Revisiting the therapeutic threshold in tuberculosis Care: Lessons from Southern Africa’s dual-method approach

Dear Editor,

The study by Keter et al. [1] is a valuable contribution to operationalizing the therapeutic threshold (ThT) in tuberculosis (TB) care, particularly in high-burden settings. Previous work in Rwanda has shown that clinicians’ reluctance to treat smear-negative TB often stems from uncertainty in balancing false positive and false negative risks [2]. By integrating the adapted nominal group technique (aNGT) with clinical vignettes (CVs), the authors combine prescriptive and descriptive approaches to capture both structured consensus and real-world clinical reasoning [3,4].

We commend the methodological innovation; however, combining aNGT and CV assessments in a single session may influence the stability of ThT estimates between clinical and community contexts. Sequential weighting of false positive (FP) and false negative (FN) harms without a washout or separate participant groups could lead to cognitive carryover effects—potentially muting setting-specific differences [5]. Addressing this in future designs would strengthen the validity of the method.

Additionally, the overestimation of TB probability in CVs—possibly driven by clinicians’ desire to justify treatment—warrants attention. This bias could result in higher-than-true ThT values, affecting policy if thresholds are embedded in guidelines without adjustment. Incorporating objective epidemiological data into vignette calibration, or coupling vignettes with Bayesian probability training, may mitigate this risk.

From a programmatic perspective, the finding that clinicians tolerate roughly three FP cases to prevent two FN cases underscores a public health–oriented tolerance for overtreatment [1,3]. While this may reduce transmission, it could also increase drug exposure in non-diseased individuals—raising concerns about adverse effects, antimicrobial resistance, and resource allocation. Explicitly balancing these trade-offs in national TB guidelines could help align frontline practice with strategic priorities.

In summary, Keter et al. [1] provide a replicable, context-sensitive method for estimating ThT. To maximize its impact, future work should minimize design-related biases, validate thresholds against prospective clinical outcomes, and ensure that policy adoption includes safeguards against both under- and overtreatment.

Ethical approval

This letter does not involve any research on human participants or animals. No ethical approval was required for its preparation. All sources cited are publicly available and properly referenced.

CRediT authorship contribution statement

Chadaporn N. Gordon: Conceptualization, Validation, Writing – original draft, Writing – review & editing. Nav La: Validation, Writing – review & editing. Schawanya K. Rattanapitoon: Supervision, Writing – original draft, Writing – review & editing. Nathkapach K. Rattanapitoon: Conceptualization, Supervision, Writing – original draft, Writing – review & editing.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.