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.
Highlights
Group B Streptococcus (GBS) is an important cause of disease in young infants, stillbirths, pregnant and post-partum women
A primary composite endpoint of serious and fatal events associated with GBS, including cases of invasive GBS disease in neonates, infants and stillbirths would be highly relevant as a common entity, better reflect true burden and reduce sample size requirements for estimation of the effect of new interventions
Follow-up of infants with invasive GBS disease for at least 18 months is needed if neurodevelopmental impairment outcomes are to be included, and this should be considered to better understand the burden of long-term neurodevelopmental impairment associated with invasive GBS disease in infancy
Summary
Cohort studies with antenatal recruitment, and follow-up through 89 days after delivery, are preferred. Surveillance can be used to provide incidence data with denominators based on hospital catchment population, or facility based births. Both are subject to bias which should be assessed and reported. Inclusion of stillbirths and infants (0–89 days) preferred. Standardised clinical assessment using defined clinical criteria preferred. Infants (0–89 days) recommended for primary composite endpoint. Post-abortion and postpartum women for additional endpoints. Standardised clinical assessment and sampling based on presence of defined clinical criteria essential. Standardised operating procedures with sensitive methods (automated blood cultures, selective agar), and quality assurance according to clinical development stage. Follow-up of infants with invasive GBS disease (and appropriate controls) for at least 18 months is needed if neurodevelopmental impairment outcomes are to be included, and this should be considered to better understand the burden of long-term neurodevelopmental impairment associated with invasive GBS disease in infancy
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