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Observational Study
. 2025 Jun;44(6):1471-1480.
doi: 10.1007/s10096-025-05116-6. Epub 2025 Apr 7.

Additional biomarkers and emm types associated with group A streptococcal toxic shock syndrome: a Japanese nationwide observational study

Shigeo Hanada #  1   2 , Takeaki Wajima  3 , Misako Takata  4 , Miyuki Morozumi  4 , Yukio Sato  5 , Junichi Sasaki  5 , Satoshi Iwata  4 , Kimiko Ubukata #  4   6
Affiliations
Observational Study

Additional biomarkers and emm types associated with group A streptococcal toxic shock syndrome: a Japanese nationwide observational study

Shigeo Hanada et al. Eur J Clin Microbiol Infect Dis. 2025 Jun.

Abstract

Purpose: The incidence of invasive Group A Streptococcus (iGAS) infection and streptococcal toxic shock syndrome (STSS) is increasing. Early detection and diagnosis of cases that may progress to STSS are currently difficult. In this study, we aimed to identify biomarkers and emm type, one of the virulence factors, associated with STSS development.

Methods: In this multicentre observational study including patients with iGAS infection (n = 305), we investigated the relative associations of host factors, clinical manifestations, biomarkers, and emm type with STSS.

Results: The overall mortality rate was 15.4%; the fatality rate within 28 days of admission was higher in patients with STSS (67.9%, 38/56) than in those without (3.6%, 9/249). The most predominant type was emm1 (38%), detected in 73.2% of the patients with STSS. Risk factors for STSS identified by multivariable analysis included underlying kidney disease (odds ratio [OR], 10.7; 95% confidence interval [CI], 2.1-54.0, p = 0.004), bacteraemia without primary focus (OR, 3.6; 95% CI 1.2-11.1, p = 0.023), necrotizing fasciitis (OR, 8.7; 95% CI 2.6-29.4, p < 0.001), white blood cell count (WBC) < 4,000/µL (OR, 7.8; 95% CI 2.4-25.6, p = 0.001), serum creatine kinase (CK) ≥ 300 U/L (OR, 7.5; 95% CI 2.8-19.8, p < 0.001), and emm1 (OR, 5.2; 95% CI 2.0-13.4, p = 0.001).

Conclusion: WBC < 4,000/µL and CK level ≥ 300 U/L on admission are additional relevant biomarkers for STSS prediction. The most predominant iGAS type, emm1, was significantly associated with STSS.

Keywords: Emm type; Biomarker; Invasive group A Streptococcus infection; Streptococcal toxic shock syndrome.

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Conflict of interest statement

Declarations. Ethical approval: This study was conducted in accordance with the Declaration of Helsinki and Guidelines for Epidemiologic Studies issued by the Japanese Ministry of Health, Labor, and Welfare. The study protocol was approved by the Institutional Review Board of the Keio University School of Medicine Ethics Committee (approval number: 20130455). Consent to participate: The need for written informed consent was waived owing to the use of anonymized stored samples and data. Patient medical records in the database were obtained anonymously using a survey form completed by the attending physicians. Consent to publish: Not applicable. Competing interests: The following authors received financial support within the last 3 years: K. U. from Pfizer Japan Inc., HORIBA, Ltd., and Abbott Diagnostics Medical Co., Ltd., J. S. from Roche Diagnostics K.K., Sysmex Corporation, Asahi Kasei Pharma Corporation, Shionogi & Co., Ltd., and Pfizer Japan Inc. All other authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Association of age with streptococcal toxic shock syndrome (STSS) and outcomes within 28 days of hospitalisation in the patients with invasive S. pyogenes infections (n = 305). STSS was identified in 18.4% (n = 56) patients according to the CDC criteria, and the mortality rate was 15.4% (n = 47). The median age was 59 years (IQR 36–71 years)
Fig. 2
Fig. 2
Relationship between diagnosis of streptococcal toxic shock syndrome (STSS) and length of hospital stay in fatal cases of invasive S. pyogenes infections (A) and Kaplan–Meier estimates of the probability of 28-day survival (B). The mortality rate was 67.9% (38/56) in STSS cases and 3.6% (9/249) in non-STSS cases
Fig. 3
Fig. 3
Relationship between emm types of the isolates and streptococcal toxic shock syndrome (STSS) in patients with invasive S. pyogenes infections. A significant difference was observed between STSS and non-STSS in the emm1 and emm89 types (emm1, OR 6.3; 95% CI 3.3–12.2, p < 0.001; emm89, OR 0.1; 95% CI 0.0-0.6, p = 0.002)
See this image and copyright information in PMC

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