A 15-year Single-center Analysis of Late-onset Group B Streptococcus Infection Correlating Clinical Severity With Pathogen Virulence Determinants.

Abstract

Group B Streptococcus (GBS) is a major cause of infant meningitis, often requiring intensive care. The molecular determinants of severe disease (meningitis/Intensive Care Unit (ICU) admission) remain unclear. Although late-onset disease (LOD) and very late-onset disease (VLOD) appear clinically similar, their genomic distinctions are not well described. We characterized invasive GBS isolates from 87 patients at Boston Children's Hospital over 15 years using whole-genome sequencing. Isolate diversity was compared with global samples. We assessed vaccine coverage, antimicrobial resistance, and the relationships between clinical features or pathogen virulence factors and disease severity or age of onset using regression models adjusted for population structure and multiple testing. Of the 87 patients, 44.3% required ICU care and 18.6% had meningitis. Five serotypes and six clonal complexes were identified, with hypervirulent clones CC17/cpsIII and CC23/cpsIa predominating. All isolates contained candidate polysaccharide conjugate and/or protein vaccine targets and were susceptible to penicillin and vancomycin; 38% were erythromycin-resistant and 29% clindamycin-resistant. ICU admission correlated with specific hematologic abnormalities, but meningitis did not. No known virulence factors were associated with ICU admission or meningitis. LOD and VLOD isolates showed no major genomic differences, though the PI-2A1 pilus gene was more frequent in VLOD. Invasive GBS disease in infants frequently results in ICU admission and meningitis, yet no pathogen genomic features predicted these outcomes highlighting the likelihood of host response factors in determining outcomes. The similar clinical and genomic profiles of LOD and VLOD suggest their current classification may be arbitrary, with implications for surveillance and management.