In the last 10–15 years, there has been a global resurgence of scarlet fever, an infection historically associated with significant morbidity and mortality. It is unknown whether scarlet fever incidence has increased in Australia. We aimed to examine the incidence, predictors and severity of scarlet fever in the state of Victoria, Australia from 2007 to 2017, analyzing scarlet fever emergency department (ED) presentations, hospitalizations and deaths. Of the 1 578 scarlet fever cases during the study period, most occurred in children aged <10 years (1 344, 85%), in males (882, 56%), and during winter and spring months (918, 57%). There were no deaths with scarlet fever, however, 374 cases (24%) were admitted to hospital. The annual incidence of scarlet fever was stable during the study period (mean, 2.5; range, 1.9–3.1 cases per 100 000). Annual incidence was highest in children aged <5 years (19.3 per 100 000), and was 21% higher in males than females, adjusting for age and year (incidence rate ratio, 1.21, 95%CI 1.09–1.34). Whilst scarlet fever ED presentations and hospitalizations were stable in Victoria from 2007 to 2017, the recent identification of a Streptococcus pyogenes variant in Australia associated with epidemic scarlet fever overseas highlights the risk of future outbreaks.

Introduction: According to the Public Health Agency of Canada, the rate of invasive Group A Streptococcus (iGAS) has more than doubled since it first became a notifiable disease in 2000. Our objectives were to describe the clinical and laboratory characteristics of iGAS in a geographic area that sees a relatively high volume of cases annually. Methods: We conducted a retrospective chart review of all adult and pediatric patients presenting to the Thunder Bay Regional Health Sciences Centre Emergency Department from January 2016 to December 2017 with a hospital discharge diagnosis of iGAS infection using ICD-10 codes. Patient demographics, host characteristics, triage vital signs, laboratory values, culture sites, and disposition were analyzed using univariate and bivariate statistics. Results: Forty-five cases of iGAS were identified over 2 years, with a mean age of 45 years (SD 18). The most prevalent associations were male sex (69%), diabetes mellitus (44%), current or previous alcohol abuse (38%), and current or previous intravenous drug use (33%). Prevalence of iGAS was roughly two times the national average in 2016 (11.5 per 100,000) and four times the national average in 2017 (25.5 per 100,000). Mean triage vital signs included a systolic blood pressure of 126 mmHg (SD 24), diastolic blood pressure of 73 mmHg (SD 16), temperature of 37.3°C (SD 1.4), oxygen saturation of 97% (SD 2), heart rate of 113 beats per minute (SD 22), and respiratory rate of 22 breaths per minute (SD 7). Mean laboratory values revealed a white blood cell count of 17,500 cells/μL (SD 9,800) and C-reactive protein of 243 mg/L (SD 144). A higher Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score was positively correlated with longer hospital length of stay (r = 0.46, p < 0.01). Conclusion: Despite its morbidity and mortality, iGAS infections often present insidiously with only mild abnormalities in triage vital signs, and require a high index of suspicion by the emergency physician for a prompt diagnosis, particularly in at-risk populations such as patients with diabetes mellitus or those who misuse alcohol or drugs.

Acute rheumatic fever (ARF), an auto-immune response to a group A Streptococcus infection and precursor to rheumatic heart disease (RHD), remains endemic in many socio-economically disadvantaged settings. A Global Resolution on ARF and RHD was recently adopted at the 71st World Health Assembly where governments committed to improving efforts to prevent and control ARF and RHD. To inform these efforts, the objectives of this study were to examine associations between childhood ARF in the UK between 1958 and 1969 and a range of environmental and social factors. Of 17 416 children from the nationally representative birth cohort of the National Child Development Study, ARF was reported in 23 children during early childhood (between birth and the 7-year follow-up) and in 29 additional children during middle childhood (between the 7- and 11-year follow-ups). Risk factors associated with ARF in both early and middle childhood were: a large family size; attendance at a private nursery or class; a history of nephritis, kidney or urinary tract infections; and a history of throat or ear infections. Risk factors for ARF in early childhood alone were families with fathers in a professional or semi-professional occupation and families who moved out of their local neighbourhood. Risk factors in late childhood alone included overcrowding and free school meals. These data suggest that prevention strategies in ARF endemic settings may be enhanced by targeting, for example, new members entering a community and children in environments of close contact, such as a nursery or shared bedrooms.

Streptococcus pyogenes (or Group A Streptococcus, GAS) is a Gram-positive human pathogen responsible for a diverse array of superficial, invasive and immune-related diseases. GAS infections have historically been diseases of poverty and overcrowding, and remain a significant problem in the developing world and in disadvantaged populations within developed countries. With improved living conditions and access to antibiotics, the rates of GAS diseases in developed societies have gradually declined during the 20th century. However, genetic changes in circulating GAS strains and/or changes in host susceptibility to infection can lead to dramatic increases in the rates of specific diseases. No situations exemplify this more than the global upsurge of invasive GAS disease that originated in the 1980s and the regional increases in scarlet fever in north-east Asia and the UK. In each case, increased disease rates have been associated with the emergence of new GAS strains with increased disease-causing capability. Global surveillance for new GAS strains with increased virulence is important and determining why certain populations suddenly become susceptible to circulating strains remains a research priority. Here, we overview the changing epidemiology of GAS infections and the genetic alterations that accompany the emergence of GAS strains with increased capacity to cause disease.

Invasive group A streptococcal (iGAS) infections cause severe disease and death, especially in residents of long-term care facilities (LTCFs). In order to inform iGAS prevention, we compared the risk of iGAS in LTCF residents and community residents. We identified LTCF residents among cases of iGAS from national surveillance (2009–2010) using postcode matching, and cases of hospital-acquired infections via hospital admission records. We used Poisson regression to calculate incidence rate ratios (IRR) and logistic regression to explore factors associated with case fatality rate (CFR). A total of 2741 laboratory-confirmed iGAS cases were matched to a hospital admission: 156 (6%) were defined as hospital-acquired. Out of the total cases, 96 (3·5%) were LTCF residents. Compared with community residents, LTCF residents over 75 years of age had a higher risk of iGAS infection (IRR = 1·7; 95% CI 1·3–2·1) and CFR (OR = 2·3; 95% CI 1·3–3·8). Amongst community-acquired cases, the risk of iGAS in LTCF residents between 75 and 84 years of age doubled (IRR = 2·7; 95% CI 1·8–3·9) compared with their community counterparts. The CFR among community-acquired cases was higher in LTCF residents than community residents (21% vs. 11%). Age remained associated with death in our final model. Our study showed that, even controlling for age, LTCF residents have a higher risk of acquiring and dying from iGAS. Whilst existing co-morbidities may explain this, it is reasonable to assume that the institutional setting may facilitate transmission. Therefore, cases in LTCF require prompt investigation together with a better understanding of factors contributing to the acquisition of infection.

Impetigo is common in remote Indigenous children of northern Australia, with the primary driver in this context being Streptococcus pyogenes [or group A Streptococcus (GAS)]. To reduce the high burden of impetigo, the transmission dynamics of GAS must be more clearly elucidated. We performed whole genome sequencing on 31 GAS isolates collected in a single community from children in 11 households with ⩾2 GAS-infected children. We aimed to determine whether transmission was occurring principally within households or across the community. The 31 isolates were represented by nine multilocus sequence types and isolates within each sequence type differed from one another by only 0–3 single nucleotide polymorphisms. There was evidence of extensive transmission both within households and across the community. Our findings suggest that strategies to reduce the burden of impetigo in this setting will need to extend beyond individual households, and incorporate multi-faceted, community-wide approaches.

Epidemiological data regarding group A streptococcal (GAS) infections in South East Asia are scarce with no information from Laos. We characterized emm types, emm clusters and the antibiotic resistance profile of 124 GAS isolates recovered in Laos during 2004–2013. Most strains were recovered from skin and invasive infections (76% and 19%, respectively). Thirty-four emm types were identified as belonging to 12 emm clusters and no novel emm types were identified. No significant differences were observed in the distribution of emm types or emm clusters according to age or site of recovery (skin or invasive infections). There was moderate strain diversity in this country but considerable differences in emm-type distribution between Laos, Thailand and Cambodia. Vaccine coverage was high for the J8 vaccine candidate. The theoretical coverage for the 30-valent vaccine candidate needs further investigation. Antibiotic resistance was moderate to erythromycin and chloramphenicol (8% and 7%, respectively) and low to ofloxacin (<1%).

Although the incidence of invasive group A streptococcal disease in northern Australia is very high, little is known of the regional epidemiology and molecular characteristics. We conducted a case series of Northern Territory residents reported between 2011 and 2013 with Streptococcus pyogenes isolates from a normally sterile site. Of the 128 reported episodes, the incidence was disproportionately high in the Indigenous population at 69·7/100 000 compared to 8·8/100 000 in the non-Indigenous population. Novel to the Northern Territory is the extremely high incidence in haemodialysis patients of 2205·9/100 000 population; and for whom targeted infection control measures could prevent transmission. The incidences in the tropical north and semi-arid Central Australian regions were similar. Case fatality was 8% (10/128) and streptococcal toxic shock syndrome occurred in 14 (11%) episodes. Molecular typing of 82 isolates identified 28 emm types, of which 63 (77%) were represented by four emm clusters. Typing confirmed transmission between infant twins. While the diverse range of emm types presents a challenge for effective coverage by vaccine formulations, the limited number of emm clusters raises optimism should cluster-specific cross-protection prove efficacious. Further studies are required to determine effectiveness of chemoprophylaxis for contacts and to inform public health response.

The objective of this study was to estimate the direct financial costs of hospital care for management of invasive group A streptococcal (GAS) infections using hospital records for cases diagnosed in England. We linked laboratory-confirmed cases (n = 3696) identified through national surveillance to hospital episode statistics and reimbursement codes. From these codes we estimated the direct hospital costs of admissions. Almost all notified invasive GAS cases (92% of 3696) were successfully matched to a primary hospital admission. Of these, secondary admissions (within 30 days of primary admission) were further identified for 593 (17%). After exclusion of nosocomial cases (12%), the median costs of primary and secondary hospital admissions were estimated by subgroup analysis as £1984–£2212 per case, totalling £4·43–£6·34 million per year in England. With adjustment for unmatched cases this equated to £4·84–£6·93 million per year. Adults aged 16–64 years accounted for 48% of costs but only 40% of cases, largely due to an increased number of surgical procedures. The direct costs of hospital admissions for invasive GAS infection are substantial. These estimated costs will contribute to a full assessment of the total economic burden of invasive GAS infection as a means to assess potential savings through prevention measures.

In order to investigate for possible differences between paediatric and adult invasive Streptococcus pyogenes (iGAS) infections, a total of 142 cases were identified in 17 Greek hospitals during 2003–2007, of which 96 were children and 46 adults. Bacteraemia, soft tissue infections, streptococcal toxic shock syndrome (STSS), and necrotizing fasciitis were the main clinical presentations (67·6%, 45·1%, 13·4%, and 12·0% of cases, respectively). Bacteraemia and lymphadenitis were significantly more frequent in children (P = 0·019 and 0·021, respectively), whereas STSS was more frequent in adults (P = 0·017). The main predisposing factors in children were varicella and streptococcal pharyngotonsillitis (25% and 19·8%, respectively), as opposed to malignancy, intravenous drug abuse and diabetes mellitus in adults (19·6%, 15·2% and 10·9%, respectively). Of the two dominant emm-types, 1 and 12 (28·2% and 8·5%, respectively), the proportion of emm-type 12 remained stable during the study period, whereas emm-type 1 rates fluctuated considerably. Strains of emm-type 1 from children were associated with erythromycin susceptibility, STSS and intensive-care-unit admission, whereas emm-type 12 isolates from adults were associated with erythromycin and clindamycin resistance. Finally, specific emm-types were detected exclusively in adults or in children. In conclusion, several clinical and epidemiological differences were detected, that could prove useful in designing age-focused strategies for prevention and treatment of iGAS infections.

A 15-h stay in a paediatric intensive care unit by a girl with generalized dermal lesions superinfected with Streptococcus pyogenes led to four streptococcal infections in healthcare workers. Phenotypic and molecular analyses of the strains revealed that four isolates, characterized as emm87/ST62/T28, were identical to the isolate obtained from the index case. The occurrence of this outbreak, despite of the girl's brief hospital stay and appropriate patient management, highlights the high transmissibility of this pathogen.

Streptococcus pyogenes causes a variety of infections because of virulence factors such as capsular hyaluronic acid and M protein. The aim of this study was to determine emm types and capsule phenotype in 110 isolates of S. pyogenes from patients with invasive (sterile sites) and non-invasive (mainly pharyngitis) infections in Chile, and the relationship between both virulence factors. The most abundant types found were emm12, emm1, emm4 and emm28 and their distribution was similar to that seen in Latin America and developed countries, but very different from that in Asia and Pacific Island countries. Ten of 16 emm types identified in pharyngeal isolates were found in sterile-site isolates, and three of nine emm types of sterile-site isolates occurred in pharyngeal isolates; three emm subtypes were novel. The amount of hyaluronic acid was significantly higher in sterile-site isolates but did not differ substantially among emm types. Only three isolates were markedly capsulate and two of them had mutations in the csrR gene that codes for a repressor of capsule synthesis genes. We found a non-random association between emm types and csrR gene alleles suggesting that horizontal gene transfer is not freely occurring in the population.

The incidence of serious skin infections in New Zealand children is significantly higher than in comparative countries. This study aimed to describe the epidemiology of these infections and identify changes in disease distribution over time. Discharge data were analysed for all children admitted to a New Zealand public hospital with a serious skin infection during the period 1990–2007. Patient and admission variables were compared between 1990–1999 and 2000–2007. The incidence of serious skin infections almost doubled from 298·0/100 000 in 1990 to 547·3/100 000 in 2007. The highest rates were observed in boys, preschool-aged children, Māori and Pacific children, those living in deprived neighbourhoods, urban areas and northern regions. Over time there were disproportionate increases in infection rates in Māori and Pacific children and children from highly deprived areas. Serious skin infections are an increasing problem for New Zealand children. Worsening ethnic and socioeconomic health inequalities may be contributing to increasing rates.

Invasive group A streptococcal (GAS) disease is a condition of clinical and public health significance. We conducted epidemiological analyses to determine if the presence of gastrointestinal (GI) complaints (diarrhea and/or vomiting) early in the course of invasive GAS disease is associated with either of two severe outcomes: GAS necrotizing fasciitis, or hospital mortality. Subjects were hospitalized for invasive GAS disease throughout the state of Florida, USA, during a 4-year period. Multiple imputation using the Markov chain Monte Carlo method was used to replace missing values with plausible values. Excluding cases with missing data resulted in a sample size of 138 invasive GAS patients (the complete subject analysis) while the imputed datasets contained 257 records. GI symptomatology within 48 h of hospital admission was not associated with hospital mortality in either the complete subject analysis [adjusted odds ratio (aOR) 0·86, 95% confidence interval (CI) 0·31–2·39] or in the imputed datasets. GI symptoms were significantly associated with GAS necrotizing fasciitis in the complete subject analysis (aOR 4·64, 95% CI 1·18–18·23) and in the imputed datasets but only in patients aged <55 years. The common cause of GI symptoms and necrotizing fasciitis may be streptococcal exotoxins. Clinicians who are treating young individuals presumed to be in the early stages of invasive GAS disease should take note of GI symptoms and remain vigilant for the development of a GAS necrotizing soft-tissue infection.

Streptococcus pyogenes group A (GAS) is a primary human pathogen. We performed genetic emm sequence and serological T-antigen typing of 819 mostly invasive GAS isolates recovered in Israel during 1996–2005. Of the 72 emm types found, the six most prevalent types (1, 81, 89, 14, 28, 5) comprised 30·2% of all isolates, and emm-type changes were observed over the years. The predicted coverage of the 26-valent S. pyogenes vaccine formulated for usage in the USA was predicted to be only ~60%. On the basis of different emm–T antigen type associations, some Israeli strains are probably different clonal types than those found in USA. About 2% of GAS had emm types that were originally associated with S. dysgalactiae subsp. equisimilis emm genes. Therefore, routine emm typing allows meaningful GAS strain surveillance, and provides data relevant to better vaccine coverage.

The characteristics of 359 group A streptococcal (GAS) isolates collected from Chinese paediatric patients in two periods (1993–1994, 2005–2006) were studied. Isolates were assigned to emm types and assayed for eight superantigen (SAg) genes (speA, speC, speH, speI, speG, speJ, ssa, SMEZ). Types emm1 and emm12 were consistently the most prevalent during the two periods, while others varied in frequency. GAS isolates carrying six or more SAg genes increased from 46·53% (1993–1994) to 78·39% (2005–2006); ssa, speH and speJ genes (P<0·05) increased but speA declined (P<0·05). SAg gene profiles were closely associated with the emm type, but strains of the same emm type sometimes carried different SAg genes in the two periods. No significant difference in emm-type distribution and SAg gene profile was noted between isolates from different diseases. These data may contribute towards the development of a GAS vaccine in China.

The streptococcal pyrogenic toxins A, B, and C (SPEA, SPEB, and SPEC) are responsible for the fever, rash, and other toxicities associated with scarlet fever and streptococcal toxic shock syndrome. This role, together with the ubiquity of diseases caused by Streptococcus pyogenes, have prompted structural analyses of SPEA by several groups. Papageorgiou et al. (1999) have recently reported the structure of SPEA crystallized in the absence of zinc. Zinc has been shown to be important in the ability of some staphylococcal and streptococcal toxins to stimulate proliferation of CD4+ T-cells. Since cadmium is more electron dense than zinc and typically binds interchangeably, we grew crystals in the presence of 10 mM CdCl2. Crystals have been obtained in three space groups, and the structure in the P212121 crystal form has been refined to 1.9 Å resolution. The structural analysis revealed an identical tetramer as well as a novel tetrahedral cluster of cadmium in all three crystal forms on a disulfide loop encompassing residues 87–98. No cadmium was bound at the site homologous to the zinc site in staphylococcal enterotoxins C (SECs) despite the high structural homology between SPEA and SECs. Subsequent soaking of crystals grown in the presence of cadmium in 10 mM ZnCl2 showed that zinc binds in this site (indicating it can discriminate between zinc and cadmium ions) using the three ligands (Asp77, His106, and His110) homologous to the SECs plus a fourth ligand (Glu33).