Tatiana Metcalf, PhDc MPH

Nominated From: University of Washington

Research Site: Lima, Peru

Project: TB Meningitis/Lab dx techniques using CSF

Primary Mentor: Joe Zunt

Research Project Background

Tuberculous meningitis (TBM) is considered the most severe form of tuberculosis – causing substantial morbidity and mortality, particularly in HIV-infected patients. One of the greatest challenges clinicians face is in making a rapid and accurate diagnosis allowing for the initiation of immediate and appropriate treatment. Although there are many more TB diagnostics in the pipeline today the majority have been approved for and validated only in sputum. Moreover, newly available tests fall short in obtaining an adequate diagnosis for smear negative TB, especially in HIV-infected persons. There is a paucity of literature regarding the use of cerebrospinal fluid (CSF) samples in newer diagnostic techniques. The main objective of this study is to evaluate and validate diagnostic techniques in CSF against the “gold standard” in clinically diagnosed TBM adult patients with and without concomitant HIV at a TB reference hospital in Lima, Peru. The diagnostic tests to be evaluated are derived from several major disciplines: Bacteriology, Biochemistry & Immunology, and Molecular Biology. We will evaluate test performance in CSF for the detection of M.tuberculosis, resistance to first and second line drugs, and identification of the infecting strain. For detection of M.tb and resistance, we will determine the sensitivity, specificity, time-to-detection, and efficacy in HIV positive populations. We will also identify infecting strains and evaluate their influence in the clinical evolution of TB meningitis.