New rapid test finds hidden drug-resistant TB in Zambia

Tuberculosis remains a major health challenge in Zambia, and rising drug resistance makes timely diagnosis and the right treatment more important than ever. The country has traditionally relied on rifampicin as a proxy for multidrug resistance, which means some types of resistance can be missed. To address that gap, a team led by corresponding author Phallon B. Mwaba evaluated the practical use of a newer test, Xpert MTB/XDR, which can detect resistance to isoniazid, fluoroquinolone, Ethionamide and aminoglycosides in addition to rifampicin. The researchers used data from an intensive, four-week active case finding surge carried out in May 2025 across 39 high-TB-burden facilities in five provinces of Zambia. Rather than testing only patients who showed rifampicin resistance, the program reflexively applied Xpert MTB/XDR to bacteriologically confirmed tuberculosis cases identified by Xpert MTB/RIF Ultra, regardless of their rifampicin status. The goal was to see whether adding reflex Xpert MTB/XDR testing in routine workflows was feasible and whether it would uncover drug resistance that rifampicin-centered diagnostics could miss.

The surge identified 509 tuberculosis patients, of whom 361 (70.9%) were bacteriologically confirmed by Xpert MTB/RIF Ultra. From those 361, 335 (92.8%) were eligible for reflex Xpert MTB/XDR testing and 299 (89.3% of eligible) actually underwent the reflex test. Results were successfully retrieved for 282 patients (94.3% of those tested). Among the 282 with XDR results, 24 patients (8.5%) had a form of drug-resistant tuberculosis. Mono-resistance to rifampicin was found in 10 patients (3.5%) and mono-resistance to isoniazid in 9 patients (3.2%), both more common than multi-drug-resistant tuberculosis, which was identified in 3 patients (1.1%). Only one patient (0.4%) had Pre-XDR TB. Importantly, non-rifampicin resistance — specifically isoniazid mono-resistance and isoniazid combined with fluoroquinolone or ethionamide resistance — was detected in 9 patients (3.2% of all patients with XDR TB results), representing 37.5% of all drug-resistant tuberculosis cases found.

These findings show that reflex Xpert MTB/XDR testing can rapidly uncover clinically important forms of drug resistance that would be missed if programs look only for rifampicin resistance. By identifying isoniazid mono-resistance and combinations of resistance involving fluoroquinolone or Ethionamide, the test can help clinicians choose more effective, individualized treatments earlier, potentially preventing further amplification of resistance. The study authors argue that integrating MTB/XDR into routine diagnostic algorithms in high-burden settings like Zambia could improve early drug-resistant tuberculosis detection and patient management. However, realizing that potential requires national scale-up paired with laboratory strengthening, capacity building, and robust data systems to ensure tests are run, results are retrieved, and care pathways are adjusted accordingly. In short, the programmatic use of Xpert MTB/XDR in routine workflows appears feasible and valuable for finding hidden drug-resistant TB cases quickly.