**8. The future of TB diagnostics**

**6.1. Detection of antibodies**

146 Tuberculosis - Current Issues in Diagnosis and Management

**6.2. Detection of antigens**

Although the detection of antibodies against MTB in the blood is a relatively simple and costeffective method, recent meta-analyses and systematic reviews concluded that commer‐ cial serological tests provided inconsistent results [23,24]. As the overall test performance and data quality of these assays were poor, the WHO currently recommends against their

Antibodies against lipoarabinomannans, A60, 38Kd and 16 Kd are mostly studied [25].

Lipoarabinomannan (LAM) was identified as a promising target for antigen detection for TB diagnosis due to its temperature stability and could be detected in urine. LAM-based assays are currently being developed by a number of commercial companies, and preliminary re‐ sults indicate their potential applicability in the rapid diagnosis of TB by detecting LAM in a variety of body fluids, including urine [26]. LAM-based assays are included in the WHO TB diagnosis re-tooling programme [27] and forma part of a Foundation for Innovative New

MTB antigen detection provides direct evidence of TB. Such as LAM, 65Kd, 14 Kd antigens were widely used. It is very quick and easy to perform. Main limitation is low sensitivity (detect high levels of antibody). It does not rule out TB in patients with poor antibody re‐ sponse as in HIV and malnutrition and not specific due to cross reactivity with other species

Because of the difficulties with the tuberculin test interpretation, the interferon-gamma assay test was developed. Two available formats of the interferon-gamma release assays are; the Quantiferon-TB Gold and T Spot-TB test. The IGRA assay is based on the ability of the MTB antigens, which includes the Early Secretory Antigen Target 6 (ESAT-6) and Culture Filtrate Protein 10 (CFP-10) to stimulate host production of interferon –gamma. These antigens are not present in NTM or in BCG vaccine, so, these tests can distinguish latent TB infection from BCG immunization and NTM infections. Requiring a single visit to draw a blood sample and result available within 24 hours are main advantages. It does not boost immune response measured by subsequent tests which can happen with tuberculin skin test. It does not cause to readers bias as in tuberculin skin test and not affected by prior BCG vaccination. Blood must be processed within 12 hours while leu‐ kocytes are still viable. There are limited data for sensitivity of IGRAs in children young‐ er 17 years of age and immunocompromised patients e.g. HIV/AIDS, diabetics, treatment

use for the diagnosis of pulmonary and extrapulmonary TB.

Diagnostics (FIND) funded TB Project [19,28].

of mycobacteria in the environment [26].

with immunosuppressive drugs [29].

**7. Interferon-Gamma Release Assays (IGRA)**

The rapid technological evolution in the laboratory diagnosis of TB, especially in the ap‐ plication of molecular biology h as diminished the time required for identification and susceptibility testing. Continuous effort endeavor for increasing reproducibility, improv‐ ment of performance and cost containment. WHO founded an organisation (FIND-Foun‐ dation for Innovative New Diagnostics) for researching fast, relible and inexpensive tests as given Table 1 [28].


LFI sensitivity increase: Alternative quantitative fluorescence (LFI) sensitivity increase

**Table 1. WHO projects for TB diagnostic tests.** LAMP TB: Loop mediated isothermal amplification (LAMP) for TB
