Non-sputum-based samples and biomarkers for detection of Mycobacterium tuberculosis: the hope to improve childhood and HIV-associated tuberculosis diagnosis

In 2014, the World Health Organisation (WHO) published target product profiles (TPP) for development of novel tuberculosis (TB) diagnostics. One of the key highlights is the need for point-of-care non-sputum-based tests capable of detecting all forms of TB through identification of characteristic biomarkers or biosignatures. Compared to the limitations associated with sputum-based TB tests, non-sputum samples are easy to collect, non-invasive, with potential to improve TB diagnosis among children and among people living with HIV/AIDS (PLHIV). This review gives an overview of the existing evidence on TB diagnostic studies of non-sputum-based samples collected non-invasively from or through the oral-gastrointestinal tract (GI) and nasal pharynx regions of humans and the biomarkers detected. We further summarized evidence of these biomarkers and sample types from research done in paediatric and PLHIV. The review identified; saliva, cough aerosols, oral swabs, oral wash, dental plaque, tongue swabs, face mask sampling, exhaled breath, and stool, as the non-sputum samples investigated. These biomarkers can be categorized into Deoxyribose Nucleic Acid (DNA), Ribonucleic Acid (RNA), inflammatory, antigen-antibody, volatile and non-volatile compounds, microbiome and microbiota. The biomarkers identified were derived both from the host and pathogen. Similar biomarkers were identified in the general population, children and among PLHIV. These biomarkers have been detected by either already approved simple point of care or sophisticated devices. Differences in methodology and sample types investigated, small sample size of children and PLHIV populations, bias due to confounding factors, were some of the identified challenges in these studies. There is need to conduct larger and standardized multi centre studies to evaluate non-sputum-based biomarker-based tests in children and PLHIV.