Invasive Group a Streptococcal Disease in Pregnant Women and Young Children Worldwide: Systematic Review and Meta-Analyses

Background: The incidence of invasive disease caused by group A Streptococcus (GAS) has recently increased in multiple countries. To inform interventions such as GAS vaccines currently in development, we estimated the incidence of invasive GAS (iGAS) disease, including death and disability outcomes, among two high risk groups—pregnant women and children under 5 years of age. Methods: We searched a range of databases and sought unpublished data to identify inputs (1 st January 2000 and 30 th June 2020) to calculate pooled incidence of iGAS disease, case fatality risks (CFRs), and neurodevelopmental impairment among pregnant women, neonates, infants, and children (under 5 years of age). Findings: We identified 950 published articles and 29 unpublished datasets for consideration. Of these 20 studies were eligible for meta-analyses; no studies among pregnant women or on neurodevelopmental impairment in low- and middle-income countries (LMICs) were available. In high income countries (HICs), iGAS incidence among pregnant women was 0·12/1000 live births (95%CI 0·11-0·14). Worldwide iGAS incidence estimates included: neonates, 0·04/1000 live births (0·03-0·05); infants, 0·13/1000 live births (0·10-0·16); and, children aged 0-5 years, 0·09/1000 person-years (95%CI 0·07-0·10). Incidences among children were higher in LMICs, particularly in neonates (0·12/1000 live births; 95%CI 0·00-0·24) compared to HICs (0·02/1000 live births; 0·00-0.03). CFRs among young children were high, particularly among neonates in LMICs (61%; 95%CI 33-89%). Interpretation: We found a high disease incidence and risk of death among young children with iGAS, particularly in LMICs. Notably, for LMICs, limited data are available for neonates and children, and no data are available for pregnant women. Incidences are likely underestimated, particularly in LMICs, due to limited GAS surveillance. Improving available data is essential to inform GAS vaccine development and evaluation. Funding: ACSe is funded by The Wellcome Trust. ACSt is funded by a Viertel Senior Medical Research Fellowship. Declaration of Interest: We declare no competing interests