Background

Tuberculous meningitis (TBM) is the leading cause of bacterial meningitis in children in many global settings and the most lethal and disabling form of tuberculosis, disproportionately affecting infants and young children. TBM can affect patients of all ages, however the peak incidence of disease is seen in early childhood (2-4 years of age) when the brain is still developing.

Death and long-term disability from TBM remain unacceptably high with 20% of children with TBM dying and over 50% of those who survive suffering some form of long-term disability. Although children have lower mortality than adults with TBM, they can suffer serious long-term physical and neurocognitive sequelae which have substantial socioeconomic impact.

Diagnosing TBM in children can be challenging owing to non-specific symptoms often mistaken for other common childhood infections, the paucibacillary nature of disease and inadequately sensitive tools to diagnose the disease.  Delays in diagnosis and initiation of appropriate therapy invariably result in poor outcomes and much of the damage has already occurred even before the child is started on therapy.  There is an urgent need to diagnose early and better understand the mechanisms of disease in children with TBM. In doing so, new knowledge will help direct future research into novel host-directed therapy and reduce the burden of disability

Aims

The aim of this study is to evaluate mortality and in-depth neurodevelopmental outcomes in a cohort of Vietnamese and Indonesian children with TBM, characterize clinical and neuroradiological phenotypes and disease severity (PediPOT cohort). We aim to integrate clinical data and specimens using new “omic” technology to determine specific metabolomic and inflammatory protein pathways, including tryptophan metabolism, which may influence death and disability in paediatric TBM.