KRISTINA TRELL FACULTY of MEDICINE | LUND UNIVERSITY Department of Clinical Sciences Division of Infection Medicine
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Clinical and molecular studies of -haemolytic streptococci Trell, Kristina 2019 Document Version: Publisher's PDF, also known as Version of record Link to publication Citation for published version (APA): Trell, K. (2019). Clinical and molecular studies of β-haemolytic streptococci. Lund University: Faculty of Medicine. 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LUND UNIVERSITY PO Box 117 221 00 Lund +46 46-222 00 00 Clinical and molecular studies of β-haemolytic streptococci Trell, Kristina 2019 Document Version: Publisher's PDF, also known as Version of record Link to publication Citation for published version (APA): Trell, K. (2019). Clinical and molecular studies of β-haemolytic streptococci. Lund: Lund University, Faculty of Medicine. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. LUND UNIVERSITY PO Box 117 221 00 Lund +46 46-222 00 00 Clinical and molecular studies of ß-haemolytic streptococci KRISTINA TRELL FACULTY OF MEDICINE | LUND UNIVERSITY Department of Clinical Sciences Division of Infection Medicine Lund University, Faculty of Medicine 198407 Doctoral Dissertation Series 2019:111 ISBN 978-91-7619-840-7 789176 ISSN 1652-8220 9 Clinical and molecular studies of β-haemolytic streptococci Kristina Trell DOCTORAL DISSERTATION With due permission of the Faculty of Medicine, Lund University, Sweden. To be defended in Belfragesalen, BMC D15, on November 15th 2019 at 09:00. Faculty opponent Steinar Skrede University of Bergen, Norway Organization Document name LUND UNIVERSITY Doctoral dissertation Department of Clinical Sciences Date of issue Division of Infection Medicine November 15th 2019 Author(s) Kristina Trell Sponsoring organization Title and subtitle Clinical and molecular studies of β-haemolytic streptococci Abstract Beta-haemolytic streptococci (BHS) are important causes of human infections and they have traditionally been grouped according to Lancefield antigens. The spectrum of infections caused by BHS includes pharyngitis, skin infections, bacteraemia/sepsis, endocarditis, septic arthritis and meningitis. The most studied BHS is the group A Streptococcus (GAS), which concurs with the species Streptococcus pyogenes (SP). In the last decades, several studies have shown an increase of invasive infections caused by beta-haemolytic streptococci group C (GCS) and group G (GGS). GCS and GGS cause clinical disease similar to GAS. The vast majority of clinical isolates associated with human infections, that are identified as GCS and GGS belong to the species Streptococcus dysgalactiae (SD). With the introduction of Matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) in routine diagnostics, it became possible to determine species of GGS and GCS. GCS and GGS exhibit the M-protein, a known virulence factor in GAS infections. The M-protein is encoded by the emm-gene and sequencing of this gene can be used for typing purposes. In the first study, isolates of GCS and GGS from different sites of isolation (throat, wound, and blood) were species determined and emm-typed to investigate if certain types have a predilection to cause particular infections. We found that GCS and GGS express different emm-types and that GCS and GGS from different sites of isolation were similar, suggesting that emm-types are not associated to certain disease presentations. In the second study, subjects with recurrent bacteraemia with GCS and GGS were identified and compared to controls with only one episode of bacteraemia to detect risk factors for recurrence. In the 23 patients with recurrent episodes of SD bacteraemia, most recurrences were caused by the same emm-type suggesting a host-specific colonization. In addition, no specific emm-types or other clinical factors were significantly associated with recurrences. Among GCS causing human infections, isolates of Streptococcus equi (SE) have been found. In the third study, the clinical course of patients with bacteraemia with SE was described and the isolates were typed through sequencing of the gene encoding the M-like protein SzP. Eighteen cases of SE were found during a thirteen-year period, which confirms that SE is a rare cause of infection in humans. No temporal or geographical clustering was found in our material. Our study also indicated that sporadic cases of SE bacteraemia have a favourable prognosis. In the fourth work, we investigated the possibility of using cultures for diagnostic purposes by determining the perianal colonization with BHS in patients with erysipelas compared with a control group. In the group with erysipelas, 44% of the patients were colonized with BHS compared with 4 % of the patients in the control group. The BHS found were most commonly GGS and when subjected to MALDI-TOF MS, these were found to be SD. We concluded that SD colonizes the perianal area in a substantial proportion of patients with erysipelas. SP is a well-known cause of postpartum infections and is still causing significant morbidity and mortality worldwide. In the final study, we described the use of whole genome sequencing (WGS) to investigate an outbreak of postpartum SP emm75 infections related to an asymptomatic carrier working in a maternity ward. Source identification and WGS proved to be vital for outbreak control. Key words Beta-haemolytic streptococci, Streptococcus dysgalactiae, MALDI-TOF MS, Streptococcus equi, Streptococcus pyogenes, Erysipelas, Endometritis Classification system and/or index terms (if any) Supplementary bibliographical information Language English ISSN 1652-8220 Lund University, Faculty of Medicine Doctoral ISBN 978-91-7619-840-7 Dissertation Series 2019:111 Recipient’s notes Number of pages 76 Price Security classification I, the undersigned, being the copyright owner of the abstract of the above-mentioned dissertation, hereby grant to all reference sources permission to publish and disseminate the abstract of the above-mentioned dissertation. Signature Date 2019-10-18 Clinical and molecular studies of β-haemolytic streptococci Kristina Trell Kristina Trell Division of Infection Medicine Department of Clinical Sciences Faculty of Medicine Lund University Biomedical Center, B14 Tornavägen 10 221 84 Lund Sweden Email: [email protected] The cover photo is a modified version of a pus specimen with Streptococcus pyogenes from the CDC photo bank Copyright Kristina Trell Paper 1 © Publisher Paper 2 © Publisher Paper 3 © Publisher Paper 4 © Publisher Paper 5 © by the Authors (Manuscript unpublished) Faculty of Medicine Department of Clinical Sciences, Lund ISBN 78-91-7619-840-7 ISSN 1652-8220 Lund University, Faculty of Medicine Doctoral Dissertation Series 2019:111 Printed in Sweden by Media-Tryck, Lund University, 2019 To my family Table of Contents List of papers ............................................................................................................ 9 Abbreviations ......................................................................................................... 11 Abstract .................................................................................................................. 13 Introduction ............................................................................................................ 15 Brief history of β-haemolytic streptococci ........................................................ 15 Methods for identification and typing of β-haemolytic streptococci ............... 16 Phenotypic methods for identification ..................................................................... 16 16S rRNA ................................................................................................................ 17 MALDI-TOF MS .................................................................................................... 17 Emm- and SzP-typing .............................................................................................