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Norén, Torbjörn
Publications (10 of 20) Show all publications
Kumar, N., Browne, H. P., Viciani, E., Forster, S. C., Clare, S., Harcourt, K., . . . Lawley, T. D. (2019). Adaptation of host transmission cycle during Clostridium difficile speciation [Letter to the editor]. Nature Genetics, 51(9), 1315-1320
Open this publication in new window or tab >>Adaptation of host transmission cycle during Clostridium difficile speciation
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2019 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 9, p. 1315-1320Article in journal, Letter (Refereed) Published
Abstract [en]

Bacterial speciation is a fundamental evolutionary process characterized by diverging genotypic and phenotypic properties. However, the selective forces that affect genetic adaptations and how they relate to the biological changes that underpin the formation of a new bacterial species remain poorly understood. Here, we show that the spore-forming, healthcare-associated enteropathogen Clostridium difficile is actively undergoing speciation. Through large-scale genomic analysis of 906 strains, we demonstrate that the ongoing speciation process is linked to positive selection on core genes in the newly forming species that are involved in sporulation and the metabolism of simple dietary sugars. Functional validation shows that the new C. difficile produces spores that are more resistant and have increased sporulation and host colonization capacity when glucose or fructose is available for metabolism. Thus, we report the formation of an emerging C. difficile species, selected for metabolizing simple dietary sugars and producing high levels of resistant spores, that is adapted for healthcare-mediated transmission.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Evolutionary Biology
Identifiers
urn:nbn:se:oru:diva-75827 (URN)10.1038/s41588-019-0478-8 (DOI)000484010800007 ()31406348 (PubMedID)2-s2.0-85070814630 (Scopus ID)
Funder
Wellcome trust, 098051
Note

Funding Agencies:

UK Medical Research Council  PF451  MR/K000511/1 

Australian National Health and Medical Research Council  1091097  1159239 

Victorian Government's Operational Infrastructure Support Program  

Available from: 2019-08-23 Created: 2019-08-23 Last updated: 2019-11-15Bibliographically approved
Rosdahl, A., Herzog, C., Frösner, G., Norén, T., Rombo, L. & Askling, H. H. (2019). Corrigendum to " An extra priming dose of hepatitis A vaccine to adult patients with rheumatoid arthritis and drug induced immunosuppression - A prospective, open-label, multi-center study" [Trav. Med. Infect. Dis. 21, January-February 2018, 43-50]. Travel Medicine and Infectious Disease, 27, 115-115
Open this publication in new window or tab >>Corrigendum to " An extra priming dose of hepatitis A vaccine to adult patients with rheumatoid arthritis and drug induced immunosuppression - A prospective, open-label, multi-center study" [Trav. Med. Infect. Dis. 21, January-February 2018, 43-50]
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2019 (English)In: Travel Medicine and Infectious Disease, ISSN 1477-8939, E-ISSN 1873-0442, Vol. 27, p. 115-115Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Public Health, Global Health, Social Medicine and Epidemiology Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-69608 (URN)10.1016/j.tmaid.2018.09.008 (DOI)000457729300020 ()30292695 (PubMedID)2-s2.0-85054154539 (Scopus ID)
Note

This corrects the article "An extra priming dose of hepatitis A vaccine to adult patients with rheumatoid arthritis and drug induced immunosuppression: A prospective, open-label, multi-center study", DOI: 10.1016/j.tmaid.2017.12.004

Available from: 2018-10-16 Created: 2018-10-16 Last updated: 2019-02-19Bibliographically approved
Rizzardi, K., Åkerlund, T., Norén, T. & Matussek, A. (2019). Impact of ribotype on Clostridioides difficile diagnostics. European Journal of Clinical Microbiology and Infectious Diseases
Open this publication in new window or tab >>Impact of ribotype on Clostridioides difficile diagnostics
2019 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373Article in journal (Refereed) Epub ahead of print
Abstract [en]

This study investigates the performance of diagnostic methods for detection of Clostridioides difficile infection in Sweden, including impact of PCR ribotype on diagnostic performance. Between 2011 and 2016, a total of 17,878 stool samples from 26 laboratories were tested by either well-type enzyme immunoassays (EIAs), membrane bound EIAs, cell cytotoxicity neutralization assay (CTA), or nucleic acid amplification tests (NAATs) and subsequently cultured for C. difficile. Roughly half of the samples (9454/17878) were subjected to diagnostic testing both on the fecal sample and on the 1323 isolated C. difficile strains. All C. difficile isolates were typed by PCR ribotyping, and the isolates were classified as toxigenic or non-toxigenic based on the empirical knowledge of the association between toxin-positivity and ribotype. The overall sensitivity, specificity, and positive and negative predictive values were highest for NAATs and membrane EIAs. Ribotype-specific sensitivity varied greatly between methods and ribotypes. All methods had 100% sensitivity against ribotype 027 and 013. For other types, the sensitivity ranged from 33 to 85% in fecal samples and from 78 to 100% on isolates. For the most prevalent ribotypes (014, 020, and 001), the sensitivity varied between 38 and 100% in the fecal samples, with the lowest sensitivity observed for well-type EIAs and CTA. The large variation in diagnostic sensitivity implies that type distribution significantly affects the outcome when evaluating diagnostic performance. Furthermore, performing comparative studies of diagnostic tests in settings with high prevalence of ribotype 027 will overestimate the general performance of diagnostic tests.

Place, publisher, year, edition, pages
Springer, 2019
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:oru:diva-78893 (URN)10.1007/s10096-019-03772-z (DOI)000504621100001 ()31884555 (PubMedID)
Funder
Swedish National Institute of Public Health
Available from: 2020-01-09 Created: 2020-01-09 Last updated: 2020-01-10Bibliographically approved
Rosdahl, A., Herzog, C., Frösner, G., Norén, T., Rombo, L. & Askling, H. H. (2018). An extra priming dose of hepatitis A vaccine to adult patients with rheumatoid arthritis and drug induced immunosuppression: A prospective, open-label, multi-center study. Travel Medicine and Infectious Disease, 21, 43-50
Open this publication in new window or tab >>An extra priming dose of hepatitis A vaccine to adult patients with rheumatoid arthritis and drug induced immunosuppression: A prospective, open-label, multi-center study
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2018 (English)In: Travel Medicine and Infectious Disease, ISSN 1477-8939, E-ISSN 1873-0442, Vol. 21, p. 43-50Article in journal (Refereed) Published
Abstract [en]

Background: Previous studies have indicated that a pre-travel single dose of hepatitis A vaccine is not sufficient as protection against hepatitis A in immunocompromised travelers. We evaluated if an extra dose of hepatitis A vaccine given shortly prior to traveling ensures seroconversion.

Method: Patients with rheumatoid arthritis (n = 69, median age = 55 years) treated with Tumor Necrosis Factor inhibitor(TNFi) and/or Methotrexate (MTX) were immunized with two doses of hepatitis A vaccine, either as double dose or four weeks apart, followed by a booster dose at six months. Furthermore, 48 healthy individuals, median age = 60 years were immunized with two doses, six months apart. Anti-hepatitis A antibodies were measured at 0, 1, 2, 6, 7 and 12 months.

Results: Two months after the initial vaccination, 84% of the RA patients had protective antibodies, compared to 85% of the healthy individuals. There was no significant difference between the two vaccine schedules. At twelve months, 99% of RA patients and 100% of healthy individuals had seroprotective antibodies.

Conclusion: An extra priming dos of hepatitis A vaccine prior to traveling offered an acceptable protection in individuals treated with TNFi and/or MTX. This constitutes an attractive pre-travel solution to this vulnerable group of patients.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Hepatitis A, Vaccine, Rheumatoid arthritis, Immunosuppression, Methotrexate, TNF-Inhibitors
National Category
Public Health, Global Health, Social Medicine and Epidemiology Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-65919 (URN)10.1016/j.tmaid.2017.12.004 (DOI)000426614600006 ()29229311 (PubMedID)2-s2.0-85037718947 (Scopus ID)
Note

Funding Agencies:

Uppsala-Örebro Regional Research Council  RFR-30790 

Regional Research committee of Örebro lan  OLL-259611  OLL-459691 OLL-671751 

Scandinavian Society for Antimicrobial Chemotherapy Foundation  SLS-171941 

Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2018-10-18Bibliographically approved
Tschudin-Sutter, S., Kuijper, E. J., Durovic, A., Vehreschild, M. J., Barbut, F., Eckert, C., . . . Widmer, A. F. (2018). Guidance document for prevention of Clostridium difficile infection in acute healthcare settings. Clinical Microbiology and Infection, 24(10), 1051-1054, Article ID S1198-743X(18)30195-2.
Open this publication in new window or tab >>Guidance document for prevention of Clostridium difficile infection in acute healthcare settings
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2018 (English)In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 24, no 10, p. 1051-1054, article id S1198-743X(18)30195-2Article in journal (Refereed) Published
Abstract [en]

SCOPE: Clostridium difficile infection (CDI) is the most important infective cause of healthcare-associated diarrhoea in high income countries and one of the most important healthcare-associated pathogens in both Europe and the United States. It is associated with high morbidity and mortality resulting in both societal and financial burden. A significant proportion of this burden is potentially preventable by a combination of targeted infection prevention and control measures and antimicrobial stewardship. The aim of this guidance document is to provide an update on recommendations for prevention of CDI in acute care settings to provide guidance to those responsible for institutional infection prevention and control programmes.

METHODS: An expert group was set up by the European society of clinical microbiology and infectious diseases (ESCMID) Study Group for C. difficile (ESGCD), which performed a systematic review of the literature on prevention of CDI in adults hospitalized in acute care settings and derived respective recommendations according to the GRADE approach. Recommendations are stratified for both outbreak and endemic settings.

QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: This guidance document provides thirty-six statements on strategies to prevent CDI in acute care settings, including 18 strong recommendations. No recommendation was provided for three questions.

Place, publisher, year, edition, pages
Blackwell Publishing, 2018
National Category
Infectious Medicine Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:oru:diva-69228 (URN)10.1016/j.cmi.2018.02.020 (DOI)000444923000007 ()29505879 (PubMedID)2-s2.0-85045890611 (Scopus ID)
Note

Funding agency:

ESCMID

Available from: 2018-10-04 Created: 2018-10-04 Last updated: 2018-10-04Bibliographically approved
Rizzardi, K., Norén, T., Aspevall, O., Mäkitalo, B., Toepfer, M., Johansson, Å. & Åkerlund, T. (2018). National Surveillance for Clostridioides difficile Infection, Sweden, 2009-2016. Emerging Infectious Diseases, 24(9), 1617-1625
Open this publication in new window or tab >>National Surveillance for Clostridioides difficile Infection, Sweden, 2009-2016
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2018 (English)In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 24, no 9, p. 1617-1625Article in journal (Refereed) Published
Abstract [en]

We report results from a national surveillance program for Clostridioides difficile infection (CDI) in Sweden, where CDI incidence decreased by 22% and the proportion of multidrug-resistant isolates decreased by 80% during 2012-2016. Variation in incidence between counties also diminished during this period, which might be attributable to implementation of nucleic acid amplification testing as the primary diagnostic tool for most laboratories. In contrast to other studies, our study did not indicate increased CDI incidence attributable the introduction of nucleic acid amplification testing. Our results also suggest that successful implementation of hygiene measures is the major cause of the observed incidence decrease. Despite substantial reductions in CDI incidence and prevalence of multidrug-resistant isolates, Sweden still has one of the highest CDI incidence levels in Europe. This finding is unexpected and warrants further investigation, given that Sweden has among the lowest levels of antimicrobial drug use.

Place, publisher, year, edition, pages
Centers for Disease Control and Prevention, 2018
National Category
Infectious Medicine Immunology in the medical area
Identifiers
urn:nbn:se:oru:diva-68762 (URN)10.3201/eid2409.171658 (DOI)000441877400002 ()30124193 (PubMedID)
Funder
Public Health Agency of Sweden
Available from: 2018-09-10 Created: 2018-09-10 Last updated: 2018-09-10Bibliographically approved
Gili, N. J., Norén, T., Törnquist, E., Crafoord, S. & Bäckman, A. (2018). Preoperative preparation of eye with chlorhexidine solution significantly reduces bacterial load prior to 23-gauge vitrectomy in Swedish health care. BMC Ophthalmology, 18, Article ID 167.
Open this publication in new window or tab >>Preoperative preparation of eye with chlorhexidine solution significantly reduces bacterial load prior to 23-gauge vitrectomy in Swedish health care
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2018 (English)In: BMC Ophthalmology, ISSN 1471-2415, E-ISSN 1471-2415, Vol. 18, article id 167Article in journal (Refereed) Published
Abstract [en]

Background: Bacteria in the conjunctiva present a potential risk of vitreous cavity infection during 23-gauge pars plana vitrectomy (PPV). Current preoperative procedures used in Sweden include irrigation with chlorhexidine solution (CHX) 0.05% only and no iodine solutions. We evaluated the bacterial diversity and load before and after this single antibacterial measure.

Methods: In a prospective, consecutive cohort we investigated bacterial growth in samples from 40 eyes in 39 consecutive individuals subjected to vitrectomy. A conjunctival specimen was collected from each preoperative patient before and after irrigating of eye with CHX, 0.05% solution. Iodine was not used during any part of the surgery. One drop of chloramphenicol was administered prior to surgery. Samples from vitreous cavity were collected at the beginning and end of vitrectomy. All conjunctival specimens were cultured for different species and quantified using colony forming units (CFU).

Results: There was a significant 82% reduction in the total number of CFUs for all bacteria in all eyes (P < 0.0001), and 90% reduction for coagulase negative staphylococci (CoNS) alone (P = 0.0002). The number of eyes with positive bacterial growth in conjunctival samples decreased from 33 to 18 after irrigation with CHX (P = 0.0023). The most common bacteria prior to surgery were CoNS (70%), Propionibacterium acnes (55%) and Corynebacterium species (36%). No case of post-vitrectomy endophthalmitis was reported during mean follow-up time, which was 4.6 +/- 2.3 (range; 1.5 to 9) months.

Conclusions: Patients undergoing PPV harbored bacteria in conjunctiva capable of causing post-vitrectomy endophthalmitis. Preoperative preparation with CHX significantly reduced the bacterial load in the conjunctival samples subsequently leading to very low inoculation rates in recovered vitreous samples. Thus, CHX used as a single disinfectant agent might be an effective preoperative procedure for eye surgery in Sweden. This is a relatively small study but the results could be a reference for other intraocular surgeries.

Place, publisher, year, edition, pages
BioMed Central, 2018
Keywords
Conjunctival colonization, chlorhexidine solution, Endophthalmitis, Microorganisms, Small-gauge vitrectomy
National Category
Ophthalmology
Identifiers
urn:nbn:se:oru:diva-68241 (URN)10.1186/s12886-018-0844-9 (DOI)000438213500001 ()29996791 (PubMedID)2-s2.0-85049846037 (Scopus ID)
Note

Funding Agencies:

Örebro University Hospital (Sweden)  

Örebro county Council-Research funds  

Available from: 2018-07-27 Created: 2018-07-27 Last updated: 2018-07-27Bibliographically approved
König, J., Siebenhaar, A., Högenauer, C., Arkkila, P., Nieuwdorp, M., Norén, T., . . . Brummer, R. J. (2017). Consensus report: Faecal microbiota transfer - clinical applications and procedures. Alimentary Pharmacology and Therapeutics, 45(2), 222-239
Open this publication in new window or tab >>Consensus report: Faecal microbiota transfer - clinical applications and procedures
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2017 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 45, no 2, p. 222-239Article in journal (Refereed) Published
Abstract [en]

Background: Faecal microbiota transplantation or transfer (FMT) aims at replacing or reinforcing the gut microbiota of a patient with the microbiota from a healthy donor. Not many controlled or randomised studies have been published evaluating the use of FMT for other diseases than Clostridium difficile infection, making it difficult for clinicians to decide on a suitable indication.

Aim: To provide an expert consensus on current clinical indications, applications and methodological aspects of FMT.

Methods: Well-acknowledged experts from various countries in Europe have contributed to this article. After literature review, consensus has been achieved by repetitive circulation of the statements and the full manuscript among all authors with intermittent adaptation to comments (using a modified Delphi process). Levels of evidence and agreement were rated according to the GRADE system. Consensus was defined a priori as agreement by at least 75% of the authors.

Results: Key recommendations include the use of FMT in recurrent C. difficile infection characterised by at least two previous standard treatments without persistent cure, as well as its consideration in severe and severe-complicated C. difficile infection as an alternative to total colectomy in case of early failure of antimicrobial therapy. FMT in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS) and metabolic syndrome should only be performed in research settings.

Conclusions: Faecal microbiota transplantation or transfer is a promising treatment for a variety of diseases in which the intestinal microbiota is disturbed. For indications other than C. difficile infection, more evidence is needed before more concrete recommendations can be made.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell Publishing Inc., 2017
National Category
Gastroenterology and Hepatology Pharmacology and Toxicology
Identifiers
urn:nbn:se:oru:diva-53881 (URN)10.1111/apt.13868 (DOI)000389441900003 ()27891639 (PubMedID)2-s2.0-85002170778 (Scopus ID)
Note

Funding Agencies:

Seres Therapeutics

AbbVie

Astellas

Biogen

Janssen

MSD

Mundipharma

Takeda Summit Therapeutics

FalkFoundation

Takeda

Available from: 2016-12-12 Created: 2016-12-12 Last updated: 2019-03-26Bibliographically approved
Johansson, K., Karlsson, H. & Norén, T. (2016). Clostridium difficile infection diagnostics: evaluation of the C. DIFF Quik Chek Complete assay, a rapid enzyme immunoassay for detection of toxigenic C. difficile in clinical stool samples. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 124(11), 1016-1020
Open this publication in new window or tab >>Clostridium difficile infection diagnostics: evaluation of the C. DIFF Quik Chek Complete assay, a rapid enzyme immunoassay for detection of toxigenic C. difficile in clinical stool samples
2016 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, no 11, p. 1016-1020Article in journal (Refereed) Published
Abstract [en]

Diagnostic testing for Clostridium difficile infection (CDI) has, in recent years, seen the introduction of rapid dual-EIA (enzyme immunoassay) tests combining species-specific glutamate dehydrogenase (GDH) with toxin A/B. In a prospective study, we compared the C. DIFF Quik Chek Complete test to a combination of selective culture (SC) and loop-mediated isothermal amplification (LAMP) of the toxin A gene. Of 419 specimens, 68 were positive in SC including 62 positive in LAMP (14.7%). The combined EIA yielded 82 GDH positives of which 47 were confirmed toxin A/B positive (11%) corresponding to a sensitivity and specificity of 94% for GDH EIA compared to SC and for toxin A/B EIA a sensitivity of 71% and a specificity of 99% compared to LAMP. Twenty different PCR ribotypes were evenly distributed except for UK 081 where only 25% were toxin A/B positive compared to LAMP. We propose a primary use of a combined GDH toxin A/B EIA permitting a sensitive 1-h result of 379 of 419 (90%, all negatives plus GDH and toxin EIA positives) referred specimens. The remaining 10% being GDH positive should be tested for toxin A/B gene on the same day and positive results left to a final decision by the physician.

Place, publisher, year, edition, pages
Hoboken, NJ, USA: Wiley-Blackwell Publishing Inc., 2016
Keywords
Clostridium difficile, diagnostics, glutamate dehydrogenase, toxin A/B EIA
National Category
Clinical Laboratory Medicine Immunology in the medical area Microbiology in the medical area
Identifiers
urn:nbn:se:oru:diva-52522 (URN)10.1111/apm.12595 (DOI)000388264900014 ()27651167 (PubMedID)2-s2.0-84992088607 (Scopus ID)
Available from: 2016-09-26 Created: 2016-09-26 Last updated: 2018-09-11Bibliographically approved
Säll, O., Johansson, K. & Norén, T. (2015). Low colonization rates of Clostridium difficile among patients and healthcare workers at Örebro University Hospital in Sweden. Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), 123(3), 240-244
Open this publication in new window or tab >>Low colonization rates of Clostridium difficile among patients and healthcare workers at Örebro University Hospital in Sweden
2015 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 123, no 3, p. 240-244Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate the rate of asymptomatic colonization rate of Clostridium difficile among both healthcare workers (HCWs) and patients in a hospital ward in Sweden. In a prospective observational study, asymptomatic HCWs (n=22) (22/60; 37%) attending patients in an infectious disease ward in Sweden participated and were screened once for C. difficile. At the same time, 58 consecutive patients (58/227; 26%) admitted to the same ward were screened for C. difficile, first at admission and thereafter two times weekly. Fecal samples were obtained by rectal swabs and cultured anaerobically using both cycloserine-cefoxitin-fructose agar and enrichment (Cooked Meat broth). All samples were also tested by loop-mediated isothermal amplification and isolates were tested for the presence of toxin A or B by enzyme immunoassay. None of the analyzed fecal samples from HCWs contained C. difficile. Among the patients during a 2-month observational period, three of the 58 patients (5.2%) were culture positive regarding C. difficile on admission and one additional patient became asymptomatically colonized with C. difficile during the hospital stay. Thus, the colonization rates were 0% (0/22) (95% confidence interval (CI): 0-15.4%) among HCWs and 5.2% (3/58) (95% CI: 1.1-14.4%) among patients at admission. As the HCWs were screened only once, we have not studied transient colonization. In conclusion, with observed low colonization rates, we find no support that HCWs would be an important source for C. difficile transmission.

Keywords
Clostridium difficile, healthcare worker, colonization, Clostridium difficile infection, Prevalence
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
urn:nbn:se:oru:diva-43934 (URN)10.1111/apm.12353 (DOI)000350298700009 ()25627981 (PubMedID)2-s2.0-84923481212 (Scopus ID)
Available from: 2015-03-30 Created: 2015-03-30 Last updated: 2018-09-04Bibliographically approved
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