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  • 1.
    Abdeldaim, Guma M. K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    PCR detection of haemophilus influenzae from respiratory specimens2013In: PCR Detection of Microbial Pathogens / [ed] Mark Wilks, Humana Press, 2013, 2, p. 115-123Chapter in book (Refereed)
    Abstract [en]

    The detection of Haemophilus influenzae by conventional methods like culture is time-consuming and may give false-negative results, especially during ongoing antibiotic treatment. Therefore, non-culture based methods that are sensitive, specific, and rapid are valuable for early diagnosis and effective therapy. Here we describe a quantitative real-time PCR assay based on the outer membrane P6 gene omp6, to detect H. influenzae and its application on respiratory tract specimens.

  • 2.
    Abdeldaim, Guma M. K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Stralin, Kristoffer
    Olcen, Per
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Molling, Paula
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Quantitative fucK gene polymerase chain reaction on sputum and nasopharyngeal secretions to detect Haemophilus influenzae pneumonia2013In: Diagnostic microbiology and infectious disease, ISSN 0732-8893, E-ISSN 1879-0070, Vol. 76, no 2, p. 141-146Article in journal (Refereed)
    Abstract [en]

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

  • 3.
    Abdeldaim, Guma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology. Benghazi Univ, Fac Med, Dept Med Microbiol & Parasitol, Benghazi, Libya..
    Svensson, Erik
    Statens Serum Inst, Int Reference Lab Mycobacteriol, Copenhagen, Denmark..
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Duplex detection of the Mycobacterium tuberculosis complex and medically important non-tuberculosis mycobacteria by real-time PCR based on the rnpB gene2016In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, no 11, p. 991-995Article in journal (Refereed)
    Abstract [en]

    A duplex real-time PCR based on the rnpB gene was developed for Mycobacterium spp. The assay was specific for the Mycobacterium tuberculosis complex (MTB) and also detected all 19 tested species of non-tuberculous mycobacteria (NTM). The assay was evaluated on 404 clinical samples: 290 respiratory samples and 114 from tissue and other nonrespiratory body sites. M. tuberculosis was detected by culture in 40 samples and in 30 samples by the assay. The MTB assay showed a sensitivity similar to Roche Cobas Amplicor MTB-PCR (Roche Molecular Systems, Pleasanton, CA, USA). There were only nine samples with non-tuberculous mycobacteria detected by culture. Six of them were detected by the PCR assay.

  • 4.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Lytsy, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Ronne-Engström, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Surgical site infections in standard neurosurgery procedures-a study of incidence, impact and potential risk factors2014In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 28, no 2, p. 270-275Article in journal (Refereed)
    Abstract [en]

    Objectives. Surgical site infections (SSIs) may be devastating for the patient and they carry high economic costs. Studies of SSI after neurosurgery report an incidence of 1 - 11%. However, patient material, follow-up time and definition of SSI have varied. In the present study we prospectively recorded the prevalence of SSI 3 months after standard intracranial neurosurgical procedures. The incidence, impact and risk factors of SSI were analysed. Methods. We included patients admitted during 2010 to our unit for postoperative care after standard neurosurgical procedures. SSI was defined as evident with positive cultures from surgical samples or CSF, and/or purulent discharge during reoperation. Follow-up was done after 3 and 12 months and statistics was obtained after 3 months. The predictive values on the outcome of demographic and clinical factors describing the surgical procedure were evaluated using linear regression. Results. A total of 448 patients were included in the study and underwent a total of 466 procedures. Within 3 and 12 months, 33 and 88 patients, respectively, had died. Of the surviving patients, 20 (4.3% of procedures) developed infections within 3 months and another 3 (4.9% of procedures) within 12 months. Risk factors for SSI were meningioma, longer operation time, craniotomy, dural substitute, and staples in wound closure. Patients with SSI had significantly longer hospital stay. Multivariate analysis showed that factors found significant in univariate analysis frequently occur together. Discussion. We studied the prevalence of SSI after 3 and 12 months in a prospective 1-year material with standard neurosurgical procedures and found it to be 4.3% and 4.9%, respectively. The analysis of the results showed that a combination of parameters indicating a longer and more complicated procedure predicted the development of SSI. Our conclusion is that the prevention of SSI has to be done at many levels, especially with patients undergoing long surgical procedures.

  • 5. Ahsan, Murshidul
    et al.
    Hasan, Badrul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Algotsson, Magnus
    Sarenbo, Sirkku
    Handling and Welfare of Bovine Livestock at Local Abattoirs in Bangladesh2014In: Journal of Applied Animal Welfare Science, ISSN 1088-8705, E-ISSN 1532-7604, Vol. 17, no 4, p. 340-353Article in journal (Refereed)
    Abstract [en]

    The World Organization for Animal Health (OIE) allows rope casting and the tying of legs for nonhuman animals laughter without stunning. The handling and welfare of bovine livestock (Bosindicus and Bubalus bubalis) were studied in 8 local abattoirs in 5 districts of Bangladesh. A total of 302 animals were evaluated. At the local abattoirs, approximately 1/3 of the cattle and water buffalo were eithere maciated orinjured/sick. The size and vigor of the animals determined the casting method. Small and weak animals were cast on concrete floors by lifting a foreleg followed by pushing, or simply by twisting the head of the animal and then binding the legs with rope. Vigorous animals such as buffalo were castusing ropes and human force. Bleeding was slow and flaying was sometimes initiated before the animals were unconscious. Pulling and tearing of the trachea and pouring of water into the exposed trache a shortly after cutting were also observed in some cases.The over all animal handling was unnecessarily rough and he OIE standards were not implemented. Animals are subjected to considerable mistreatment, and there is an urgent need for the training nde ducation of the staff in a battoirs concerning humanes laughtering practices as well as a need to build moderns laughtering plants in Bangladesh.

  • 6.
    Alpkvist, Helena
    et al.
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med Huddinge, Infect Dis Unit, Stockholm, Sweden..
    Athlin, Simon
    Univ Orebro, Dept Infect Dis, Fac Med & Hlth, SE-70182 Orebro, Sweden..
    Naucler, Pontus
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Infect Dis Unit, Stockholm, Sweden..
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Abdeldaim, Guma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. Benghazi Univ, Dept Med Microbiol & Parasitol, Fac Med, Benghazi, Libya..
    Slotved, Hans-Christian
    Statens Serum Inst, Dept Microbiol & Infect Control, DK-2300 Copenhagen, Denmark..
    Hedlund, Jonas
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Infect Dis Unit, Stockholm, Sweden..
    Stralin, Kristoffer
    Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.;Karolinska Inst, Dept Med Huddinge, Infect Dis Unit, Stockholm, Sweden.;Univ Orebro, Dept Infect Dis, Fac Med & Hlth, SE-70182 Orebro, Sweden..
    Clinical and Microbiological Factors Associated with High Nasopharyngeal Pneumococcal Density in Patients with Pneumococcal Pneumonia2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, article id e0140112Article in journal (Refereed)
    Abstract [en]

    Background We aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia. Methods Adult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/ or culture of respiratory secretions and/or urinary antigen test. Results Of 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p<0.0001). The median NP pneumococcal density of DNA positive patients with pneumococcal etiology was 6.83 log(10) DNA copies/mL (range 1.79-9.50). In a multivariate analysis of patients with pneumococcal etiology, a high pneumococcal density was independently associated with severe pneumonia (Pneumonia Severity Index risk class IV-V), symptom duration >= 2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient's own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54-82% and positive predictive values of 37-56%, indicating suboptimal performance. Conclusions Pneumonia severity, symptom duration similar to 2 days, and a medium/high serum immunoglobulin titer against the patient's own serotype were independently associated with a high NP pneumococcal density. NP pneumococcal density has limited value for detection of severe pneumococcal pneumonia.

  • 7.
    Andersson, Madelen
    et al.
    Blekinge Hosp, Dept Infect Dis, Karlskrona, Sweden..
    Resman, Fredrik
    Lund Univ, Dept Translat Med Med Microbiol, Malmo, Sweden..
    Eitrem, Rickard
    Dept Communicable Dis Control Cty Blekinge, Karlskrona, Sweden..
    Drobni, Peter
    Dept Clin Microbiol Cty Kronoberg, Vaxjo Karlskrona, Sweden..
    Riesbeck, Kristian
    Lund Univ, Dept Translat Med Med Microbiol, Malmo, Sweden..
    Kahlmeter, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology. Dept Clin Microbiol Cty Kronoberg, Vaxjo Karlskrona, Sweden..
    Sundqvist, Martin
    Dept Clin Microbiol Cty Kronoberg, Vaxjo Karlskrona, Sweden.;Univ Orebro, Fac Med & Hlth, Dept Lab Med Clin Microbiol, SE-70182 Orebro, Sweden..
    Outbreak of a beta-lactam resistant non-typeable Haemophilus influenzae sequence type 14 associated with severe clinical outcomes2015In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, article id 581Article in journal (Refereed)
    Abstract [en]

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

  • 8. Aspenstrom-Fagerlund, Bitte
    et al.
    Tallkvist, Jonas
    Ilbäck, Nils-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Glynn, Anders W.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Oleic acid increases intestinal absorption of the BCRP/ABCG2 substrate, mitoxantrone, in mice2015In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 237, no 2, p. 133-139Article in journal (Refereed)
    Abstract [en]

    The efflux transporter breast cancer resistance protein (BCRP/ABCG2) decrease intestinal absorption of many food toxicants. Oleic acid increases absorption of the specific BCRP substrate mitoxantrone (MXR), and also BCRP gene expression in human intestinal Caco-2 cells, suggesting that oleic acid affect the BCRP function. Here, we investigated the effect of oleic acid on intestinal absorption of MXR in mice. Mice were orally dosed with 2.4 g oleic acid/kg b.w. and 1 mg MXR/kg b.w., and sacrificed 30, 60, 90 or 120 min after exposure, or were exposed to 0.6, 2.4 or 4.8 g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 90 min after exposure. Mice were also treated with Ko143 together with MXR and sacrificed after 60 min, as a positive control of BCRP-mediated effects on MXR absorption. Absorption of MXR increased after exposure to oleic acid at all doses, and also after exposure to Ko143. Intestinal BCRP gene expression tended to increase 120 min after oleic acid exposure. Our results in mice demonstrate that oleic acid decreases BCRP-mediated efflux, causing increased intestinal MXR absorption in mice. These findings may have implications in humans, concomitantly exposed to oleic acid and food contaminants that, similarly as MXR, are substrates of BCRP.

  • 9. Athlin, Simon
    et al.
    Kaltoft, Margit
    Slotved, Hans-Christian
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Holmberg, Hans
    Konradsen, Helle Bossen
    Stralin, Kristoffer
    Association between Serotype-Specific Antibody Response and Serotype Characteristics in Patients with Pneumococcal Pneumonia, with Special Reference to Degree of Encapsulation and Invasive Potential2014In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 11, p. 1541-1549Article in journal (Refereed)
    Abstract [en]

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

  • 10.
    Atterby, Clara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ramey, Andrew M.
    Gustafsson Hall, Gabriel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Järhult, Josef
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Börjesson, Stefan
    Bonnedahl, Jonas
    Increased prevalence of antibiotic resistant E. coli in gulls sampled in Southcentral Alaska is associated with urban environments2016In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 6, no 1, article id 32334Article in journal (Refereed)
    Abstract [en]

    Background : Antibiotic-resistant bacteria pose challenges to healthcare delivery systems globally; however, limited information is available regarding the prevalence and spread of such bacteria in the environment. The aim of this study was to compare the prevalence of antibiotic-resistant bacteria in large-bodied gulls ( Larus spp.) at urban and remote locations in Southcentral Alaska to gain inference into the association between antibiotic resistance in wildlife and anthropogenically influenced habitats. Methods : Escherichia coli was cultured ( n 115 isolates) from fecal samples of gulls (n 160) collected from a remote location, Middleton Island, and a more urban setting on the Kenai Peninsula. Results : Screening of E. coli from fecal samples collected from glaucous-winged gulls ( Larus glaucescens )at Middleton Island revealed 8% of isolates were resistant to one or more antibiotics and 2% of the isolates were resistant to three or more antibiotics. In contrast, 55% of E. coli isolates derived from fecal samples collected from large-bodied gulls (i.e. glaucous, herring [ Larus argentatus ], and potentially hybrid gulls) on the Kenai Peninsula were resistant to one or more antibiotics and 22% were resistant to three or more antibiotics. In addition, total of 16% of the gull samples from locations on the Kenai Peninsula harbored extended-spectrum cephalosporin-resistant E. coli isolates (extended-spectrum beta-lactamases [ESBL] and plasmid-encoded AmpC [pAmpC]), in contrast to Middleton Island where no ESBL- or pAmpC-producing isolates were detected. Conclusion : Our findings indicate that increased prevalence of antibiotic resistance is associated with urban environments in Southcentral Alaska and presumably influenced by anthropogenic impacts. Further investigation is warranted to assess how migratory birds may maintain and spread antimicrobial-resistant bacteria of relevance to human and animal health.

  • 11.
    Benachenhou, Farid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Sperber, Göran O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Bongcam-Rudloff, Erik
    Andersson, Goran
    Boeke, Jef D.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Conserved structure and inferred evolutionary history of long terminal repeats (LTRs)2013In: Mobile DNA, ISSN 1759-8753, E-ISSN 1759-8753, Vol. 4, p. 5-Article in journal (Refereed)
    Abstract [en]

    Background: Long terminal repeats (LTRs, consisting of U3-R-U5 portions) are important elements of retroviruses and related retrotransposons. They are difficult to analyse due to their variability. The aim was to obtain a more comprehensive view of structure, diversity and phylogeny of LTRs than hitherto possible. Results: Hidden Markov models (HMM) were created for 11 clades of LTRs belonging to Retroviridae (class III retroviruses), animal Metaviridae (Gypsy/Ty3) elements and plant Pseudoviridae (Copia/Ty1) elements, complementing our work with Orthoretrovirus HMMs. The great variation in LTR length of plant Metaviridae and the few divergent animal Pseudoviridae prevented building HMMs from both of these groups. Animal Metaviridae LTRs had the same conserved motifs as retroviral LTRs, confirming that the two groups are closely related. The conserved motifs were the short inverted repeats (SIRs), integrase recognition signals (5' TGTTRNR ... YNYAACA 3'); the polyadenylation signal or AATAAA motif; a GT-rich stretch downstream of the polyadenylation signal; and a less conserved AT-rich stretch corresponding to the core promoter element, the TATA box. Plant Pseudoviridae LTRs differed slightly in having a conserved TATA-box, TATATA, but no conserved polyadenylation signal, plus a much shorter R region. The sensitivity of the HMMs for detection in genomic sequences was around 50% for most models, at a relatively high specificity, suitable for genome screening. The HMMs yielded consensus sequences, which were aligned by creating an HMM model (a 'Superviterbi' alignment). This yielded a phylogenetic tree that was compared with a Pol-based tree. Both LTR and Pol trees supported monophyly of retroviruses. In both, Pseudoviridae was ancestral to all other LTR retrotransposons. However, the LTR trees showed the chromovirus portion of Metaviridae clustering together with Pseudoviridae, dividing Metaviridae into two portions with distinct phylogeny. Conclusion: The HMMs clearly demonstrated a unitary conserved structure of LTRs, supporting that they arose once during evolution. We attempted to follow the evolution of LTRs by tracing their functional foundations, that is, acquisition of RNAse H, a combined promoter/polyadenylation site, integrase, hairpin priming and the primer binding site (PBS). Available information did not support a simple evolutionary chain of events.

  • 12. Bengtsson, Daniel
    et al.
    Avril, Alexis
    Gunnarsson, Gunnar
    Elmberg, Johan
    Soderquist, Par
    Norevik, Gabriel
    Tolf, Conny
    Safi, Kamran
    Fiedler, Wolfgang
    Wikelski, Martin
    Olsén, Bjorn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Waldenström, Jonas
    Movements, Home-Range Size and Habitat Selection of Mallards during Autumn Migration2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, p. e100764-Article in journal (Refereed)
    Abstract [en]

    The mallard (Anas platyrhynchos) is a focal species in game management, epidemiology and ornithology, but comparably little research has focused on the ecology of the migration seasons. We studied habitat use, time-budgets, home-range sizes, habitat selection, and movements based on spatial data collected with GPS devices attached to wild mallards trapped at an autumn stopover site in the Northwest European flyway. Sixteen individuals (13 males, 3 females) were followed for 15-38 days in October to December 2010. Forty-nine percent (SD = 8.4%) of the ducks' total time, and 85% of the day-time (SD = 28.3%), was spent at sheltered reefs and bays on the coast. Two ducks used ponds, rather than coast, as day-roosts instead. Mallards spent most of the night (76% of total time, SD = 15.8%) on wetlands, mainly on alvar steppe, or in various flooded areas (e.g. coastal meadows). Crop fields with maize were also selectively utilized. Movements between roosting and foraging areas mainly took place at dawn and dusk, and the home-ranges observed in our study are among the largest ever documented for mallards (mean = 6,859 ha; SD = 5,872 ha). This study provides insights into relatively unknown aspects of mallard ecology. The fact that autumn-staging migratory mallards have a well-developed diel activity pattern tightly linked to the use of specific habitats has implications for wetland management, hunting and conservation, as well as for the epidemiology of diseases shared between wildlife and domestic animals.

  • 13. Bengtsson, S.
    et al.
    Bjelkenbrant, C.
    Kahlmeter, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Validation of EUCAST zone diameter breakpoints against reference broth microdilution2014In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 20, no 6, p. O353-O360Article in journal (Refereed)
    Abstract [en]

    The European Committee on Antimicrobial Susceptibility Testing (EUCAST) began harmonizing clinical breakpoints in Europe 2002. In 2009, work to develop a disc diffusion method began and the first disc diffusion breakpoints calibrated to EUCAST clinical MIC breakpoints were published in December 2009. In this study we validated EUCAST clinical zone diameter breakpoints against the International Standard Organization (ISO) reference broth microdilution. A collection of 544 isolates (238 Gram-negative and 306 Gram-positive) were tested against a panel of antimicrobial agents. Antimicrobial susceptibility testing was performed with broth microdilution as described by ISO and disc diffusion in accordance with EUCAST methodology. Inhibition zone diameters and MIC values were interpreted and categorized (S, I and R) according to EUCAST clinical breakpoint table version 2.0. Categorical agreement (CA) as well as minor (mD), major (MD) and very major (VMD) discrepancies were determined. There was in general good correlation between susceptibility test results obtained with disc diffusion and broth microdilution. Overall CA was 97.3% for all combinations of organisms and antimicrobial agents (n = 5231) and the overall discrepancy rates were 110 (2.1%) mD, 24 (0.5%) MD and 7 (0.1%) VMD. The overall CA for Gram-positive and Gram-negative organisms were 98.7% (2346 tests) and 96.2% (2942 tests), respectively. Seven VMD were observed, five for Gram-positive organisms (coagulase negative staphylococci (n = 2) and Staphylococcus aureus (n = 3)) and two for Gram-negative organisms (Pseudomonas aeruginosa). Minor discrepancies were mainly observed in Gram-negatives and were related to different antimicrobial agents and species.

  • 14. Berenjian, Saideh
    et al.
    Hu, Kefei
    Abedi-Valugerdi, Manuchehr
    Hassan, Moustapha
    Hassan, Sadia Bashir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Morein, Bror
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    The nanoparticulate Quillaja saponin KGI exerts anti-proliferative eff ects by down-regulation of cell cycle molecules in U937 and HL-60 human leukemia cells2014In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 55, no 7, p. 1618-1624Article in journal (Refereed)
    Abstract [en]

    Cancer cells are characterized by uncontrolled replication involving loss of control of cyclin dependent kinases (CDKs) and cyclins, and by abolished differentiation. In this study we introduce KGI, which is a nanoparticle with a Quillaja saponin as an active molecule. By the use of RNA array analysis and confirmation at the protein level, we show that KGI affects myeloid leukemia cells (in particular, the U937 monoblast cancer cell) by the following mechanisms: (A) ceasing cell replication via proteasome degradation, (B) down-regulation of key molecules at check points between G1/S and G2/M phases, (C) reduction of thymidine kinase activity, followed by (D) exit to differentiation and production of interleukin-8 (IL-8), eventually leading to apoptosis. Leukemia cell lines (U937 and HL-60 cells) were exposed to KGI for 8 h, after which the drug was removed. The cancer cells did not revert to replication over the following 10 days. Thus our findings suggest that the nanoparticle KGI inhibits proliferation and promotes differentiation in leukemic cells by interfering with the cell cycle process.

  • 15.
    Bergfors, Assar
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Leenheer, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology. Univ Tsukuba, PhD Program Human Biol, Sch Integrat & Global Majors, Tsukuba, Ibaraki 3058577, Japan..
    Bergqvist, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Ameur, Adam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Analysis of hepatitis C NS5A resistance associated polymorphisms using ultra deep single molecule real time (SMRT) sequencing2016In: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 126, p. 81-89Article in journal (Refereed)
    Abstract [en]

    Development of Hepatitis C virus (HCV) resistance against direct-acting antivirals (DAAs), including NS5A inhibitors, is an obstacle to successful treatment of HCV when DAAs are used in sub-optimal combinations. Furthermore, it has been shown that baseline (pre-existing) resistance against DAAs is present in treatment naive-patients and this will potentially complicate future treatment strategies in different HCV genotypes (GTs). Thus the aim was to detect low levels of NS5A resistant associated variants (RAVs) in a limited sample set of treatment-naive patients of HCV GT1a and 3a, since such polymorphisms can display in vitro resistance as high as 60000 fold. Ultra-deep single molecule real time (SMRT) sequencing with the Pacific Biosciences (PacBio) RSII instrument was used to detect these RAVs. The SMRT sequencing was conducted on ten samples; three of them positive with Sanger sequencing (GT1a Q30H and Y93N, and GT3a Y93H), five GT1a samples, and two GT3a non-positive samples. The same methods were applied to the HCV GT1a H77-plasmid in a dilution series, in order to determine the error rates of replication, which in turn was used to determine the limit of detection (LOD), as defined by mean + 3SD, of minority variants down to 0.24%. We found important baseline NS5A RAVs at levels between 0.24 and 0.5%, which could potentially have clinical relevance. This new method with low level detection of baseline RAVs could be useful in predicting the most cost-efficient combination of DAA treatment, and reduce the treatment duration for an HCV infected individual.

  • 16. Bjohle, J.
    et al.
    Bergqvist, J.
    Gronowitz, J. Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Johansson, H.
    Carlsson, L.
    Einbeigi, Z.
    Linderholm, B.
    Loman, N.
    Malmberg, M.
    Soderberg, M.
    Sundquist, M.
    Walz, T. M.
    Ferno, M.
    Bergh, J.
    Hatschek, T.
    Serum thymidine kinase activity compared with CA 15-3 in locally advanced and metastatic breast cancer within a randomized trial2013In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 139, no 3, p. 751-758Article in journal (Refereed)
    Abstract [en]

    The primary objective was to estimate serum thymidine kinase 1 (TK1) activity, reflecting total body cell proliferation rate including cancer cell proliferation, in women with loco regional inoperable or metastatic breast cancer participating in a prospective and randomized study. Secondary objectives were to analyze TK1 in relation to progression-free survival (PFS), overall survival (OS), therapy response and other tumour characteristics, including CA 15-3, widely used as a standard serum marker for disease progression. TK1 and CA 15-3 were analysed in 198 serum samples collected prospectively from women included in the randomized TEX trial between December 2002 and June 2007. TK1 activity was determined by the ELISA based DiviTum (TM) assay, and CA 15-3 analyses was generated with the electrochemiluminescence immunoassay Cobas Elecsys CA 15-3 II. High pre-treatment TK1 activity predicted shorter PFS (10 vs. 15 months p = 0.02) and OS (21 vs. 38 months, p < 0.0001), respectively. After adjustment for age, metastatic site and study treatment TK1 showed a trend as predictor of PFS (p = 0.059) and was an independent prognostic factor for OS, (HR 1.81, 95 % confidence interval (CI) 1.26-2.61, p = 0.001). There was a trend of shortened OS for women with high CA 15-3 (p = 0.054) in univariate analysis, but not after adjustment for the above mentioned covariates. Both TK1 (p = 0.0011) and CA 15-3 (p = 0.0004) predicted response to treatment. There were statistically different distributions of TK1 and CA 15-3 in relation to the site of metastases. TK1 activity measured by DiviTum (TM) predicted therapy response, PFS and OS in loco regional inoperable or disseminated breast cancer. These results suggest that this factor is a useful serum marker. In the present material, a prognostic value of CA 15-3 could not be proven.

  • 17.
    Blomberg, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Blomberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Sjösten, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Sheikholvaezin, Ali
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Bölin-Wiener, Agnes
    Elfaitouri, Amal
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Hessel, Sanna
    Gottfries, Carl-Gerhard
    Zachrisson, Olof
    Öhrmalm, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Jobs, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Pipkorn, Ruediger
    No Evidence for Xenotropic Murine Leukemia-Related Virus Infection in Sweden Using Internally Controlled Multiepitope Suspension Array Serology2012In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 19, no 9, p. 1399-1410Article in journal (Refereed)
    Abstract [en]

    Many syndromes have a large number of differential diagnoses, a situation which calls for multiplex diagnostic systems. Myalgic encephalomyelitis (ME), also named chronic fatigue syndrome (CFS), is a common disease of unknown etiology. A mouse retrovirus, xenotropic murine leukemia-related virus (XMRV), was found in ME/CFS patients and blood donors, but this was not corroborated. However, the paucity of serological investigations on XMRV in humans prompted us to develop a serological assay which cover many aspects of XMRV antigenicity. It is a novel suspension array method, using a multiplex IgG assay with nine recombinant proteins from the env and gag genes of XMRV and 38 peptides based on known epitopes of vertebrate gamma-retroviruses. IgG antibodies were sought in 520 blood donors and 85 ME/CFS patients and in positive-and negative-control sera from animals. We found no differences in seroreactivity between blood donors and ME/CFS patients for any of the antigens. This did not support an association between ME/CFS and XMRV infection. The multiplex serological system had several advantages: (i) biotinylated protein G allowed us to run both human and animal sera, which is essential because of a lack of XMRV-positive humans; (ii) a novel quality control was a pan-peptide positive-control rabbit serum; and (iii) synthetic XMRV Gag peptides with degenerate positions covering most of the variation of murine leukemia-like viruses did not give higher background than nondegenerate analogs. The principle may be used for creation of variant tolerant peptide serologies. Thus, our system allows rational large-scale serological assays with built-in quality control.

  • 18.
    Blomqvist, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Christerson, Linus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Waldenström, Jonas
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Chlamydia psittaciin Swedish Wetland Birds: A Risk to Zoonotic Infection2012In: Avian diseases, ISSN 0005-2086, E-ISSN 1938-4351, Vol. 56, no 4, p. 737-740Article in journal (Refereed)
    Abstract [en]

    Chlamydia psittaci in birds may be transmitted to humans and cause respiratory infections, sometimes as severe disease. Our study investigated the C. psittaci prevalence in migratory birds in Sweden by real-time PCR. Fecal specimens or cloacal swabs were collected from 497 birds from 22 different species, mainly mallards (Anas platyrhynchos), at two bird observatories in Sweden. DNA from C. psittaci was found in six (1.2%) birds from three different species. Five of the positive specimens were infected with four novel strains of C. psittaci, based on sequencing of partial 16S rRNA gene and ompA gene, and the sixth was indentified as a recently described Chlamydiaceae-like bacterium. Considering exposure to humans it is concluded that the risk of zoonotic infection is low.

  • 19. Bolisetty, M.
    et al.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Benachenhou, Farid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Sperber, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Beemon, K.
    Unexpected diversity and expression of avian endogenous retroviruses2012In: mBio, ISSN 2161-2129, Vol. 3, no 5, p. e00344-12Article in journal (Refereed)
    Abstract [en]

    Endogenous retroviruses (ERVs) were identified and characterized in three avian genomes to gain insight into early retroviral evolution. Using the computer program RetroTector to detect relatively intact ERVs, we identified 500 ERVs in the chicken genome, 150 in the turkey genome, and 1,200 in the zebra finch genome. Previous studies suggested that endogenous alpharetroviruses were present in chicken genomes. In this analysis, a small number of alpharetroviruses were seen in the chicken and turkey genomes; however, these were greatly outnumbered by beta-like, gamma-like, and alphabeta proviruses. While the avian ERVs belonged to the same major groups as mammalian ERVs, they were more heterogeneous. In particular, the beta-like viruses revealed an evolutionary continuum with the gradual acquisition and loss of betaretroviral markers and a transition from beta to alphabeta and then to alpharetroviruses. Thus, it appears that birds may resemble a melting pot for early ERV evolution. Many of the ERVs were integrated in clusters on chromosomes, often near centromeres. About 25% of the chicken ERVs were in or near cellular transcription units; this is nearly random. The majority of these integrations were in the sense orientation in introns. A higher-than-random number of integrations were >100 kb from the nearest gene. Deep-sequencing studies of chicken embryo fibroblasts revealed that about 20% of the 500 ERVs were transcribed and translated. A subset of these were also transcribed in vivo in chickens, showing tissue-specific patterns of expression.

  • 20. Bonnedahl, Jonas
    et al.
    Hernandez, Jorge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Stedt, Johan
    Waldenstrom, Jonas
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Drobni, Mirva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Extended-Spectrum beta-Lactamases in Escherichia coli and Klebsiella pneumoniae in Gulls, Alaska, USA2014In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 20, no 5, p. 897-899Article in journal (Refereed)
  • 21.
    Bonnedahl, Jonas
    et al.
    Linnaeus Univ, Sch Nat Sci, Ctr Ecol & Evolut Microbial Model Syst, SE-39182 Kalmar, Sweden.;Kalmar Cty Hosp, Dept Infect Dis, SE-39185 Kalmar, Sweden..
    Stedt, Johan
    Linnaeus Univ, Sch Nat Sci, Ctr Ecol & Evolut Microbial Model Syst, SE-39182 Kalmar, Sweden..
    Waldenstrom, Jonas
    Linnaeus Univ, Sch Nat Sci, Ctr Ecol & Evolut Microbial Model Syst, SE-39182 Kalmar, Sweden..
    Svensson, Lovisa
    Linnaeus Univ, Sch Nat Sci, Ctr Ecol & Evolut Microbial Model Syst, SE-39182 Kalmar, Sweden..
    Drobni, Mirva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Olsen, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Comparison of Extended-Spectrum beta-Lactamase (ESBL) CTX-M Genotypes in Franklin Gulls from Canada and Chile2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, article id e0141315Article in journal (Refereed)
    Abstract [en]

    Migratory birds have been suggested to contribute to long-distance dispersal of antimicrobial resistant bacteria, but tests of this hypothesis are lacking. In this study we determined resistance profiles and genotypes of ESBL-producing bacteria in randomly selected Escherichia coli from Franklin's gulls (Leucophaeus pipixcan) at breeding sites in Canada and compared with similar data from the gulls' wintering grounds in Chile. Resistant E. coli phenotypes were common, most notably to ampicillin (30.1%) and cefadroxil (15.1%). Furthermore, 17.0% of the gulls in Canada carried ESBL producing bacteria, which is higher than reported from human datasets from the same country. However, compared to gulls sampled in Chile (30.1%) the prevalence of ESBL was much lower. The dominant ESBL variants in Canada were bla(CTX-M-14) and bla(CTX-M-15) and differed in proportions to the data from Chile. We hypothesize that the observed differences in ESBL variants are more likely linked to recent exposure to bacteria from anthropogenic sources, suggesting high local dissemination of resistant bacteria both at breeding and non-breeding times rather than a significant trans-hemispheric exchange through migrating birds.

  • 22. Cadeddu, Marta
    et al.
    Vargiu, Laura
    Rodriguez-Tome, Patricia
    Sperber, Göran O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Tramontano, Enzo
    Identification and analysis of HML2 sequences in human genome assembly GRCh37/hg192013In: Retrovirology, ISSN 1742-4690, E-ISSN 1742-4690, Vol. 10, no S1, p. P9-Article in journal (Other academic)
  • 23.
    Cai, Yanling
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Photocatalytic inactivation of biofilms on bioactive dental adhesives2014In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 102, no 1, p. 62-67Article in journal (Refereed)
    Abstract [en]

    Biofilms are the most prevalent mode of microbial life in nature and are 10-1000 times more resistant to antibiotics than planktonic bacteria. Persistent biofilm growth associated at the margin of a dental restoration often leads to secondary caries, which remains a challenge in restorative dentistry. In this work, we present the first in vitro evaluation of on-demand photocatalytic inactivation of biofilm on a novel dental adhesive containing TiO2 nanoparticles. Streptococcus mutans biofilm was cultured on this photocatalytic surface for 16 h before photocatalytic treatment with ultraviolet-A (UV-A) light. UV-A doses ranging from 3 to 43 J/cm(2) were applied to the surface and the resulting viability of biofilms was evaluated with a metabolic activity assay incorporating phenol red that provided a quantitative measure of the reduction in viability due to the photocatalytic treatments. We show that an UV-A irradiation dose of 8.4 J/cm(2) leads to one order of magnitude reduction in the number of biofilm bacteria on the surface of the dental adhesives while as much as 5-6 orders of magnitude reduction in the corresponding number can be achieved with a dose of 43 J/cm(2). This material maintains its functional properties as an adhesive in restorative dentistry while offering the possibility of a novel dental procedure in the treatment or prevention of bacterial infections via on-demand UV-A irradiation. Similar materials could be developed for the treatment of additional indications such as peri-implantits.

  • 24. Camussone, C. M.
    et al.
    Pujato, N.
    Renna, M. S.
    Veaute, C. M.
    Morein, Bror
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Marcipar, I. S.
    Calvinho, L. F.
    Immune response and functional role of antibodies raised in heifers against a Staphylococcus aureus CP5 lysate and recombinant antigens vaccine formulated with Iscom Matrix adjuvant2014In: Veterinary Immunology and Immunopathology, ISSN 0165-2427, E-ISSN 1873-2534, Vol. 162, no 3-4, p. 96-107Article in journal (Refereed)
    Abstract [en]

    Staphylococcus aureus is the most frequently isolated pathogen from bovine intramammary infections worldwide. Commercially available vaccines for mastitis control are composed either of S. aureus lysates or inactivated whole-cells formulated with traditional adjuvants. We recently showed the ability of a S. aureus CP5 lysate vaccine adjuvanted with Iscom Matrix to generate a longer lasting specific antibody response in blood and milk with improved opsonic capacity compared with a S. aureus CP5 whole-cell formulation. The aim of the present study was to obtain an experimental immunogen composed of lysed cells of a CP5 S. aureus strain supplemented with recombinant clumping factor A fibronectin binding protein A and beta-toxin formulated with Iscom Matrix characterize the immune response generated when immunizing pregnant heifers and assess the functional role of antibodies raised against this immunogen in experimental models. Both a lysate vaccine and a lysate + recombinant antigens vaccine elicited antibodies that promoted neutrophil phagocytosis and inhibited internalization into mammary epithelial cells in vitro. Incorporation of defined antigenic molecules to the lysate formulation elicited a strong specific humoral immune response against both lysate and recombinant antigens and was associated with higher expression of regulatory and pro-inflammatory cytokines. In addition antibodies were efficient for blocking S. aureus binding to bovine fibrinogen and fibronectin and neutralizing beta-toxin effect in vitro placing these antigens as candidates to be included in a formulation directed to prevent staphylococcal bovine mastitis. (C) 2014 Elsevier B.V. All rights reserved.

  • 25. Camussone, C. M.
    et al.
    Veaute, C. M.
    Porporatto, C.
    Morein, Bror
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Marcipar, I. S.
    Calvinho, L. F.
    Immune response of heifers against a Staphylococcus aureus CP5 whole cell vaccine formulated with ISCOMATRIX™ adjuvant2013In: Journal of dairy research (Print), ISSN 0022-0299, E-ISSN 1469-7629, Vol. 80, no 1, p. 72-80Article in journal (Refereed)
    Abstract [en]

    The shortcomings of Staphylococcus aureus vaccines to control bovine mastitis have been attributed to insufficient capacity of the vaccines to induce opsonizing antibodies and to stimulate cellular immune responses. Types of antigen, administration route and adjuvant used in a vaccine formulation have been identified as critical factors for the development of opsonic antibodies. Current commercially available vaccines for Staph. aureus bovine mastitis control are formulated with Al(OH)3 and oil-based adjuvants. The aim of this study was to evaluate the immune response of heifers immunized with a Staph. aureus CP5 whole cell vaccine formulated either with Al(OH)3 or ISCOMATRIX ™. Twenty primigravid Holstein dairy heifers in the last trimester of gestation were immunized either with a vaccine formulated with ISCOMATRIX™ (n = 6), Al(OH)3 (n = 7), or saline solution (placebo) (n = 7). Immunization was carried out 38 and 10 d before calving. Heifers vaccinated with Staph. aureus adjuvanted with ISCOMATRIX™ responded with significantly higher levels of anti-bacterin and anti-CP5 IgG and IgG2 in sera than animals in the Al(OH)3 or control groups. Animals in the ISCOMATRIX™ group responded with significantly higher anti-bacterin specific IgG in whey than animals in the Al(OH)3 and control groups, detected from the first week post calving until 60 d of lactation. Sera from animals inoculated with Staph. aureus in ISCOMATRIX™, obtained 7 d post partum, significantly increased both the number of neutrophils ingesting bacteria and the number of bacteria being ingested by the neutrophils, compared with sera obtained from heifers vaccinated with Al(OH)3 or non-vaccinated controls. These features coupled to safety of the ISCOMATRIX™ formulation, warrant additional studies.

  • 26. Camussone, Cecilia M.
    et al.
    Veaute, Carolina M.
    Pujato, Nazarena
    Morein, Bror
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Marcipar, Ivan S.
    Calvinho, Luis F.
    Immune response of heifers against a Staphylococcus aureus CP5 whole cell and lysate vaccine formulated with ISCOM Matrix adjuvant2014In: Research in Veterinary Science, ISSN 0034-5288, E-ISSN 1532-2661, Vol. 96, no 1, p. 86-94Article in journal (Refereed)
    Abstract [en]

    Staphylococcus aureus is the most frequently isolated pathogen from bovine intramammary infections worldwide. Commercially available vaccines for mastitis control are composed either of S. aureus lysates or whole-cells formulated with traditional adjuvants. We recently showed the ability of a S. aureus CP5 whole-cell vaccine adjuvanted with ISCOM Matrix to increase specific antibodies production in blood and milk, improving opsonic capacity, compared with the same vaccine formulated with Al(OH)(3). However, there is no information about the use of ISCOM Matrix for the formulation of bacterial lysates. The aim of this study was to characterize the innate and humoral immune responses induced by a S. aureus CP5 whole-cell or lysate vaccine, formulated with ISCOM Matrix after immunization of pregnant heifers. Both immunogens stimulated strong humoral immune responses in blood and milk, raising antibodies that increased opsonic capacity. Lysate formulation generated a higher and longer lasting antibody titer and stimulated a higher expression of regulatory and pro-inflammatory cytokines compared with the whole-cell vaccine. (C) 2013 Elsevier Ltd. All rights reserved.

  • 27. Chapman, Joanne R
    et al.
    Helin, Anu S
    Wille, Michelle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Atterby, Clara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Järhult, Josef D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Fridlund, Jimmy S
    Waldenström, Jonas
    A Panel of Stably Expressed Reference Genes for Real-Time qPCR Gene Expression Studies of Mallards (Anas platyrhynchos)2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 2, article id e0149454Article in journal (Refereed)
    Abstract [en]

    Determining which reference genes have the highest stability, and are therefore appropriate for normalising data, is a crucial step in the design of real-time quantitative PCR (qPCR) gene expression studies. This is particularly warranted in non-model and ecologically important species for which appropriate reference genes are lacking, such as the mallard-a key reservoir of many diseases with relevance for human and livestock health. Previous studies assessing gene expression changes as a consequence of infection in mallards have nearly universally used β-actin and/or GAPDH as reference genes without confirming their suitability as normalisers. The use of reference genes at random, without regard for stability of expression across treatment groups, can result in erroneous interpretation of data. Here, eleven putative reference genes for use in gene expression studies of the mallard were evaluated, across six different tissues, using a low pathogenic avian influenza A virus infection model. Tissue type influenced the selection of reference genes, whereby different genes were stable in blood, spleen, lung, gastrointestinal tract and colon. β-actin and GAPDH generally displayed low stability and are therefore inappropriate reference genes in many cases. The use of different algorithms (GeNorm and NormFinder) affected stability rankings, but for both algorithms it was possible to find a combination of two stable reference genes with which to normalise qPCR data in mallards. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies in ducks. The fact that nearly all previous studies of the influence of pathogen infection on mallard gene expression have used a single, non-validated reference gene is problematic. The toolkit of putative reference genes provided here offers a solid foundation for future studies of gene expression in mallards and other waterfowl.

  • 28.
    Christerson, Linus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Bom, Reinier J. M.
    Bruisten, Sylvia M.
    Yass, Resha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Hardick, Justin
    Bratt, Goran
    Gaydos, Charlotte A.
    Morre, Servaas A.
    Herrmann, Bjorn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Chlamydia trachomatis Strains Show Specific Clustering for Men Who Have Sex with Men Compared to Heterosexual Populations in Sweden, the Netherlands, and the United States2012In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 50, no 11, p. 3548-3555Article in journal (Refereed)
    Abstract [en]

    High-resolution genotyping of Chlamydia trachomatis improves the characterization of strains infecting different patient groups and sexual networks. In this study, multilocus sequence typing (MLST) and ompA sequence determination were used for an analysis of C. trachomatis strains from 203 men who have sex with men (MSM) from Sweden, the Netherlands, and the United States. The results obtained were compared with data from 153 heterosexual women from Sweden and the Netherlands. The overlap in MLST/ompA profiles between MSM from Sweden and the Netherlands was 68%, while the overlap between heterosexual populations from these countries was only 18%. The distribution of genotypes in MSM from the United States was less similar to that in MSM from the European countries, with 45% and 46% overlaps for MSM in Sweden and the Netherlands, respectively. Minimum-spanning-tree analysis of MLST/ompA sequence types identified two large clusters that contained almost exclusively samples from MSM and comprised 74% of all MSM samples. Three other clusters were predominated by samples from women but also contained MSM specimens. Of 19 detected variants of the MLST target CT144, three variants were highly associated with MSM. Our study supports the hypotheses of both tissue tropism as well as epidemiological network structures as explanations for the linkage between specific genetic variants and sexual orientation.

  • 29.
    Danielsson, Axel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Palanisamy, Navaneethan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Golbob, Sultan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Yin, Hong
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Hedlund, Johan
    Sylvan, Staffan
    Lennerstrand, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Transmission of hepatitis C virus among intravenous drug users in the Uppsala region of Sweden2014In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 4, article id 22251Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Epidemiology and transmission patterns of hepatitis C virus (HCV) are important subjects as we enter a new era of treatment with directly acting antivirals (DAAs). The highest prevalence of HCV in developed countries is found among intravenous drug users (IDUs), where unsafe needle sharing practices provide the main route of infection. Efforts to prohibit the continuous spread of HCV among these groups have been initiated by the community services and health care providers. Our goal was to understand how HCV was transmitted among IDUs within a limited population group. We provide a retrospective study (2005-2007) of the HCV transmission patterns in a population of IDUs in the Uppsala region of Sweden.

    METHOD: Eighty-two serum samples were collected from IDUs in Uppsala County. Our reverse transcription nested polymerase chain reaction (RT-nested PCR) and sequencing method enabled a comprehensive genetic analysis for a broad spectrum of genotypes of two relatively conserved regions, NS5B and NS3, that encodes for the viral polymerase and protease, respectively. HCV RNA in serum samples was amplified and sequenced with in-house primers. Sequence similarities between individuals and subgroups were analyzed with maximum likelihood (ML) phylogenetic trees. Published HCV reference sequences from other geographic regions and countries were also included for clarity.

    RESULTS: Phylogenetic analysis was possible for 59 NS5B (72%) and 29 NS3 (35%) sequences from Uppsala patients. Additionally, we also included 15 NS3 sequences from Örebro patients, making a total of 44 NS3 sequences for the analysis. By analyzing the NS3 sequences, two transmission sets were found between the IDUs (>98% sequence identity), with one set consisting of two individuals and another set consisting of three individuals. In addition, the phylogenetic analysis done with our serum samples displayed clusters that distinguished them from the reference sequences.

    CONCLUSION: Our method seems to enable us to trace the HCV transmission between IDUs. Furthermore, the method is fairly independent of the time of infection because the method uses relatively conserved HCV sequence regions (i.e. NS5B and NS3).

  • 30. Darkahi, Bahman
    et al.
    Sandblom, Gabriel
    Liljeholm, Hakan
    Videhult, Per
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Rasmussen, Ib Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Biliary Microflora in Patients Undergoing Cholecystectomy2014In: Surgical Infections, ISSN 1096-2964, E-ISSN 1557-8674, Vol. 15, no 3, p. 262-265Article in journal (Refereed)
    Abstract [en]

    Background: The management of acute cholecystitis requires a sound knowledge of the biliary microflora. Methods: Bile samples were taken for culture according to a standard routine during all cholecystectomies performed from April 2007 to February 2009 in the Department of Surgery at Enkoping Hospital. The use of antibiotics within the 3-mo period before surgery, indication for surgery, prophylactic antibiotics, and post-operative complications were recorded prospectively. Results: Altogether, 246 procedures were performed during the study period, of which 149 (62%) were done on women. The mean (SD) age of the study subjects was 49 +/- 16y. Bacterial growth was seen in cultures from 34 (14%) of the subjects. The mean age of subjects with positive cultures was 64y and that of subjects with negative cultures was 47y (p<0.001). Positive culture was seen in 16 (31%) of the 51 patients who underwent operations for acute cholecystitis, whereas positive cultures were obtained in 18 of 195 patients without acute cholecystitis (9%) (p<0.001). Resistance to ampicillin was recorded in three of 34 (9%) of the cultures with bacterial growth, to co-trimoxazole in one of the 34 (3%) cultures, to fluoroquinolones in one of the 34 (3%) cultures, and to cephalosporins in one of the 34 (3%) cultures. Resistance to piperacillin-tazobactam was not observed in any of the cultures. In multivariable logistic regression analysis, a positive culture was the only factor significantly associated with risk for post-operative infectious complications (p<0.05). Discussion: Bacterial growth in the bile is observed more often in patients undergoing surgery for acute cholecystitis. The microflora of the bile is probably important for the outcome of surgery, but further studies are required for assessing the effectiveness of measures for preventing infectious post-operative complications.

  • 31. Demirel, Isak
    et al.
    Vumma, Ravi
    Mohlin, Camilla
    Svensson, Lovisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Save, Susanne
    Persson, Katarina
    Nitric Oxide Activates IL-6 Production and Expression in Human Renal Epithelial Cells2012In: American Journal of Nephrology, ISSN 0250-8095, E-ISSN 1421-9670, Vol. 36, no 6, p. 524-530Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Increased nitric oxide (NO) production or inducible form of NO synthase activity have been documented in patients suffering from urinary tract infection (UTI), but the role of NO in this infection is unclear. We investigated whether NO can affect the host response in human renal epithelial cells by modulating IL-6 production and mRNA expression. Methods: The human renal epithelial cell line A498 was infected with a uropathogenic Escherichia coli (UPEC) strain and/or the NO donor DETA/NO. The IL-6 production and mRNA expression were evaluated by ELISA and real-time RT-PCR. IL-6 mRNA stability was evaluated by analyzing mRNA degradation by real-time RT-PCR. Results: DETA/NO caused a significant (p < 0.05) increase in IL-6 production. Inhibitors of p38 MAPK and ERK1/2 signaling, but not JNK, were shown to significantly suppress DETA/NO-induced IL-6 production. UPEC-induced IL-6 production was further increased (by 73 +/- 23%, p < 0.05) in the presence of DETA/NO. The IL-6 mRNA expression increased 2.1 +/- 0.17-fold in response to DETA/NO, while the UPEC-evoked increase was pronounced (20 +/- 4.5-fold). A synergistic effect of DETA/NO on UPEC-induced IL-6 expression was found (33 +/- 7.2-fold increase). The IL-6 mRNA stability studies showed that DETA/NO partially attenuated UPEC-induced degradation of IL-6 mRNA. Conclusions: NO was found to stimulate IL-6 in renal epithelial cells through p38 MAPK and ERK1/2 signaling pathways and also to increase IL-6 mRNA stability in UPEC-infected cells. This study proposes a new role for NO in the host response during UTI by modulating the transcription and production of the cytokine IL-6.

  • 32.
    Dicksved, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ellström, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Engstrand, Lars
    Rautelin, Hilpi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Susceptibility to Campylobacter Infection Is Associated with the Species Composition of the Human Fecal Microbiota2014In: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 5, no 5, p. e01212-14-Article in journal (Refereed)
    Abstract [en]

    The gut microbiota is essential for human health, but very little is known about how the composition of this ecosystem can influence and respond to bacterial infections. Here we address this by prospectively studying the gut microbiota composition before, during, and after natural Campylobacter infection in exposed poultry abattoir workers. The gut microbiota composition was analyzed with 16S amplicon sequencing of fecal samples from poultry abattoir workers during the peak season of Campylobacter infection in Sweden. The gut microbiota compositions were compared between individuals who became culture positive for Campylobacter and those who remained negative. Individuals who became Campylobacter positive had a significantly higher abundance of Bacteroides (P = 0.007) and Escherichia (P = 0.002) species than those who remained culture negative. Furthermore, this group had a significantly higher abundance of Phascolarctobacterium (P = 0.017) and Streptococcus (P = 0.034) sequences than the Campylobacter-negative group, which had an overrepresentation of Clostridiales (P = 0.017), unclassified Lachnospiraceae (P = 0.008), and Anaerovorax (P = 0.015) sequences. Intraindividual comparisons of the fecal microbiota compositions yielded small differences over time in Campylobacter-negative participants, but significant long-term changes were found in the Campylobacter-positive group (P < 0.005). The results suggest that the abundance of specific genera in the microbiota reduces resistance to Campylobacter colonization in humans and that Campylobacter infection can have long-term effects on the composition of the human fecal microbiota. IMPORTANCE Studies using mouse models have made important contributions to our understanding of the role of the gut microbiota in resistance to bacterial enteropathogen colonization. The relative abundances of Escherichia coli and Bacteroides species have been pointed out as important determinants of susceptibility to Gram-negative pathogens in general and Campylobacter infection in particular. In this study, we assessed the role of the human gut microbiota in resistance to Campylobacter colonization by studying abattoir workers that are heavily exposed to these bacteria. Individuals with a certain composition of the gut microbiota became culture positive for Campylobacter. As their microbiotas were characterized by high abundances of Bacteroides spp. and E. coli, well in line with the findings with mouse models, these bacterial species likely play an important role in colonization resistance also in humans.

  • 33. Duodu, Samuel
    et al.
    Madslien, Knut
    Hjelm, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Molin, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Paziewska-Harris, Anna
    Harris, Philip D.
    Colquhoun, Duncan J.
    Ytrehus, Bjornar
    Bartonella Infections in Deer Keds (Lipoptena cervi) and Moose (Alces alces) in Norway2013In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 79, no 1, p. 322-327Article in journal (Refereed)
    Abstract [en]

    Infections with Bartonella spp. have been recognized as emerging zoonotic diseases in humans. Large knowledge gaps exist, however, relating to reservoirs, vectors, and transmission of these bacteria. We describe identification by culture, PCR, and housekeeping gene sequencing of Bartonella spp. in fed, wingless deer keds (Lipoptena cervi), deer ked pupae, and blood samples collected from moose, Alces alces, sampled within the deer ked distribution range in Norway. Direct sequencing from moose blood sampled in a deer ked-free area also indicated Bartonella infection but at a much lower prevalence. The sequencing data suggested the presence of mixed infections involving two species of Bartonella within the deer ked range, while moose outside the range appeared to be infected with a single species. Bartonella were not detected or cultured from unfed winged deer keds. The results may indicate that long-term bacteremia in the moose represents a reservoir of infection and that L. cervi acts as a vector for the spread of infection of Bartonella spp. Further research is needed to evaluate the role of L. cervi in the transmission of Bartonella to animals and humans and the possible pathogenicity of these bacteria for humans and animals.

  • 34.
    Edvinsson, Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Ilbäck, Nils-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Frisk, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Nyström-Rosander, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Trace Element Changes in Thoracic Aortic Dissection2016In: Biological Trace Element Research, ISSN 0163-4984, E-ISSN 1559-0720, Vol. 169, no 2, p. 159-163Article in journal (Refereed)
    Abstract [en]

    Thoracic aortic dissection is a life-threatening condition with an incompletely understood pathogenesis. Trace elements are essential for the functioning of different processes in the body, including the immune system and associated responses to infection/inflammation. Because inflammation may be part of the pathogenesis of thoracic aortic dissection, we investigated whether trace element changes associated with inflammation occur in serum and tissue samples during the disease. The study included 21 patients undergoing surgery for thoracic aortic dissection, 10 forensic autopsy specimens for tissue controls and 23 healthy blood donors for serum controls. Levels of magnesium (Mg), calcium (Ca), vanadium (V), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), cadmium (Cd) and mercury (Hg) were measured in the aortic tissue and serum by inductively coupled plasma-mass spectrometry (ICP-MS). In the serum, Ca, V, Cu and Zn decreased, whereas Fe increased. In the tissue, Cu and Zn decreased and Fe tended to increase. The Cu/Zn ratio in the serum, a marker of infection/inflammation, did not change in the patients. Concerning trace element changes in the serum and tissue, our data do not support the hypothesis that inflammation is involved in the pathogenesis of thoracic aortic dissection.

  • 35.
    Edvinsson, Marie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Nilsson, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Nyström-Rosander, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    No evidence of Chlamydophila spp. or other intracellular bacteria in mitral valves.2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 164, no 2, p. 249-250Article in journal (Refereed)
  • 36.
    Elfaitouri, Amal
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Herrmann, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Bölin-Wiener, Agnes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Wang, Yilin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Gottfries, Carl-Gerhard
    Zachrisson, Olof
    Pipkorn, Ruediger
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Epitopes of Microbial and Human Heat Shock Protein 60 and Their Recognition in Myalgic Encephalomyelitis2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, p. 55-Article in journal (Refereed)
    Abstract [en]

    Myalgic encephalomyelitis (ME, also called Chronic Fatigue Syndrome), a common disease with chronic fatigability, cognitive dysfunction and myalgia of unknown etiology, often starts with an infection. The chaperonin human heat shock protein 60 (HSP60) occurs in mitochondria and in bacteria, is highly conserved, antigenic and a major autoantigen. The anti-HSP60 humoral (IgG and IgM) immune response was studied in 69 ME patients and 76 blood donors (BD) (the Training set) with recombinant human and E coli HSP60, and 136 30-mer overlapping and targeted peptides from HSP60 of humans, Chlamydia, Mycoplasma and 26 other species in a multiplex suspension array. Peptides from HSP60 helix I had a chaperonin-like activity, but these and other HSP60 peptides also bound IgG and IgM with an ME preference, theoretically indicating a competition between HSP60 function and antibody binding. A HSP60-based panel of 25 antigens was selected. When evaluated with 61 other ME and 399 non-ME samples (331 BD, 20 Multiple Sclerosis and 48 Systemic Lupus Erythematosus patients), a peptide from Chlamydia pneumoniae HSP60 detected IgM in 15 of 61 (24%) of ME, and in 1 of 399 non-ME at a high cutoff (p<0.0001). IgM to specific cross-reactive epitopes of human and microbial HSP60 occurs in a subset of ME, compatible with infection-induced autoimmunity.

  • 37.
    Elfving, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
    Epidemiological and Bacteriological Aspects of Spotted Fever Rickettsioses in Humans, Vectors and Mammals in Sweden2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Rickettsiae are obligate intracellular gram-negative bacteria transmitted by arthropod vectors. Rickettsiae sometimes cause disease in humans, typically with high fever, headache and occasionally an eschar.

    In Sweden, Rickettsia helvetica, belonging to the spotted fever group, is the only tick-transmitted rickettsia found free in nature. The pathogenic roll of R. helvetica has not been fully investigated, but it has been implicated in aneruptive fever and cardiac disease.

    This thesis describes parts of the transmission pathways of rickettsiae in Sweden. Rickettsia infection rates in ticks collected from birds were analysed, and the birds’ role as disseminators and reservoirs was studied. We found that more than one in ten ticks was infected with rickettsia bacteria, predominantly R. helvetica, and that migrating birds contribute not only to long-distance dispersion of bacteria, but also to an inflow of novel and potentially pathogenic rickettsia species, in this case R. monacensis and R. sp. strain Davousti-like species, into Sweden.

    Further, wild and domestic animals were found to have seroreactivity against R. helvetica, which shows that they are exposed and susceptible to rickettsia. Their role as reservoirs has not been determined, yet they may indirectly be involved in transmission of rickettsia to humans by infected ticks feeding on them.

    The seroreactivity in humans was also studied. Patients investigated for suspected Borrelioses and blood donors had detectable antibodies against Rickettsia spp., with the highest prevalence detected in the suspected Borreliosis group. This shows that humans in Sweden are exposed to and develop an immune response against rickettsia. The suspicion that R. helvetica may cause severe symptoms was verified by a patient with subacute meningitis where the bacterium was shown for the first time to cause an invasive infection with CNS involvement and where the bacterium was isolated from the patient’s cerebrospinal fluid.

    Growth characteristics and morphology of R. helvetica were studied to better understand invasiveness and virulence. The findings indicate that the invasiveness is comparable with other rickettsia, though R. helvetica seems to have a stable but slightly slower growth. 

    Rickettsia helvetica is endemic in Sweden and therefore needs to be considered when investigating disease after a tick bite.

    List of papers
    1. Seroprevalence of Rickettsia spp. infection among tick-bitten patients and blood donors in Sweden
    Open this publication in new window or tab >>Seroprevalence of Rickettsia spp. infection among tick-bitten patients and blood donors in Sweden
    2008 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 40, no 1, p. 74-77Article in journal (Refereed) Published
    Abstract [en]

    Serum samples from 236 Swedish patients with symptoms of infectious disease appearing after a tick bite were analysed for the presence of antibodies to Rickettsia helvetica, the only rickettsial species so far isolated from ticks in Sweden. Of these subjects, 137 had tested seropositive for Borrelia burgdorferi. For control purposes, sera from 161 healthy blood donors were examined. A total of 10/397 samples (2.6%) showed IgG-antibodies to R. helvetica at or above a titre of 1/80 as cut-off. 6/137 (4.4%) belonged to the Borrelia positive group, 3/99 (3.0%) to the tick-bitten but Borrelia negative group and 1/161 (0.6%) to the control group. The difference between the tick-exposed groups and the control group was significant in Pearson's 2-sided chi(2) test. In 1 serum sample the presence of antibodies to R. helvetica was further confirmed by Western immunoblot. The study shows that infection with Rickettsia spp. as well as coinfection with Lyme borreliosis needs to be considered in the diagnosis of tick-transmitted infections in Sweden. Owing to a known occurrence of immunological cross-reactivites, however, the results must be cautiously interpreted with regard to species of Rickettsia involved.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-103987 (URN)10.1080/00365540701509907 (DOI)000252311200014 ()17852905 (PubMedID)
    Available from: 2009-05-26 Created: 2009-05-26 Last updated: 2018-02-25Bibliographically approved
    2. Dissemination of Spotted Fever Rickettsia Agents in Europe by Migrating Birds
    Open this publication in new window or tab >>Dissemination of Spotted Fever Rickettsia Agents in Europe by Migrating Birds
    Show others...
    2010 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 1, p. e8572-Article in journal (Refereed) Published
    Abstract [en]

    Migratory birds are known to play a role as long-distance vectors for many microorganisms. To investigate whether this is true of rickettsial agents as well, we characterized tick infestation and gathered ticks from 13,260 migratory passerine birds in Sweden. A total of 1127 Ixodes spp. ticks were removed from these birds and the extracted DNA from 957 of them was available for analyses. The DNA was assayed for detection of Rickettsia spp. using real-time PCR, followed by DNA sequencing for species identification. Rickettsia spp. organisms were detected in 108 (11.3%) of the ticks. Rickettsia helvetica, a spotted fever rickettsia associated with human infections, was predominant among the PCR-positive samples. In 9 (0.8%) of the ticks, the partial sequences of 17kDa and ompB genes showed the greatest similarity to Rickettsia monacensis, an etiologic agent of Mediterranean spotted fever-like illness, previously described in southern Europe as well as to the Rickettsia sp.IrITA3 strain. For 15 (1.4%) of the ticks, the 17kDa, ompB, gltA and ompA genes showed the greatest similarity to Rickettsia sp. strain Davousti, Rickettsia japonica and Rickettsia heilongjiangensis, all closely phylogenetically related, the former previously found in Amblyomma tholloni ticks in Africa and previously not detected in Ixodes spp. ticks. The infestation prevalence of ticks infected with rickettsial organisms was four times higher among ground foraging birds than among other bird species, but the two groups were equally competent in transmitting Rickettsia species. The birds did not seem to serve as reservoir hosts for Rickettsia spp., but in one case it seems likely that the bird was rickettsiemic and that the ticks had acquired the bacteria from the blood of the bird. In conclusion, migratory passerine birds host epidemiologically important vector ticks and Rickettsia species and contribute to the geographic distribution of spotted fever rickettsial agents and their diseases.

    Keywords
    Ixodes, ticks, birds, infestation, rickettsia, spotted fever
    National Category
    Microbiology in the medical area
    Identifiers
    urn:nbn:se:uu:diva-113683 (URN)10.1371/journal.pone.0008572 (DOI)000273338500015 ()20052286 (PubMedID)
    Available from: 2010-02-02 Created: 2010-02-02 Last updated: 2018-01-12Bibliographically approved
    3. Rickettsia helvetica in patient with meningitis, Sweden, 2006
    Open this publication in new window or tab >>Rickettsia helvetica in patient with meningitis, Sweden, 2006
    2010 (English)In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 16, no 3, p. 490-492Article in journal (Refereed) Published
    Abstract [en]

    Pathogenicity of Rickettsia helvetica is relatively unknown. We isolated a spotted fever group rickettsial organism from a patient with subacute meningitis. Nucleotide sequences of the 16S rRNA, ompB, and 17kDa genes identified the isolate as R. helvetica. This organism may be associated with serious infections such as central nervous system disorders.

    National Category
    Medical and Health Sciences Infectious Medicine Clinical Laboratory Medicine
    Identifiers
    urn:nbn:se:uu:diva-125294 (URN)10.3201/eid1603.090184 (DOI)000275404700018 ()20202426 (PubMedID)
    Available from: 2010-05-14 Created: 2010-05-14 Last updated: 2018-03-02Bibliographically approved
    4. Life cycle, growth characteristics and host cell response of Rickettsia helvetica in a Vero cell line
    Open this publication in new window or tab >>Life cycle, growth characteristics and host cell response of Rickettsia helvetica in a Vero cell line
    2012 (English)In: Experimental & applied acarology, ISSN 0168-8162, E-ISSN 1572-9702, Vol. 56, no 2, p. 179-187Article in journal (Refereed) Published
    Abstract [en]

    Rickettsia helvetica, a spotted fever rickettsia and emerging pathogen with Ixodes ricinus ticks as the main vector, is an agent of human disease and may cause febrile illness as well as meningitis. In three parallel series the isolated standard type of R. helvetica, obtained from a PCR-positive I. ricinus tick, was high-passaged and propagated in a Vero cell line. By using quantitative real-time PCR, the generation time from inoculation to stationary phase of growth was calculated to 20-22 h. In the static cultivation system the stationary phase was observed from the seventh day after inoculation, and there was no observed degradation of R. helvetica DNA during the 14 days studied. Microscopy showed that the organisms invaded the host cells rapidly and were primarily found free in the cytoplasm and only occasionally located in the nucleus. Four days after inoculation some of the host cells were broken and many indifferent stages of cytoplasmic organic decomposition were seen. However the R. helvetica organism did not show any morphologic alterations and the number of organisms was stable after the replication peak which may indicate that R. helvetica is adapted to growth in a Vero cell line and/or that the phase of degradation occurs later than the 14 days studied. The findings differ from what has been reported for other rickettsiae of the spotted fever group and may be of importance for invasiveness and virulence of R. helvetica.

    Keywords
    rickettsia, qPCR, vero cells, life cycle, ultrastructure
    National Category
    Microbiology
    Research subject
    Infectious Diseases
    Identifiers
    urn:nbn:se:uu:diva-166778 (URN)10.1007/s10493-011-9508-7 (DOI)000299078900010 ()
    Note

    Correction in: Experimental and Applied Acarology, Vol 56, Issue 2, pp 189-190

    DOI: 10.1007/s10493-011-9509-6

    Available from: 2012-01-13 Created: 2012-01-13 Last updated: 2017-12-08Bibliographically approved
    5. Seroreactivity to Rickettsia spp. in Wild and Domestic Mammals in Sweden
    Open this publication in new window or tab >>Seroreactivity to Rickettsia spp. in Wild and Domestic Mammals in Sweden
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Sera were collected from wild and domestic mammals in Sweden and tested using indirect immunofluorescence assay to detect antibodies against Rickettsia spp. Considering sera with a titre > 1:64 as positive, 23.1% (104/450) of the animals scored positive. The percentages of seropositivity were: 21.5% (23/107) in deer, 23.3% (21/90) in moose, 36.5% (23/61) in horses, 22.2% (20/90) in cats and 17.0% (17/100) in dogs. In deer, 85% (91/107) also tested positive for Anaplasma phagocytophilum with a titre cut-off of 1:80. The findings indicate that these animal species may act as reservoir hosts of Rickettsia spp. and that deer may act as hosts for both tested organisms.