New rapid sputum test could speed tuberculosis treatment decisions

Treatment failure in pulmonary tuberculosis remains a serious problem because existing tools to judge whether therapy is working are slow or inaccurate. To address that gap, a team led by Nobuo Saito is running a prospective longitudinal study in Nairobi, Kenya, to test a rapid laboratory tool that measures a bacterial molecule called lipoarabinomannan (LAM) in sputum. The PATHFAST TB LAM Ag assay (PATHFAST-LAM) is an automated chemiluminescent enzyme immunoassay designed to quantify LAM in sputum within one hour with minimal manual handling. Earlier work showed a strong correlation between sputum LAM concentration and culture-based bacterial load, but the assay has not been prospectively evaluated to see whether early changes in LAM predict which patients will have poor outcomes. The new study will enroll newly diagnosed, bacteriologically confirmed pulmonary TB patients at Rhodes Chest Clinic and Mbagathi County Referral Hospital and follow them through the standard six-month treatment course. The protocol has ethical approval from the Kenya Medical Research Institute (KEMRI/SERU/CRDR/124/5241) and Nagasaki University (250619327) and is registered at ClinicalTrials.gov (NCT07157904).

The study will collect sputum frequently during treatment — weekly during weeks 1–4, biweekly during weeks 5–12, and monthly during months 3–6 — and will measure LAM concentrations at each time point using the PATHFAST-LAM assay. The primary goal is to assess whether changes in sputum LAM concentration during the intensive phase (from baseline to week 4 and/or week 8) can predict a composite poor outcome. That composite outcome is defined as any of the following: positive sputum culture at month 6, treatment failure, death during treatment, or relapse within three months after treatment completion. The primary endpoint will be the area under the receiver operating characteristic curve (AUC from ROC analysis) for change in sputum LAM concentration predicting the composite poor outcome. The team will identify an optimal cut-off for LAM change and estimate sensitivity and specificity with 95% confidence intervals using 2×2 tables. The protocol uses an adaptive design that permits sample-size re-estimation after an interim analysis, allowing the study to adjust enrollment if needed to ensure robust results.

If changes in sputum LAM measured by PATHFAST-LAM do predict poor clinical outcomes, the assay could become a practical treatment monitoring tool that delivers objective, quantitative results within an hour. Such a tool could help clinicians identify failing regimens earlier than current methods allow and make timely decisions about treatment changes or intensified care. The study is the first prospective evaluation linking PATHFAST-LAM sputum concentrations to clinical outcomes in pulmonary TB, and its real-time, longitudinal sampling will provide insight into how LAM levels change during therapy. However, the protocol notes limits: this study will not fully evaluate cost-effectiveness or the practicalities of routine implementation, so further work would be needed before widespread adoption. The investigators plan to share findings in peer-reviewed journals and scientific meetings, which will determine whether PATHFAST-LAM moves from promising laboratory tool to a clinically useful test for monitoring TB treatment.