Ongoing epidemic of scarlet fever in Shanghai and the emergence of M1UK lineage group A Streptococcus: a 14-year surveillance study across the COVID-19 pandemic period

Abstract

Background: The surge of group A Streptococcus (GAS) infections in regional countries warranted attention in the post-COVID-19 era. The resurgence of notifiable scarlet fever in China has been a public health issue since 2011. We conducted a consecutive 14-year surveillance study to analyse dynamic epidemiological profiles of scarlet fever from the perspective of epidemic trend and molecular evolution of GAS strains.

Methods: From 2011 to 2024, epidemiological data on notifiable cases of scarlet fever and 3370 GAS isolates from children with scarlet fever were analysed. Incidence rates were calculated as the mean rate per 100,000 population with 95% CIs. Whole genome sequencing was performed on 332 emm12 and 248 emm1 isolates.

Findings: From 2011 to 2024, a total of 25,539 cases of scarlet fever were reported in Shanghai. The mean incidence declined from 17.1/100,000 population (95%CI 9.7-24.3, pre-COVID-19 period) to 4.8/100,000 population (2.0-10.1, post-COVID-19 period). Children aged 4-9 years represented 85.6% of cases. Sixteen emm types were identified with predominance of emm12 (66.4%) and emm1 (29.8%). The annual proportions of emm12 and emm1 alternatively fluctuated with a cycle of six years. GAS isolates displayed >90% resistance rate to erythromycin, clindamycin, and tetracycline. The distribution of emm types, antimicrobial resistance rates and profiles, and differences in superantigen genes carried by the emm12 and emm1 isolates were similar in the pre- and post-COVID-19 periods. Phylogenetic analysis indicated 96.7% of emm12 isolates belonged to Clade II, harbouring ICE-emm12 and ΦHKU.vir. Among the emm1 isolates, the proportions of the ST1274 isolates increased from 10.5% (pre-COVID-19 period) to 73.7% (post-COVID-19 period). Four novel M1_UK isolates were found in Shanghai, with distinctive characteristics of presence of speC and ssa.

Interpretation: Persistent and periodic predominance of emm12 and emm1 types was responsible for the annual epidemic of scarlet fever in Shanghai. A marked decline in the incidence of scarlet fever in the last 5 years in Shanghai may be associated with enhanced type-specific immunity among the susceptible population and enhanced infection control measures, awareness, and actions in child institutions in the post-COVID-19 era. The emergence of the M1_UK isolates with some distinctive characteristics and ST1274 lineage warrants further attention and continuous surveillance in China.

Funding: Shanghai municipal three-year action plan for strengthening the construction of the public health system 2023-2025 (GWVI-2.1.2); Research project of Shanghai Minhang District Health Commission (2024MW45).

Keywords: Genomic evolution; Group A Streptococcus; M1UK; Scarlet fever; emm type.

Fig. 1

Epidemiological characterizations of scarlet fever in Shanghai from 2011 to 2024. (a) Epidemic trend of scarlet fever in Shanghai and a sentinel hospital. An ongoing resurgence of scarlet fever in Shanghai since 2011. Monthly distribution of patients with scarlet fever in our hospital from 2011 to 2019 (b) and 2020 to 2024 (c). (d) Incidence proportion by age in our hospital.

Fig. 2

Distribution of emm types among GAS strains and profiles of superantigen genes among emm12 and emm1 GAS strains. (a) The emm12 and emm1 strains were predominant during the epidemic of scarlet fever in Shanghai since 2011. ∗ From January to May. (b) Eleven superantigen genes were compared between emm12 and emm1 GAS strains. ∗∗∗∗ means p < 0.0001. ns, non-significant difference.

Fig. 3

Phylogenetic analysis of emm12 GAS genomes based on single nucleotide polymorphisms (SNPs). The analysis involved genomes from this study (n = 332), mainland China public genomes (n = 9), Hong Kong of China (n = 9), United Kingdom (n = 7), Australia (n = 3), the United States (n = 1), and Lebanon (n = 1). The distribution of selected virulence genes, mobile elements, and antibiotic resistance genes is indicated.

Fig. 4

Phylogenetic analysis of emm1 GAS genomes based on single nucleotide polymorphisms (SNPs). The analysis involved genomes from this study (n = 248), mainland China public genomes (n = 12), Hong Kong of China (n = 9), United Kingdom (n = 39), and Denmark (n = 1). The distribution of selected virulence genes, mobile elements, and antibiotic resistance genes is indicated. The four isolates assigned to M1_UK in this study are indicated with black star.