**5. Urine sample tests in TB diagnosis**

Advocacy toward non-invasive, non-sputum simple TB diagnosis has pushed research into different directions including the use of urine sample from presumptive TB patients. There are a number of target TB biomarkers in urine including volatile compounds, proteins, and TB antigen.

In a study by Cannas and colleagues [61], traces of mycobacteria DNA were detected in the urine of TB patients at 79% while the controls were negative. In addition, proteins produced in lung lesions and excreted in urine were also recognized by immunoglobulin G (IgG) from active TB patients [62]. Other TB protein biomarkers in the urine of TB patients have been reported by Young and colleagues [63]. In a similar study, Lim and friends [64] tested urine for TB by using a colorimetric sensor array (CSA). Urine headspace analysis showed discrimination between TB and control patients with 85.5% sensitivity and 79.5% specificity. Analysis of volatile organic compounds using headspace gas chromatography/mass spectrometry (GC/MS) showed increased levels of o-xylene and isopropyl acetate and decreased levels of 3-pentanol, dimethylstyrene, and cymol in the urine of TB patients compared to controls with respiratory diseases other than TB [65].

For each of the time slice, the alveolar gradient is calculated by taking: ¼ Vb /Ib Va/Ia.

of room air.

**6.3. Identification of biomarker time slices**

Where, Vb is the integrated abundance of analytes detected by mass spectroscopy in a breath, and Ib is the area under the curve (AUC) of the chromatographic peak associated with the internal standard. Va and Ia denote corresponding values derived from the associated sample

Paralleling of Diagnostic Endeavor for Control of Mycobacterial Infections and Tuberculosis

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The alveolar gradients are identified by comparing the patients positive or negative for active pulmonary TB and rank them as candidate biomarkers according to the value of the C-statistic that is, the AUC of the receiver operating characteristic (ROC) curve [69]. The Kovats Index windows for active TB are clearly distinct from controls in a test that takes 6 min. The detec-

TB testing using breath provides hope for a future non-invasive diagnostic procedure. Phillips et al. have put effort to assess the presence of volatile organic compounds in the breath of active TB patients. A special device collected and concentrated breath from TB patients and controls at point-of-care centers. However, the procedure requires special set up and equip-

In the diagnosis of tuberculosis in both humans and animals, the challenges have always been the availability of better and affordable diagnostic methods. While conventional tests such as ZN test for sputum has been in place and are the gold standard, it can miss some cases due to low-sensitivity. Mycobacterial cultures can improve detection but takes longer to get results. Molecular characterization to nucleotide level that is, through sequencing is perfect but usually unaffordable in low-income countries diagnostic settings. In addition, DNA isolation, species identification, and obtaining cultures from a sophisticated system may face limitations as well. All these challenges necessitate for advocacy focusing on innovations that deliver better tools to confidently diagnose TB and at affordable costs [71]. Although, international and national laboratory partnerships are encouraged particularly to boost diagnostic services in resource-poor countries, the need for diagnostic tests that allow rapid testing at point-of-care is necessary [72]. However, all these need acceptance by health authorities in respective countries for incorporation into countries diagnostic algorithms while ensuring inherent and adequate quality assurance programs in dedicated laboratories. In marginalized communities, refusal of diagnosis, high indirect costs, and anticipated treatment side-effects have posed barriers to TB diagnosis [73]. All these need to be considered if we want to perform right diagnosis and management of tuberculosis across endemic regions. Screening programs for both human and animal tuberculosis could cut the costs of modern molecular diagnostics and characterization but these programs are costly and might currently not be of primary priority by responsible authorities. Otherwise, screening programs despite potentially expected high initial capital investment, their value on cutting down diagnostic costs for TB cannot be overemphasized.

tion of TB biomarkers is 80% accurate with 71.2% sensitivity and 72% specificity [70].

ment and may not be suitable in low-income endemic settings.

**7. Challenges in diagnosis of tuberculosis**

Urine-based TB diagnostic procedures can only detect biomarkers related to active TB and not latent TB. However, the promising feature is that it can detect extra pulmonary TB. Nevertheless, more researches are required to unravel the practicability of the tests.
