Group A Streptococcal Infection

Streptococcus pyogenes, a gram-positive bacterium commonly referred to as group A Streptococcus (GAS) is a notable human pathogen that poses a substantial danger to global health care, infecting over 18 million individuals and causing more than 500,000 fatalities each year.1 GAS can induce a spectrum of clinical infections, ranging from mild conditions such as pharyngitis and impetigo to severe invasive infections (iGAS), including sepsis, streptococcal toxic shock syndrome (STSS), and necrotizing fasciitis. Erysipelas, glomerulonephritis, suppurative tonsillitis, scarlet fever, and rheumatic fever are further diseases attributable to GAS.2 GAS infection rates progressively diminished throughout the 20th century in Western nations, primarily attributable to enhanced living standards and increased availability of antibiotics. The severity of GAS infections escalates when they coincide with other viral infections, suggesting a credible hypothesis regarding the potential for COVID-19 to facilitate coinfections with invasive group A Streptococcus (iGAS), hence contributing to the notable rise in iGAS infections during the pandemic.3 Post–COVID-19, there has been a significant rise in GAS infection rates in Europe, the United States, Australia, and New Zealand, raising global alarm.4–6 The study entitled “A case series of invasive (iGAS) and non-invasive (non-iGAS) pediatric group A Streptococcal infections at a tertiary health care center: resurgence and concomitant viral infections” authored by Fields et al. statistically supports this premise.7 They performed a retrospective chart review and compared the GAS and iGAS cases between July 1, 2021, and June 30, 2023. They noted an increase in the incidence of GAS and iGAS infection during the post–COVID-19 period (July 1, 2022–June 30, 2023) as well as concomitant infection with influenza virus. The reasons for the emergence of GAS infections internationally are summarized as follows. Initially, this may be attributed to the confinement of children during the COVID-19 epidemic, resulting in heightened vulnerability to the pathogen—termed “immune debt.”6 The diminished exposure to GAS during the COVID-19 lockdown has resulted in insufficient immunity against GAS in certain children, hindering the natural development of immunity levels and resulting in a higher prevalence of susceptible youngsters. Moreover, initial GAS infection may be readily confused with SARS-CoV-2 Omicron infection by both parents and health care professionals, as it presents with pharyngitis-like symptoms (fever and sore throat), thus delaying the initiation of proper antibiotic therapy.8 Secondly, alterations in the bacterial genome and virulence may render GAS more susceptible, exemplified by the rise in GAS infections in 2014, which coincided with an increase in iGAS infections and the introduction of significant virulent GAS lineages.9 Infections caused by iGAS typically continue to advance, necessitating timely treatment interventions to reduce morbidity and death in affected individuals. Various virulence factors are associated with the complex mechanisms of GAS infection. The synthesis of exotoxins and certain surface proteins, including M-proteins encoded by the emm gene, is linked to significant virulence factors of GAS.10 The emm genotyping establishes the basis for identifying outbreaks and the severity of diseases caused by GAS. Certain emm strains, particularly emm1, have been linked to iGAS cases, including necrotizing fasciitis and STSS, exhibiting exacerbated clinical symptoms. Additionally, GAS is linked to many virulence factors known as superantigens (T-cell superantigens), some of which reside on chromosomes, whereas others are associated with prophages, perhaps contributing to SSTS.10 In 2011, an unforeseen increase in the occurrence of scarlet fever was documented in mainland China and Hong Kong.11 A prophage including superantigens (SSA and SpeC) and DNase (Spd1) in a macrolide-resistant emm12 strain was identified as a significant outbreak isolate of scarlet fever in these areas. Similarly, a superantigen overexpressing emm1 strain known as M1UK, recognized as an outbreak strain in England in 2016, is presently proliferating across European nations and parts of North America, Australia, New Zealand, Canada, and Taiwan.12,13 Prophage carrying superantigens were identified in 26% of the M1UK lineage scarlet fever isolates in Australia, further indicating that mobile genetic elements are a significant risk factor for future increases in GAS infections.14 Infection with iGAS correlates with the cotransmission of several winter viruses, including respiratory syncytial virus and influenza, as infection with one pathogen may elevate the susceptibility to a secondary disease, facilitating the entry of GAS by compromising the respiratory barrier. The severity of respiratory infections markedly escalates during concurrent bacterial infections or subsequent to viral infections (secondary infections).15 The predominant cause of severe and fatal bronchopneumonia is secondary influenza A infection with Streptococcus pneumoniae or GAS, and both influenza A and B viruses are linked to an elevated risk of severe GAS infection.16 There are unresolved enigmas in the control of GAS infections. Use of rapid antigen test for bedside diagnosis of GAS and early initiation of antibiotics can alleviate clinical symptoms, reduce transmission, and avoid complications. Although GAS remains susceptible to β-lactam antibiotics, failures in clinical settings have been recorded throughout decades, for reasons that remain inadequately understood. Recent reports of reduced penicillin susceptibility in GAS due to PBP mutation are concerning.17 Clinicians must remain vigilant regarding the potential rise in invasive cases, maintain a high index of suspicion for pertinent patients, and offer suitable safety recommendations, as the prompt identification of individuals infected with iGAS and the timely initiation of targeted and supportive treatment can be lifesaving. Notwithstanding the challenges, there is optimism that an efficacious GAS vaccine will be available in the near future.

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