Molecular and epidemiological aspects of Streptococcus pyogenes disease in Finland : Severe infections and bacterial, non-necrotizing cellulitis

Tuula Siljander, Molecular and epidemiological aspects of Streptococcus pyogenes disease in Finland: Severe infections and bacterial, non-necrotizing cellulitis. National Institute for Health and Welfare, Research 23|2009. 160 pages. Helsinki, Finland 2009. ISBN 978-952-245-174-3 (print); ISBN 978-952-245-175-0 (pdf) Background and aims. Streptococcus pyogenes (group A streptococcus, GAS) causes a variety of infections ranging from mild pharyngitis to severe, invasive infections such as bacteraemia. The predominant GAS strains in invasive disease vary over time and geographic region. In 2006, the Finnish nationwide surveillance showed an increase in invasive GAS disease, and clinicians were alarmed by the severe disease manifestations and poor outcome. These events prompted investigation of recent trends in incidence, outcome, and bacterial types. Bacterial, non-necrotizing cellulitis and erysipelas are localised and potentially recurrent infections of the skin. The aim of the study was to identify the β-haemolytic streptococci causing cellulitis and erysipelas infections in Finland. Methods. This study was based on national, population-based surveillance for invasive group A streptococcal (iGAS) disease. A case was defined as S. pyogenes isolated from blood or cerebrospinal fluid. Cases and the corresponding isolates were included during 1995-2007. Case-patients’ 7-day outcome was obtained for 2004-2007. Isolates during 1995-2006 were T serotyped and during 2004-2007 emm typed. Additionally, all serotype T28 isolates since 1995 were emm typed. Isolates of an uncommon type emm84 were characterised by pulsed-field gel electrophoresis (PFGE) and superantigen profiling. Susceptibility to erythromycin, clindamycin and tetracycline was determined for all isolates during 2004-2007 and to levofloxacin during 2005-2007. A case-control study of patients hospitalised for acute non-necrotizing cellulitis was conducted during April 2004-March 2005. Bacterial swab samples were obtained from skin lesions; blood culture samples were taken for detection of bacteraemia. Throat cultures of patients, family members and control subjects were assessed for pharyngeal carrier status. β-haemolytic streptococci and Staphylococcus aureus were isolated and identified; group A and G streptococci were analysed by T and emm typing and PFGE. Results. During 1995-2007, the annual incidence of iGAS disease fluctuated (range by year, 1.1-3.9 cases per 100,000 population) but had an increasing trend, with peaks in 2002 (2.9) and in 2006-2007 (3.1-3.9). During 1998-2007, 1318 cases of iGAS were identified (55% in males), with an average annual incidence of 2.5 cases per 100,000. Males had a higher incidence than females, especially among persons aged 45-64 years, while females had a higher incidence than males among persons aged 25-34 years. Occasional peaks of cases occurred during midwinter and midsummer. During 1995-2007, a total of 1457 iGAS isolates were analysed. The five most prevalent T types during 1995-2006 were T28 (29%), T1 (13%), TB3264 (12%), T12 (7%) and T8 (6%). The most common emm types during 2004-2007 were 28 (21%), 1 (16%), 84 (10%), 75 (7%), and 89 (6%). The prevalence of types T/emm1 and T/emm28 fluctuated during the study, with T/emm1 being the most predominant type in 1997-1998 and 2007 and T/emm28 in 1995-1996 and 20002006. Among T28 isolates, six different emm types were found during 1995-2006, with emm28 predominating. Among emm84 isolates, six PFGE strain types, with one dominating clone were found. Overall, 1.5% of the isolates were resistant to erythromycin, 0.5% to clindamycin and 16% to tetracycline. Females, especially of child-bearing age (15-44 years), had more infections by emm28 than males. The overall 7-day case fatality during 2004-2007 was 8%, peaking in 2005 (12%). Cases with emm1 infections were associated with higher than average case fatality (14%), whereas that of emm84 was 7%, and of emm28 only 2%. A total of 90 patients with acute non-necrotizing cellulitis, 90 control subjects and 38 family members were recruited to a case-control study. β-haemolytic streptococci were isolated from 26 (29%) of 90 patients, either from skin lesions (24 patients) or blood (2 patients). Group G streptococcus (GGS, Streptococcus dysgalactiae subsp. equisimilis) was isolated most commoly (22%), followed by GAS (7%). GGS was also carried in the pharynx of 7% of patients and 13% of household members but was missing in control subjects. Several emm and PFGE types were found among the isolates. Six patients (7%) had recurrent infections during the study. In two patients, the same strain of GGS with identical emm and PFGE types was isolated from two consecutive episodes. Conclusions. The incidence of iGAS disease had an increasing trend during the past ten years in Finland. Ageand sex-specific differences in the incidence rate and seasonal patterns were observed, and presumably differences in the predisposing factors and underlying conditions contribute to these distinctions. Changes in the emm type prevalence were associated with the increase in incidence and case fatality. The case fatality rate for S. pyogenes infections remained at a reasonably low level (8% overall) compared to that of other developed countries (mostly exceeding 10%). emm typing is sufficient for general epidemiological surveillance of iGAS disease, but for cluster or outbreak investigations, higher discriminatory power can be achieved when it is complemented by other techniques, such as PFGE. In the case-control study, unexpectedly GGS, instead of GAS, predominated in acute non-necrotizing cellulitis. A predominance of GGS was also seen in the throat of case-patients and their family members, but not in control subjects. No clear predominance of a specific emm type was seen. The recurrent nature of cellulitis became evident. This study adds to our understanding of the molecular epidemiology of S. pyogenes infections in Finland and provides a basis for comparison to other countries and future trends. Global emm type and outcome surveillance remain important in order to detect changes in the type distribution potentially leading to increasing incidence and case fatality.