A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfillment for the degree Masters of Medicine in Paediatrics (MMed) Johannesburg 2014 / Introduction Mycobacterium tuberculosis meningitis (TBM) is a severe manifestation of extra-pulmonary tuberculosis (EPTB) in children, particularly under 5 years of age. Children are vulnerable to EPTB as they are immunologically immature and unable to contain Mycobacterium tuberculosis (MTB) infection in the lung. Common neurological sequelae of TBM include focal motor deficits, vision loss and hydrocephalus. Early stage diagnosis and timeous anti-tuberculosis treatment decreases the case fatality rate of TBM. Objective To characterise the burden, clinical presentation, laboratory markers and short-term outcome of TBM in HIV-infected and HIV-uninfected children. Methods The electronic databases of admission of children at Chris Hani Baragwanath Academic Hospital (CHBAH), between January 2006 and December 2011 with a diagnosis of TBM were reviewed. Individual patient records were retrospectively reviewed for clinical and laboratory data. In addition, admissions from the neurosurgery wards were also reviewed. In patients whose medical records were unavailable, laboratory data was used. Results The overall incidence of TBM in 2006 was 6.96 per 100 000 (95% Confidence Interval [95%CI]: 4.46-10.36), peaked at 9.87 per 100 000 (95% CI: 6.91-13.67) in 2009 and subsequently declined to 3.18 per 100 000 by 2011 (95% CI: 1.64-5.56). There was a 38.6% (95% CI: 10.0-58.0; p=0.011) reduction in the overall incidence of TBM when comparing the period 2006-2009 with the period 2010-2011. This decline was particularly evident in HIV-infected children (49.6% reduction; 95%CI: 1.05-74.35; p=0.042). There were no differences in the clinical symptoms of TBM or tuberculosis between HIV-infected and -uninfected children. Previous history of TB was significantly higher in HIV-infected children compared to HIV-uninfected children (OR 4.63; 1.40-15.22; p=0.011). Tuberculin skin test positive-reactivity (OR 0.09; 0.02-0.43; p=0.002) and sputum culture positivity (OR 0.29; 0.10-0.86; p=0.025) were less common in HIV-infected compared to -uninfected children. Cerebrospinal fluid cytology and biochemistry results were similar between HIV-infected compared to -uninfected children. Morbidity (22.7% in HIV-infected vs. 33.0% in -uninfected) and mortality (6.4% in HIV-infected vs. 6.9% in -uninfected) were similar between HIV-infected and -uninfected children. Conclusion The incidence of TBM has decreased over the study period 2006 to 2011.This decrease was temporally associated with an increase in the uptake of antiretroviral treatment in HIV-infected individuals.