Grant: Fellowship - Priority Announcement - HIV/AIDS and/or STBBI

Tuberculosis is an infection caused by the bacterium Mycobacterium tuberculosis that causes significant suffering worldwide. It remains a challenging condition to diagnose, especially in patients infected with HIV, as they often have forms of disease with few bacteria to detect. In addition, children who have difficulty producing phlegm, and patients who have tuberculosis outside the lungs, also pose diagnostic difficulty. In these cases, invasive sampling (typically a needle-based procedure such as biopsy, or a sample from the lower back to obtain cerebrospinal fluid) is often required. To address this need, we have developed a simple and non-invasive laboratory test to diagnose tuberculosis from blood and urine samples. More specifically, this test is a multiplexed nucleic acid amplification test (NAAT) for detection of Mycobacterium tuberculosis cell-free DNA. The assay has thus far been tested on 126 blood samples from adult patients with tuberculosis in the lungs, and Stanford Hospital patients with tuberculosis outside the lungs and patients without tuberculosis, with an overall sensitivity of 74% and specificity of 100%. The proposed study aims to comprehensively assess and optimize the test performance characteristics of this assay in HIV-positive and negative patients, with the aim of developing it into a point-of-care test. This new test shows potential to improve timely diagnosis of tuberculosis, and thus reduce transmission of the infection to other people. It also may improve targeted anti-tuberculosis therapy by limiting treatment to those who test positive, and avoid unnecessary side-effects in those who test negative.