Emm1 Isolates Research Articles

Invasive Group A Streptococcus Hypervirulent M1UK Clone, Canada, 2018-2023.

To determine invasive group A Streptococcus trends in Canada, we characterized emm1 isolates collected during 2018-2023. The percentage of hypervirulent M1UK lineage isolates increased significantly, from 22.1% in 2018 to 60.2% in 2023. Genomic analysis identified geographically and temporally associated clusters and genes associated with virulent bacteriophage acquisition.

Nationwide upsurge in invasive disease in the context of longitudinal surveillance of carriage and invasive Streptococcus pyogenes 2009-2023, the Netherlands: a molecular epidemiological study.

Since 2022, many countries have reported an upsurge in invasive group A streptococcal (iGAS) infections. We explored whether changes in Streptococcus pyogenes carriage rates or emergence of strains with potentially altered virulence, such as emm1 variants M1UK and M1DK, contributed to the 2022/2023 surge in the Netherlands. We determined emm (sub)type distribution for 2,698 invasive and 351 S. pyogenes carriage isolates collected between January 2009 and March 2023. Genetic evolution of emm1 was analyzed by whole-genome sequencing of 497 emm1 isolates. The nationwide iGAS upsurge coincided with a sharp increase of emm1.0 from 18% (18/100) of invasive isolates in Q1 2022 to 58% (388/670) in Q1 2023 (Fisher's exact test, P < 0.0001). M1UK became dominant among invasive emm1 isolates in 2016 and further expanded from 72% in Q1 2022 to 96% in Q1 2023. Phylogenetic comparison revealed evolution and clonal expansion of four new M1UK clades in 2022/2023. DNase Spd1 and superantigen SpeC were acquired in 9% (46/497) of emm1 isolates. S. pyogenes carriage rates and emm1 proportions in carriage isolates remained stable during this surge, and the expansion of M1UK in iGAS was not reflected in carriage isolates. During the 2022/2023 iGAS surge in the Netherlands, expansion of four new M1UK clades was observed among invasive isolates, but not carriage isolates, suggesting increased virulence and fitness of M1UK compared to contemporary M1 strains. The emergence of more virulent clades has important implications for public health strategies such as antibiotic prophylaxis for close contacts of iGAS patients.IMPORTANCEThis study describes the molecular epidemiology of invasive group A streptococcal (iGAS) infections in the Netherlands based on >3,000 Streptococcus pyogenes isolates from both asymptomatic carriers and iGAS patients collected before, during, and after the COVID-19 pandemic period (2009-2023) and is the first to assess whether changes in carriage rates or carried emm types contributed to the alarming post-COVID-19 upsurge in iGAS infections. We show that the 2022/2023 iGAS surge coincided with a sharp increase of emm1, particularly the toxicogenic M1UK variant, in invasive isolates, but not in carriage isolates. These findings suggest that increased virulence and fitness of M1UK likely contributes to an increased dissemination between hosts. The emergence of a more virulent and fit lineage has important implications for iGAS control interventions such as antibiotic prophylaxis for close contacts of iGAS patients and calls for a reappraisal of iGAS control interventions and guidelines.

Molecular characterization of Streptococcus pyogenes (StrepA) non-invasive isolates during the 2022-2023 UK upsurge.

At the end of 2022 into early 2023, the UK Health Security Agency reported unusually high levels of scarlet fever and invasive disease caused by Streptococcus pyogenes (StrepA or group A Streptococcus). During this time, we collected and genome-sequenced 341 non-invasive throat and skin S. pyogenes isolates identified during routine clinical diagnostic testing in Sheffield, a large UK city. We compared the data with that obtained from a similar collection of 165 isolates from 2016 to 2017. Numbers of throat-associated isolates collected peaked in early December 2022, reflecting the national scarlet fever upsurge, while skin infections peaked later in December. The most common emm-types in 2022-2023 were emm1 (28.7 %), emm12 (24.9 %) and emm22 (7.7 %) in throat and emm1 (22 %), emm12 (10 %), emm76 (18 %) and emm49 (7 %) in skin. While all emm1 isolates were the M1UK lineage, the comparison with 2016-2017 revealed diverse lineages in other emm-types, including emm12, and emergent lineages within other types including a new acapsular emm75 lineage, demonstrating that the upsurge was not completely driven by a single genotype. The analysis of the capsule locus predicted that only 51 % of throat isolates would produce capsule compared with 78% of skin isolates. Ninety per cent of throat isolates were also predicted to have high NADase and streptolysin O (SLO) expression, based on the promoter sequence, compared with only 56% of skin isolates. Our study has highlighted the value in analysis of non-invasive isolates to characterize tissue tropisms, as well as changing strain diversity and emerging genomic features which may have implications for spillover into invasive disease and future S. pyogenes upsurges.

Molecular Epidemiology of Group A Streptococcus Isolated from Children in Beijing during 2011 to 2019

Abstract Objective This study aimed to examine the characteristics of Group A Streptococcus (GAS) infection and identify the emm genotypes and the superantigen gene of GAS strains isolated from children from 2011 to 2019 in Tongzhou District, Beijing. Methods Pharyngeal swab samples from children with scarlet fever or pharyngeal infection were collected and tested for GAS. In GAS isolates, emm genotypes and superantigen genes were identified. Logistic regression models were used to explore the correlations between demographic characteristics, clinical manifestations, and GAS infection. Results In total, 172/1,214 (14.2%) GAS were isolated. The GAS infection rate in children with scarlet fever was 47.5%, higher than 8.5% in children with pharyngeal infection (p &lt; 0.001). The risk of GAS infection was associated with oral mucosal congestion in children with scarlet fever, and older age, tonsillitis, and rash in children with pharyngeal infection. Seven emm genotypes were detected in 164 GAS isolated strains, of which emm12 and emm1 accounted for 47.0 and 46.3%, respectively. Among 112 GAS isolates, the top 5 detection rates of superantigen genes were speF 100.0%, speG 100.0%, speB 98.2%, speC 94.6%, and smeZ 82.1%. Higher proportions of speA, speJ, and speK were detected in emm1 isolates, while speH and speI were more common in emm12 isolates (p &lt; 0.001). Conclusion The changing predominant type expanded the knowledge of the circulating emm types, which should be considered in future vaccine development.

Detection of toxigenic M1UK lineage group A Streptococcus clones in Taiwan

BackgroundA new sublineage of emm1 group A Streptococcus (GAS), M1UK, has emerged in Europe, North America, and Australia. Notably, a significant portion of emm1 isolates in Asia, particularly in Hong Kong and mainland China, acquired scarlet fever-associated prophages following the 2011 Hong Kong scarlet fever outbreak. However, the presence of the M1UK sublineage has not yet been detected in Asia. MethodsThis study included 181 GAS isolates (2011–2021). The emm type of these isolates were determined, and 21 emm1 isolates from blood or pleural fluid (2011–2021) and 10 emm1 isolates from throat swabs (2016–2018) underwent analysis. The presence of the scarlet fever-associated prophages and the specific single nucleotide polymorphisms of the M1UK clone were determined by polymerase chain reaction and the genome sequencing. ResultsThe M1UK lineage strains from throat swab and blood samples were identified. One of the M1UK strain in Taiwan carried the scarlet fever-associated prophage and therefore acquired the ssa, speC, and spd1 toxin repertoire. Nonetheless, the increase of M1UK was not observed until 2021, and there was a reduction in the diversity of emm types in 2020–2021, possibly due to the COVID-19 pandemic restriction policies in Taiwan. ConclusionsOur results suggested that the M1UK lineage clone has introduced in Taiwan. In Taiwan, the COVID-19 restrictions were officially released in March 2023; therefore, it would be crucial to continuously monitor the M1UK expansion and its related diseases in the post COVID-19 era.

Epidemiological changes in invasive Streptococcus pyogenes infection during the UK alert period: A molecular comparative analysis from a tertiary Spanish hospital in 2023

ObjectivesTo study the genomic epidemiology of Streptococcus pyogenes causing bloodstream infections (GAS-BSI) in a Spanish tertiary hospital during the United Kingdom invasive S. pyogenes outbreak alert. MethodsRetrospective epidemiological analysis of GAS-BSI during the January–May 2017–2023 period. WGS was performed using Ion torrent GeneStudio™ S5 system for emm typing and identification of superantigen genes in S. pyogenes isolated during the 2022–2023 UK outbreak alert. ResultsDuring 2023, there were more cases of GAS-BSI compared to the same period of previous year with a non-significant increase in children. Fourteen isolates were sequenced. The emm1 (6/14, 42.9%) and emm12 (2/14, 14.3%) types predominated; 5 of 6 (75%) emm1 isolates were from the M1UK clone. The most detected superantigen genes were speG (12/14, 85.7%), speC (10/14, 71.4%), speJ (7/14, 50%), and speA (5/15, 33.3%). speA and speJ were predominant in M1UK clone. ConclusionsOur genomic epidemiology in 2023 is similar to the reported data from the UK outbreak alert in the same period and different from previous national S. pyogenes surveillance reports.

Prevalence of the M1UK sublineage among emm1 Streptococcus pyogenes invasive strains isolated in the Czech Republic from December 2022 to May 2023.

Since December 2022, an increase in invasive disease caused by Streptococcus pyogenes has been observed in the Czech Republic, with a shift in the clinical presentation and age of patients. Unlike in previous years, invasive disease is more common in children and adolescents under 18 years of age and in previously healthy middle-aged adults. An increase has been noticed in the number of S. pyogenes isolates from primarily sterile sites such as haemoculture, cerebrospinal fluid, pleural effusion fluid, joint fluid, and postmortem specimens. Routine emm gene typing revealed emm1 to be the predominant emm type of S. pyogenes. Between January 2023 and July 2023, 46% of all S. pyogenes isolates from invasive cases were assigned to the emm1 type. The globallyspread M1UK sublineage is characterized by differences in the expression of seven genes, including the streptococcal pyrogenic toxin A (speA) gene, compared to historical emm1 iGAS strains. The aim of this study is to determine whether the more toxigenic M1UK sublineage is associated with the increase in invasive disease in the Czech Republic. Whole genome sequencing of 41 S. pyogenes isolates from patients with invasive disease recovered in the Czech Republic in 2018 and 2019 and from December 2022 to May 2023 was performed using the MiSeq instrument (Illumina). Bioinformatics analysis was performed using freely available online tools the Bacterial and Viral Bioinformatics Resource Center. Based on whole genome sequencing data of 41 emm1 isolates of S. pyogenes from patients with invasive infectious disease recovered in 2018 and 2019 and from December 2022 to May 2023, the M1UK sublineage was found to be predominant from December 2022 to May 2023. The reason for the spread of the M1UK sublineage in the Czech Republic late in 2022 and in the first half of 2023 is not entirely clear, but it may be related to reduced immunity due to limited GAS transmission during lockdowns, especially in children. Another factor that may have contributed to the high incidence of invasive infectious diseases is the seasonal circulation of respiratory viruses.

Population of invasive group A streptococci isolates from a German tertiary care center is dominated by the hypertoxigenic virulent M1UK genotype.

Hypertoxigenic Streptococcus pyogenes emm1 lineage M1UK has recently been associated with upsurges of invasive infections and scarlet fever in several countries, but whole-genome sequencing surveillance data of lineages circulating in Germany is lacking. In this study, we investigated recent iGAS isolates from our laboratory at a German tertiary care center for the presence of the M1UK lineage. Whole-genome sequencing was employed to characterize a collection of 47 consecutive non-copy isolates recovered from blood cultures (21) and tissue samples (26) in our laboratory between October 2022 and April 2023. M protein gene (emm) typing distinguished 14 different emm types, with emm1 (17) being the dominant type. Single-nucleotide polymorphism (SNP) analysis confirmed the presence of all 27 SNPs characteristic for the M1UK lineage in 14 of 17 emm1 isolates. This study has shown for the first time that M1UK is present in Germany and might constitute a driving force in the observed surge of GAS infections. This observation mirrors developments in the UK and other countries and underscores the importance of WGS surveillance to understand the epidemiology of GAS.

A worldwide population of Streptococcus pyogenes strains circulating among school-aged children in Auckland, New Zealand: a genomic epidemiology analysis

Acute rheumatic fever (ARF) is a serious post-infectious sequala of Group A Streptococcus (GAS, Streptococcus pyogenes). In New Zealand (NZ) ARF is a major cause of health inequity. This study describes the genomic analysis of GAS isolates associated with childhood skin and throat infections in Auckland NZ. Isolates (n=469) collected between March 2018 and October 2019 from the throats and skin of children (5-14 years) underwent whole genomic sequencing. Equal representation across three ethnic groups was ensured through sample quotas with isolates obtained from Indigenous Māori (n=157, 33%), NZ European/Other (n=149, 32%) and Pacific Peoples children (n=163, 35%). Using in silico techniques isolates were classified, assessed for diversity, and examined for distribution differences between groups. Comparisons were also made with GAS strains identified globally. Genomic analysis revealed a diverse population consisting of 65 distinct sequence clusters. These sequence clusters spanned 49 emm-types, with 11 emm-types comprised of several, distinct sequence clusters. There is evidence of multiple global introductions of different lineages into the population, as well as local clonal expansion. The M1UK lineage comprised 35% of all emm1 isolates. The GAS population was characterized by a high diversity of strains, resembling patterns observed in low- and middle-income countries. However, strains associated with outbreaks and antimicrobial resistance commonly found in high-income countries were also observed. This unique combination poses challenges for vaccine development, disease management and control. The work was supported by the Health Research Council of New Zealand (HRC), award number 16/005.

Epidemiological changes in invasive Streptococcus pyogenes infection during the UK alert period: A molecular comparative analysis from a tertiary Spanish hospital in 2023

ObjectivesTo study the genomic epidemiology of Streptococcus pyogenes causing bloodstream infections (GAS-BSI) in a Spanish tertiary hospital during the United Kingdom invasive S. pyogenes outbreak alert. MethodsRetrospective epidemiological analysis of GAS-BSI during the January–May 2017–2023 period. WGS was performed using Ion torrent GeneStudio™ S5 system for emm typing and identification of superantigen genes in S. pyogenes isolated during the 2022–2023 UK outbreak alert. ResultsDuring 2023, there were more cases of GAS-BSI compared to the same period of previous year with a non-significant increase in children. Fourteen isolates were sequenced. The emm1 (6/14, 42.9%) and emm12 (2/14, 14.3%) types predominated; 5 of 6 (75%) emm1 isolates were from the M1UK clone. The most detected superantigen genes were speG (12/14, 85.7%), speC (10/14, 71.4%), speJ (7/14, 50%), and speA (5/15, 33.3%). speA and speJ were predominant in M1UK clone. ConclusionsOur genomic epidemiology in 2023 is similar to the reported data from the UK outbreak alert in the same period and different from previous national S. pyogenes surveillance reports.

Sustained increase of paediatric invasive Streptococcus pyogenes infections dominated by M1UK and diverse emm12 isolates, Portugal, September 2022 to May 2023.

Since autumn 2022, observed numbers of paediatric invasive group A Streptococcus infections in Portugal (n = 89) were higher than in pre-COVID-19 seasons. Between September 2022 and May 2023, the dominant diagnoses were pneumonia (25/79), mostly with empyema (20/25), and sepsis (22/79). A number of cases required admission to intensive care (27/79) and surgery (35/79), and the case fatality rate was 5.1% (4/79). Genomic sequencing (n = 55) revealed multiple genetic lineages, dominated by the M1UK sublineage (26/55) and more diverse emm12 isolates (12/55).

Emerging Invasive Group A Streptococcus M1UK Lineage Detected by Allele-Specific PCR, England, 20201.

Increasing reports of invasive Streptococcus pyogenes infections mandate surveillance for toxigenic lineage M1UK. An allele-specific PCR was developed to distinguish M1UK from other emm1 strains. The M1UK lineage represented 91% of invasive emm1 isolates in England in 2020. Allele-specific PCR will permit surveillance for M1UK without need for genome sequencing.

The ongoing Streptococcus pyogenes (Group A Streptococcus) outbreak in London, United Kingdom, in December 2022: a molecular epidemiology study

ObjectivesEpidemiological and whole-genome sequencing analysis of an ongoing outbreak of Streptococcus pyogenes (Group A Streptococcus) in London (United Kingdom). MethodsProspective identification of Group A Streptococcus cases from a diagnostic laboratory serving central and south London between 27 November and 10 December 2022. Case notes were reviewed and isolates were retrieved. Case numbers were compared with the previous 5 years. Whole-genome sequencing was performed with long-read, nanopore technology for emm typing and identification of superantigen genes. Associations of pathogen-related factors with an invasive disease were assessed by single-variable and multi-variable logistic regression. ResultsCase numbers began increasing in October 2022 from a baseline of 2.0 cases per day, and in December 2022, the average daily case numbers reached 10.8 cases per day, four-fold the number usually seen in winter. A total of 113 cases were identified during the prospective study period. Three quarters (86/113, 76%) were paediatric cases, including 2 deaths. Of 113 cases, 11 (10%) were invasive. In total, 56 isolates were successfully sequenced, including 10 of 11 (91%) invasive isolates. The emm12 (33/56, 59%) and emm1 (9/56, 16%) types were predominant, with 7 of 9 (78%) emm1 isolates being from the M1uk clone. The majority of invasive isolates had superantigen genes spea (7/10, 70%) and spej (8/10, 80%), whereas, in non-invasive isolates, these superantigen genes were found less frequently (spea: 5/46, 11% and spej: 7/46, 15%). By multivariable analysis of pathogen-related factors, spea (OR 8.9, CI 1.4–57, p 0.020) and spej (OR 12, CI 1.8–78, p 0.011) were associated with invasive disease. Conclusionsemm12 and emm1 types predominate in the ongoing outbreak, which mainly affects children. In this outbreak, the spea and spej superantigen genes are associated with the severity of presentation.

Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic Antibodies.

The human pathogen Streptococcus pyogenes causes substantial morbidity and mortality. It is unclear if antibodies developed after infections with this pathogen are opsonic and if they are strain specific or more broadly protective. Here, we quantified the opsonic-antibody response following invasive S. pyogenes infection. Four patients with S. pyogenes bacteremia between 2018 and 2020 at Skåne University Hospital in Lund, Sweden, were prospectively enrolled. Acute- and convalescent-phase sera were obtained, and the S. pyogenes isolates were genome sequenced (emm118, emm85, and two emm1 isolates). Quantitative antibody binding and phagocytosis assays were used to evaluate isolate-dependent opsonic antibody function in response to infection. Antibody binding increased modestly against the infecting isolate and across emm types in convalescent- compared to acute-phase sera for all patients. For two patients, phagocytosis increased in convalescent-phase serum both for the infecting isolate and across types. The increase was only across types for one patient, and one had no improvement. No correlation to the clinical outcomes was observed. Invasive S. pyogenes infections result in a modestly increased antibody binding with differential opsonic capacity, both nonfunctional binding and broadly opsonic binding across types. These findings question the dogma that an invasive infection should lead to a strong type-specific antibody increase rather than a more modest but broadly reactive response, as seen in these patients. Furthermore, our results indicate that an increase in antibody titers might not be indicative of an opsonic response and highlight the importance of evaluating antibody function in S. pyogenes infections. IMPORTANCE The bacterium Streptococcus pyogenes is a common cause of both mild and severe human diseases resulting in substantial morbidity and mortality each year. No vaccines are available, and our understanding of the antibody response to this human pathogen is still incomplete. Here, we carefully analyzed the opsonic antibody response following invasive infection in four patients. Unexpectedly, the patients did not always generate opsonic antibodies against the specific infecting strain. Instead, we found that some patients could generate cross-opsonic antibodies, leading to phagocytosis of bacteria across strains. The emergence of cross-opsonic antibodies is likely important for long-term immunity against S. pyogenes. Our findings question the dogma that mostly strain-specific immunity is developed after infection and add to our overall understanding of how immunity to S. pyogenes can evolve.

Consistent Biofilm Formation by Streptococcus pyogenes emm 1 Isolated From Patients With Necrotizing Soft Tissue Infections.

ObjectivesBiofilm formation has been demonstrated in muscle and soft tissue samples from patients with necrotizing soft tissue infection (NSTI) caused by Streptococcus pyogenes, but the clinical importance of this observation is not clear. Although M-protein has been shown to be important for in vitro biofilm formation in S. pyogenes, the evidence for an association between emm type and biofilm forming capacity is conflicting. Here we characterize the biofilm forming capacity in a collection of S. pyogenes isolates causing NSTI, and relate this to emm type of the isolates and clinical characteristics of the patients.MethodsBacterial isolates and clinical data were obtained from NSTI patients enrolled in a multicenter prospective observational study. Biofilm forming capacity was determined using a microtiter plate assay.ResultsAmong 57 cases, the three most frequently encountered emm types were emm1 (n = 22), emm3 (n = 13), and emm28 (n = 7). The distribution of biofilm forming capacity in emm1 was qualitatively (narrow-ranged normal distribution) and quantitatively (21/22 isolates in the intermediate range) different from other emm types (wide ranged, multimodal distribution with 5/35 isolates in the same range as emm1). There were no significant associations between biofilm forming capacity and clinical characteristics of the patients.ConclusionsThe biofilm forming capacity of emm1 isolates was uniform and differed significantly from other emm types. The impact of biofilm formation in NSTI caused by S. pyogenes on clinical outcomes remains uncertain.

Population Genomic Molecular Epidemiological Study of Macrolide-Resistant Streptococcus pyogenes in Iceland, 1995 to 2016: Identification of a Large Clonal Population with a pbp2x Mutation Conferring Reduced In Vitro β-Lactam Susceptibility.

Resistance to macrolide antibiotics is a global concern in the treatment of Streptococcus pyogenes (group A Streptococcus [GAS]) infections. In Iceland, since the detection of the first macrolide-resistant isolate in 1998, three epidemic waves of macrolide-resistant GAS infections have occurred, with peaks in 1999, 2004, and 2008. We conducted whole-genome sequencing of all 1,575 available GAS macrolide-resistant clinical isolates of all infection types collected at the national reference laboratory in Reykjavik, Iceland, from 1998 to 2016. Among 1,515 erythromycin-resistant isolates, 90.3% were of only three emm types, emm4 (n = 713), emm6 (n = 324), and emm12 (n = 332), with each being predominant in a distinct epidemic peak. The antibiotic efflux pump genes, mef(A) and msr(D), were present on chimeric mobile genetic elements in 99.3% of the macrolide-resistant isolates of these emm types. Of note, in addition to macrolide resistance, virtually all emm12 isolates had a single amino acid substitution in penicillin-binding protein PBP2X that conferred a 2-fold increased penicillin G and ampicillin MIC among the isolates tested. We conclude that each of the three large epidemic peaks of macrolide-resistant GAS infections occurring in Iceland since 1998 was caused by the emergence and clonal expansion of progenitor strains, with macrolide resistance being conferred predominantly by inducible Mef(A) and Msr(D) drug efflux pumps. The occurrence of emm12 strains with macrolide resistance and decreased beta-lactam susceptibility was unexpected and is of public health concern.

Epidemiological analysis of Group A Streptococcus infections in a hospital in Beijing, China.

Our study aimed to investigate the epidemiological and molecular characteristics of isolates collected from Group A Streptococcus (GAS) infections in children in Beijing China during the year 2019. Emm typing, superantigens, and erythromycin resistance genotypes were determined by PCR. Antimicrobial susceptibility testing was performed as recommended by Clinical Laboratory Standards Institute (CLSI). A total of 271 GAS isolates were collected. Thirteen different emm types, including 31 subtypes, were identified. The most prevalent emm types were emm12 (52.77%), emm1 (36.9%), emm3.1 (2.95%), and emm75.0 (2.95%). Two variant subtypes, STC36.0 and STG840.2, were identified. There was no difference in the portion of emm12 and emm1 isolates in scarlet fever, impetigo, and psoriasis. The majority of superantigens detected were smeZ (94.46%), speC (91.14%), and ssa (74.91%), followed by speH (56.46%), speI (45.76%), speJ (36.9%), and speA (34.32%). More scarlet fever isolates harbored speA (35.6%) and speJ (38.4%), more psoriasis isolates harbored speI (57.9%), and more impetigo isolates harbored ssa (89.7%). Isolates were universally susceptible to penicillin and resistant to erythromycin (94.83%). Moreover, 89.67% erythromycin resistance isolates harbored the ermB gene. The erythromycin resistance rate of the isolates from the three diseases was different. Scarlet fever is the common streptococcal infectious disease in dermatology. Emm12 and emm1 were the most prevalent emm types. The most prevalent superantigens detected were smeZ, spec, and ssa. There is association between diversity of superantigens and disease manifestation. Hence, continuous surveillance of GAS molecular epidemiological characterizations in different diseases is needed.

Increase of emm1 isolates among group A Streptococcus strains causing scarlet fever in Shanghai, China

ObjectiveScarlet fever epidemics caused by group A Streptococcus (GAS) have been ongoing in China since 2011. However, limited data are available on the dynamic molecular characterizations of the epidemic strains. MethodEpidemiological data of scarlet fever in Shanghai were obtained from the National Notifiable Infectious Disease Surveillance System. Throat swabs of patients with scarlet fever and asymptomatic school-age children were cultured. Illumina sequencing was performed on 39emm1 isolates. ResultsThe annual incidence of scarlet fever was 7.5–19.4/100,000 persons in Shanghai during 2011–2015, with an average GAS carriage rate being 7.6% in school-age children. The proportion ofemm1 GAS strains increased from 3.8% in 2011 to 48.6% in 2014; they harbored a superantigen profile similar to emm12 isolates, except for the speA gene. Two predominant clones, SH001-emm12, and SH002-emm1, circulated in 66.9% of scarlet fever cases and 44.8% of carriers. Genomic analysis showed emm1 isolates throughout China constituted distinct clades, enriched by the presence of mobile genetic elements carrying the multidrug-resistant determinants ermB and tetM and virulence genes speA, speC, and spd1. ConclusionA significant increase in the proportion ofemm1 strains occurred in the GAS population, causing scarlet fever in China. Ongoing surveillance is warranted to monitor the dynamic changes of GAS clones.

Molecular Characterization of Streptococcus pyogenes Causing Invasive Disease in Pediatric Population in Spain A 12-year Study.

To perform a comprehensive description of the epidemiology of Streptococcus pyogenes invasive disease in the pediatric population in 2 regions of Spain (Catalonia and Gipuzkoa) through 12 years. All S. pyogenes isolates causing invasive disease in pediatric patients between 2005 and 2016 were included. The emm-type and the presence of 13 exotoxin genes (speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ, ssa and slo) were determined in all 93 available isolates and the Multi Locus Sequece Typing in 10% of isolates of each different emm-type. Overall, 103 cases of S. pyogenes invasive infections were detected: 77 in Catalonia and 26 in Gipuzkoa, being 50.5% females. The incidence rate per 100,000 children was 2.5 for Gipuzkoa and 2.6 for Catalonia, with no significant temporal trends. The median age was 30 months. The most frequent clinical presentations were: pneumonia (26.2%), bacteremia/sepsis (23.3%), septic arthritis/osteomyelitis (22.3%), cellulitis/mastoiditis (12.6%) and meningitis (6.8%). Eight children developed streptococcal toxic shock syndrome. Nine cases were preceded by varicella infection. The associated mortality rate was 3.9%. Three isolates were resistant to erythromycin, being one of them also resistant to clindamycin and 4 isolates were resistant to levofloxacine. Forteen different emm-types were detected being emm1/ST28 (40.9%) the most frequent clone in both regions followed by emm12/ST36-ST242, emm6/ST382, emm3/ST15, emm75/ST150 and emm4/ST38-39. speA gene was only detected in emm1 and emm3 isolates. Eight exotoxins were enough to assign an emm-type with a very high degree of accuracy (95%). The 30-valent vaccine would include 96.8% of isolates.

Emergence of dominant toxigenic M1T1 Streptococcus pyogenes clone during increased scarlet fever activity in England: a population-based molecular epidemiological study

SummaryBackgroundSince 2014, England has seen increased scarlet fever activity unprecedented in modern times. In 2016, England's scarlet fever seasonal rise coincided with an unexpected elevation in invasive Streptococcus pyogenes infections. We describe the molecular epidemiological investigation of these events.MethodsWe analysed changes in S pyogenes emm genotypes, and notifications of scarlet fever and invasive disease in 2014–16 using regional (northwest London) and national (England and Wales) data. Genomes of 135 non-invasive and 552 invasive emm1 isolates from 2009–16 were analysed and compared with 2800 global emm1 sequences. Transcript and protein expression of streptococcal pyrogenic exotoxin A (SpeA; also known as scarlet fever or erythrogenic toxin A) in sequenced, non-invasive emm1 isolates was quantified by real-time PCR and western blot analyses.FindingsCoincident with national increases in scarlet fever and invasive disease notifications, emm1 S pyogenes upper respiratory tract isolates increased significantly in northwest London in the March to May period, from five (5%) of 96 isolates in 2014, to 28 (19%) of 147 isolates in 2015 (p=0·0021 vs 2014 values), to 47 (33%) of 144 in 2016 (p=0·0080 vs 2015 values). Similarly, invasive emm1 isolates collected nationally in the same period increased from 183 (31%) of 587 in 2015 to 267 (42%) of 637 in 2016 (p<0·0001). Sequences of emm1 isolates from 2009–16 showed emergence of a new emm1 lineage (designated M1UK)—with overlap of pharyngitis, scarlet fever, and invasive M1UK strains—which could be genotypically distinguished from pandemic emm1 isolates (M1global) by 27 single-nucleotide polymorphisms. Median SpeA protein concentration in supernatant was nine-times higher among M1UK isolates (190·2 ng/mL [IQR 168·9–200·4]; n=10) than M1global isolates (20·9 ng/mL [0·0–27·3]; n=10; p<0·0001). M1UK expanded nationally to represent 252 (84%) of all 299 emm1 genomes in 2016. Phylogenetic analysis of published datasets identified single M1UK isolates in Denmark and the USA.InterpretationA dominant new emm1 S pyogenes lineage characterised by increased SpeA production has emerged during increased S pyogenes activity in England. The expanded reservoir of M1UK and recognised invasive potential of emm1 S pyogenes provide plausible explanation for the increased incidence of invasive disease, and rationale for global surveillance.FundingUK Medical Research Council, UK National Institute for Health Research, Wellcome Trust, Rosetrees Trust, Stoneygate Trust.