Omar Siddiqi Laboratory

Background

Tuberculous meningitis (TBM) is associated with a high degree of morbidity and mortality. Neurological complications of the disease can be devastating particularly in resource limited settings. Although treatment for TBM is widely available throughout sub-Saharan Africa, it is often delayed or commenced empirically due to a lack of adequate diagnostic testing to help guide treatment. This is particularly concerning in a setting of high HIV prevalence such as Zambia where the population is particularly vulnerable to TB infection. Zambia carries one of the largest HIV burdens in the world with an overall prevalence of 12.7% that approaches 25-35% in the urban population. The current practice in numerous HIV-endemic settings is to place all patients with TBM on steroid treatment regardless of the HIV status and degree of immunosuppression. This is particularly concerning when anti-tuberculosis (ATT) treatment is started empirically on an already immunocompromised HIV patient who may sustain further immunosuppression due to steroid therapy. As a result, there is an urgent need to improve TBM diagnostics, recognize patients who may benefit from steroid treatment, and identify those at risk for TB related neurological complications.

Project Title

Novel CSF Diagnostics and Genotype Markers of Tuberculous Meningitis in Zambia.

Purpose

To improve the diagnosis of TBM through the use of novel diagnostic tests on CSF and employ genetic testing to investigate markers of neuroinflammation. First, we will attempt to improve the diagnosis of tuberculous meningitis (TBM) through the use of point-of-care testing on CSF. Second, we will examine host genetic factors as they relate to survival. Third, we will correlate host genetic factors with neuroinflammatory changes seen on neuroimaging. The goal of this study is to aid the clinical management and bring greater insight into the pathogenic mechanisms of inflammation in TBM.