Impact case study database

National guidelines, practice, and policy

Heath’s work in defining the national GBS-disease burden and risk factors resulted in formulation and implementation of the first and then updated national guidelines for the prevention of early onset neonatal GBS disease based on intrapartum prophylactic antibiotics given to women with defined risk factors [A (RCOG Greentop guidelines 2017), B]. Prior to this, there were no agreed national policies to reduce GBS infection in infants.

The updated guidelines resulted in changes to the UK screening pathway, enabling more mothers to receive antibiotics during pregnancy and the likely prevention of many cases of GBS disease. Based on risk factors including mode of delivery, rupture of membranes and known carriage of GBS, 25% of live births were originally targeted for prophylaxis. In 2017, the addition of preterm infants as a risk group, resulted in an additional 7% of all live-births being added to the screening pathway [A]. These numbers equate to approximately 160,000 mothers being eligible to receive antibiotics in labour in the UK per year, potentially preventing many cases of early onset GBS disease.

While the relative incidence of early vs. late onset disease, and the case fatality rate of early onset disease both decreased between 2014 and 2015 compared with surveillance between 2000 and 2001(case fatality decreased from 10.6% to 5.2%), the work also clearly established the need for a new strategy to address both early and late onset GBS disease.

This work culminated in Professors Heath and Le Doare’s membership of the UK Department of Health GBS research steering committee, which made recommendations for future research to prevent GBS in the UK [C]. These made clear the critical need for a new strategy focused on maternal vaccination, a body of work that the group is now leading.

Impact on practitioners and patients: Educating clinicians and parents about neonatal meningitis

The group’s work to educate clinicians and parents about neonatal infection, meningitis and, specifically, GBS, has directly informed guidance nationally and internationally. The RCPCH, Meningitis Now and Meningitis Research Foundation have developed tools for the recognition and management of neonatal meningitis via online tools [Da (with over 1,000 hits)], clinical algorithms [Db] and patient information [Dc], which are all derived from this research (please see testimonial letter from MRF) [E].

Global Policy and Regulatory body endorsement of maternal vaccinations

Based on their contributions, both Professors Heath and Le Doare sit on the World Health Organisation (WHO) subcommittee addressing GBS vaccine development issues and have contributed to critical reports on the Preferred Product Characteristics and Vaccine Value Proposition, culminating in the WHO scientific advisory group of experts on immunisation (SAGE) agreement to prioritise GBS vaccine licensure for global use [F, G].

Furthermore, they instigated a pivotal meeting between the GASTON consortium (led by Le Doare, and funded by BMGF) and the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in 2018. This resulted in acceptance of the principle of a pathway based on correlates of protection toward licensure of GBS vaccines, providing the support needed for policy makers to recommend its implementation [H].

As a result, the US FDA, the Medicines and Healthcare products Regulatory Agency (MHRA)/ EMA and WHO have endorsed the group’s proposed route to facilitate GBS vaccine licensure, representing a step change in the way that vaccines are licenced and facilitating potential accelerated licensure for other maternal vaccines.

Impact on maternal vaccine safety

Professor Heath’s work with the Brighton Collaboration GAIA project resulted in the development of standards for assessing vaccine safety in pregnancy [6 (in research above)]. Professor Heath presented guidelines to the WHO Global advisory Committee on Vaccine Safety in June 2016. The committee then recommended their widespread use [I]. These guidelines have been implemented as the gold standard for assessing maternal vaccine safety in clinical trials, facilitating maternal vaccine development for other important indications (e.g. respiratory syncytial virus (RSV), pertussis [I]), as well as GBS.

Commercial impact

The group’s work to develop a pathway to a maternal GBS vaccine, endorsed by regulatory and global policy bodies, and backed by cost effectiveness data, has led to significant charitable and commercial investment. Funding for studies in the UK (MRC), Europe (EDCTP), South Africa (BMGF) and Uganda (BMGF) has been secured. Pfizer and Minervax, the two leading vaccine candidate manufacturers, are also undertaking phase 2b trials of their products, within the St George’s led EDCTP-funded PREPARE consortium with results available by 2024 [J]. It is anticipated that these vaccine trials with immunological endpoints, known from the serocorrelate work to be protective, can lead to a vaccine being licenced by 2025.