Vaccines for maternal immunization against Group B Streptococcus disease: WHO perspectives on case ascertainment and case definitions

Abstract

Group B Streptococcus (GBS) is an important cause of disease in young infants, stillbirths, pregnant and post-partum women. GBS vaccines for maternal immunization are in development aiming to reduce this burden. Standardisation of case definitions and ascertainment methodologies for GBS disease is needed to support future trials of maternal GBS vaccines. Considerations presented here may also serve to promote consistency in observational studies and surveillance, to better establish disease burden. The World Health Organization convened a working group to provide consensus guidance for case ascertainment and case definitions of GBS disease in stillbirths, infants, pregnant and post-partum women, with feedback sought from external stakeholders. In intervention studies, case capture and case ascertainment for GBS disease should be based on antenatal recruitment of women, with active follow-up, systematic clinical assessment, standardised sampling strategies and optimised laboratory methods. Confirmed cases of invasive GBS disease in stillbirths or infants should be included in a primary composite endpoint for vaccine efficacy studies, with GBS cultured from a usually sterile body site (may be post-mortem). For additional endpoints, or observational studies, confirmed cases of GBS sepsis in pregnant and post-partum women should be assessed. Culture independent diagnostic tests (CIDTs) may detect additional presumed cases, however, the use of these diagnostics needs further evaluation. Efficacy of vaccination against maternal and neonatal GBS colonisation, and maternal GBS urinary tract infection could be included as additional, separate, endpoints and/or in observational studies. Whilst the focus here is on specific GBS disease outcomes, intervention studies also present an opportunity to establish the contribution of GBS across adverse perinatal outcomes, including all-cause stillbirth, preterm birth and neonatal encephalopathy.

Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and Development: An International Consensus Statement

“…Importantly, identification and treatment of colonized mothers can be difficult and expensive, particularly in LMICs, where the incidence of neonatal invasive GBS disease is higher compared to HICs (201). Development of GBS vaccines for immunization in pregnancy and its use in LMICs has been identified as a priority by the WHO (202).…”

Preventive Allergen-Specific Vaccination Against Allergy: Mission Possible?

“…The concept of maternal vaccination is in fact quite well-accepted in the field of infectious diseases. Maternal vaccination is considered particularly in the field of influenza ( 104 , 105 ), group B streptococcus diseases ( 106 ), pertussis ( 107 ), and several other infectious diseases as safe and effective ( 108 – 110 ).…”

A Solution to Antifolate Resistance in Group B Streptococcus : Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim

“…GBS is a leading cause of neonatal sepsis, pneumonia, and meningitis (9)(10)(11)(12)(13)(14). Recent data also suggest that GBS is a frequent cause of chorioamnionitis, endometritis, pneumonia, and urosepsis in adults with underlying medical conditions (i.e., diabetes mellitus or immunosuppression) (15)(16)(17)(18)(19). As these patterns of pathogenesis suggest, GBS is considered a saprophytic organism, i.e., invasive GBS disease is most commonly observed in weakened hosts.…”