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  • 301. Wolter, Nicole
    et al.
    Cohen, Cheryl
    Tempia, Stefano
    Madhi, Shabir A.
    Venter, Marietjie
    Moyes, Jocelyn
    Walaza, Sibongile
    Kgokong, Babatyi Malope
    Groome, Michelle
    du Plessis, Mignon
    Pretorius, Marthi
    Dawood, Halima
    Kahn, Kathleen
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Center for Global Health Research.
    Variava, Ebrahim
    Klugman, Keith P.
    von Gottberg, Anne
    HIV and Influenza Virus Infections Are Associated With Increased Blood Pneumococcal Load: A Prospective, Hospital-Based Observational Study in South Africa, 2009-20112014In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 209, no 1, p. 56-65Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 304.
    Zettervall, Carl-Johan
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Anderl, Ines
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Williams, Michael
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Palmer, Ruth
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    Kurucz, Eva
    Ando, Istvan
    Hultmark, Dan
    Umeå University, Faculty of Medicine, Umeå Centre for Molecular Pathogenesis (UCMP) (Faculty of Medicine).
    A directed screen for genes involved in Drosophila blood cell activation2004In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 101, no 39, p. 14192-14197Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

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

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

  • 308.
    Åhlund, Monika K
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Rydén, Patrik
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Sjöstedt, Anders
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Stöven, Svenja
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Directed screen of Francisella novicida virulence determinants using Drosophila melanogaster2010In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 78, no 7, p. 3118-3128Article in journal (Refereed)
    Abstract [en]

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

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

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

  • 310.
    Åström, Morgan
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Using 2-pyridones as molecular tools to understand chlamydiae genetics2015Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
4567 301 - 310 of 310
CiteExportLink to result list
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