Current Applications of Non-invasive, Non-Sputum-Based Diagnostic Tests for Pulmonary Tuberculosis
Abstract
Tuberculosis (TB) remains one of the leading infectious causes of death worldwide. Sputum is the primary specimen for pulmonary TB (PTB) diagnosis through culture, smear microscopy, and nucleic acid amplification tests (NAATs). However, sputum collection is often difficult in high-risk groups such as children, the elderly, and immunocompromised patients. Also, sputum induction poses biosafety risks and performs poorly in paucibacillary disease. To address these limitations, alternative non-invasive specimens, including saliva, oral swabs, urine, and stool, have been investigated over the past decade for PTB diagnosis. This review synthesises evidence on diagnostic accuracy, target populations, and assay platforms. Saliva and oral swabs are easy to collect and well accepted by patients, with sensitivities ranging from 30–100% and specificity from 80–100%, though yield depends on collection method and bacillary load. Urine lipoarabinomannan (LAM) assays provide another option: the AlereLAM test is endorsed by the World Health Organization (WHO) for people living with HIV with CD4 counts ≤100 cells/µL, with pooled sensitivities of 25–55% and specificities of 75-95%. The newer FujiLAM assay, currently under evaluation, shows higher sensitivity (40–85%) and specificity (85-95%). Stool Xpert Ultra achieves 35–85% sensitivity and 85–100% specificity, offering particular value in children unable to expectorate sputum. These findings highlight best-use scenarios such as urine LAM in advanced HIV, stool testing in children, and oral swabs in elderly or sputum-scarce populations. Future progress in biomarker discovery, simplified processing, and portable molecular platforms will be critical for scaling up non-sputum diagnostics and closing diagnostic gaps in the vulnerable groups.
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