A Population-based Study of Beta-hemolytic Streptococcal Bacteremia: Epidemiological, clinical and molecular characteristics

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dc.contributor.author Rantala, Sari -
dc.date.accessioned 2012-12-03T12:08:43Z
dc.date.available 2012-12-03T12:08:43Z
dc.date.issued 2012 -
dc.identifier.isbn 978-951-44-8714-9 -
dc.identifier.uri http://tampub.uta.fi/handle/10024/66868
dc.description.abstract Beetahemolyyttisten streptokokkien aiheuttamat verenmyrkytykset: epidemiologiaa, kliinisiä ja molekyyliepidemiologisia ominaispiirteitä Beetahemolyyttisiä streptokokkeja ovat Lancefield-ryhmän A- streptokokki eli Streptococcus pyogenes, Lancefield-ryhmän B- streptokokki eli Streptococcus agalactiae, sekä Lancefield-ryhmän C- ja G-streptokokit. Viimeisten tutkimusten mukaan isopesäkkeiset C-ja G ryhmän streptokokit on luokiteltu Streptococcus dysgalactiae subsp. equisimilis-nimiseksi bakteeriksi. Beetahemolyyttiset streptokokit aiheuttavat mm. nielu- ja iho-infektioita ja verenmyrkytyksiä. M-proteiini on bakteerin tärkein virulenssitekijä. M-proteiinia koodaavan geenin sekvenssointiin perustuvaa tyypitystä (emm-tyypitys) käytetään epidemiologisessa tutkimuksessa. Emm-geeni tyypityksellä on A-streptokokilla tunnistettu noin 150 emm tyyppiä ja G-streptokokilla noin 50 emm tyyppiä. Tutkimus perustui väestöpohjaiseen beetahemolyyttisten streptokokkien aiheuttamien verenmyrkytysten seurantaan aikuisilla. Väitöstutkimuksessa selvitettiin retrospektiivisesti sairauskertomuksista 10 vuoden ajalta (v.1995-2004) beetahemolyyttisten streptokokkien aiheuttamien verenmyrkytysten riskitekijöitä, taudinkuvaa ja ennustetta Pirkanmaalla Suomessa. Tapausmääritelmänä oli veren positiivinen A-, B-, C- tai G-ryhmän beetahemolyyttinen streptokokkiviljelylöydös ja kliininen verenmyrkytyksen taudinkuva. Potilaita oli yhteensä 309 ja bakteremiaepisodeja 314. Tutkimuksessa selvitettiin eri emm tyyppien merkitystä verenmyrkytyksen vaikeusasteeseen ja tappavuuteen. Kaikki A-, C- ja G- ryhmän veriviljelykannat emm-tyypitettiin. Harvinaisille Streptococcus dysgalactiae subsp. equisimilis kannoille ja kannoille, joille emm tyyppiä ei saatu määritettyä, tehtiin pulssikenttä-geelielektroforeesi (PFGE)-tyypitys. S. pyogenes kannoille tehtiin superantigeenien määritys. Väitöstutkimuksessa havaittiin G-streptokokin aiheuttamien verenmyrkytysten ilmaantuvuuden suureneminen Pirkanmaalla. Ihorikot altistavat A- ja G-streptokokin aiheuttamille verenmyrkytyksille ja ihoinfektiot olivat tärkein infektion lähtökohta A- ja G-streptokokin aiheuttamissa verenmyrkytyksissä. Tutkimuksessa todettiin myös, että aiempi ruusuinfektio näytti suojaavan kuolemalta beetahemolyyttisissä verenmyrkytyksessä. Selluliitti infektion lähtökohtana liittyy hyvään ennusteeseen. Kuumeen esiintyminen parantaa ennustetta. Alkoholismi, vaikea perustauti, matala leukosyyttitaso ja korkea plasman C-reaktiivinen proteiini (CRP)- taso lisäsivät kuolemanvaaraa. Streptococcus dysgalactiae subsp. equisimilis (C- ja G-streptokokki) verenmyrkytyksessä todettiin harvinaisten emm-tyyppien liittyvän suurempaan tappavuuteen (3- kertainen vaara) ja vaikeampaan taudinkuvaan (4-kertainen vaara). C- ja G-streptokokkin aiheuttamissa verenmyrkytyksessä iho-ja pehmytkudosinfektioita kuten esim. selluliittia esiintyi tilastollisesti enemmän yleisten emm-tyyppien aiheuttamissa infektioissa. A-streptokokin emm-tyyppien, superantigeenien ja infektion lähtökohdan välillä ei todettu yhteyttä. Nykyinen kehitteillä oleva A-streptokokkirokote kattaa vain 62%:a verenmyrkytyksiä aiheuttavista emm-tyypeistä Pirkanmaalla. fi
dc.description.abstract A Population-based Study of Beta-hemolytic Streptococcal Bacteremia: Epidemiological, clinical and molecular characteristics Background and aims. The serogroups A (Streptococcus pyogenes, GAS), B (Streptococcus agalactiae, GBS), C and G (GCS and GGS) are generally defined as beta-hemolytic streptococci. Human large colony-forming groups C and G streptococci are now classified as S. dysgalactiae subsp. equisimilis. Beta-hemolytic streptococci cause a variety of infections ranging from mild pharyngitis and skin and soft-tissue infections to severe life-threatening infections such as bacteremia, streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF). The most common presenting clinical manifestations are infections of skin and soft-tissue, respiratory, urinary, intestinal or genital tract. S. pyogenes and S. dysgalactiae subsp. equisimilis share virulence factors. The M protein is a major virulence factor in that it confers resistance to phagocytosis. The classical M-protein serological typing was largely replaced in the late 1990s by sequence-based typing of the emm-gene encoding for the M protein. Based on the variability of the N-terminal end of the emm gene, as many as 150 defined emm types are recognized among S pyogenes isolates, and more than 50 sequence types presently described among S. dysgalactiae subsp. equisimilis isolates, respectively. The first aim of the present study was to determine the predisposing factors, clinical presentations and outcome in beta-hemolytic streptococcal bacteremia in the Pirkanmaa area, Finland. The second aim was to determine emm types of S. dysgalactiae subsp. equisimilis and S. pyogenes bacteremic isolates and the relation of emm types to the severity of bacteremia. Methods. This study was based on population-wide surveillance for beta-hemolytic streptococcal bacteremia in adults. The predisposing factors, clinical presentations and outcome in beta-hemolytic streptococcal bacteremia during the 10-year observation period (1995-2004) in Pirkanmaa, Finland, was studied retrospectively. A case was defined as a positive blood culture for group A, B, C or G beta-hemolytic streptococci. The number of patients was 309 and the number of bacteremia episodes was 314. All risk factors associated with severe disease and mortality were analyzed. S. pyogenes and S. dysgalactiae subsp. equisimilis isolates were emm-typed. Non-typable S. dysgalactiae subsp. equisimilis strains and strains isolated from patients with recurrent GGS bacteremia were characterized using pulsed field gel electrophoresis (PFGE). Isolates of S. pyogenes were superantigen profiled. Results. The incidence of GGS bacteremia increased statistically significantly during the study period (p=0.013). Skin infections as the presenting manifestation were particularly common in patients with GAS and GGS bacteremia. A history of previous cellulitis seemed to be a protecting factor against death (p=0.014). Fever was associated with a good prognosis. Alcoholism, ultimately or rapidly fatal underlying disease, high plasma C-reactive protein (CRP) level and leukopenia on admission predicted a poor outcome. StG480, stG6, stG485, stG643, stC6979, stG166b and stC74a were the seven most common emm types, covering 75 % of S. dysgalactiae subsp. equisimilis isolates. The mortality (p=0.01) and severity of the disease (p=0.001) were higher in S. dysgalactiae subsp. equisimilis bacteremia caused by rare emm types than those caused by common types. Skin and soft-tissue infections such as cellulitis were significantly more frequent clinical manifestations in episodes caused by common than rare types (p=0.007). No association was found between emm type, underlying diseases and disease manifestations of S. pyogenes bacteremia. No association was found between single SAg genes and presenting clinical manifestations of S. pyogenes infections. The putative 26-valent GAS vaccine could have covered 62% of the isolates causing invasive disease in the Pirkanmaa Health District during the study period. Conclusions. The incidence of GGS bacteremia was increasing in Pirkanmaa, Finland, during 1995-2004. A similar trend in incidence has also been noted in Denmark. Disruption of the cutaneous barrier as a predisposing factor and skin infections as a presenting infection focus were particularly common in patients with GAS and GGS bacteremia. A history of previous cellulitis seemed to be a protecting factor against death (p=0.014). Also cellulitis as the presenting clinical manifestation predicted a favourable outcome. Confusion, a lowered level of consciousness or dyspnea as the first sign or symptom were markers of a poor prognosis, while fever seemed to be a protecting factor against death. Alcoholism, ultimately or rapidly fatal underlying disease, high plasma CRP level and leukopenia on admission implied a poor prognosis. It is important to identify factors associated with a poor prognosis in order to find patients most likely to benefit from possible preventive measures as well as needing more intensive therapeutic regimens. The mortality (p=0.01) and severity of the disease (p=0.001) were higher in S. dysgalactiae subsp. equisimilis bacteremia caused by rare emm types as against common types. Skin and soft-tissue infections such as cellulitis were significantly more frequent clinical manifestations among common than among rare emm types (p=0.007). No associations between GAS emm types, SAg genes and disease manifestations were observed. The current formulation of GAS vaccine would provide only limited coverage of GAS emm types in Finland. en
dc.language.iso en -
dc.publisher Tampere University Press -
dc.relation.isformatof 978-951-44-8713-2 -
dc.title A Population-based Study of Beta-hemolytic Streptococcal Bacteremia: Epidemiological, clinical and molecular characteristics -
dc.type.ontasot fi=Väitöskirja | en=Doctoral dissertation| -
dc.identifier.urn urn:isbn:978-951-44-8714-9 -
dc.relation.numberinseries 1701 -
dc.seriesname Acta Universitatis Tamperensis -
dc.administrativeunit fi=Lääketieteen yksikkö | en=School of Medicine| -
dc.oldstats 64 -
dc.seriesname.electronic Acta Electronica Universitatis Tamperensis -
dc.relation.numberinserieselectronic 1167 -
dc.publisher.electronic Tampere University Press -
dc.subject.study Sisätautioppi / Infektiotaudit - Internal Medicine / Infectious Diseases -
dc.date.dissertation 2012-03-09 -
dc.onsale 1 -

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