Inflammatory mediators and neurodevelopmental morbidity associated with invasive Group B Streptococcus (GBS) disease early in life.

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An important cause of neonatal sepsis in developed and developing countries is Streptococcus agalactiae or Group B Streptococcus (GBS), a Gram-positive β-haemolytic, encapsulated diplococci. Pregnancy related GBS colonisation may lead to infant invasive GBS disease (iGBS), including meningitis or sepsis, with high mortality risk. There were an estimated 319,000 invasive GBS disease cases in infants under 3 months of age in 2015, 90,000 of which were fatal and a further 10,000 of whom developed moderate to severe neurological disabilities primarily secondary to GBS meningitis. In addition, recent studies highlight that adverse NDI outcomes are also extending to survivors of iGBS sepsis. Of the estimated mortality and morbidity associated with GBS disease in neonates, more than half were in Africa. To reduce the incidence of neonatal GBS disease, it is important to understand the long-term consequences of the disease. There is a dearth of information on the long-term outcomes of neonatal GBS infection, such as neurodevelopmental impairment. Combined with long-term morbidity and mortality outcomes, these data are particularly important to assess the burden of disease in more detail and to evaluate the economic burden. Thus, the aim of project A is to further investigate the risk of neurodevelopmental impairment (NDI) and socioemotional behaviours in children who survived neonatal or infant invasive (iGBS) disease in South Africa and Mozambique. For project B we will also measure long-term health related quality of life and economic costs that arise as a consequence of iGBS disease. The acute inflammatory response caused by GBS and the bacteria itself, most likely leads to neurological disabilities. Thus, to complement the human based studies assessing the NDI in iGBS survivors we aim to undertake a study characterizing the immune response in iGBS survivors (project C). In line with human studies investigating the immune response to iGBS disease in neonates, we aim to also undertake a series of in vitro and in vivo animal studies aimed at determining the primary drivers of inflammation, apoptosis and the long-lasting CNS sequelae associated with neonatal iGBS disease (project D). In particular we will exlpore the role of neutrophils and neutrophil extracellular traps in the pathogenesis of GBS-induced haematogenous meningitis and potential neuronal damage. The work program is focused on educational development / advancement for young early-career trainees in Africa, ranging from paediatricians, research technicians to doctoral and postdoctoral candidates within the consortium also reaching out to other African sites and partners outside of Mozambique and South Africa. The career developmental plan is centrally organized, to ensure high standards of training to gain more insights into iGBS disease and the implementation of strategies to alleviate the burden of not only iGBS disease, but also other causes and neonatal sepsis and meningitis in Africa.