Biomarker Analysis for Diagnosing and Treatment Monitoring in Extrapulmonary Tuberculosis Patients in Nairobi, Kenya (BioTube)

Tuberculosis (TB) remains a global health threat with high incidence, especially in Africa. The proportion of extrapulmonary TB (EPTB) can escalate up to 36% in areas with a high HIV prevalence. Effectively managing and controlling EPTB in high-burden regions, such as Kenya, faces obstacles owing to the limitations of the current diagnostic tools. Traditional methods, such as smear microscopy and culture, often fail to detect EPTB due to the paucibacillary nature of the disease and while newer molecular techniques such as Xpert MTB/RIF have improved the diagnosis of pulmonary TB, they demonstrate reduced sensitivity for EPTB. The inadequacy of these tools results in delayed or missed diagnosis, contributing to higher morbidity and mortality. This underscores the urgent need for more sensitive, non-invasive diagnostic methods that can be applied in resource-limited settings like Kenya. This study aims to establish a biomarker-based diagnostic method for EPTB, using biomarkers such as lipoarabinomannan (LAM), MPT64, and Ag85B to diagnose and to monitor treatment response. Additionally, to clarify the characteristics and causative microorganisms of patients suspected of having TB but yielded negative results. Techniques such as ultrasensitive enzyme-linked immunosorbent assays (ELISA) and urine concentration methods will be employed to improve detection sensitivity. It also seeks to explore the extent of non-tuberculosis mycobacteria (NTM) and fungal infections in patients in patients presenting as presumed TB.

This prospective cohort study will be conducted at Kenyatta National Hospital and Mbagathi County Hospital in Nairobi, enrolling 763 adult patients with presumed extrapulmonary TB (EPTB) and 150 control participants from November 2024 to October 2028 Clinical and demographic data, along with sputum, blood, and urine samples, will be collected at enrolment for microbiological tests and biomarker analysis. The accuracy of biomarkers will be assessed by comparing their sensitivity and specificity against established diagnostic standards. For confirmed EPTB cases (n=50), follow-up samples will be collected during TB treatment to monitor biomarker trends alongside the patient's clinical progress.

This study can enhance EPTB diagnosis by evaluating the diagnostic profile of candidate biomarkers in urine or blood samples. The findings may lead to the development of accurate, non-invasive diagnostic tools suited for resource-limited settings, improving early detection and treatment outcomes. Additionally, by clarifying the epidemiological and microbiological profiles of TB, NTM, and fungal infections, the study could guide more targeted clinical management strategies, ultimately improving patient care in high-burden regions.