Pediatric invasive group A Streptococcal infections on the rise during respiratory virus outbreak

In a recent study published in the journal Open Forum Infectious Diseases, researchers performed an interrupted time-series-type analysis to assess the incidence of invasive Group A streptococcal (iGAS) infections among children, with associated risk factors, molecular and clinical characteristics, before and after the coronavirus disease 2019 (COVID-19) pandemic.

Study: Unexpected Increase in Invasive Group A Streptococcal Infections in Children Following Respiratory Viruses Outbreak in France: a 15-Year Time-Series Analysis. Image Credit: Prrrettty / Shutterstock.com

Background

Infections by Streptococcus pyogenes, a type of iGAS, can result in diseases such as bacteriemia, osteoarticular or soft tissue infections, toxic shock syndrome (TSS), and pleural empyema. These infections have affected millions of individuals globally, especially young children, with many of these infections severe and resulting in adverse outcomes, including fatality.

Varicella zoster virus (VZV) co-infections and the use of non-steroidal-type of anti-inflammatory drugs (NSAIDs) elevate the risk of pediatric invasive GAS infections. Additionally, recent studies have reported an association between respiratory viral infections and iGAS.

A remarkably high incidence of iGAS infections, particularly among children, has been reported toward the end of 2022. However, the extent of these infections and their bacterial and clinical characteristics relative to the period before COVID-19 are not clear.

About the study

In the present non-randomized, monocentric, and retrospective study, researchers assess changes in the incidence of iGAS infections associated with the COVID-19 pandemic.

The study comprised pediatric individuals below 18 years of age who were hospitalized at the Robert Debré University tertiary care hospital in France due to iGAS infections between January 1, 2008, and December 31, 2022. Infections were detected using polymerase chain reaction (PCR) or culture among streptococcal-TSS (S-TSS) or necrotizing fasciitis patients, according to the United States working group for severe-type infections caused by Streptococci.

Clinical, biological, and demographic data were obtained from the participants. Molecular and microbiological data were obtained from the hospital’s microbiology laboratory.

The team performed Emm (M protein gene) genotyping, assessed the virulence gene profiles for GAS, and determined the rates of invasive GAS infections among every 1,000 hospital-admitted children based on pediatric hospitalizations. In addition, the counts of respiratory pathogenic organisms, which were detected using nasopharyngeal multiplexed PCR among children hospitalized due to acute respiratory symptoms between January 1, 2019, and December 30, 2022, were documented.  

Respiratory infections included those caused by the respiratory syncytial virus (RSV), adenovirus, influenza virus, parainfluenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and metapneumovirus. The study periods included the pre-COVID-19-associated non-pharmaceutical intervention (NPI) period between January 2008 and March 2020, the NPI period between April 2020 and April 2021, and the NPI-relaxation period between May 2021 and December 2022. The team performed quasi-Poisson-type regression modeling and calculated the odds ratios (OR).

Results

In total, 135 pediatric iGAS infection-associated hospitalizations were reported among the study participants, with a mean age of three years. During the pre-NPI period, the quarterly rate of invasive GAS infections among every 1,000 hospitalizations was stable. However, the implementation of NPI during March 2020 significantly reduced the quarterly rate of iGAS infections among every 1,000 hospitalizations with an OR of 0.3.

Post-NPI relaxation, a notable rise in the quarterly rate of iGAS infections among every 1,000 hospitalizations, especially between October and December 2022, was observed (OR 6.8). The peak in iGAS infections between October and December 2022 was observed concomitantly with a rise in the circulation of respiratory viruses, especially influenza.

During the final three months, 60% tested positive for respiratory viruses through nasopharyngeal viral swab-PCR, rising to 100% for pleural cavity empyema. During the pre-NPI period, the main clinical presentations comprised osteoarticular infections (39%), TSS/bacteremia (33%), pleural cavity empyema (15%), and cutaneous infections (6%). A shift was observed in the prime clinical manifestations during the final study period, likely associated with an increased percentage of pleural cavity empyema from 15% to 33%.

The inflammatory syndrome intensity and adverse outcomes, which included pediatric intensive care unit (PICU) admissions and deaths, were comparable between the three study periods. Post-NPI relaxation, there was no association between iGAS infections and VZV infections.

M protein genotype distribution was comparable between the study periods. M protein genotyping and virulence genes profile indicated that no leading clones emerged during the rise in iGAS infections.

Conclusions

The study findings showed a remarkable rise in iGAS infections since October 2022, mainly involving pleural empyema, co-occurring with a respiratory virus outbreak. Therefore, physicians must be aware of the elevated risk of pediatric iGAS infections, particularly in settings with an intense circulation of respiratory viruses.

The rise in iGAS infections was associated with various M protein gene types, with identical distribution as that in the pre-COVID-19 period. There were no iGAS cases related to preceding or coinciding Varicella zoster virus infections in 2022; however, there is likely an association between iGAS and the rate of iGAS infections and respiratory pathogens, especially the influenza virus.

Further research, including randomized controlled trials, must be conducted, evaluating pediatric susceptibility to iGAS and whole-genome sequencing (WGS) of iGAS strains.