Neurodevelopmental impairment associated with neonatal invasive group B Streptococcus disease: Are animal models on track in understanding the mechanisms at play?

Abstract

Invasive Group B Streptococcus (iGBS) disease is a prominent cause of neurodevelopmental impairment (NDI) in neonates. While the clinical manifestation of iGBS disease in neonates may include pneumonia and meningitis, generalised sepsis without focus is the most frequent manifestation of iGBS disease in neonates. Though recent human based studies highlighted meningitis as an important manifestation in infants with NDI following iGBS disease, they also noted that ∼18% of neonates present with NDI following iGBS related sepsis. Thus, it is important to not only understand the long-term pathophysiological changes associated with NDI in iGBS meningitis survivors, but so too for iGBS sepsis survivors. Since the late 1970's animal models have been used to unravel the pathophysiology of neonatal iGBS disease. These studies have inoculated neonatal or pregnant animals with GBS via various peripheral or central routes. The greatest challenge with using animal models to study NDI associated with neonatal iGBS disease, is effectively mimicking the clinical presentations of pneumonia, sepsis, and meningitis, while inducing relevant pathophysiological changes and ensuring animals survival, so as to test the neurodevelopment of the animals. This review aims to evaluate the validity of neonatal rodent models, specifically in studying NDI associated with neonatal iGBS disease and explore possible future avenues of research in addressing long-term NDI in the clinical setting.