Tuberculosis Diagnostics and Biomarkers: Needs, Challenges, Recent Advances, and Opportunities

Abstract

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics.

Tuberculosis screening in high human immunodeficiency virus prevalence settings: turning promise into reality [State of the art series. Active case finding/screening. Number 5 in the series]

“…45 As no current TB screening algorithm is ideal, compromises have to be made. 46,47 In practice, TB screening usually starts with either symptoms or X-ray, 48 although there is increasing use of Xpert® MTB/RIF (Cepheid, Sunnyvale, CA, USA) as both initial and confirmatory test. 9,[49][50][51] The performance of all tests tends to be less good due to lower sensitivity when used for screening than for patient-initiated diagnostic testing, as the spectrum of undiagnosed disease detected is shifted towards earlier, paucibacillary cases (Figures 2 and 3): this includes culture, smear microscopy and Xpert.…”

The Impact of Tuberculosis among Immigrants: Epidemiology and Strategies of Control in High-Income Countries—Current Data and Literature Review

“…Confirmation of resistant-TB and identification of potentially effective drugs in an optimized combination treatment regimen should be done on the basis of antimicrobial DST. However, only 22% of countries worldwide routinely perform cultures and DST, and only 48% of the 46 countries in the WHO Africa region have ever undertaken a drug-resistance survey [4,73]. Moreover, DST is often too expensive, especially in high-burden countries, and in many settings it is neglected because of the lack of SLD [73,74].…”

Tuberculosis: A Literature Review

“…The National Institute for Health & Clinical Excellence (NICE), the European Centre for Disease Prevention & Control (ECDC), and the Centers for Disease Control & Prevention (CDC) has recommended the interferon-gamma release assay (IGRAs) or tuberculin skin test (TST) for diagnosticate the latent M. tuberculosis infection 30,31,32 . The interferon-gamma release assay (IGRAs) is expensive, sensitive but it is less specific, whereas the tuberculin skin test (TST) is less expensive 33 . (Figure 3: Alternative strategies for screening for LTBI 57 ).…”