By Rochita R. Kadam, MD, and Philip R. Fischer, MD, DTM&H
Rochita Kadam is a senior pediatric resident at Sheikh Shakhbout Medical City in Abu Dhabi, United Arab Emirates. Dr. Fischer is Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN; Department of Pediatrics, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates.
SYNOPSIS: Around the world, rates of severe illness caused by group A Streptococcus are rising. Possible explanations for the increase include immunity-altering, post-pandemic changes in exposure to respiratory pathogens and the emergence of new pathogenic M strains of Streptococcus.
SOURCE: Iro MA, Goldacre MJ, Morris EJ, Goldacre R. Hospital admissions for group A streptococcal infections in England: Current rates and historical perspective. Lancet Infect Dis 2023;23:e326-e327.
Media reports in Europe have called attention to rising rates of illness caused by group A Streptococcus. Since most of those reports have been based on legally required epidemiological reporting of scarlet fever and invasive streptococcal infection, and realizing these reports might be prone to reporting bias, Iro et al corroborated the findings by reviewing hospital admission data for severe illness caused by group A streptococcal (GAS) infection.
Iro et al used data from England’s Hospital Episode Statistics to analyze admission rates from January 2000 through December 2022, focusing on admissions associated with GAS diagnoses in children younger than age 18 years. The authors compared numbers of admissions to national, age-specific, monthly population data to determine rates of infection over time.
From 2000 through the end of 2019, there was a gradual increase in GAS infection cases requiring admission from 2000 (0.52 per 100,000 population) to 2019 (2.36 per 100,000 population), with admission rates usually peaking in the spring and declining in the fall and winter. GAS admission rates dropped precipitously in April 2020 to 0.62 per 100,000 population and stayed at that lower level until spring 2022. Then, rates rose again (as happened during spring in the pre-pandemic era) and kept rising throughout the year to reach 4.32 per 100,000 population by December 2022. Most of this unprecedented winter increase in GAS admissions was caused by high rates in children younger than age 15 years who logged 16.16 admissions per 100,000 population. Among the total pediatric population, preschool-age children were the most likely to be admitted. Researchers noted similar patterns for the various presentations of GAS disease, including scarlet fever and streptococcal sepsis. Case fatality rates caused by GAS disease reached 0.17 per 100,000 population in December 2022.
The authors noted the dramatic rise in hospitalizations and deaths from GAS disease could be attributed to a truly higher incidence rate or to more antigen testing and specificity of diagnostic coding in medical documentation. They explained the post-pandemic rise in GAS hospitalization rates might stem from consequences of personal and group protection measures during the pandemic that left younger individuals without the previous usual exposures that would stimulate streptococcal immunity, while leaving older individuals with less repeated streptococcal exposure, prompting a waning of previously established anti-streptococcal immunity. Concurrently, the higher hospitalization rates could be because of changes in the streptococci themselves instead of just because of human changes; indeed, there has been emergence of the emm1 (M1UK) streptococcal sublineage, which is known to be highly transmissible and markedly toxigenic.
COMMENTARY
Concern for rising rates of severe GAS disease is not limited to England. Similar reports have emerged from various parts of Europe and the United States. There was a reported fourfold increase in the incidence of GAS infections in children during winter 2022 in Spain vs. previous seasons.1 A similar rise in invasive GAS infections was noted in children in Colorado and Minnesota between October and December 2022.2
Group A streptococci are prevalent in communities, with up to 20% of school children colonized.3 Beyond the common occurrence of streptococcal pharyngitis, group A streptococci can lead to invasive infections, including sepsis, streptococcal shock syndrome, meningitis, necrotizing fasciitis, and osteoarticular infections. Additionally, infections with group A streptococci can cause post-infectious immunological sequelae in the form of rheumatic fever and post-streptococcal glomerulonephritis caused by antigenic mimicry with the streptococcal M protein in association with an abnormal immune response. Thus, accurate diagnosis and timely management are crucial in limiting both invasive disease and serious immune-mediated complications.
Overtesting and overtreatment of GAS lead to unnecessary costs and unpleasant adverse effects of antimicrobial agents. For children with pharyngitis, testing can be limited to those older than age 3 years with strong suspicion of GAS pharyngitis who do not display symptoms and/or other signs of viral respiratory infections, such as rhinorrhea, cough, hoarseness, or oral ulcerations. Screening can be performed by using a rapid antigen detecting test or a bacterial throat culture. As rapid tests can be variably sensitive, corroborate negative results with bacterial culture in children with strong suspicion of streptococcal infection for a more accurate diagnosis. This is crucial so children with true GAS infections do not go undiagnosed and untreated. As Iro et al demonstrated, GAS can cause severe invasive disease with devastating consequences far beyond the throat. This also would help in antimicrobial stewardship by reducing antibiotic use in children who do not require it. Appropriate detection and treatment also help prevent bacteria transmission, alleviating disease burden.4
The rising rates of pediatric invasive GAS infections is crucial in understanding the trend and epidemiology of invasive GAS cases. There are two plausible theories that have emerged in various studies over the past year. First, the effects of lockdowns imposed during the COVID-19 pandemic, resulting in a surge caused by weaker immunity to GAS and wider exposure to viruses and GAS after lifting lockdowns worldwide. A report in January 2023 illustrated an emerging incidence of invasive GAS infections among children, particularly osteoarticular cases requiring surgical management.5 Out of those diagnosed with osteoarticular infections in fall 2022, more children had contracted preceding varicella or upper respiratory tract infections vs. previous years.5 The authors of a more extensive retrospective study conducted in France summarized the trends of GAS infections requiring admissions over the past 15 years in children younger than age 18 years.6 Researchers observed a dramatic rise in invasive GAS infections per 1,000 admissions per three months vs. pre-pandemic years.6 Interestingly, the authors observed the peak of infection rates happened concomitantly with a major influenza outbreak in the region.6
A second possible theory attributes the rising infections to the emergence of newer strains of GAS like M1UK, specifically in the United Kingdom, which has been found to be more immunogenic and displays higher rates of transmission among children.5 Earlier this year, the emergence of a more virulent emm4 lineage of GAS was reported from the Netherlands.7
There is progress, slowly, toward developing a GAS vaccine. The Strep A Vaccine Global Consortium, established in 2019, consolidates efforts and expedites Streptococcus pyogenes vaccine development globally. There are eight vaccine candidates in various phases of trials.8 Meanwhile, vaccination against influenza and varicella can help reduce those two risk factors that have predisposed some individuals to severe GAS disease.
REFERENCES
1. Cobo-Vázquez E, Aguilera-Alonso D, Carrasco-Colom J, et al. Increasing incidence and severity of invasive group A streptococcal disease in Spanish children in 2019-2022. Lancet Reg Health Eur 2023;27:100597.
2. Barnes M, Youngkin E, Zipprich J, et al. Notes from the field: Increase in pediatric invasive group A Streptococcus infections - Colorado and Minnesota, October-December 2022. MMWR Morb Mortal Weekly Rep 2023;72:256-267.
3. Oliver J, Malliya Wadu E, Pierse N, et al. Group A Streptococcus pharyngitis and pharyngeal carriage: A meta-analysis. PLoS Negl Trop Dis 2018;12:e000633.
4. Thompson TZ, McMullen AR. Group A Streptococcus testing in pediatrics: The move to point-of-care molecular testing. J Clin Microbiol 2020;58:e01494-19.
5. Pigeolet M, Haumont E, Rubinsztajn R, et al. Increase in paediatric group A streptococcal infections. Lancet Infect Dis 2023;23:282.
6. Lassoued Y, Assad Z, Ouldali N, et al. Unexpected increase in invasive group A streptococcal infections in children after respiratory viruses outbreak in France: A 15-year time-series analysis. Open Forum Infect Dis 2023;10:ofad188.
7. van der Putten BCL, Bril-Keijzers WCM, Rumke LW, et al. Novel emm4 lineage associated with an upsurge in invasive group A streptococcal disease in the Netherlands, 2022. Microb Genom 2023;9:mgen001026.
8. Walkinshaw DR, Wright MEE, Mullin AE, et al. The Streptococcus pyogenes vaccine landscape. NPJ Vaccines 2023;8:16.
Around the world, rates of severe illness caused by group A Streptococcus are rising. Possible explanations for the increase include immunity-altering, post-pandemic changes in exposure to respiratory pathogens and the emergence of new pathogenic M strains of Streptococcus.
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