Evaluating the PATHFAST TB LAM Ag assay as a treatment monitoring tool for pulmonary tuberculosis: protocol for a prospective longitudinal study in Nairobi, Kenya

Abstract Background Treatment failure remains a major challenge in tuberculosis (TB) management. Rapid and objective assessment of treatment response is essential, as existing tools have limited accuracy and slow turnaround times. The PATHFAST TB LAM Ag assay (PATHFAST-LAM), an automated chemiluminescent enzyme immunoassay, was developed to quantify lipoarabinomannan (LAM) in sputum within one hour. Previous studies have shown a strong correlation between sputum LAM concentration and culture-based bacterial load. However, its clinical utility for predicting poor outcomes during treatment has not been prospectively evaluated. Methods and analysis We will conduct a prospective longitudinal study enrolling newly diagnosed, bacteriologically confirmed pulmonary TB patients at Rhodes Chest Clinic and Mbagathi County Referral Hospital in Nairobi, Kenya. We will follow participants throughout the 6-month treatment course, attempting to collect sputum weekly during weeks 1–4, biweekly during weeks 5–12, and monthly during months 3–6. We will measure LAM concentrations at these time points using the PATHFAST-LAM assay. The primary outcome is to assess whether changes in sputum LAM concentration during the intensive phase (baseline to week 4 and/or week 8) predict a composite poor outcome, defined as positive sputum culture at month 6, treatment failure, death during treatment, or relapse within three months after treatment completion. The primary endpoint is the area under the curve (AUC) from the receiver operating characteristic (ROC) analysis, representing the predictive performance of changes in sputum LAM concentration for the composite poor outcome. We will identify the optimal cut-off value for LAM change and estimate sensitivity and specificity with 95% confidence intervals using 2×2 tables. We will apply an adaptive design that allows sample-size re-estimation after interim analysis. Ethics and dissemination The study was approved by the Kenya Medical Research Institute (KEMRI/SERU/CRDR/124/5241) and Nagasaki University (250619327), and registered at ClinicalTrials.gov ( NCT07157904 ). Findings will be disseminated through peer-reviewed publications and scientific meetings. Article Summary Strengths and limitations of this study PATHFAST TB LAM Ag Assay (PATHFAST-LAM) automatically measures LAM in sputum and provides rapid, quantitative results within an hour, requiring minimal manual handling. This is the first prospective longitudinal study to evaluate sputum LAM concentrations as measured by PATHFAST-LAM in relation to clinical outcomes among patients with pulmonary tuberculosis (PTB). The study’s prospective design allows real-time assessment of sputum LAM dynamics throughout treatment and follow-up, providing valuable data on temporal changes linked to treatment outcomes. This study enables clinical evaluation of the potential of PATHFAST-LAM as a new treatment monitoring tool (TMT) for PTB. The cost-effectiveness and feasibility of implementation in routine practice are not fully evaluated in this study.