Distribution of <Emphasis Type="Italic">emm</Emphasis> types in invasive and non-invasive group A and G streptococci

Our study describes the emm type distributions of invasive and non-invasive group A streptococci (GAS) and group G streptococci (GGS) strains in one of the biggest Health Districts in Finland. A total of 571 GAS or GGS were recovered from patients with invasive or non-invasive infections during a 1-year period in 2008–2009 in Pirkanmaa Health District in Finland. We describe here the emm type distributions of GAS and GGS collected from throat (n = 246), pus (n = 217), deep tissue (n = 56) and blood (n = 52). The most common emm types among GAS were emm77, emm1, emm28, emm89 and emm12. Among GGS, the most common emm types were stG480, stG643, stG6, stC6979 and stG485. Some emm types were found to associate with certain infection focus. In GAS, emm77 associated with pus isolates, whereas emm1 and emm12 were more frequent among throat isolates. In GGS, stG480 was more commonly found from throat isolates.     

Molecular characterisation of invasive <Emphasis Type="Italic">Streptococcus pyogenes</Emphasis> isolates from Hungary obtained in 2004 and 2005

Our aim was to characterise by molecular techniques group A streptococci isolated from invasive infections in Hungary in 2004–2005. Twenty-six nonduplicate invasive GAS isolates were selected and examined. The mortality rate proved high (52.3%) for those cases (n = 21) where data were available. Predominant emm types were emm1 (n = 13, 50%) and emm80 (n = 5, 19.2%), but other M types (emm4, emm28, emm66, emm81.1, emm82, emm84) were also identified. Eight different PFGE types were distinguished, and each emm type showed an individual PFGE pattern. Our results show that—similarly to results obtained in several other countries—emm type 1 strains predominate among invasive GAS isolates, and that emm 1 type strains recovered from severe streptococcal infections were associated with the presence of the speA gene. The rate for macrolide resistance proved low: only two isolates showed elevated MICs for erythromycin.     

emm gene diversity, superantigen gene profiles and presence of SlaA among clinical isolates of group A, C and G streptococci from western Norway

In order to investigate molecular characteristics of beta-hemolytic streptococcal isolates from western Norway, we analysed the entire emm gene sequences, obtained superantigen gene profiles and determined the prevalence of the gene encoding streptococcal phospholipase A2 (SlaA) of 165 non-invasive and 34 contemporary invasive group A, C and G streptococci (GAS, GCS and GGS). Among the 25 GAS and 26 GCS/GGS emm subtypes identified, only emm3.1 was significantly associated with invasive disease. M protein size variation within GAS and GCS/GGS emm types was frequently identified. Two non-invasive and one invasive GGS possessed emm genes that translated to truncated M proteins as a result of frameshift mutations. Results suggestive of recombinations between emm or emm-like gene segments were found in isolates of emm4 and stG485 types. One non-invasive GGS possessed speC, speG, speH, speI and smeZ, and another non-invasive GGS harboured SlaA. speA and SlaA were over-represented among invasive GAS, probably because they were associated with emm3. speG ^dys was identified in 83% of invasive and 63% of non-invasive GCS/GGS and correlated with certain emm subtypes. Our results indicate the invasive potential of isolates belonging to emm3, and show substantial emm gene diversity and possible lateral gene transfers in our streptococcal population.     

Streptococcus pyogenes bacteraemia, emm types and superantigen profiles

The aim of this study was to investigate the emm types and superantigen profiles of bacteraemic group A streptococcal (GAS; Streptococcus pyogenes) isolates and to detect possible associations between the molecular characteristics of isolates and the clinical presentations of disease. In this population-based study, 87 bacteraemic GAS isolates from adult patients in Pirkanmaa Health District (HD), Finland, during the period 1995–2004 were emm typed and genotyped for superantigen (SAg) profiles. The epidemiological and clinical data of the patients were analysed with the microbiological characterisation data. Among the 87 isolates, 18 different emm types were found. emm1, emm28 and emm81 were the three most common types, covering 52% of isolates. The prevalence of specific emm types showed high variability during the 10-year study period. We could not find any association between the emm type and clinical features of bacteraemic infection, such as underlying diseases, disease manifestations or case fatality. Of nine superantigen genes examined, speA and speC were identified in 20 and 30% of the strains, respectively. No association was found between disease manifestation and the presence of single superantigen genes. The 26-valent GAS vaccine would have covered only 62% of isolates causing invasive disease in Pirkanmaa HD during the study period.     

Epidemiological and molecular analysis of Streptococcus pyogenes isolates causing invasive disease in Spain (1998–2009): comparison with non-invasive isolates

The incidence, clinical manifestations, and circulating clones involved in Streptococcus pyogenes invasive disease was analyzed in two regions of Spain between 1998 and 2009. The annual average incidence of invasive disease was 2 episodes per 100,000 inhabitants (3.1 for children and 1.9 for adults). The most frequent clinical manifestations were cellulitis (41.3%), bacteremia without focus (19.0%), streptococcal toxic shock syndrome (12.6%), and pneumonia (7.7%). Among 247 invasive isolates analyzed, the most prevalent clones were emm1/ST28 (27.9%), emm3/ST15-406 (9.8%), and emm4/ST39 (6.5%). The emm1/ST28 clone was the only clone detected each year throughout the study period and was associated with more than one third of all fatal outcomes. When invasive isolates were compared with 1,189 non-invasive isolates, the emm1/ST28 clone was significantly associated with invasive disease. The speA and ssa genes were more frequent among invasive emm1 and emm4 isolates, respectively. Forty-two (17%) invasive isolates were resistant to erythromycin (21 harbored the mef gene and 21 the ermB or ermA genes). Twenty-two (8.9%) isolates had reduced susceptibility to ciprofloxacin (minimum inhibitory concentration [MIC] 2–8 μg/mL) and 32 (13%) were tetracycline-resistant (tetM or tetO gene). In conclusion, the emm1 type was overrepresented among invasive cases and was associated with high mortality rates.     

Molecular characteristics of pharyngeal and invasive emm3 Streptococcus pyogenes strains from Norway, 1988–2003

A major virulence factor of group A streptococci (GAS) is the M protein. Strains with the M3 type are more often associated with necrotizing fasciitis (NF) and streptococcal toxic shock syndrome, and have a higher case fatality rate than strains of other M types. To better understand the epidemiology of M3 GAS strains in Norway, we analyzed 59 invasive and 69 pharyngeal isolates with respect to prophage content, allelic variation in emm3, mtsR encoding the metal transporter of Streptococcus repressor (mtsR), and sclB coding for streptococcal collagen-like protein B. The Norwegian emm3 strains were very homogeneous, mainly harboring the emm allele 3.1 and prophage profile ΦG3.01. Other prophage profiles were transient. The mutation in mtsR known to truncate the protein and result in decreased capacity to cause NF was not found in our isolates. The sclB gene usually harbored five or eight contiguous repeats of a CAAAA pentanucleotide sequence and a highly modular and variable collagen structural motif (CSM) region with 9 and 12 amino acid M3-specific conserved motif repeats distributed across the entire CSM region. Strains with 5 CAAAA repeats emerged in 1993 and these strains were associated with the increase in invasive M3 cases in the period 1993–2003.     

Epidemiology Analysis of Streptococcus pyogenes in a Hospital in Southern Taiwan by Use of the Updated emm Cluster Typing System

emm typing is the most widely used molecular typing method for the human pathogen Streptococcus pyogenes (group A streptococcus [GAS]). emm typing is based on a small variable region of the emm gene; however, the emm cluster typing system defines GAS types according to the nearly complete sequence of the emm gene. Therefore, emm cluster typing is considered to provide more information regarding the functional and structural properties of M proteins in different emm types of GAS. In the present study, 677 isolates collected between 1994 and 2008 in a hospital in southern Taiwan were analyzed by the emm cluster typing system. emm clusters A-C4, E1, E6, and A-C3 were the most prevalent emm cluster types and accounted for 67.4% of total isolates. emm clusters A-C4 and E1 were associated with noninvasive diseases, whereas E6 was significantly associated with both invasive and noninvasive manifestations. In addition, emm clusters D4, E2, and E3 were significantly associated with invasive manifestations. Furthermore, we found that the functional properties of M protein, including low fibrinogen-binding and high IgG-binding activities, were correlated significantly with invasive manifestations. In summary, the present study provides updated epidemiological information on GAS emm cluster types in southern Taiwan.     

Description of macrolide-resistant and potential virulent clones of Streptococcus pyogenes causing asymptomatic colonization during 2000–2006 in the Lisbon area

The asymptomatic oropharyngeal colonization rate by Streptococcus pyogenes was 10.7% in children (901 among 8,405 children 0–16 years old) and 3.3% in adults (37 among 1,126 households of children) in the Lisbon area during 2000–2006. Macrolide-resistant S. pyogenes from children (n = 149) was variable with time: 9.8–10.7% in 2000–2002, 28.1% in 2003, 19.6–2.7% in 2004–2005 and 14.6% in 2006. Eight lineages (97.3% of isolates) were identified based on at least 80% similarity of PFGE patterns, T types, emm types and multilocus sequence types (ST). The elevated frequency of macrolide resistance was associated with M phenotype lineages I (emm12/ST36) and V (emm4, emm75/ST39 and a novel emmstMrp6 type) and with one cMLS_B lineage IV (emm28/ST52) known to be associated with upper respiratory tract and invasive infections. Significant associations (p < 0.05) between emm type/virulence genotype were found, such as emm1/speA ⁺ ssa ^-, emm4/ssa ⁺ prtF1 ⁺, emm12/speA ^- ssa ^-. The high prevalence (>20%) of speC, prtF1 or ssa was probably caused either by clonal dissemination (speC), or to horizontal gene transfer events (prtF1 and ssa). This report contributes to a better understanding of the molecular epidemiology and evolution of macrolide-resistant S. pyogenes causing symptom-free oropharyngeal colonization. These colonizing strains carry macrolide resistance and virulence genes capable of being transferred to other bacterial species sharing the same niche.     

Epidemiology and Molecular Characterization of Macrolide-Resistant Streptococcus pyogenes in Taiwan

Our multicenter nationwide surveillance data indicated that erythromycin (ERY) resistance among group A Streptococcus (GAS) isolates in Taiwan declined from 53.1% in 1998 and 2000 to 14.6% in 2002 and 2004 and 10.7% in 2006 to 2010 (P < 0.01). The present study aimed to assess the epidemiology of GAS in Taiwan and identify factors associated with ERY resistance. All 127 ERY-resistant (ERY^r) isolates and 128 randomly selected ERY-susceptible (ERY^s) isolates recovered from 1998 to 2010 were emm typed. ERY^r isolates were also characterized by ERY resistance phenotype and mechanisms and pulsed-field gel electrophoresis (PFGE). Multilocus sequence typing was performed on selected ERY^r isolates. The predominant emm types in ERY^r isolates were emm22 (n = 33, 26.0%), emm12 (n = 24, 18.9%), emm4 (n = 21, 16.5%), and emm106 (n = 15, 11.8%). In ERY^s isolates, emm12 (n = 27, 21.9%), emm1 (n = 18, 14.1%), emm106 (n = 16, 12.5%), and emm11 (n = 9, 7.1%) predominated. The most common ERY resistance phenotype was the M phenotype (resistant to macrolides) (70.9%), with all but one isolate carrying mef(A), followed by the constitutive macrolide-lincosamide-streptogramin B resistance (cMLS_B) phenotype (26.8%), with isolates carrying erm(B) or erm(TR). ERY^r isolates of the emm12-sequence type 36 (ST36) lineage with the cMLS_B phenotype were mostly present before 2004, while those of the emm22-ST46 lineage with the M phenotype predominated in later years. Recovery from respiratory (throat swab) specimens was an independent factor associated with ERY resistance. emm1 and emm11 GAS isolates were significantly associated with ERY^s, while emm22 was detected only in ERY^r GAS. In addition, emm106 isolates were prevalent among the abscess/pus isolates, whereas emm12 isolates were strongly associated with a respiratory (throat) origin. In addition to identifying factors associated with ERY resistance in GAS, our study provides helpful information on the changing GAS epidemiology in Taiwan.     

Epidemiology, outcome and emm types of invasive group A streptococcal infections in Finland

In 2006, Finnish nationwide surveillance showed an increase of invasive group A streptococcal (iGAS) disease and clinicians were alarmed by severe disease manifestations, prompting the investigation of recent trends and outcome for iGAS. A case of iGAS was defined as Streptococcus pyogenes isolated from blood or cerebrospinal fluid. Cases during 1998–2007 and isolates during 2004–2007 were included. Case-patients’ 7-day outcome was available for 2004–2007. Isolates were emm typed. A total of 1,318 cases of iGAS were identified. The average annual incidence was 2.5/100,000 population. The rate was higher in males than females in persons aged 45–64 years, but lower in persons aged 25–34 years. The annual incidence was highest in 2007 (3.9/100,000). Occasional peaks occurred during midwinter and midsummer. The most common emm types were 28 (21%), 1 (16%), 84 (10%), 75 (7%) and 89 (6%). During 2004–2007, emm1 replaced emm28 as the most predominant type. The overall case fatality was 8%. Cases with emm1 were associated with high case fatality (14% vs. 8% in other types; p < 0.02); that of emm28 infections was 2% (p < 0.01). Changes in emm type prevalence influenced incidence and case fatality. Differences in age- and sex-specific incidence and seasonal patterns suggest variations in predisposing factors and underlying conditions.     

Epidemiological markers of Streptococcus pyogenes strains in Tunisia

To further understand the epidemiology of Streptococcus pyogenes or group A streptococcus (GAS) infections in Tunisia, phenotypic and genomic markers of GAS isolates, including antibiotic susceptibility, biotypes, T and emm types and toxin gene profiles, have been characterized. A total of 103 isolates, collected between 2000 and 2006, were investigated; 47 were recovered from invasive infections, and 56 from non-invasive infections. Rates of tesistance to tetracycline, erythromycin, clindamycin and rifampin were 70.8%, 4.8%, 4.8% and 0.9%, respectively. High levels of resistance to streptomycin and kanamycin were observed in 1.9% and 4.8% of isolates, respectively. Biotype 3 was most common. Twenty different T patterns were observed, with a predominance of T3/13/B3264, and 38 different emm types. In both invasive and non-invasive isolates, emm118 (9.7%), emm42 (8.7%), emm1 (7.8%), st432 (6.8%), emm28 (5.8%) and emm76 (5.8%) were the most prevalent types; emm1, emm76 and emm18 were mainly observed among invasive infections, whereas emm118 (12.5%), emm42 (10.7%) and emm28 (8.9%) were predominant among non-invasive infections. The speB gene was detected in all isolates, but there were variable frequencies of speA, speC and ssa (20.3%, 32% and 25.2% respectively). Significant associations of emm1, emm18 and emm3 with speA and of emm4 and st432 with ssa were found. This first report from Tunisia revealed a unique emm distribution of GAS that differs from those of other regions. This information on the distribution of such emm types will be useful for the development of an appropriate vaccine in a country where the incidence of rheumatic fever remains high.     

Epidemiology of Invasive Group A Streptococcal Disease in Alaska, 2001 to 2013

The Arctic Investigations Program (AIP) began surveillance for invasive group A streptococcal (GAS) infections in Alaska in 2000 as part of the invasive bacterial diseases population-based laboratory surveillance program. Between 2001 and 2013, there were 516 cases of GAS infection reported, for an overall annual incidence of 5.8 cases per 100,000 persons with 56 deaths (case fatality rate, 10.7%). Of the 516 confirmed cases of invasive GAS infection, 422 (82%) had isolates available for laboratory analysis. All isolates were susceptible to penicillin, cefotaxime, and levofloxacin. Resistance to tetracycline, erythromycin, and clindamycin was seen in 11% (n = 8), 5.8% (n = 20), and 1.2% (n = 4) of the isolates, respectively. A total of 51 emm types were identified, of which emm1 (11.1%) was the most prevalent, followed by emm82 (8.8%), emm49 (7.8%), emm12 and emm3 (6.6% each), emm89 (6.2%), emm108 (5.5%), emm28 (4.7%), emm92 (4%), and emm41 (3.8%). The five most common emm types accounted for 41% of isolates. The emm types in the proposed 26-valent and 30-valent vaccines accounted for 56% and 78% of all cases, respectively. GAS remains an important cause of invasive bacterial disease in Alaska. Continued surveillance of GAS infections will help improve understanding of the epidemiology of invasive disease, with an impact on disease control, notification of outbreaks, and vaccine development.     

Distribution of emm genotypes in group A streptococcus isolates of Korean children from 2012 to 2019

ObjectivesChanges in the epidemiology of group A streptococcus (GAS) infection is related to emm genotype. We studied the distribution of emm genotypes and their antibiotic susceptibility among Korean children.MethodsIsolates from children with GAS infection between 2012 and 2019 were collected. emm typing and cluster analysis was performed according to the Centers for Disease Control emm cluster classification. Antimicrobial susceptibility was tested using the E-test and resistance genes were analyzed for macrolide resistant phenotypes.ResultsAmong 169 GAS isolates, 115 were from children with scarlet fever. Among invasive isolates, emm1 (6/22, 27.3%), emm12 (4/22, 18.2%), and emm4 (4/22, 18.2%) were most common. In scarlet fever, although emm4 (38/115, 33.0%) was the most prevalent throughout the study period, emm4 was replaced by emm3 (28/90, 31.1%) during an outbreak in 2017–2018. Among all isolates, only 2 (1.2%) exhibited erythromycin resistance and harbored both ermA and ermB genes.ConclusionsIn this analysis of GAS isolated from Korean children, emm1 was the most prevalent in invasive infection. In scarlet fever, emm4 was prevalent throughout the study period, with an increase in emm3 during 2017–2018. GAS isolates during 2012–2019 demonstrated low erythromycin resistance.     

Clinical and epidemiological aspects of invasive Streptococcus pyogenes infections in Denmark during 2003 and 2004

Active surveillance of invasive group A streptococcal (GAS) infections was conducted in Denmark during 2003 and 2004 as a part of the Strep-EURO initiative. The main objective was to improve understanding of the epidemiology of invasive GAS disease in Denmark. During the 2 years, 278 cases were reported, corresponding to a mean annual incidence of 2.6 cases per 100,000 inhabitants. The vast majority of isolates, 253 (91%), were from blood, with the remaining 25 (9%) being from cerebrospinal fluid, joints, or other normally sterile sites. The mean case fatality rate (CFR) was 20%, with the rate being higher in patients more than 70 years of age (36.5%). For streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis the CFRs were 53% and 25%, respectively. Out of 16 T types recorded, three predominated: T28 (23%), T1 (22%), and the cluster T3/13/B3264 (14%). Among 29 different emm types, emm28 and emm1 accounted for 51% of strains, followed by emm3 (11%), emm89 (7%), and emm12 (5.5%). Low resistance rates were detected for macrolide-lincosamide-streptogramin B (MLS_B) antibiotics (3%) and tetracycline (8%); two isolates exhibited coresistance to tetracycline and macrolides. Of nine pyrogenic exotoxin (superantigen) genes examined, speA and speC were identified in 58% and 40% of the strains, respectively; either of the genes was present in all strains causing STSS. Most strains harbored speG (99%). ssa was present in 14% of the isolates only. In Denmark, as in comparable countries, GAS invasive disease shows a sustained, high endemicity, with involvement of both established and emerging streptococcal emm and T types.     

Different alleles of the fcrA/mrp gene of Streptococcus pyogenes encode M-related proteins exhibiting an identical immunoglobulin-binding pattern

  The majority of group A streptococci (GAS, Streptococcus pyogenes) express immunoglobulin (Ig)-binding proteins. The genes encoding these proteins belong either to the emm or the emm-related (fcrA/mrp and enn) gene family and are located in close proximity on the GAS genome, where they form part of the vir regulon. In the present study analysis of sequence data of the 5′ terminal portions of the fcrA/mrp genes from GAS isolates representing 37 different M serotypes led to a classification of six different types. Thus, although fcrA/mrp genes exhibit an allelic polymorphism, they do not display the high degree of N-terminal sequence diversity found among emm genes. The nucleotide sequences of the fcrA/mrp genes from 3 GAS isolates, belonging to serotypes M8, M9, and M13 and representing newly characterized fcrA/mrp gene types, are reported. Analysis of the Ig-binding properties of recombinant FcrA/Mrp8, 9, and 13 proteins, demonstrated a similar Ig-binding profile being reactive with human IgG subclasses 1, 2, and 4. This pattern is identical to that previously described for other recombinant fcrA/mrp4, 49, 64/14 and 76 gene products, indicating that this property is not affected by the N-terminal variability. Evidence for recombination between an fcrA/mrp and an mga gene was observed in an M-type 33 strain isolate providing further support for the concept of gene rearrangement contributing to the diversity of vir regulon gene products. Received: 31 January 1996     

Invasive group A streptococcal infection in children: clinical manifestations and molecular characterization in a French pediatric tertiary care center

Invasive group A streptococcal (GAS) infections have a broad and evolving clinical spectrum, associated with various GAS genotypes and/or virulence factors that are only poorly described in children. We aimed to assess the clinical and molecular characteristics of invasive GAS infections in 28 children admitted from 2000 to 2007 at a large French pediatric tertiary care center. The GAS isolates were characterized molecularly by emm-typing and by the determination of the main virulence factors: speA, speB, speC, smeZ-1, ssa, sic, and silC. The median age of the children was 2.9 years. Osteoarticular infection (OAI) was the main clinical manifestation (n?=?15/28, 53%). emm-1 predominated (n?=?10/28), followed by emm-12, 3, and 4. No significant correlation was found between emm type and clinical manifestations, but emm-1 predominated in cases of OAI (n?=?7/15) and was associated with speA, speB, smeZ-1, and sic virulence factor genes. In this pediatric study, we describe a predominance of OAI associated with emm-1 GAS. Further larger international pediatric studies, including host immunity evaluation, are needed in order to better assess the pathogenesis of GAS infection in children.     

Streptococcus pyogenes emm Types and Clusters during a 7-Year Period (2007 to 2013) in Pharyngeal and Nonpharyngeal Pediatric Isolates

Group A streptococcus (GAS) is an important cause of morbidity and mortality worldwide. Surveillance of emm types has important implications, as it can provide baseline information for possible implementation of vaccination. A total of 1,349 GAS pediatric isolates were collected during a 7-year period (2007 to 2013); emm typing was completed for 1,282 pharyngeal (84%) or nonpharyngeal (16%) isolates, and emm clusters and temporal changes were analyzed. Thirty-five different emm types, including 14 subtypes, were identified. The most prevalent emm types identified were 1 (16.7%), 12 (13.6%), 77 (10.9%), 4 (10.8%), 28 (10.4%), 6 (6.8%), 3 (6.6%), and 89 (6.6%), accounting for 82.3% of total isolates. Rheumatogenic emm types comprised 16.3% of total isolates. The emm types 12, 4, and 77 were more prevalent among pharyngeal isolates, and the emm types 1, 89, 6, 75, and 11 were more prevalent among nonpharyngeal isolates. The emm types identified belonged to 13 emm clusters, and the 8 most prevalent clusters comprised 97% of all isolates. There were statistically significant decreases in the prevalence of emm types 12, 4, 5, and 61 and increases in the prevalence of emm types 89, 75, and 11, compared with the period 2001 to 2006. The proposed 30-valent GAS vaccine, which is currently in preclinical studies, encompasses 97.2% of the emm types detected in our study and 97.4% of the erythromycin-resistant strains. In addition, it includes 93.3% of the emm types involved in bacteremia. A much greater diversity of GAS emm types was identified in our area than described previously. Seasonal fluctuations and the introduction of new emm types were observed. Continuous surveillance of emm types is needed in order to evaluate the possible benefits of an M protein-based GAS vaccine.     

Changing Epidemiology of Streptococcus pyogenes emm Types and Associated Invasive and Noninvasive Infections in Southern Taiwan

A total of 242 isolates were recovered from 76 patients with invasive diseases, 89 with scarlet fever, and 77 with pharyngitis. The most frequent emm types were types 12 (43.4%), 4 (18.2%), and 1 (16.9%). emm12 reemerged in 2005 and peaked in 2007. emm11 was recovered only from patients with invasive disease.Streptococcus pyogenes, a group A Streptococcus (GAS) species, produces many diseases, ranging from impetigo, pharyngitis, and scarlet fever to life-threatening sepsis, necrotizing fasciitis, and streptococcal toxic shock syndrome (STSS) (8). M protein that is encoded by the emm gene is a major virulence factor of GAS. Different M protein types are epidemiologically related to particular clinical syndromes; e.g., emm28 was isolated more frequently than other types among women with puerperal sepsis (6, 10, 14). M1, M2, M3, M4, M6, M18, and M22 strains are associated with outbreaks of scarlet fever (1, 11, 15, 18, 20, 22-24), while M1 and M3 are highly associated with severe invasive disease (19, 25, 27) and M18 is associated with acute rheumatic fever (7).The distribution of emm types in cases of invasive diseases tends to vary over time and within different geographic regions. In the United States, the most common emm types were 1, 28, 12, 3, and 11 during the period from 1995 to 1999 (19). emm types 1, 3, and 12 were predominant from 2000 to 2004 (21). In Europe, the distribution of the emm types differs among countries (16). For example, in Denmark, emm1 and emm28 were the most prevalent types from 2001 to 2004, whereas in Greece, emm1 and emm12 were predominant from 2003 to 2005. In Sweden, four emm types, 89, 81, 28, and 1, accounted for 56% of 746 patients with invasive GAS diseases during the period from 2002 to 2004. In Taiwan, emm1 associated with invasive GAS disease, while emm12 was more often associated with noninvasive GAS disease (13). The purpose of the current study was to investigate the changing epidemiology, genetic diversity, and epidemic virulence of GAS infections over a 10-year period in southern Taiwan, utilizing M genotyping and pulsed-field gel electrophoresis (PFGE) analysis.Clinical isolates of S. pyogenes was obtained from patients seen at the National Cheng Kung University Hospital, Tainan City, Taiwan, from 1998 to 2007. They were divided into strains isolated from patients with invasive diseases or those from patients with noninvasive diseases. Invasive isolates were defined as those obtained from sterile body sites (blood, cerebrospinal, joint, pleural, peritoneal, or pericardial fluids) or from nonsterile sites (wounds associated with STSS or necrotizing fasciitis). Noninvasive strains were defined as GAS isolates obtained from patients with asymptomatic nasopharyngeal colonization, pharyngitis, scarlet fever, erysipelas, and impetigo.A total of 242 nonduplicate GAS isolates recovered from normally sterile sites (165 from throat swabs, 30 from wounds, 25 from pus, 12 from blood, 10 from other materials) were collected. The mean age of patients with invasive diseases was significantly greater than that of those with noninvasive diseases (28.5 ± 27 years versus 8.7 ± 7.9 years [P < 0.0001]). Among the 76 patients with invasive diseases, 58 (76.3%) patients had skin and soft-tissue infections. Three had necrotizing fasciitis, eight had STSS, four had severe sepsis, and three had complicated infections including pneumonia or mastoiditis. Among the 166 patients with noninvasive diseases, 77 (46%) had pharyngitis (including one with lymphadenitis), and 89 (54%) had scarlet fever (including 59 patients with pharyngitis).The distribution of emm types among patients with invasive and noninvasive diseases (subdivided into those with scarlet fever and those with pharyngitis) is shown in Table ​Table1.1. GAS emm sequence typing was based on the 5′ end of the emm gene within the emm chromosomal region (2, 3). A unique emm type was defined as having ≥95% sequence identity to any other known emm type over 160 bp near the 5′ end of the gene, using a BLAST search (http://www.cdc.gov/ncidod/biotech/strep/strepblast.htm). Twenty emm sequence types were identified among the 242 GAS isolates, including types 1, 4, 6, 11, 12, 13, 22, 33, 49, 57, 77, 81, 82, 85, 87, 92, 94, 101, 102, and 123. The leading emm types were 12 (43.4%), 4 (18.2%), 1 (16.9%), 11 (4.5%), 6 (3.7%), and 22 (2.5%) (Table ​(Table1).1). All of the emm types were associated with both invasive and noninvasive diseases except for emm11, which was recovered only from patients with invasive disease. emm22 and other less frequent types were more likely to be associated with invasive diseases (P < 0.0001). The emm types 1, 4, 6, and 12 accounted for 82.2% of all patients with GAS infections, 95.2% of the patients with noninvasive diseases, and 53.9% of the patients with invasive disease. The most common type, emm12, was also significantly associated with noninvasive disease (85.7%) (P < 0.0001).

TABLE 1.

Distribution of Streptococcus pyogenes emm types isolated from 1998 to 2007 according to clinical characteristics

Clinical aspects of invasive infections with Streptococcus dysgalactiae ssp. equisimilis in Japan: differences with respect to Streptococcus pyogenes and Streptococcus agalactiae infections

Streptococcus dysgalactiae ssp. equisimilis (SDSE) is increasingly being identified as a pathogen responsible for invasive and non-invasive infections. We compared the clinical features of invasive SDSE infections with those of invasive infections caused by Streptococcus pyogenes (group A streptococcus (GAS)) and Streptococcus agalactiae (group B streptococcus (GBS)). Active surveillance for invasive SDSE, GAS and GBS was maintained over 1 year at 142 medical institutions throughout Japan. Clinical information was collected together with isolates, which were characterized microbiologically. Two hundred and thirty-one invasive SDSE infections were identified, 97 other patients had infections with GAS, and 151 had infections with GBS. The median age of the SDSE patients was 75 years; 51% were male and 79% had underlying diseases. Forty-two SDSE patients (19%) presented to the emergency department. Among the 150 patients (65%) for whom follow-up was completed, 19 (13%) died and eight (5%) had post-infective sequelae (poor outcome). Insufficient white blood cell responses (<5000 cells/µL) and thrombocytopenia on admission each suggested significantly higher risk of poor outcome (ORs 3.6 and 4.5, respectively). Of 229 isolates, 55 (24%) showed an stG6792 emm type, which was significantly associated with poor outcome (OR 2.4). Clinical manifestations of invasive SDSE infections were distinct from those of invasive GBS infections. Primary-care doctors should consider invasive SDSE infections when treating elderly patients.     

Lateral genetic transfers between group A and G streptococci for M-like genes are ongoing

Previously we described a long-polymerase chain reaction (PCR) method to amplify a 4–7 kb target containing most of the components of the vir regulon (mga,emm-like genes andscpA) in a number of group A streptococcus (GAS) isolates.¹In contrast to GAS, strains of human group G streptococcus (GGS) gave approximately 1.6 or 1.8 kb products. Sequence analysis of the amplified products issued from GGS templates revealed a mosaic consisting of upstream sequence frommga(the gene for positive regulator of vir regulon), an unidentified open reading frame, a short segment ofemm(the gene for M protein, an antiphagocytic molecule) and an upstream sequence ofscp(C5a-peptidase gene). A full lengthscpGis present immediately downstream from the mosaic segment in the human GGS genome. The GGS PCR fragment did not code formgaor full lengthemm. All human GGS isolates are known to code foremmbut the gene is separated fromscpGby at least 10 kb.²Our data, obtained using long-PCR and unrelated strains of GGS, confirm this. We could not detect a homologue ofmgain human GGS by hybridization analysis. The mosaic sequence suggests that enbloc transfer of the vir regulon from GAS to a GGS progenitor may have occurred, following which deletion and rearrangement events may have taken place. Partial nucleotide sequences ofemmcorresponding to the variable domain of M proteins from three local GGS isolates were determined. One sequence (emmGGS6) is 99% identical toemmfrom a geographicaly separated isolate of GGS recently described.³emmGGS6 also has significant homology withemmfrom a GAS strain (STDONALD) isolated from the same geographical area as was GGS6. The twoemmsequences (emmGGS6 andemmSTDONALD) revealed frameshift-compensatory frameshift mutations relative to each other, contributing to lower amino acid homology between the two predicted M proteins. SinceemmSTDONALD has no known relatives within the 80 or soemmsequences in the database, we speculate that it could have been laterally acquired from GGS. Horizontal transfers between GGS and GAS may be ongoing.