Prevalence and Clinical Implications of Pyrazinamide Resistance in Newly Diagnosed TB Patients in Uganda

Abstract

Background: Globally, 10.8 million people were diagnosed with tuberculosis during 2023 causing approximately 1.3 million deaths. This study aimed to assess the prevalence and characterization of pyrazinamide resistance by detecting the pncA gene among newly diagnosed Mycobacterium tuberculosis patients attending Bombo General Military Hospital, Central Uganda. Methods: Cross-sectional study looking at newly diagnosed TB patients in Bombo General Military Hospital. The sputum samples were confirmed TB positive using GeneXpert PCR technology, DNA extraction using the CTAB method, DNA amplification, and finally gel electrophoresis for pncA gene detection. Results: A total of 166 sputum-positive tuberculosis samples were analyzed. Males were 91/166(55%), while 115 (70%) of the positive sputum samples were positive HIV status. The majority (96%) of the newly diagnosed Mycobacterium tuberculosis patients showed no detection of rifampicin resistance, while the rest 6/160 (4%) showed indeterminate rifampicin resistance. Of the 52 (31%) patients with positive pncA gene, 29 (56%) had HIV positive status 18 (34%) had unknown HIV status and 5 (10%) had negative HIV status. It was observed that only one patient 1 (2%) showed both rifampicin and pyrazinamide resistance and was a female patient aged 42 years of age with positive HIV status and positive pncA gene status. Conclusion: This study reveals the important trends regarding drug resistance and its relationship with HIV status. The majority of patients (96%) did not exhibit rifampicin resistance, suggesting that multi-drug-resistant tuberculosis is not widespread among the newly diagnosed cases. The majority (56%) of the patients with the pncA gene mutation, were HIV-positive. This highlights the potential vulnerability of HIV-positive TB patients to multidrug resistance though the overall pyrazinamide resistance rate remains low.