Translating drug-resistant tuberculosis surveillance into molecular-biophotonic diagnostic innovation in rural Eastern Cape, South Africa.

Abstract

Background: Drug-resistant tuberculosis (DR-TB) remains a major public health challenge in South Africa, particularly in rural settings with constrained access to rapid molecular diagnostics. There is a need to identify locally relevant molecular targets that could inform the future development of affordable point-of-care (POC) diagnostic platforms. This study used routine DR-TB surveillance data to develop an epidemiology-guided framework for prioritizing molecular targets for future molecular-biophotonic diagnostic development.

Methods: A retrospective secondary analysis was conducted using routine DR-TB programme data from 402 patients managed at two decentralized treatment facilities in the rural Eastern Cape Province, South Africa, between 2020 and 2024. Resistance categories, treatment outcomes, and programme vulnerability indicators were analysed descriptively. A diagnostic prioritization framework integrating disease burden, frequency of resistance categories, treatment outcome vulnerability, programme impact, and potential suitability for decentralized implementation was used to prioritize established resistance-associated molecular targets. Molecular targets were informed by published evidence; no isolate-level mutation analysis, sequencing, biosensor development, or analytical or clinical validation of a diagnostic platform was performed.

Results: Rifampicin-resistant tuberculosis (RR-TB) (47.5%) and multidrug-resistant tuberculosis (MDR-TB) (44.3%) accounted for 91.8% of DR-TB cases, while pre-extensively drug-resistant tuberculosis (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) accounted for 5.7% and 2.5%, respectively. Declining treatment success and increasing proportions of unevaluated outcomes among RR-TB and MDR-TB indicated programme vulnerability; however, the available data did not permit causal attribution of these patterns to diagnostic limitations. The framework prioritized rpoB, katG, and inhA as high-priority targets, followed by gyrA, gyrB, rrs, and eis as medium-priority targets, with embB, pncA, Rv0678, atpE, and pepQ identified for future expansion. These targets were conceptually mapped to candidate biophotonic biosensing approaches; their diagnostic performance and POC suitability were not evaluated in this study.

Conclusions: This study proposes an epidemiology-guided framework for prioritizing molecular targets for future DR-TB diagnostic development in rural settings. The molecular-biophotonic component is conceptual and does not represent a validated diagnostic technology. Mutation-level characterization, biosensor development, analytical evaluation, and prospective clinical validation are required to determine the performance, feasibility, and potential POC applicability of the proposed approach.