Pregnancy associated Group B Streptococcus disease: Phase 1 & 2
Group B Streptococcus (GBS; Streptococcus agalactiae) is a leading cause of infant sepsis and meningitis and the World Health Organization (WHO) has identified the development of a GBS vaccine for maternal immunization in pregnancy as a priority. In 2017, members of the Newborn & Child Development Team, with multiple international partners and collaborators, published the first systematic estimates of the global burden of maternal and neonatal GBS disease in Clinical Infectious Diseases journal. A second phase of the project is now underway, in collaboration with the WHO, to develop an investment case for a GBS vaccine for pregnant women. Both phases of the work are funded by the Bill & Melinda Gates Foundation.
Estimating the worldwide burden of Group B Streptococcus infections in pregnant women, stillbirths and children (2015-2017) (First phase)
This first phase aimed to review and estimate the worldwide burden of maternal GBS colonization and pregnancy-associated GBS disease, neonatal GBS disease and its associated mortality as well as association with other adverse perinatal outcomes: stillbirth, neonatal encephalopathy, neurodevelopmental impairment, preterm birth and others. The project more than doubled previously available data through comprehensive systematic reviews and use of unpublished data from collaborators worldwide, and the results formed the first systematic estimates of worldwide burden of GBS disease associated with pregnancy. The project also investigated the number of cases preventable with a maternal GBS vaccine.
Key study findings:
- An estimated 21.7 million (18% or 1 in 5) pregnant women are infected with GBS globally, most of whom are untreated and unidentified
- The highest numbers of colonised pregnant women in 2015 were found in India (2.5 million), China (1.9 million), Nigeria (1.1 million), the USA (0.9 million) and Indonesia (0.8 million)
- Key data gaps include stillbirths (especially in Asia), disability after GBS sepsis, and maternal GBS disease
- The estimates are likely to be underestimates of the true burden of GBS
- A maternal GBS vaccine with 80% efficacy and 90% coverage could prevent 231,000 infant and maternal GBS cases, in turn reducing other outcomes such as stillbirths, deaths and later impairment.
- 11 papers were published in a supplement in 2017: https://academic.oup.com/cid/issue/65/suppl_2
- Overview presentation of the findings presented at the American Society of Tropical Medicine & Hygiene in Baltimore, USA, in 2017: http://bit.ly/2N2c04i
- Slides presented at the 1st International Symposium on ‘Streptococcus agalactiae’ Disease in Cape Town in 2018: http://bit.ly/2TBB7fo
Developing an investment case for Group B Streptococcus vaccines (2017-2021) (Second phase)
Traditionally, decisions on vaccine adoption in national immunization programs have primarily been based on vaccine efficacy and safety; however, this approach has often led to delays in vaccine uptake in low- and middle-income countries, where the burden of disease is often the highest. Instead, building an investment case defined by a broader population benefit of new candidate vaccines, like GBS vaccine, will aid in short- and long-term investment in product development and facilitate global and national policy decisions.
Developing the investment case for GBS vaccines will be jointly implemented with LSTHM and WHO, and will be informed by assessing the preventable burden of the disease, estimating the expected cost and gains from vaccinating pregnant women, and understanding the operational and implementation considerations. LSHTM will lead on the burden of GBS disease and economic evaluations of maternal GSB vaccination, while WHO will lead on the operationalisation considerations and the overall coordination of the investment case. Given the limited data currently available for inclusion in estimates of long-term outcomes of GBS identified in the first phase of the project, the second phase of this project aims to improve these gaps by gathering new data on long-term health outcomes for survivors of infant invasive GBS disease and the GBS-associated economic outcomes. The project will use these data to more accurately assess health (e.g. DALYs) and socioeconomic burden associated with worldwide maternal and newborn GBS disease.
Publications/resources: A study protocol is forthcoming and will be published in 2020. A second supplement of the findings is planned for 2021.