whereas inflammation in transgenic and wild-type mice was mild and transient. Taken together, our studies identify a central role for monocyte/macrophage NADPH oxidase in controlling fungal infection and in limiting acute lung inflammation. The Journal of Immunology, 2013, 190: 4175-4184.

  • 105. Groome, Michelle J.
    et al.
    Page, Nicola
    Cortese, Margaret M.
    Moyes, Jocelyn
    Zar, Heather J.
    Kapongo, Constant N.
    Mulligan, Christine
    Diedericks, Ralph
    Cohen, Cheryl
    Fleming, Jessica A.
    Seheri, Mapaseka
    Mphahlele, Jeffrey
    Walaza, Sibongile
    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 Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa ; INDEPTH Network, Accra, Ghana.
    Chhagan, Meera
    Steele, A. Duncan
    Parashar, Umesh D.
    Zell, Elizabeth R.
    Madhi, Shabir A.
    Effectiveness of monovalent human rotavirus vaccine against admission to hospital for acute rotavirus diarrhoea in South African children: a case-control study2014In: Lancet. Infectious diseases (Print), ISSN 1473-3099, E-ISSN 1474-4457, Vol. 14, no 11, p. 1096-1104Article in journal (Refereed)
    Abstract [en]

    Background The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting with a high prevalence of HIV infection needs to be established. We assessed the vaccine effectiveness of monovalent human rotavirus vaccine in preventing admission to hospital for acute rotavirus diarrhoea, after its introduction at age 6 and 14 weeks into South Africa's national immunisation programme. Methods This case-control study was done at seven hospitals in South Africa between April 19,2010, and Oct 31,2012. The hospitals were located in a range of urban, pen-urban, and rural settings, with varying rates of population HIV infection. Cases were children aged from 18 weeks to 23 months who were age-eligible to have received at least one dose of the human rotavirus vaccine (ie, those born after June 14,2009) admitted to hospital with laboratory-confirmed acute rotavirus diarrhoea, and the primary control group was children admitted to hospital with diarrhoea testing negative for rotavirus. A second control group comprised children admitted to a subset of three of the seven hospitals with respiratory illness. The primary endpoint was adjusted vaccine effectiveness (1 adjusted odds ratio x100%) in children aged from 18 weeks to 23 months and was calculated by unconditional logistic regression. This study is registered on the South African National Clinical Trial Register, number DOH-27-0512-3247. Findings Of 540 rotavirus-positive cases, 278 children (52%) received two doses, 126 (23%) one dose, and 136 (25%) no doses of human rotavirus vaccine, compared with 1434 rotavirus-negative controls of whom 856 (60%) received two doses, 334 (23%) one dose, and 244 (17%) no doses. Adjusted vaccine effectiveness using rotavirus-negative controls was 57% (95% CI 40-68) for two doses and 40% (16-57) for one dose; estimates were similar when respiratory controls were used as the control group. Adjusted vaccine effectiveness for two doses was similar between age groups 18 weeks-11 months (54%, 95% CI 32-68) and 12-23 months (61%, 35-77), and was similar in HIV-exposed-uninfected (64%, 95% CI 34-80) and HIV-unexposed-uninfected children (54%, 31-69). Interpretation Human rotavirus vaccine provided sustained protection against admission to hospital for acute rotavirus diarrhoea during the first and second years of life. This finding is encouraging and establishes the public health value of rotavirus vaccine in an African setting, especially as rotavirus vaccines are introduced into an increasing number of African countries.

  • 106.
    Gylfe, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Cajander, Sara
    Wahab, Tara
    Angelin, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Melioidos: en viktig diagnos vid svår sjukdom efter utlandsresa2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, article id ERRRArticle in journal (Other academic)
  • 107.
    Gylfe, Åsa
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Ribers, Åsa
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Forsman, Oscar
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Bucht, Göran
    Alenius, Gerd-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Wållberg-Jonsson, Solveig
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Mosquitoborne Sindbis Virus Infection and Long-Term Illness2018In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 24, no 6, p. 1141-1142Article in journal (Refereed)
    Abstract [en]

    An unexpected human outbreak of the mosquitoborne Sindbis virus occurred in a previously nonendemic area of Sweden. At follow-up, 6-8 months after infection, 39% of patients had chronic arthralgia that affected their daily activities. Vectorborne infections may disseminate rapidly into new areas and cause acute and chronic disease.

  • 108. Gyuranecz, Miklos
    et al.
    Birdsell, Dawn N.
    Splettstoesser, Wolf
    Seibold, Erik
    Beckstrom-Sternberg, Stephen M.
    Makrai, Laszlo
    Fodor, Laszlo
    Fabbi, Massimo
    Vicari, Nadia
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Busch, Joseph D.
    Vogler, Amy J.
    Keim, Paul
    Wagner, David M.
    Phylogeography of Francisella tularensis subsp holarctica, Europe2012In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 18, no 2, p. 290-293Article in journal (Refereed)
    Abstract [en]

    Francisella tularensis subsp. holarctica isolates from Austria, Germany, Hungary, Italy, and Romania were placed into an existing phylogeographic framework. Isolates from Italy were assigned to phylogenetic group B.FTNF002-00; the other isolates, to group B.13. Most F tularensis subsp. holarctica isolates from Europe belong to these 2 geographically segregated groups.

  • 109. Haemig, Paul
    et al.
    Sjöstedt de Luna, Sara
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Grafström, Anton
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Lithner, Stefan
    Linneaus University.
    Lundkvist, Åke
    Swedish Institute for Infectious Disease Control (SMI), Solna.
    Waldenström, Jonas
    Linneaus University.
    Kindberg, Jonas
    Swedish University of Agricultural Sciences, Umeå.
    Stedt, Johan
    Linnaeus University.
    Olsen, Björn
    Uppsala University.
    Forecasting risk of tick-borne encephalitis (TBE): Using data from wildlife and climate to predict next year’s number of human victims2011In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 43, p. 366-372Article in journal (Refereed)
    Abstract [en]

    Background: Over the past quarter century, the incidence of tick-borne encephalitis (TBE) has increased in most European nations. However, the number of humans stricken by the disease varies from year to year. A method for predicting major increases and decreases is needed. Methods: We assembled a 25-y database (1984–2008) of the number of human TBE victims and wildlife and climate data for the Stockholm region of Sweden, and used it to create easy-to-use mathematical models that predict increases and decreases in the number of humans stricken by TBE. Results: Our best model, which uses December precipitation and mink (Neovison vison, formerly Mustela vison) bagging figures, successfully predicted every major increase or decrease in TBE during the past quarter century, with a minimum of false alarms. However, this model was not efficient in predicting small increases and decreases. Conclusions: Predictions from our models can be used to determine when preventive and adaptive programmes should be implemented. For example, in years when the frequency of TBE in humans is predicted to be high, vector control could be intensified where infested ticks have a higher probability of encountering humans, such as at playgrounds, bathing lakes, barbecue areas and camping facilities. Because our models use only wildlife and climate data, they can be used even when the human population is vaccinated. Another advantage is that because our models employ data from previously-established databases, no additional funding for surveillance is required.

  • 110. Hamer, Davidson H.
    et al.
    Barbre, Kira A.
    Chen, Lin H.
    Grobusch, Martin P.
    Schlagenhauf, Patricia
    Goorhuis, Abraham
    van Genderen, Perry J. J.
    Molina, Israel
    Asgeirsson, Hilmir
    Kozarsky, Phyllis E.
    Caumes, Eric
    Hagmann, Stefan H.
    Mockenhaupt, Frank P.
    Eperon, Gilles
    Barnett, Elizabeth D.
    Bottieau, Emmanuel
    Boggild, Andrea K.
    Gautret, Philippe
    Hynes, Noreen A.
    Kuhn, Susan
    Lash, Ryan
    Leder, Karin
    Libman, Michael
    Malvy, Denis J. M.
    Perret, Cecilia
    Rothe, Camilla
    Schwartz, Eli
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Cetron, Martin S.
    Esposito, Douglas H.
    Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016 A GeoSentinel Analysis2017In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 166, no 2, p. 99-108Article in journal (Refereed)
    Abstract [en]

    Background: Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. Objective: To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Design: Descriptive, using GeoSentinel records. Setting: 63 travel and tropical medicine clinics in 30 countries. Patients: Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. Measurements: Frequencies of demographic, trip, and clinical characteristics and complications. Results: Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain-Barre syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). Limitation: Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. Conclusion: These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission.

  • 111. Hansson, Marit
    et al.
    Stockfelt, Leo
    Urazalin, Marat
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Andersson, Rune
    HIV/AIDS awareness and risk behavior among students in Semey, Kazakhstan: a cross-sectional survey.2008In: BMC International Health and Human Rights, ISSN 1472-698X, E-ISSN 1472-698X, Vol. 8, p. 14-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Until recently, young people in Kazakhstan have been only moderately affected by the global HIV epidemic. Today, however, the HIV epidemic in Central Asia is one of the most rapidly increasing epidemics in the world. It is mainly concentrated to vulnerable groups such as intravenous drug users, sex workers, the purchasers of sexual services and the financially marginalized. Young, sexually active people may however be the gateway for the epidemic to the general population, and knowledge about their attitudes and behavior is therefore important in planning preventive measures. METHODS: To gather information about young students and their attitudes and knowledge about HIV/AIDS, we collected 600 structured questionnaires and made 23 semi-structured interviews among three groups of students. Response rate was 99%. RESULTS: Almost 99% of the respondents had heard of HIV/AIDS, and 89% could identify ways to protect oneself against sexually transmitted HIV/AIDS. The main routes of transmission, sexual contact without condom and intravenous drug use, were both identified by 97% of the students. Twenty-five percent of the female students and 75% of the male students had had one or more sexual partners. More than 30% of the young men had purchased sex, and homosexuality was widely stigmatized. CONCLUSION: Risks for the spread of HIV/AIDS among young people in Kazakhstan include prostitution as well as stigmatization of the HIV positive and of homosexuals. Protective factors are good knowledge about risks and protection, and opportunities to talk and gather information about sexuality and HIV/AIDS.

  • 112.
    Hassan, Osama Ahmed
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Public Health Institute, Khartoum, Sudan.
    Affognon, Hippolyte
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Mburu, Peter
    Sang, Rosemary
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    The One Health approach to identify knowledge, attitudes and practices that affect community involvement in the control of Rift Valley fever outbreaks2017In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 11, no 2, article id e0005383Article in journal (Refereed)
    Abstract [en]

    Rift Valley fever (RVF) is a viral mosquito-borne disease with the potential for global expansion, causes hemorrhagic fever, and has a high case fatality rate in young animals and in humans. Using a cross-sectional community-based study design, we investigated the knowledge, attitudes and practices of people living in small village in Sudan with respect to RVF outbreaks. A special One Health questionnaire was developed to compile data from 235 heads of household concerning their knowledge, attitudes, and practices with regard to controlling RVF. Although the 2007 RVF outbreak in Sudan had negatively affected the participants' food availability and livestock income, the participants did not fully understand how to identify RVF symptoms and risk factors for both humans and livestock. For example, the participants mistakenly believed that avoiding livestock that had suffered spontaneous abortions was the least important risk factor for RVF. Although the majority noticed an increase in mosquito population during the 2007 RVF outbreak, few used impregnated bed nets as preventive measures. The community was reluctant to notify the authorities about RVF suspicion in livestock, a sentinel for human RVF infection. Almost all the respondents stressed that they would not receive any compensation for their dead livestock if they notified the authorities. In addition, the participants believed that controlling RVF outbreaks was mainly the responsibility of human health authorities rather than veterinary authorities. The majority of the participants were aware that RVF could spread from one region to another within the country. Participants received most their information about RVF from social networks and the mass media, rather than the health system or veterinarians. Because the perceived role of the community in controlling RVF was fragmented, the probability of RVF spread increased.

  • 113.
    Hassan, Osama Ahmed
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Department of Epidemiology and Diseases Control, Public Health Institute, Federal Ministry of Health, Khartoum, Sudan.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    A need for One Health approach: lessons learned from outbreaks of Rift Valley fever in Saudi Arabia and Sudan2014In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 4, article id 20710Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Rift Valley fever (RVF) is an emerging viral zoonosis that impacts human and animal health. It is transmitted from animals to humans directly through exposure to blood, body fluids, or tissues of infected animals or via mosquito bites. The disease is endemic to Africa but has recently spread to Saudi Arabia and Yemen. Our aim was to compare two major outbreaks of RVF in Saudi Arabia (2000) and Sudan (2007) from a One Health perspective.

    METHODS: Using the terms 'Saudi Arabia', 'Sudan', and 'RVF', articles were identified by searching PubMed, Google Scholar, and web pages of international organizations as well as local sources in Saudi Arabia and Sudan.

    RESULTS: The outbreak in Saudi Arabia caused 883 human cases, with a case fatality rate of 14% and more than 40,000 dead sheep and goats. In Sudan, 698 human cases of RVF were recognized (case fatality, 31.5%), but no records of affected animals were available. The ecology and environment of the affected areas were similar with irrigation canals and excessive rains providing an attractive habitat for mosquito vectors to multiply. The outbreaks resulted in livestock trade bans leading to a vast economic impact on the animal market in the two countries. The surveillance system in Sudan showed a lack of data management and communication between the regional and federal health authorities, while in Saudi Arabia which is the stronger economy, better capacity and contingency plans resulted in efficient countermeasures. Studies of the epidemiology and vectors were also performed in Saudi Arabia, while in Sudan these issues were only partly studied.

    CONCLUSION: We conclude that a One Health approach is the best option to mitigate outbreaks of RVF. Collaboration between veterinary, health, and environmental authorities both on national and regional levels is needed.

  • 114.
    Hessle, Pontus
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    IgdE homologues - a potential novel immunomodulating enzyme family of Streptococci: Proteases of high specificity linking Streptococcal species to their host organisms2016Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 115. Hjertqvist, Marika
    et al.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Klingström, Jonas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Sex patterns in diagnoses of tularaemia, Sweden 1997-20082010In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 60, no 2, p. 186-187Article in journal (Refereed)
  • 116. Hjertqvist, Marika
    et al.
    Klein, Sabra L
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Klingström, Jonas
    Mortality rate patterns for hemorrhagic fever with renal syndrome caused by Puumala virus2010In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 16, no 10, p. 1584-1586Article in journal (Refereed)
    Abstract [en]

    To investigate nephropathia epidemica in Sweden during 1997-2007, we determined case-fatality rates for 5,282 patients with this disease. Overall, 0.4% died of acute nephropathia epidemica ≤3 months after diagnosis. Case-fatality rates increased with age. Only women showed an increased case-fatality rate during the first year after diagnosis.

  • 117. Hoffman, Tove
    et al.
    Lindeborg, Mats
    Barboutis, Christos
    Erciyas-Yavuz, Kiraz
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Fransson, Thord
    Figuerola, Jordi
    Jaenson, Thomas G. T.
    Kiat, Yosef
    Lindgren, Per-Eric
    Lundkvist, Åke
    Mohamed, Nahla
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Moutailler, Sara
    Nyström, Fredrik
    Olsen, Björn
    Salaneck, Erik
    Alkhurma Hemorrhagic Fever Virus RNA in Hyalomma rufipes Ticks Infesting Migratory Birds, Europe and Asia Minor2018In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 24, no 5, p. 879-882Article in journal (Refereed)
    Abstract [en]

    Alkhurma hemorrhagic fever virus RNA was detected in immature Hyalomma rufipes ticks infesting northward migratory birds caught in the North Mediterranean Basin. This finding suggests a role for birds in the ecology of the Alkhurma hemorrhagic fever virus and a potential mechanism for dissemination to novel regions. Increased surveillance is warranted.

  • 118. Hoffner, S.
    et al.
    Angeby, K.
    Sturegard, E.
    Jonsson, B.
    Johansson, A.
    Sellin, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Werngren, J.
    Proficiency of drug susceptibility testing of Mycobacterium tuberculosis against pyrazinamide: the Swedish experience2013In: The International Journal of Tuberculosis and Lung Disease, ISSN 1027-3719, E-ISSN 1815-7920, Vol. 17, no 11, p. 1486-1490Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Pyrazinamide (PZA) is a key drug in the treatment of tuberculosis (TB), including multidrug-resistant TB. Drug susceptibility testing (DST) of Mycobacterium tuberculosis against PZA is not included in the World Health Organization's yearly proficiency testing. There is an increasing need to establish quality control of PZA DST. OBJECTIVE: To evaluate the performance of PZA DST and to introduce a quality assurance system for the test in Sweden. METHOD: Panels with PZA-susceptible and -resistant isolates were used in three rounds of proficiency testing in all five Swedish clinical TB laboratories and our reference laboratory. All laboratories used the MGIT 960 system. Minimum inhibitory concentrations (MICs) were determined and the pncA gene was sequenced to further characterise the 52 panel strains. RESULTS: Good agreement was seen between the phenotypic PZA DST and pncA sequence data, and MIC determination confirmed high levels of resistance. However, in contrast to other drugs, for which correct proficiency test results were observed, specificity problems occurred for PZA DST in some laboratories. CONCLUSIONS: In Sweden, using panel testing, differences were seen in the proficiency of TB laboratories in correctly identifying PZA susceptibility. Improved results were noted in the third round; PZA has therefore been included in yearly proficiency testing.

  • 119.
    Holme, Petter
    et al.
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Masuda, Naoki
    Umeå University, Faculty of Science and Technology, Department of Physics.
    The Basic Reproduction Number as a Predictor for Epidemic Outbreaks in Temporal Networks2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 3, article id e0120567Article in journal (Refereed)
    Abstract [en]

    The basic reproduction number R-0-the number of individuals directly infected by an infectious person in an otherwise susceptible population-is arguably the most widely used estimator of how severe an epidemic outbreak can be. This severity can be more directly measured as the fraction of people infected once the outbreak is over, Omega. In traditional mathematical epidemiology and common formulations of static network epidemiology, there is a deterministic relationship between R-0 and Omega. However, if one considers disease spreading on a temporal contact network-where one knows when contacts happen, not only between whom-then larger R-0 does not necessarily imply larger Omega. In this paper, we numerically investigate the relationship between R-0 and Omega for a set of empirical temporal networks of human contacts. Among 31 explanatory descriptors of temporal network structure, we identify those that make R-0 an imperfect predictor of Omega. We find that descriptors related to both temporal and topological aspects affect the relationship between R-0 and Omega, but in different ways.

  • 120.
    Holmström, Anna
    et al.
    Umeå University, Faculty of Medicine, Microbiology.
    Rosqvist, Roland
    Umeå University, Faculty of Medicine, Microbiology.
    Wolf-Watz, Hans
    Umeå University, Faculty of Medicine, Microbiology.
    Forsberg, Åke
    Umeå University, Faculty of Medicine, Microbiology.
    Virulence plasmid-encoded YopK is essential for Yersinia pseudotuberculosis to cause systemic infection in mice.1995In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 63, no 6, p. 2269-2276Article in journal (Refereed)
    Abstract [en]

    The virulence plasmid common to pathogenic Yersinia species encodes a number of secreted proteins denoted Yops (Yersinia outer proteins). Here, we identify and characterize a novel plasmid-encoded virulence determinant of Yersinia pseudotuberculosis, YopK. The yopK gene was found to be conserved among the three pathogenic Yersinia species and to be homologous to the previously described yopQ and yopK genes of Y. enterocolitica and Y. pestis, respectively. Similar to the other Yops, YopK expression and secretion were shown to be regulated by temperature and by the extracellular Ca2+ concentration; thus, yopK is part of the yop regulon. In addition, YopK secretion was mediated by the specific Yop secretion system. In Y. pseudotuberculosis, YopK was shown neither to have a role in this bacterium's ability to resist phagocytosis by macrophages nor to cause cytotoxicity in HeLa cells. YopK was, however, shown to be required for the bacterium to cause a systemic infection in both intraperitoneally and orally infected mice. Characterization of the infection kinetics showed that, similarly to the wild-type strain, the yopK mutant strain colonized and persisted in the Peyer's patches of orally infected mice. A yopE mutant which is impaired in cytotoxicity and in antiphagocytosis was, however, found to be rapidly cleared from these lymphoid organs. Neither the yopK nor the yopE mutant strain could overcome the primary host defense and reach the spleen. This finding implies that YopK acts at a different level during the infections process than the antiphagocytic YopE cytotoxin does.

  • 121.
    Horcajo, Pilar
    et al.
    Centro de Biología Molecular ‘‘Severo Ochoa,’’ Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas, Madrid, Spain.
    de Pedro, Miguel A
    Centro de Biología Molecular ‘‘Severo Ochoa,’’ Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas, Madrid, Spain.
    Cava, Felipe
    Centro de Biología Molecular ‘‘Severo Ochoa,’’ Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas, Madrid, Spain.
    Peptidoglycan plasticity in bacteria: stress-induced peptidoglycan editing by noncanonical D-amino acids2012In: Microbial Drug Resistance, ISSN 1076-6294, E-ISSN 1931-8448, Vol. 18, no 3, p. 306-313Article in journal (Refereed)
    Abstract [en]

    It has been generally assumed that the role of D-amino acids in bacterial physiology is rather limited. However, recent new evidence demonstrated that millimolar concentrations of noncanonical D-amino acids are synthesized and released to the environment by bacteria from diverse phyla. These D-amino acids help bacteria adapt to environmental challenges by modulating the structure and composition of the peptidoglycan (PG). This regulation, which appears to be well conserved among bacterial species, occurs principally through the incorporation of the D-amino acids into the terminus of the peptide moiety of muropeptides. These findings revived interest in studies investigating D-amino acids as an exciting and trendy topic in current microbiology, which considers them as fundamental players in different aspects of bacterial physiology. In this article, we provide an overview of the origins of research on the effects of D-amino acids in the biology of bacterial cell walls, including their recent implication as key factors for stress-associated PG remodeling.

  • 122.
    Horstick, Olaf
    et al.
    Institute of Public Health, University of Heidelberg, Heidelberg, Germany.
    Tozan, Yesim
    Institute of Public Health, University of Heidelberg, Heidelberg, Germany ; Steinhardt School of Culture, Education and Human Development and Global Institute of Public Health, New York University, New York, New York, United States of America.
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Institute of Public Health, University of Heidelberg, Heidelberg, Germany ; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
    Reviewing dengue: still a neglected tropical disease?2015In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 9, no 4, article id e0003632Article, review/survey (Refereed)
    Abstract [en]

    Dengue is currently listed as a "neglected tropical disease" (NTD). But is dengue still an NTD or not? Classifying dengue as an NTD may carry advantages, but is it justified? This review considers the criteria for the definition of an NTD, the current diverse lists of NTDs by different stakeholders, and the commonalities and differences of dengue with other NTDs. We also review the current research gaps and research activities and the adequacy of funding for dengue research and development (R&D) (2003-2013). NTD definitions have been developed to a higher precision since the early 2000s, with the following main features: NTDs are characterised as a) poverty related, b) endemic to the tropics and subtropics, c) lacking public health attention, d) having poor research funding and shortcomings in R&D, e) usually associated with high morbidity but low mortality, and f) often having no specific treatment available. Dengue meets most of these criteria, but not all. Although dengue predominantly affects resource-limited countries, it does not necessarily only target the poor and marginalised in those countries. Dengue increasingly attracts public health attention, and in some affected countries it is now a high profile disease. Research funding for dengue has increased exponentially in the past two decades, in particular in the area of dengue vaccine development. However, despite advances in dengue research, dengue epidemics are increasing in frequency and magnitude, and dengue is expanding to new areas. Specific treatment and a highly effective vaccine remain elusive. Major research gaps exist in the area of integrated surveillance and vector control. Hence, although dengue differs from many of the NTDs, it still meets important criteria commonly used for NTDs. The current need for increased R& D spending, shared by dengue and other NTDs, is perhaps the key reason why dengue should continue to be considered an NTD.

  • 123. Huerta-Uribe, Alejandro
    et al.
    Marjenberg, Zoe R.
    Yamaguchi, Nao
    Fitzgerald, Stephen
    Connolly, James P. R.
    Carpena, Nuria
    Uvell, Hanna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Douce, Gillian
    Elofsson, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Byron, Olwyn
    Marquez, Rudi
    Gally, David L.
    Roe, Andrew J.
    Identification and Characterization of Novel Compounds Blocking Shiga Toxin Expression in Escherichia coli O157:H72016In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 7, article id 1930Article in journal (Refereed)
    Abstract [en]

    Infections caused by Shiga toxin-producing E. coli strains constitute a health problem, as they are problematic to treat. Shiga toxin (Stx) production is a key virulence factor associated with the pathogenicity of enterohaemorrhagic E. coli (EHEC) and can result in the development of haemolytic uremic syndrome in infected patients. The genes encoding Stx are located on temperate lysogenic phages integrated into the bacterial chromosome and expression of the toxin is generally coupled to phage induction through the SOS response. We aimed to find new compounds capable of blocking expression of Stx type 2 (Stx2) as this subtype of Stx is more strongly associated with human disease. High-throughput screening of a small-molecule library identified a lead compound that reduced Stx2 expression in a dose-dependent manner. We show that the optimised compound interferes with the SOS response by directly affecting the activity and oligomerisation of RecA, thus limiting phage activation and Stx2 expression. Our work suggests that RecA is highly susceptible to inhibition and that targeting this protein is a viable approach to limiting production of Stx2 by EHEC. This type of approach has the potential to limit production and transfer of other phage induced and transduced determinants.

  • 124. Hultin, Emilie
    et al.
    Arroyo Mühr, Laila Sara
    Bzhalava, Zurab
    Hortlund, Maria
    Lagheden, Camilla
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Dillner, Joakim
    Viremia preceding multiple sclerosis: Two nested case-control studies2018In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 520, p. 21-29Article in journal (Refereed)
    Abstract [en]

    Infections have been suggested to be involved in Multiple Sclerosis (MS). We used metagenomic sequencing to detect both known and yet unknown microorganisms in 2 nested case control studies of MS. Two different cohorts were followed for MS using registry linkages. Serum samples taken before diagnosis as well as samples from matched control subjects were selected.

    In cohort1 with 75 cases and 75 controls, most viral reads were Anelloviridae-related and >95% detected among the cases. Among samples taken up to 2 years before MS diagnosis, Anellovirus species TTMV1, TTMV6 and TTV27 were significantly more common among cases. In cohort2, 93 cases and 93 controls were tested under the pre-specified hypothesis that the same association would be found. Although most viral reads were again related to Anelloviridae, no significant case-control differences were seen. We conclude that the Anelloviridae-MS association may be due to multiple hypothesis testing, but other explanations are possible.

  • 125.
    Hultin, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Sundberg, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Spontaneous Conversions of Supraventricular Tachycardia to Sinus Rhythm in Children After Premedication With Intranasal Dexmedetomidine: A Case Report2018In: A&A Practice, ISSN 2575-3126, Vol. 11, no 8, p. 219-220Article in journal (Refereed)
    Abstract [en]

    Intranasal dexmedetomidine administered as premedication before anesthesia and cardioversion appears to have the potential to facilitate the return of sinus rhythm. Two children, 3.5 and 1.5 years old, with recurrent supraventricular tachycardia in need of cardioversion have now on several occasions spontaneously returned to sinus rhythm within 20-40 minutes after intranasal administration of dexmedetomidine (4 µg/kg) with a mucosal atomization device. Both children were observed on all occasions at the pediatric outpatient clinic and could return home within 2 hours of cardioversion. For children with supraventricular tachycardia, a selective alpha2-agonist might be a valuable alternative to cardioversion with adenosine.

  • 126.
    Håglin, Lena M
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Burman, Lars Ake
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Nilsson, Mats
    Predisposing chronic diseases and hypophosphatemia in patients with influenza.2010In: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 51, no 1, p. 26-30Article in journal (Refereed)
    Abstract [en]

    Almost half of the hospitalized influenza patients have a chronic disease, which increases the risk for secondary bacterial infections and for adults >65 years influenza is related to high mortality risk. The impact of diabetes mellitus (DM), asthma bronchiale, cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD) on the risk of having a low serum phosphatemia (S-P) in addition to influenza is important to investigate as this increases both morbidity and mortality and can be prevented. Hypophosphatemia could be the explanation for reduced chemo-taxis and phagocytosis, which in addition to respiratory function may increase the risk of pneumonia and sepsis. Data for this study was collected from the medical journals retrospectively for 100 patients admitted to the Department of Infectious Diseases during the study period, 1992-94, with the clinical diagnosis influenza out of which seventy-two cases were used in the calculation. Forty-seven percent of the hospitalized influenza patients had a 2.7-fold risk of suffering from DM than of any other chronic disease and an almost significantly doubled risk of having a low S-P level with a chronic disease. The prevalence of hypophosphatemia (S-P<0.70 mmol/l) was high; 13.0% of the women and 15.0% of the men; 34.0% of all patients had S-P<0.82 mmol/l. Men, in contrast to women, showed clinical signs of a secondary bacterial infection more frequently (12/41 and 6/35, respectively). Our study gives indications for an involvement of low S-P with chronic disease.

  • 127.
    Höglund Åberg, Carola
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Molecular Periodontology.
    Kwamin, Francis
    Univ Ghana, Sch Dent, Accra, Ghana.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology, Molecular Periodontology. Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Haubek, Dorte
    Århus Univ, Dept Dent, Århus, Denmark.
    Presence of JP2 and Non-JP2 genotypes of aggregatibacter actinomycetemcomitans and periodontal attachment loss in adolescents in Ghana2012In: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 83, no 12, p. 1520-1528Article in journal (Refereed)
    Abstract [en]

    Background: Limited data are reported concerning the presence of A. actinomycetemcomitans and attachment loss (AL) in sub-Saharan countries. The authors investigate the carrier frequency of JP2 and non-JP2 genotypes of A. actinomycetemcomitans and the presence of AL in Ghanaian adolescents and evaluate socioeconomic conditions and oral hygiene practices. Methods: Five hundred individuals (mean +/- SD age: 13.2 +/- 1.5 years) in public and private schools were interviewed about demographic characteristics and oral hygiene practices and were given a full-mouth periodontal examination. Subgingival plaque samples were obtained from periodontal sites around permanent first molars and incisors. The carrier status of A. actinomycetemcomitans at the individual level was determined based on results obtained by cultivation and polymerase chain reaction. Results: The findings of this study show a relatively high carrier rate of JP2 and non-JP2 genotypes of Aggregatibacter actinomycetemcomitans in the Ghanaian adolescent population and the presence of this bacterium is associated with the occurrence of AL. The overall carrier rate of A. actinomycetemcomitans was 54.4%, and the highly leukotoxic JP2 genotype was detected in 8.8% of the study population. A total of 107 (21.4%) individuals had >= 1 tooth with AL >= 3 mm. The majority of the individuals carrying A. actinomycetemcomitans (80.1%) (P<0.001) and of the periodontally diseased individuals (91.6%) (P<0.001) were found in public schools. Conclusions: A. actinomycetemcomitans and AL were frequently found in Ghanaian adolescents. The school type was the strongest predictor of both presence of A. actinomycetemcomitans and AL.

  • 128.
    Ignatov, Dmitriy
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Johansson, Jörgen
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    RNA-mediated signal perception in pathogenic bacteria2017In: Wiley Interdisciplinary Reviews-RNA, ISSN 1757-7004, Vol. 8, no 6, article id e1429Article, review/survey (Refereed)
    Abstract [en]

    Bacterial pathogens encounter several different environments during an infection, many of them possibly being detrimental. In order to sense its surroundings and adjust the gene expression accordingly, different regulatory schemes are undertaken. With these, the bacterium appropriately can differentiate between various environmental cues to express the correct virulence factor at the appropriate time and place. An attractive regulator device is RNA, which has an outstanding ability to alter its structure in response to external stimuli, such as metabolite concentration or alterations in temperature, to control its downstream gene expression. This review will describe the function of riboswitches and thermometers, with a particular emphasis on regulatory RNAs being important for bacterial pathogenicity.

  • 129.
    Islam, Md. Koushikul
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Baudin, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Eriksson, Jonas
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Öberg, Christopher
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Habjan, Matthias
    Weber, Friedemann
    Överby, Anna K.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Evander, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    High-Throughput Screening Using a Whole-Cell Virus Replication Reporter Gene Assay to Identify Inhibitory Compounds against Rift Valley Fever Virus Infection2016In: Journal of Biomolecular Screening, ISSN 1087-0571, E-ISSN 1552-454X, Vol. 21, no 4, p. 354-362Article in journal (Refereed)
    Abstract [en]

    Rift Valley fever virus (RVFV) is an emerging virus that causes serious illness in humans and livestock. There are no approved vaccines or treatments for humans. The purpose of the study was to identify inhibitory compounds of RVFV infection without any preconceived idea of the mechanism of action. A whole-cell-based high-throughput drug screening assay was developed to screen 28,437 small chemical compounds targeting RVFV infection. To accomplish both speed and robustness, a replication-competent NSs-deleted RVFV expressing a fluorescent reporter gene was developed. Inhibition of fluorescence intensity was quantified by spectrophotometry and related to virus infection in human lung epithelial cells (A549). Cell toxicity was assessed by the Resazurin cell viability assay. After primary screening, 641 compounds were identified that inhibited RVFV infection by 80%, with 50% cell viability at 50 mu M concentration. These compounds were subjected to a second screening regarding dose-response profiles, and 63 compounds with 60% inhibition of RVFV infection at 3.12 mu M compound concentration and 50% cell viability at 25 mu M were considered hits. Of these, six compounds with high inhibitory activity were identified. In conclusion, the high-throughput assay could efficiently and safely identify several promising compounds that inhibited RVFV infection.

  • 130. Jaenisch, Thomas
    et al.
    Sakuntabhai, Anavaj
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Dengue research funded by the European commission: scientific strategies of three European dengue research consortia2013In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 7, no 12, article id e2320Article in journal (Refereed)
  • 131.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology. Umeå University, Faculty of Medicine, Clinical Microbiology, Infectious Diseases.
    A genome-wide DNA microarray analysis of Francisella tularensis strains demonstrates extensive genetic conservation within the species but identifies regions that are unique to the highly virulent F. tularensis subspecies tularensis.2002Manuscript (Other academic)
    Abstract [en]

    Francisella tularensis is a potent pathogen and a possible bioterrorism agent. Little is known, however, to explain the molecular basis for its virulence and the distinct differences in virulence found between the four recognized subspecies tularensis, mediaasiatica, holarctica, and novicida. We developed a DNA microarray based on 1,832 clones from a shotgun library used for sequencing of the highly virulent F. tularensis subspecies tularensis, strain Schu S4. This allowed a genome-wide analysis of 27 strains representing all four subspecies. Overall, the microarray analysis confirmed a limited genetic variation within the species F. tularensis, and when strains were compared, at most 3.7 % of the probes showed differential hybridization. Despite marked differences in their virulence and geographical origin, a high genomic similarity between strains of the subspecies tularensis and mediaasiatica was apparent. Within the subspecies holarctica, strains from Japan showed unique hybridization patterns. Eight Regions of Difference (RD), 0.6 - 11.5 kb in size altogether comprising 21 open reading frames, were identified that distinguished strains of the moderately virulent subspecies holarctica and the highly virulent subspecies tularensis, respectively. One of these regions, RD1, allowed for the first time the development of a F. tularensis specific PCR assay discriminating each of the four subspecies.

  • 132.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology. Umeå University, Faculty of Medicine, Clinical Microbiology, Infectious Diseases.
    Comparative analysis of PCR versus culture for diagnosis of ulceroglandular tularemia2000In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 38, no 1, p. 22-26Article in journal (Refereed)
    Abstract [en]

    PCR and culture were comparatively evaluated for their abilities to demonstrate Francisella tularensis in wound specimens from tularemia patients during an outbreak in Sweden in 1998. For transport of the specimens used for PCR, a buffer solution containing a nuclease inhibitor was used, and for transport of the specimens used for culture, a commercial transport system was selected after experimental comparison of various systems. Of 40 patients with culture- and/or serology-verified ulceroglandular tularemia, PCR detected F. tularensis DNA in 30 (75%) patients, whereas culture detected bacterial growth in 25 (62%) patients. Compared to data from a previous study, the present inclusion of a nuclease inhibitor in the transport medium did not improve the sensitivity of the PCR, whereas the sensitivity of the culture procedure was significantly increased by selection of the system used for transport. Among eight patients with clinically suspected tularemia but with negative serology and culture, specimens from four patients showed detectable DNA. In three of these patients the diagnosis was verified by the demonstration of an F. tularensis-specific T-cell response in vitro. In conclusion, PCR was more sensitive than culture for demonstration of F. tularensis in wound specimens. Besides, we showed that tularemia may proceed without development of serum antibodies, and in these patients, PCR may be of special importance for verification of the diagnosis.

  • 133.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology. Umeå University, Faculty of Medicine, Clinical Microbiology, Infectious Diseases.
    Evaluation of PCR-based methods for discrimination of Francisella species and subspecies and development of a specific PCR that distinguishes the two major subspecies of Francisella tularensis.2000In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 38, no 11, p. 4180-4185Article in journal (Refereed)
    Abstract [en]

    Previous studies have demonstrated that the four subspecies of the human pathogen Francisella tularensis, despite showing marked variations in their virulence for mammals and originating from different regions in the Northern Hemisphere, display a very close phylogenetic relationship. This property has hampered the development of generally applicable typing methods. To overcome this problem, we evaluated the use of PCR for discrimination of the subspecies using various forms of long arbitrary primers or primers specific for repetitive extragenic palindromic sequences (REP) or enterobacterial repetitive intragenic consensus (ERIC) sequences. Patterns generated by use of REP, ERIC, or long arbitrary primers allowed differentiation at the species level and of the four subspecies of F. tularensis. With each of these three methods, similar or identical clustering of strains was found, and groups of strains of different geographical origins or differing in virulence showed distinct patterns. The discriminatory indices of the methods varied from 0.57 to 0.65; thus, the patterns were not sufficiently discriminatory to distinguish individual strains. The sequence of a fragment generated by amplification with an arbitrary primer was determined, and a region showing interstrain heterogeneity was identified. Specific primers were designed, and a PCR was developed that distinguished strains of F. tularensis subsp. holarctica from strains of other F. tularensis subspecies, including strains of the highly virulent F. tularensis subsp. tularensis. Notably, one European isolate showed the genetic pattern typical of the highly virulent F. tularensis subsp. tularensis, generally believed to exist only in North America. It is proposed that a combination of the specific PCR together with one method generating subspecies-specific patterns is suitable as a rapid and relatively simple strategy for discrimination of Francisella species and subspecies.

  • 134.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Clinical Microbiology. Umeå University, Faculty of Medicine, Clinical Microbiology, Infectious Diseases.
    Extensive allelic variation among Francisella tularensis strains in a short-sequence tandem repeat region2001In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 39, no 9, p. 3140-3146Article in journal (Refereed)
    Abstract [en]

    Members of the genus Francisella and the species F. tularensis appear to be genetically very similar despite pronounced differences in virulence and geographic localization, and currently used typing methods do not allow discrimination of individual strains. Here we show that a number of short-sequence tandem repeat (SSTR) loci are present in F. tularensis genomes and that two of these loci, SSTR9 and SSTR16, are together highly discriminatory. Labeled PCR amplification products from the loci were identified by an automated DNA sequencer for size determination, and each allelic variant was sequenced. Simpson's index of diversity was 0.97 based on an analysis of 39 nonrelated F. tularensis isolates. The locus showing the highest discrimination, SSTR9, gave an index of diversity of 0.95. Thirty-two strains isolated from humans during five outbreaks of tularemia showed much less variation. For example, 11 of 12 strains isolated in the Ljusdal area, Sweden in 1995 and 1998 had identical allelic variants. Phenotypic variants of strains and extensively cultured replicates within strains did not differ, and, for example, the same allelic combination was present in 55 isolates of the live-vaccine strain of F. tularensis and another one was present in all 13 isolates of a strain passaged in animals. The analysis of short-sequence repeats of F. tularensis strains appears to be a powerful tool for discrimination of individual strains and may be useful for a detailed analysis of the epidemiology of this potent pathogen.

  • 135.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Höglund Åberg, Carola
    Umeå University, Faculty of Medicine, Department of Odontology.
    Haubek, Dorte
    Aarhus university, Denmark.
    Lindholm, Mark
    Umeå University, Faculty of Medicine, Department of Odontology.
    Jasim, Sarah
    Umeå University, Faculty of Medicine, Department of Odontology.
    Oscarsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Genetic Profiling of Aggregatibacter actinomycetemcomitans Serotype B Isolated from Periodontitis Patients Living in Sweden.2019In: Pathogens (Basel, Switzerland), ISSN 2076-0817, Vol. 8, no 3, article id E153Article in journal (Refereed)
    Abstract [en]

    The bacterium Aggregatibacter actinomycetemcomitans is associated with aggressive forms of periodontitis and with systemic diseases, such as endocarditis. By assessing a Ghanaian longitudinal adolescent cohort, we earlier recognized the cagE gene as a possible diagnostic marker for a subgroup of JP2 and non-JP2 genotype serotype b A. actinomycetemcomitans strains, associated with high leukotoxicity as determined in a semi-quantitative cell assay. This group of A. actinomycetemcomitans is associated with the progression of attachment loss. In the present work, we used conventional polymerase chain reaction (PCR) and quantitative PCR to perform the cagE genotyping of our collection of 116 selected serotype b A. actinomycetemcomitans strains, collected over a period of 15 years from periodontitis patients living in Sweden. The A. actinomycetemcomitans strains carrying cagE (referred to as cagE+; n = 49) were compared to the cagE-negative strains (n = 67), present at larger proportions in the subgingival plaque samples, and were also much more prevalent in the young (≤35 years) compared to in the old (>35 years) group of patients. Our present results underline the potential use of cagE genotyping in the risk assessment of the development of periodontal attachment loss in Swedish adolescents.

  • 136.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Dahlén, Gunnar
    Odontologi, Göteborgs Universitet.
    Bacterial virulence factors that contributes to periodontal disease2017In: Pathogenesis of periodontal disease: biological concepts for clinicians / [ed] Nagihan Bostanci, Georgios N. Belibasakis, Cham: Springer Berlin/Heidelberg, 2017, p. 31-49Chapter in book (Refereed)
    Abstract [en]

    In this chapter, the role of different microbial virulence factors in relation to the pathogenesis of periodontal diseases is addressed. These factors are molecules produced by pathogens and contribute to their pathogenicity by promoting colonization and affecting host response. The importance of different virulence factors in the life of the oral biofilm and the interplay with the host’s response is exemplified here by two of the major, and most well studied, periodontal pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Both of these microbes have great genetic intraspecies diversity and express a number of different virulence factors, which have the capacity to cause imbalance in the host’s response. A. actinomycetemcomitans is the major pathogen in aggressive forms of periodontitis (Fig. 4.1) that affect young individuals, while P. gingivalis is frequently detected in periodontal pockets of individuals with the chronic forms of the disease (Fig. 4.2). However, the role of these two bacteria in periodontal breakdown is still not entirely clear.

  • 137.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Molecular Periodontology.
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Åhren, Ann-Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jansson, Jan-Håkan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology, Cariology.
    Prevalence of systemic immunoreactivity to Aggregatibacter actinomycetemcomitans leukotoxin in relation to the incidence of myocardial infarction2011In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 11, no 1, p. 55-Article in journal (Refereed)
    Abstract [en]

    Background: Chronic infections and associated inflammatory markers are suggested risk factors for cardiovascular disease (CVD). The proinflammatory cytokine, interleukin (IL)-1, is suggested to play a role in the regulation of local inflammatory responses in both CVD and periodontitis. The leukotoxin from the periodontal pathogen Aggregatibacter actinomycetemcomitans has recently been shown to cause abundant secretion of IL-1 from macrophages. The aim of the present study was to compare the prevalence of systemic immunoreactivity to A. actinomycetemcomitans leukotoxin in myocardial infarction (MI) cases (n=532) and matched controls (n=1000) in a population-based case and referents study in northern Sweden.

    Methods: Capacity to neutralize A. actinomycetemcomitans leukotoxin was analyzed in a bioassay with leukocytes, purified leukotoxin, and plasma. Plasma samples that inhibited lactate-dehydrogenase release from leukotoxin-lysed cells by 50 % were classified as positive.

    Results: Neutralizing capacity against A. actinomycetemcomitans leukotoxin was detected in 53.3% of the plasma samples. The ability to neutralize leukotoxin correlated to increasing age in men (n=1082) but not in women (n=450). There was no correlation between presence of systemic leukotoxin neutralization capacity and the incidence of MI, except for women (n=146). Women with a low neutralizing capacity had a significantly higher incidence of MI than those who had a high neutralizing capacity.

    Conclusions: Systemic immunoreactivity against A. actinomycetemcomitans leukotoxin was found at a high prevalence in the analyzed population of adults from northern Sweden. The results from the present study do not support the hypothesis that systemic leukotoxin-neutralizing capacity can decrease the risk for MI.

  • 138.
    Johansson Kostenniemi, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Karlsson, Linda
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Silfverdal, Sven-Arne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Mehle, Christer
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    MeningiSSS: A New Predictive Score to Support Decision on Invasive Procedures to Monitor or Manage the Intracerebral Pressure in Children with Bacterial Meningitis2019In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961Article in journal (Refereed)
    Abstract [en]

    Background

    Knowing the individual child’s risk is highly useful when deciding on treatment strategies, especially when deciding on invasive procedures. In this study, we aimed to develop a new predictive score for children with bacterial meningitis and compare this with existing predictive scores and individual risk factors.

    Methods

    We developed the Meningitis Swedish Survival Score (MeningiSSS) based on a previous systematic review of risk factors. From this, we selected risk factors identified in moderate-to-high-quality studies that could be assessed at admission to the hospital. Using data acquired from medical records of 101 children with bacterial meningitis, we tested the overall capabilities of the MeningiSSS compared with four existing predictive scores using a receiver operating characteristic curve (ROC) analysis to assert the area under the curve (AUC). Finally, we tested all predictive scores at their cut-off levels using a Chi-square test. As outcome, we used a small number of predefined outcomes; in-hospital mortality, 30-day mortality, occurrence of neurological disabilities at discharge defined as Pediatric Cerebral Performance Category Scale category two to five, any type of complications occurring during the hospital stay, use of intensive care, and use of invasive procedures to monitor or manage the intracerebral pressure.

    Results

    For identifying children later undergoing invasive procedures to monitor or manage the intracerebral pressure, the MeningiSSS excelled in the ROC-analysis (AUC = 0.90) and also was the only predictive score able to identify all cases at its cut-off level (25 vs 0%, p < 0.01). For intensive care, the MeningiSSS (AUC = 0.79) and the Simple Luanda Scale (AUC = 0.75) had the best results in the ROC-analysis, whereas others performed less well (AUC ≤ 0.65). Finally, while none of the scores’ results were significantly associated with complications, an elevated score on the MeningiSSS (AUC = 0.70), Niklasson Scale (AUC = 0.72), and the Herson–Todd Scale (AUC = 0.79) was all associated with death.

    Conclusions

    The MeningiSSS outperformed existing predictive scores at identifying children later having to undergo invasive procedures to monitor or manage the intracerebral pressure in children with bacterial meningitis. Our results need further external validation before use in clinical practice. Thus, the MeningiSSS could potentially be helpful when making difficult decisions concerning intracerebral pressure management.

  • 139.
    Johansson, Patrik
    Umeå University, Faculty of Medicine, Clinical Microbiology, Virology.
    Implications of Local Puumala Hantavirus Genetics and Epidemiology for Diagnostics and Vaccine Development2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Puumala viruses, a member of the Hantavirus genus in the Bunyaviridae family, are enveloped by a lipid bilayer and possesses a tripartite single stranded RNA genome with negative polarity. The hantaviruses encode four proteins: a nucleocapsid protein (N), two membrane spanning glycoproteins (GN and GC) and a RNA dependent RNA polymerase (RdRp). Hantaviruses cause two forms of diseases, hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia, and hantavirus pulmonary syndrome (HPS) in the Americas. The hantaviruses are mainly rodent borne, and humans are mostly infected by inhalation of aerosolized rodent secrete. Human Puumala virus infection results in nephropathia epidemica (NE), a mild haemorrhagic disease.

    It is of importance to have a good understanding of the epidemiology and genetics of these viruses for the development of new diagnostic methods and for future vaccine development.

    In this thesis we determined the complete viral genome sequence and characterized the structural proteins based on studies of expression and glycosylation patterns, for a unique human virus isolate; performed a genomic analysis of local Puumala viruses and their individual rodent host, Clethrionomys glareolus, from six different locations was performed. It was seen that the virus genetic variation between different locations could be stable over relatively large distances while there could be large variation over a short distance. For the bank voles no such variation could be seen; developed and evaluated Genetic vaccines, based on PCR-generated linear DNA. We showed that it was important to protect these fragments against nuclease degradation at that attachment of a nuclear localization signal peptide further improved the immune response. We also designed, fabricated and evaluated a 2000 probe cDNA-microarray for identification and differentiation of hantaviruses. The chips was based on 12 different strains of six hantaviruses and could differentiate between both different hantaviruses and strains within one hantavirus serotype.

  • 140.
    Johansson, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Chemical, Biological and Radiological Defence, Defence Medical and Environmental Research Institute, DSO National Laboratories, 20 Science Park Drive, Singapore 118230, Singapore; CBRN Defence and Security, Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
    Olsson, Gert E
    Department of Virology, Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden; CBRN Defence and Security, Swedish Defence Research Agency, SE-901 82 Umeå, Sweden; Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, SE-901 83 Umeå, Sweden.
    Low, Hwee-Teng
    Bucht, Göran
    CBRN Defence and Security, Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Puumala hantavirus genetic variability in an endemic region (Northern Sweden)2008In: Infection, Genetics and Evolution, ISSN 1567-1348, E-ISSN 1567-7257, Vol. 8, no 3, p. 286-296Article in journal (Refereed)
    Abstract [en]

    Puumala hantavirus (PUUV), naturally harboured and shed by bank voles (Myodes [Clethrionomys] glareolus), is the etiological agent to nephropathia epidemica (NE), a mild haemorrhagic fever with renal syndrome. Both host and virus are found throughout much of the European continent and in northern Sweden NE is the second most prevalent serious febrile viral infection after influenza. The reliability of diagnostics by PCR depends on genetic variability for the detection of viral nucleic acids in unknown samples. In the present study we evaluated the genetic variability of PUUV isolated from bank voles in an area of northern Sweden highly endemic for NE. Genetic variability among bank voles was also investigated to evaluate co-evolutionary patterns. We found that the viral sequence appeared stable across the 80km study region, with the exception of the southernmost sampling site, which differed from its nearest neighbour by 7%, despite a geographical separation of only 10km. The southernmost sampling site demonstrated a higher degree of genetic similarity to PUUV previously isolated 100km south thereof; two locations appear to constitute a separate PUUV phylogenetic branch. In contrast to the viral genome, no phylogenetic variance was observed in the bank vole mtDNA in this study. Previous studies have shown that as a result of terrestrial mammals' postglacial re-colonization routes, bank voles and associated PUUV of a southern and a northern lineage established a dichotomous contact zone across the Scandinavian peninsula approximately 100-150km south of the present study sites. Our observations reveal evolutionary divergence of PUUV that has led to dissimilarities within the restricted geographical scale of the northern host re-colonization route as well. These results suggest either a static situation in which PUUV strains are regionally well adapted, or an ongoing process in which strains of PUUV circulate on a geographical scale not yet reliably described.

  • 141. Jonsson, Maria
    et al.
    Noppa, L
    Barbour, A G
    Bergström, S
    Heterogeneity of outer membrane proteins in Borrelia burgdorferi: comparison of osp operons of three isolates of different geographic origins.1992In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 60, no 5, p. 1845-53Article in journal (Refereed)
    Abstract [en]

    Biochemical and immunochemical studies of the outer membrane proteins of Borrelia burgdorferi have shown that the OspA and OspB proteins from strains of different geographic origins may differ considerably in their reactivities with monoclonal antibodies and in their apparent molecular weights. To further characterize this variation in Osp proteins between strains, the osp operons and deduced translation products from two strains, one from Sweden (ACAI) and one from eastern Russia (Ip90), were studied. Polyacrylamide gel electrophoresis and Western blot (immunoblot) analyses confirmed differences between ACAI, Ip90, and the North American strain B31 in their Osp proteins. The sequences of the ospA and ospB genes of ACAI and Ip90 were compared with that of the previously studied osp operon of B31 (S. Bergström, V. G. Bundoc, and A. G. Barbour, Mol. Microbiol. 3:479-486, 1989). The osp genes of ACAI and Ip90, like the corresponding genes of B31, were found on plasmids with apparent sizes of about 50 kb and are cotranscribed as a single unit. Pairwise comparisons of the nucleotide sequences revealed that the ospA genes of ACAI and Ip90 were 85 and 86% identical, respectively, to the ospA gene of strain B31 and 86% identical to each other. The ospB sequences of these two strains were 79% identical to the ospB gene of B31 and 81% identical to each other. There was significantly greater similarity between the ospA genes of the three different strains than there was between the ospA and ospB genes within each strain. These studies suggest that the duplication of osp genes in B. burgdorferi occurred before the geographical dispersion of strains represented by ACAI, Ip90, and B31.

  • 142. Jonsson, Mattias
    Reported cases of Hepatitis C in Region Jämtland Härjedalen between 1992 and 2017: A retrospective cohort study2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 143.
    Kaján, Gyõzõ L.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, Budapest, Hungary.
    Kajon, Adriana E.
    Pinto, Alexis Castillo
    Bartha, Dániel
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    The complete genome sequence of human adenovirus 84, a highly recombinant new Human mastadenovirus D type with a unique fiber gene2017In: Virus Research, ISSN 0168-1702, E-ISSN 1872-7492, Vol. 242, p. 79-84Article in journal (Refereed)
    Abstract [en]

    A novel human adenovirus was isolated from a pediatric case of acute respiratory disease in Panama City, Panama in 2011. The clinical isolate was initially identified as an intertypic recombinant based on hexon and fiber gene sequencing. Based on the analysis of its complete genome sequence, the novel complex recombinant Human mastadenovirus D (HAdV-D) strain was classified into a new HAdV type: HAdV-84, and it was designated Adenovirus D human/PAN/P309886/2011/84[P43H17F84]. HAdV-D types possess usually an ocular or gastrointestinal tropism, and respiratory association is scarcely reported. The virus has a novel fiber type, most closely related to, but still clearly distant from that of HAdV-36. The predicted fiber is hypothesised to bind sialic acid with lower affinity compared to HAdV-37. Bioinformatic analysis of the complete genomic sequence of HAdV-84 revealed multiple homologous recombination events and provided deeper insight into HAdV evolution.

  • 144. Kamrud, K I
    et al.
    Hooper, J W
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Department of Microbiology, Division of NBC Defense, Defense Research Establishment, Umeå, Sweden.
    Schmaljohn, C S
    Comparison of the protective efficacy of naked DNA, DNA-based Sindbis replicon, and packaged Sindbis replicon vectors expressing Hantavirus structural genes in hamsters1999In: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 263, no 1, p. 209-219Article in journal (Refereed)
    Abstract [en]

    Seoul virus (SEOV) is a member of the Hantavirus genus (family Bunyaviridae) and an etiological agent of hemorrhagic fever with renal syndrome. The medium (M) and small (S) gene segments of SEOV encode the viral envelope glycoproteins and nucleocapsid protein, respectively. We compared the immunogenicity and protective efficacy of naked DNA (pWRG7077), DNA-based Sindbis replicon (pSIN2.5), and packaged Sindbis replicon vectors (pSINrep5), containing either the M or S gene segment of SEOV in Syrian hamsters. All of the vectors elicited an anti-SEOV immune response to the expressed SEOV gene products. Vaccinated hamsters were challenged with SEOV and monitored for evidence of infection. Protection from infection was strongly associated with M-gene vaccination. A small number of S-gene-vaccinated animals also were protected. Hamsters vaccinated with the pWRG7077 vector expressing the M gene demonstrated the most consistent protection from SEOV infection and also were protected from heterologous hantavirus (Hantaan virus) infection.

  • 145.
    Kamuyu, Gathoni
    et al.
    Studies Epidemiol Epilepsy Demog Surveillance Sys, Accra, Ghana.
    Bottomley, Christian
    London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London WC1, England.
    Mageto, James
    Egerton Univ, Nakuru, Kenya.
    Lowe, Brett
    Studies Epidemiol Epilepsy Demog Surveillance Sys, Accra, Ghana.
    Wilkins, Patricia P.
    Ctr Dis Control & Prevent CDC, Div Parasit Dis & Malaria, Atlanta, GA USA.
    Noh, John C.
    Ctr Dis Control & Prevent CDC, Div Parasit Dis & Malaria, Atlanta, GA USA.
    Nutman, Thomas B.
    National Institute of Allergy & Infectious Diseases (NIAID) .
    Ngugi, Anthony K.
    Studies Epidemiol Epilepsy Demog Surveillance Sys, Accra, Ghana.
    Odhiambo, Rachael
    KEMRI Wellcome Trust Res Programme, Ctr Geog Med Res Coast, Kilifi, Kenya.
    Wagner, Ryan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. MRC/Wits Rural Public Health & Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
    Kakooza-Mwesige, Angelina
    Owusu-Agyei, Seth
    Ae-Ngibise, Kenneth
    Masanja, Honorati
    Osier, Faith H. A.
    Odermatt, Peter
    Newton, Charles R.
    Exposure to Multiple Parasites Is Associated with the Prevalence of Active Convulsive Epilepsy in Sub-Saharan Africa2014In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 8, no 5, article id e2908Article in journal (Refereed)
    Abstract [en]

    Background: Epilepsy is common in developing countries, and it is often associated with parasitic infections. We investigated the relationship between exposure to parasitic infections, particularly multiple infections and active convulsive epilepsy (ACE), in five sites across sub-Saharan Africa. Methods and Findings: A case-control design that matched on age and location was used. Blood samples were collected from 986 prevalent cases and 1,313 age-matched community controls and tested for presence of antibodies to Onchocerca volvulus, Toxocara canis, Toxoplasma gondii, Plasmodium falciparum, Taenia solium and HIV. Exposure (seropositivity) to Onchocerca volvulus (OR = 1.98; 95% CI: 1.52-2.58, p<0.001), Toxocara canis (OR = 1.52; 95% CI: 1.23-1.87, p<0.001), Toxoplasma gondii (OR = 1.28; 95% CI: 1.04-1.56, p=0.018) and higher antibody levels (top tertile) to Toxocara canis (OR = 1.70; 95% CI: 1.30-2.24, p<0.001) were associated with an increased prevalence of ACE. Exposure to multiple infections was common (73.8% of cases and 65.5% of controls had been exposed to two or more infections), and for T. gondii and O. volvulus co-infection, their combined effect on the prevalence of ACE, as determined by the relative excess risk due to interaction (RERI), was more than additive (T. gondii and O. volvulus, RERI = 1.19). The prevalence of T. solium antibodies was low (2.8% of cases and 2.2% of controls) and was not associated with ACE in the study areas. Conclusion: This study investigates how the degree of exposure to parasites and multiple parasitic infections are associated with ACE and may explain conflicting results obtained when only seropositivity is considered. The findings from this study should be further validated.

  • 146. Karadenizli, A.
    et al.
    Forsman, M.
    Simsek, H.
    Taner, M.
    Ohrman, C.
    Myrtennas, K.
    Larkeryd, A.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Ozdemir, L.
    Sjodin, A.
    Genomic analyses of Francisella tularensis strains confirm disease transmission from drinking water sources, Turkey, 2008, 2009 and 20122015In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 20, no 21Article in journal (Refereed)
    Abstract [en]

    Waterborne epidemics of tularaemia caused by Francisella tularensis are increasingly reported in Turkey. We have used whole genome sequencing to investigate if F. tularensis isolated from patients could be traced back to drinking water sources. Tonsil swabs from 33 patients diagnosed with oropharyngeal tularaemia in three outbreaks and 140 water specimens were analysed. F. tularensis subsp. holarctica was confirmed by microagglutination and PCR in 12 patients and five water specimens. Genomic analysis of three pairs of patient and water isolates from outbreaks in Sivas, Corum, and Kocaeli showed the isolates to belong to two new clusters of the F. tularensis B. 12 genetic clade. The clusters were defined by 19 and 15 single nucleotide polymorphisms (SNPs) in a multiple alignment based on 507 F. tularensis genomes. One synonymous SNP was chosen as a new canonical SNP (canSNP) for each cluster for future use in diagnostic assays. No SNP was identified between the genomes from the patient-water pair of isolates from Kocaeli, one SNP between the pair of isolates from Sivas, whereas the pair from Corum differed at seven SNPs. These results illustrate the power of whole genome sequencing for tracing F. tularensis patient isolates back to their environmental source.

  • 147.
    Karah, Nabil
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Dwibedi, Chinmay Kumar
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Sjöström, Karin
    Edquist, Petra
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Novel Aminoglycoside Resistance Transposons and Transposon-Derived Circular Forms Detected in Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates2016In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 60, no 3, p. 1801-1818Article in journal (Refereed)
    Abstract [en]

    Acinetobacter baumannii has emerged as an important opportunistic pathogen equipped with a growing number of antibiotic resistance genes. Our study investigated the molecular epidemiology and antibiotic resistance features of 28 consecutive carbapenem-resistant clinical isolates of A. baumannii collected throughout Sweden in 2012 and 2013. The isolates mainly belonged to clonal complexes (CCs) with an extensive international distribution, such as CC2 (n = 16) and CC25 (n = 7). Resistance to carbapenems was related to bla(OXA-23) (20 isolates), bla(OXA-24/40-like) (6 isolates), bla(OXA-467) (1 isolate), and ISAba1-bla(OXA-69) (1 isolate). Ceftazidime resistance was associated with bla(PER-7) in the CC25 isolates. Two classical point mutations were responsible for resistance to quinolones in all the isolates. Isolates with high levels of resistance to aminoglycosides carried the 16S rRNA methylase armA gene. The isolates also carried a variety of genes encoding aminoglycoside-modifying enzymes. Several novel structures involved in aminoglycoside resistance were identified, including Tn6279, Delta Tn6279, Ab-ST3- aadB, and different assemblies of Tn6020 and TnaphA6. Importantly, a number of circular forms related to the IS26 or ISAba125 composite trans-posons were detected. The frequent occurrence of these circular forms in the populations of several isolates indicates a potential role of these circular forms in the dissemination of antibiotic resistance genes.

  • 148.
    Karlsson, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Österlund, Anders
    Forssén, Annika
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Pharyngeal Chlamydia trachomatis is not uncommon any more2011In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 43, no 5, p. 344-348Article in journal (Refereed)
    Abstract [en]

    Background. The significance of Chlamydia trachomatis (Ct) infection in the pharynx, and possible symptoms, are under discussion. Most studies have involved only homo/bisexual men. We report findings of pharyngeal Ct (PhCt) infections in patients with long-lasting throat discomfort and the prevalence of PhCt in genitally Ct-infected young people in a Swedish primary care setting. Method. Sub-study 1 (SS1) included 48 persons aged 15-35 y, with pharyngeal discomfort for more than 14 days. Sub-study 2 (SS2) included 150 persons, aged 15-35 y, with genital Ct. Questionnaires concerning symptoms, sexual behaviour and sexual identity were completed for both groups. Samples for Ct testing were taken from the pharynx, and in SS1, samples were also collected to ascertain genital Ct. Results. In SS1, 2 of 48 persons (4%) with pharyngeal discomfort had PhCt. In all, 35 of the 48 persons (73%) included in SS1 reported unprotected oral sex during the previous year. In SS2, 11 of 92 women (12%) and 4 of 58 men (7%) tested positive for PhCt. More women (94%) than men (83%) had given unprotected oral sex. Persons with PhCt had more symptoms from the upper respiratory tract (p = 0.04). Conclusions. Some primary care patients with long-lasting throat discomfort have a PhCt infection. PhCt infection is not uncommon in genitally infected sexually active people. More heterosexual women than heterosexual men had given unprotected oral sex and were infected by Ct in the pharynx. Thus, research on PhCt should not focus on homo/bisexual men only. Information about Ct should include the risk of contracting a PhCt infection as well as a gender perspective.

  • 149.
    Kato, K
    et al.
    Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm.
    Sullivan, Patrick F
    Dept Genetics, Univ of North Carolina, Dept Medical Epid and Biostat, Karol Institutet.
    Evengård, Birgitta
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Pedersen, Nancy L
    Dept Medical Epidemiology and Biostatistis, Karolinska Institutet.
    A population-based twin study of functional somatic syndromes2009In: Psychological Medicine, ISSN 0033-2917, E-ISSN 1469-8978, Vol. 39, no 3, p. 497-505Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The mechanisms underlying the co-occurrence of the functional somatic syndromes are largely unknown. No empirical study has explicitly examined how genetic and environmental factors influence the co-morbidity of these syndromes. We aimed to examine how the co-morbidity of functional somatic syndromes is influenced by genetic and environmental factors that are in common to the syndromes. METHOD: A total of 31318 twins in the Swedish Twin Registry aged 41-64 years underwent screening interviews via a computer-assisted telephone system from 1998 to 2002. Four functional somatic syndromes (chronic widespread pain, chronic fatigue, irritable bowel syndrome, and recurrent headache) and two psychiatric disorders (major depression and generalized anxiety disorder) were assessed using structured questions based on standard criteria for each illness in a blinded manner. RESULTS: Multivariate twin analyses revealed that a common pathway model with two latent traits that were shared by the six illnesses fit best to the women's data. One of the two latent traits loaded heavily on the psychiatric disorders, whereas the other trait loaded on all four of the functional somatic syndromes, particularly chronic widespread pain, but not on the psychiatric disorders. All illnesses except the psychiatric disorders were also affected by genetic influences that were specific to each. CONCLUSIONS: The co-occurrence of functional somatic syndromes in women can be best explained by affective and sensory components in common to all these syndromes, as well as by unique influences specific to each of them. The findings clearly suggest a complex view of the multifactorial pathogenesis of these illnesses.

  • 150.
    Kinsman, John
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Angrén, John
    Umeå University, Faculty of Science and Technology, European CBRNE Center.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Furberg, Maria
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Mosquera, Paola A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Otero-García, Laura
    Snacken, René
    Derrough, Tarik
    Carrillo Santisteve, Paloma
    Ciotti, Massimo
    Tsolova, Svetla
    Preparedness and response against diseases with epidemic potential in the European Union: a qualitative case study of Middle East Respiratory Syndrome (MERS) and poliomyelitis in five member states2018In: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 18, no 1, article id 528Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: EU Decision 1082/2013/EU on serious cross-border health threats provides a legal basis for collaboration between EU Member States, and between international and European level institutions on preparedness, prevention, and mitigation in the event of a public health emergency. The Decision provides a context for the present study, which aims to identify good practices and lessons learned in preparedness and response to Middle East Respiratory Syndrome (MERS) (in UK, Greece, and Spain) and poliomyelitis (in Poland and Cyprus).

    METHODS: Based on a documentary review, followed by five week-long country visits involving a total of 61 interviews and group discussions with experts from both the health and non-health sectors, this qualitative case study has investigated six issues related to preparedness and response to MERS and poliomyelitis: national plans and overall preparedness capacity; training and exercises; risk communication; linking policy and implementation; interoperability between the health and non-health sectors; and cross-border collaboration.

    RESULTS: Preparedness and response plans for MERS and poliomyelitis were in place in the participating countries, with a high level of technical expertise available to implement them. Nevertheless, formal evaluation of the responses to previous public health emergencies have sometimes been limited, so lessons learned may not be reflected in updated plans, thereby risking mistakes being repeated in future. The nature and extent of inter-sectoral collaboration varied according to the sectors involved, with those sectors that have traditionally had good collaboration (e.g. animal health and food safety), as well as those that have a financial incentive for controlling infectious diseases (e.g. agriculture, tourism, and air travel) seen as most likely to have integrated public health preparedness and response plans. Although the formal protocols for inter-sectoral collaboration were not always up to date, good personal relations were reported within the relevant professional networks, which could be brought into play in the event of a public health emergency. Cross-border collaboration was greatly facilitated if the neighbouring country was a fellow EU Member State.

    CONCLUSIONS: Infectious disease outbreaks remain as an ongoing threat. Efforts are required to ensure that core public health capacities for the full range of preparedness and response activities are sustained.

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