Case Investigation of a Suspected Drug-Resistant Tuberculosis Patient in Chongwe District, Zambia: Importance of Accurate Molecular Diagnostics for Resistance Profiling

Background:Recurrent tuberculosis in patients with prior treatment default raises significant concern for acquired drug resistance, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. This report details the investigation of a 44-year-old male retreatment case in Zambia, initially suspected of XDR-TB. The case underscores the critical role of advanced molecular diagnostics in accurately defining resistance profiles and informing appropriate clinical and public health responses. Methods:A descriptive case investigation was conducted in Chongwe District, Zambia, in June 2025. Quantitative data were extracted from clinical and laboratory records of the index patient and close contacts, including demographic characteristics, tuberculosis treatment history, and molecular diagnostic results. Qualitative data were collected through structured interviews with the patient, a primary caregiver, and a healthcare worker to explore treatment adherence barriers and care experiences. Laboratory confirmation and drug resistance profiling were performed using GeneXpert MTB/RIF Ultra and GeneXpert MTB/XDR assays. Quantitative data were summarized using descriptive statistics, while qualitative information was thematically synthesized and integrated narratively to contextualize clinical and public health findings. Results:The index case was confirmed to have Tuberculosis but was found to have mono-resistance to Isoniazid only. No resistance to Rifampicin, Fluoroquinolones, or Group A second-line drugs was detected, thus not meeting the XDR-TB or MDR-TB case definitions. All three close contacts were screened and tested negative for Tuberculosis. Qualitative interviews revealed that prior treatment default was driven by livelihood demands, travel distance, and early symptom resolution. Structured adherence support during retreatment facilitated successful treatment completion. Conclusion:The investigation confirmed isoniazid mono-resistant TB, not XDR-TB, in a retreatment case with a history of default. Rapid molecular diagnostics were essential for accurate resistance classification and clinical guidance. The findings reinforce the necessity of enhanced adherence support and robust laboratory capacity to effectively manage drug-resistant tuberculosis in high-burden settings.