Rapid expansion and international spread of M1UK in the post-pandemic UK upsurge of Streptococcus pyogenes.

The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1global strains, invasive M1UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks.

Managing the deteriorating child with suspected group A Streptococcus infection.

Group A Streptococcus bacteria can cause various pyogenic infections such as tonsillitis, pharyngitis, scarlet fever, impetigo, erysipelas, cellulitis and pneumonia. Most group A Streptococcus infections in children are mild and respond positively to treatment with antibiotics. However, some children develop severe infection accompanied by complications such as sepsis and will require urgent treatment, which may include non-invasive or invasive ventilation and the administration of fluids and vasoactive agents. In some instances, for example if there are no beds available in the paediatric intensive care unit, these interventions may be undertaken in a ward setting. This article gives an overview of group A Streptococcus infection, including two rare but severe complications, streptococcal toxic shock syndrome and necrotising fasciitis. It uses a fictionalised case study to examine the management of the deteriorating child with suspected group A Streptococcus infection, including respiratory support, haemodynamic support and symptom management.

Out-of-season increase of puerperal fever with group A Streptococcus infection: a case-control study, Netherlands, July to August 2018.

We observed an increase in notifications of puerperal group A Streptococcus (GAS) infections in July and August 2018 throughout the Netherlands without evidence for common sources. General practitioners reported a simultaneous increase in impetigo. We hypothesised that the outbreak of puerperal GAS infections resulted from increased exposure via impetigo in the community.We conducted a case-control study to assess peripartum exposure to possible, non-invasive GAS infections using an online questionnaire. Confirmed cases were recruited through public health services while probable cases and controls were recruited through social media. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) with logistic regression analysis.We enrolled 22 confirmed and 23 probable cases, and 2,400 controls. Contact with persons with impetigo were reported by 8% of cases and 2% of controls (OR: 3.26, 95% CI: 0.98-10.88) and contact with possible GAS infections (impetigo, pharyngitis or scarlet fever) by 28% and 9%, respectively (OR: 4.12, 95% CI: 1.95-8.68). In multivariable analysis, contact with possible GAS infections remained an independent risk factor (aOR: 4.28, 95% CI: 2.02-9.09).We found an increased risk of puerperal fever after community contact with possible non-invasive GAS infections. Further study of this association is warranted.

Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes.

The re-emergence of scarlet fever poses a new global public health threat. The capacity of North-East Asian serotype M12 (emm12) Streptococcus pyogenes (group A Streptococcus, GAS) to cause scarlet fever has been linked epidemiologically to the presence of novel prophages, including prophage ΦHKU.vir encoding the secreted superantigens SSA and SpeC and the DNase Spd1. Here, we report the molecular characterization of ΦHKU.vir-encoded exotoxins. We demonstrate that streptolysin O (SLO)-induced glutathione efflux from host cellular stores is a previously unappreciated GAS virulence mechanism that promotes SSA release and activity, representing the first description of a thiol-activated bacterial superantigen. Spd1 is required for resistance to neutrophil killing. Investigating single, double and triple isogenic knockout mutants of the ΦHKU.vir-encoded exotoxins, we find that SpeC and Spd1 act synergistically to facilitate nasopharyngeal colonization in a mouse model. These results offer insight into the pathogenesis of scarlet fever-causing GAS mediated by prophage ΦHKU.vir exotoxins.

Molecular epidemiology and antimicrobial resistance of group a streptococcus recovered from patients in Beijing, China.

BACKGROUND: Group A streptococcus (GAS) is an important human pathogen responsible for a broad range of infections. Epidemiological surveillance has been crucial to detect changes in the geographical and temporal variation of the disease pattern. The objective of this study was to investigate the molecular epidemiological characteristics and antimicrobial resistance of GAS isolates from patients in Children's Hospital in Beijing. METHODS: From 2016 to 2017, pharyngeal swab samples were collected from the outpatients in Children's Hospital, Capital Institute of Pediatrics, who were diagnosed with scarlet fever. Antimicrobial susceptibility test was performed according to the distribution of conventional antibiotics and Clinical and Laboratory Standards Institute (CLSI) recommendations. The distribution of the macrolide-resistance genes (ermB, ermA, mefA), emm (M protein-coding gene) typing, and superantigens (SAg) gene profiling were examined by polymerase chain reaction (PCR). RESULTS: A total of 297 GAS isolates were collected. The susceptibility of the isolates to penicillin, ceftriaxone, and levofloxacin was 100%. The resistance rate to erythromycin and clindamycin was 98.3 and 96.6%, respectively. The dominant emm types were emm12 (65.32%), emm1 (27.61%), emm75 (2.69%), and emm89 (1.35%). Of the 297 isolates, 290 (97.64%) carried the ermB gene, and 5 (1.68%) carried the mefA gene, while none carried the ermA gene. The most common superantigen genes identified from GAS isolates were smeZ (96.97%), speC (92.59%), speG (91.58%), ssa (85.52%), speI (54.55%), speH (52.19%), and speA (34.34%). Isolates with the genotype emm1 possessed speA, speC, speG, speJ, speM, ssa, and smeZ, while emm12 possessed speC, speG, speH, speI, speM, ssa, and smeZ superantigens. CONCLUSIONS: The prevalent strain of GAS isolates in Beijing has a high resistance rate to macrolides; however, penicillin can still be the preferred antibiotic for treatment. Erythromycin resistance was predominantly mediated by ermB. The common emm types were emm12 and emm1. There was a correlation between emm and the superantigen gene. Thus, long-term monitoring and investigation of the emm types and superantigen genes of GAS prevalence are imperative.

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.

OBJECTIVE: Scarlet 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. METHOD: Epidemiological 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. RESULTS: The 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. CONCLUSION: A 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.

Genome analysis of a multidrug-resistant Streptococcus sanguis isolated from a throat swab of a child with scarlet fever.

OBJECTIVES: A multidrug-resistant strain of the opportunistic pathogen Streptococcus sanguis (S28) was isolated from a throat swab of a child with scarlet fever as a rare case. Genome sequencing and analysis of strain S28 were performed to gain a better understanding of the multidrug resistance mechanisms of S. sanguis and its relationship with scarlet fever. METHODS: The genome of S. sanguis S28 was sequenced on a Illumina HiSeq platform. Genome assembly was conducted using SOAPdenovo v.2.04 and the assembled genome sequence was submitted to NCBI for annotation. RESULTS: The 1 268 358 696bp genome of S. sanguis S28 contains 2287 coding sequences (CDS) with a GC content of 43.2%. Strain S28 possesses four antimicrobial resistance genes (ARGs), which is consistent with phenotypic analysis. A novel transposon with three genes conferring resistance to macrolide-lincosamide-streptogramin B (MLSB) antibiotics, tetracyclines and aminoglycosides was discovered. CONCLUSION: To our knowledge, this is the first report of a S. sanguis genome isolated from a throat swab of a child with scarlet fever and the first report of a transposon with three activated ARGs conferring resistance to MLSB, tetracyclines and aminoglycosides together.

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

BACKGROUND: Since 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. METHODS: We 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. FINDINGS: Coincident 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. INTERPRETATION: A 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. FUNDING: UK Medical Research Council, UK National Institute for Health Research, Wellcome Trust, Rosetrees Trust, Stoneygate Trust.

Staphylococcal scarlet fever associated with staphylococcal enterotoxin M in an elderly patient.

Staphylococcal scarlet fever (SSF) is characterized by an exanthem without enanthem, bullae, or exfoliation, and is known to be related to Staphylococcus aureus toxins, especially superantigens. It has been reported in children and young adults. Herein, we report the first case of an elderly patient with SSF caused by staphylococcal enterotoxin M (SEM), associated with otitis externa. The patient presented with maculopapular rashes on both arms, thighs, and abdomen and with erythroderma on the face, ears, neck, chest, and back, all of which was followed by desquamation on the face, ears, and trunk. A culture of ear discharge grew methicillin susceptible S. aureus that was only positive for SEM among the superantigens tested.

Detection of Epidemic Scarlet Fever Group A Streptococcus in Australia.

Sentinel hospital surveillance was instituted in Australia to detect the presence of pandemic group A Streptococcus strains causing scarlet fever. Genomic and phylogenetic analyses indicated the presence of an Australian GAS emm12 scarlet fever isolate related to United Kingdom outbreak strains. National surveillance to monitor this pandemic is recommended.

Effect of meteorological factors on scarlet fever incidence in Guangzhou City, Southern China, 2006-2017.

OBJECTIVE: To explore the relationship between meteorological factors and scarlet fever incidence from 2006 to 2017 in Guangzhou, the largest subtropical city of Southern China, and assist public health prevention and control measures. METHODS: Data for weekly scarlet fever incidence and meteorological variables from 2006 to 2017 in Guangzhou were collected from the National Notifiable Disease Report System (NNDRS) and the Guangzhou Meteorological Bureau (GZMB). Distributed lag nonlinear models (DLNMs) were conducted to estimate the effect of meteorological factors on weekly scarlet fever incidence in Guangzhou. RESULTS: We observed nonlinear effects of temperature, relative humidity, and wind velocity. The risk was the highest when the weekly mean temperature was 31 °C during lag week 14, yielding a relative risk (RR) of 1.48 (95% CI: 1.01-2.17). When relative humidity was 43.5% during lag week 0, the RR was 1.49 (95% CI: 1.04-2.12); the highest RR (1.55, 95% CI: 1.20-1.99) was reached when relative humidity was 93.5% during lag week 20. When wind velocity was 4.4 m/s during lag week 13, the RR was highest at 3.41 (95% CI: 1.57-7.44). Positive correlations were observed among weekly temperature ranges and atmospheric pressure with scarlet fever incidence, while a negative correlation was detected with aggregate rainfall. The cumulative extreme effect of meteorological variables on scarlet fever incidence was statistically significant, except for the high effect of wind velocity. CONCLUSION: Weekly mean temperature, relative humidity, and wind velocity had double-trough effects on scarlet fever incidence; high weekly temperature range, high atmospheric pressure, and low aggregate rainfall were risk factors for scarlet fever morbidity. Our findings provided preliminary, but fundamental, information that may be useful for a better understanding of epidemic trends of scarlet fever and for developing an early warning system. Laboratory surveillance for scarlet fever should be strengthened in the future.

Increased Risk for Invasive Group A Streptococcus Disease for Household Contacts of Scarlet Fever Cases, England, 2011-2016.

The incidence of scarlet fever in England and Wales is at its highest in 50 years. We estimated secondary household risk for invasive group A Streptococcus (iGAS) disease within 60 days after onset of scarlet fever. Reports of scarlet fever in England during 2011-2016 were matched by residential address to persons with laboratory-confirmed iGAS infections. We identified 11 iGAS cases in ≈189,684 household contacts and a 60-day incidence rate of 35.3 cases/100,000 person-years, which was 12.2-fold higher than the background rate (2.89). Infants and contacts >75 years of age were at highest risk. Three cases were fatal; sepsis and cellulitis were the most common manifestations. Typing for 6 iGAS cases identified emm 1.0 (n = 4), emm 4.0 (n = 1), and emm 12.0 (n = 1). Although absolute risk in household contacts was low, clinicians assessing household contacts should be aware of the risk to expedite diagnosis and initiate life-saving treatment.

You're the Flight Surgeon.

Nolan CF. You're the flight surgeon: scarlet fever. Aerosp Med Hum Perform. 2019; 90(2):139-143.

[Study on the super-antigen genes of group A Streptococcus pyogenes strains isolated from patients with scarlet fever and pharyngeal infection, in Beijing, 2015-2017].

Objective: To analyze the characteristics of super-antigen (SAg) of group A Streptococcus pyogenes (GAS), isolated from patients with scarlet fever or pharyngeal infections in Beijing between 2015-2017. Methods: Throat swab specimens from patients with scarlet fever or pharyngeal infections were collected and tested for GAS. Eleven currently known SAg genes including SpeA, speC, speG, speH, speI, speJ, speK, speL, speM, smeZ and ssa were tested by real-time PCR while M protein genes (emm genes) were amplified and sequenced by PCR. Results: A total of 377 GAS were isolated from 6 801 throat swab specimens, with the positive rate as 5.5%. There were obvious changes noticed among speC, speG, speH and speK in three years. A total of 45 SAg genes profiles were observed, according to the SAgs inclusion. There were significant differences appeared in the frequencies among two of the highest SAg genes profiles between emm1 and emm12 strains (χ(2)=38.196, P<0.001; χ(2)=72.310, P<0.001). There also appeared significant differences in the frequencies of speA, speH, speI and speJ between emm1 and emm12 strains (χ(2)=146.154, P<0.001; χ(2)=52.31, P<0.001; χ(2)=58.43, P<0.001; χ(2)=144.70, P<0.001). Conclusions: Obvious changes were noticed among SAg genes including speC, speG, speH and speK from patients with scarlet fever or pharyngeal infections in Beijing between 2015-2017. SAg genes including speA, speH, speI and speJ appeared to be associated with the emm 1 and emm 12 strains. More kinds of SAg genes profiles were isolated form GAS but with no significant differences seen in the main SAg genes profiles, during the epidemic period.

[Etiological characteristics of Streptococcus pyogenes isolated from children with scarlet fever in Tianjin from 2012 to 2016].

Objective: To investigate the etiological characteristics of Streptococcus pyogenes that caused scarlet fever from 2012 to 2016 in Tianjin. Methods: The subjects were children diagnosed clinically as scarlet fever in Tianjin scarlet fever monitoring hospital from 2012 to 2016. The exclusion criteria were children with scarlet fever who were unable to cooperate with sampling. A total of 575 cases of children's swabs were collected. Biochemical methods were used to isolate and identify the bacteria of pharynx swab, and the PCR method was used to detect the emm genotyping and superantigen speA and speC, and the resistance of the strains to 10 antibiotics was measured by K-B paper method. We compared the carrying status of superantigen genes by different types of GAS and the resistance of all GAS to different antibiotics. Results: There were 5 emm types (emm1/11/12/22/89). The dominant types were emm12 (52.9%, 100 strains) and emm1 (44.4%, 84 strains). The carrying rates of speA and speC genes were 21.7% (41 strains) and 76.7% (145 strains), respectively. The speA gene carrying rate of emm1 type GAS was 33.3% (28 strains), which were higher than that of emm12 (12% (12 strains)) (χ(2)=12.21, P<0.001). The speA and speC gene simultaneous carrying rate of emm1 type GAS was 27.4% (23 strains), which was higher than that of emm12 type (12% (12 strains)) (χ(2)=7.01, P=0.008). The percentages of the strains that were resistant to Azithromycin, Erythromycin, Clarithromycin, Clindamycin, Tetracyclin, Levofloxacin and Chloramphenicol were 96.8% (183 strains), 96.3% (182 strains), 92.1% (174 strains), 92.1% (174 strains), 73.0%(138 strains), 2.1% (4 strains) and 1.6% (3 strains), respectively. All isolates were susceptible to Penicillin, Cefazolin and Vancomycin, and there were statistical significance (χ(2)=953.28, P<0.001). Conclusion: The dominant emm types causing scarlet fever are emm12 and emm1. The frequencies of speA and speC in emm1 and emm12 are different. S.pyrogenes in Tianjin were susceptible to penicillin, cefazolin and vancomycin, but highly resistant to the clindamycin, clarithromycin, erythromycin and azithromycin.

Streptococcal group A, C and G pharyngitis in school children: a prospective cohort study in Southern India.

Diagnosing streptococcal pharyngitis in children on the basis of clinical appearance and throat culture is complicated by high colonisation rates and by the ability of other pathogens to cause clinically similar disease. To characterise the epidemiology of Lancefield Group A, C and G ß-haemolytic streptococcus (GAS, GCS and GGS, respectively) in children, we conducted a 2-year prospective study of 307 school children between 7 and 11 years old. GGS and GAS were commonly identified organisms both for silent streptococcal colonisation and symptomatic sore throat, while GCS was uncommonly found. Streptococcal culture positivity at the time of clinical pharyngitis was estimated to reflect true streptococcal pharyngitis in only 26% of instances, with the frequency varying from 54% for children rarely colonised to 1% for children frequently colonised. Numerous GAS emm types were identified, including several types previously associated with severe pharyngitis (e.g. emm types 1, 3 and 28). No severe complications were seen in any child. These data suggest that the clinical diagnosis of streptococcal pharyngitis is likely to remain difficult and that treatment decisions will remain clouded by uncertainty. There remains a need for organism-specific rapid point-of-care streptococcal diagnostic tests and tests that can distinguish between streptococcal colonisation and disease.

Scarlet Fever Epidemic in China Caused by Streptococcus pyogenes Serotype M12: Epidemiologic and Molecular Analysis.

From 2011, Hong Kong and mainland China have witnessed a sharp increase in reported cases, with subsequent reports of epidemic scarlet fever in North Asia and the United Kingdom. Here we examine epidemiological data and investigate the genomic context of the predominantly serotype M12 Streptococcus pyogenes scarlet fever isolates from mainland China. Incident case data was obtained from the Chinese Nationwide Notifiable Infectious Diseases Reporting Information System. The relative risk of scarlet fever in recent outbreak years 2011-2016 was calculated using the median age-standardised incidence rate, compared to years 2003-2010 prior this outbreak. Whole genome sequencing was performed on 32 emm12 scarlet fever isolates and 13 emm12 non-scarlet fever isolates collected from different geographic regions of China, and compared with 203 published emm12 S. pyogenes genomes predominantly from scarlet fever outbreaks in Hong Kong (n=134) and the United Kingdom (n=63). We found during the outbreak period (2011-2016), the median age-standardised incidence in China was 4.14/100,000 (95% confidence interval (CI) 4.11-4.18), 2.62-fold higher (95% CI 2.57-2.66) than that of 1.58/100,000 (95% CI 1.56-1.61) during the baseline period prior to the outbreak (2003-2010). Highest incidence was reported for children 5years of age (80.5/100,000). Streptococcal toxin encoding prophage φHKU.vir and φHKU.ssa in addition to the macrolide and tetracycline resistant ICE-emm12 and ICE-HKU397 elements were found amongst mainland China multi-clonal emm12 isolates suggesting a role in selection and expansion of scarlet fever lineages in China. Global dissemination of toxin encoded prophage has played a role in the expansion of scarlet fever emm12 clones. These findings emphasize the role of comprehensive surveillance approaches for monitoring of epidemic human disease.

Resurgence of scarlet fever in England, 2014-16: a population-based surveillance study.

BACKGROUND: After decades of decreasing scarlet fever incidence, a dramatic increase was seen in England beginning in 2014. Investigations were launched to assess clinical and epidemiological patterns and identify potential causes. METHODS: In this population-based surveillance study, we analysed statutory scarlet fever notifications held by Public Health England from 1911 to 2016 in England and Wales to identify periods of sudden escalation of scarlet fever. Characteristics of cases and outbreaks in England including frequency of complications and hospital admissions were assessed and compared with the pre-upsurge period. Isolates from throat swabs were obtained and were emm typed. FINDINGS: Data were retrieved for our analysis between Jan 1, 1911, and Dec 31, 2016. Population rates of scarlet fever increased by a factor of three between 2013 and 2014 from 8·2 to 27·2 per 100 000 (rate ratio [RR] 3·34, 95% CI 3·23-3·45; p<0·0001); further increases were observed in 2015 (30·6 per 100 000) and in 2016 (33·2 per 100 000), which reached the highest number of cases (19 206) and rate of scarlet fever notifcation since 1967. The median age of cases in 2014 was 4 years (IQR 3-7) with an incidence of 186 per 100 000 children under age 10 years. All parts of England saw an increase in incidence, with 620 outbreaks reported in 2016. Hospital admissions for scarlet fever increased by 97% between 2013 and 2016; one in 40 cases were admitted for management of the condition or potential complications. Analysis of strains (n=303) identified a diversity of emm types with emm3 (43%), emm12 (15%), emm1 (11%), and emm4 (9%) being the most common. Longitudinal analysis identified 4-yearly periodicity in population incidence of scarlet fever but of consistently lower magnitude than the current escalation. INTERPRETATION: England is experiencing an unprecedented rise in scarlet fever with the highest incidence for nearly 50 years. Reasons for this escalation are unclear and identifying these remains a public health priority. FUNDING: None.