Analysis of rpoB mutations associated with rifampicin resistance in Mycobacterium tuberculosis isolates in Malawi

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BACKGROUND: Rifampicin-resistant tuberculosis (RR-TB) remains a major challenge for TB control in Malawi, particularly in densely populated districts such as Blantyre. Most rifampicin resistance is caused by mutations in the rifampicin resistance determining region (RRDR) of the RNA Polymerase Beta gene (rpoB). This study characterized the distribution of RRDR mutations detected by GeneXpert MTB/RIF. METHODS: This was a retrospective analysis of 171 GeneXpert MTB/RIF assay results from Queen Elizabeth Central Hospital (QECH), Drug Resource Enhancement Against AIDS and Malnutrition (DREAM) Blantyre Clinic, Zingwangwa Health Centre, Limbe Health Centre, and Ndirande Health Centre located in Blantyre, Malawi. Demographic factors, along with MTB bacterial load and the mutation patterns specific to probes (A–E) resulting from GeneXpert probe hybridization failures, were examined. The patterns of probe drop-out, which indicate the inability of certain molecular beacon probes to attach to mutated target sequences, served as markers for mutation clusters within the RRDR. RESULTS: Males dominated the study group accounting for 59.1% (101) of cases, and individuals aged 30–44 years represented the largest age group (89, 52%). Probe E mutations were more prevalent, accounting for 76.02% (130) of all rifampicin resistance–associated detections, consistent with the globally prevalent S531L mutation. Probe D and probe B mutations were present in 14.04% (24) and 6.43% (11) of cases respectively, while no probe C mutations were observed. High MTB DNA yields were common in males [19 (11.1%)] in comparison to females [5 (2.9%)], suggesting delayed health-seeking behaviour among males. Overall, 35.7% (61) of participants presented with medium to high bacterial loads. CONCLUSION: The present study suggests that rifampicin resistance in Blantyre is overwhelmingly driven by mutations in the region targeted by probe E (codon 529–533), consistent with potential transmission of high fitness MDR-TB strains. Strengthened diagnostic pathways, earlier case-finding, and expanded access to drug susceptibility testing (DST) or sequencing are essential for effective MDR-TB control in Malawi.

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