Attribution of invasive group A streptococcal infections to varicella and respiratory virus circulation, the Netherlands, 2010-2023

Abstract

Background After the lifting of most COVID-19 control measures, many infectious diseases re-emerged in 2022. A strong increase in invasive group A streptococcal (iGAS) infections, among both adults and young children, was reported by several countries. Viral infections such as influenza and varicella, known risk factors for iGAS infection, also increased during 2022. We estimated the proportion of GAS skin and soft tissue infections (SSTI) in children aged 0-5 years attributable to varicella, and the proportion of GAS pneumonia/sepsis in children aged 0-5 and adults attributable to respiratory viruses in the Netherlands. Methods We performed time-series regression using weekly data on influenza A and B, RSV, hMPV and SARS-CoV-2, varicella and non-invasive GAS infections, and GAS isolates cultured from blood, lower airways, skin, pus and wounds, from January 2010 to March 2023. Results Up to 2022, approximately 50%(95%CI 36-64%) of GAS SSTI in children were attributable to varicella. Between January 2022 and March 2023, 34%(95%CI 24-43%) of GAS SSTI cases were attributable to varicella. Of iGAS pneumonia/sepsis between January 2022 and March 2023, 25%(95%CI 18-31%) and 37%(95% CI 23-53%) was attributable to respiratory virus infections in adults and children, respectively, with the largest contributor being influenza A. Conclusions Varicella and respiratory virus infections likely contributed to, but only partly explain, the observed iGAS increase among children and adults in 2022-2023 in the Netherlands. Public health measures to control viral infections, such as vaccination against varicella or influenza, might reduce the iGAS disease burden but will not suffice to curb the current high incidence.

Nationwide upsurge in invasive disease in the context of longitudinal surveillance of carriage and invasiveStreptococcus pyogenes2009-2023, the Netherlands: a molecular epidemiological study

“…Based on lower circulation of non- emm 1 speA- carrying emm types ( emm 3, emm 6) in the years before COVID-19 lockdowns, we postulate that also speA -specific immunity may have been low in post-COVID-19 years. Finally, the post-COVID-19 resurgence of iGAS-associated viruses partly contributed to the iGAS upsurge (10), especially in progression to severe lower respiratory tract infection with pleural empyema (24). Together, we conclude that the unique circumstances of a potentially more susceptible population by lower pathogen-specific immunity and high incidences of predisposing viral infections, in combination with the virulent and fit M1 UK lineage already dominant in our country in pre- pandemic years, has coalesced in optimal conditions for extensive expansion of M1 UK after COVID-19 restrictions were lifted.…”

“…It has been speculated that this reduced intermittent exposure may have caused a waning of population immunity (‘immunity debt’), resulting in an increased proportion of susceptible individuals. A previous study showed that varicella and respiratory virus infections only partly explained the iGAS increase (10). Also, iGAS incidences remained persistently higher than pre-COVID levels after viral infections declined, suggesting changes in bacterial characteristics.…”

“…Two years of COVID-19-related restriction measures have limited the transmission of and exposure to S. pyogenes and iGAS-predisposing viruses (e.g. varicella zoster virus, influenza virus) (10). It has been speculated that this reduced intermittent exposure may have caused a waning of population immunity (‘immunity debt’), resulting in an increased proportion of susceptible individuals.…”