Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review

BMC Infectious Diseases

Willy Ssengooba¹  Ivan Ibanda²  Jody E. Phelan³  Dennis Mujuni⁴  Robert Kaos Majwala⁵  Irene Turyahabwe⁶  Didas Tugumisirize⁷  Beatrice Orena⁷  Diana Nadunga⁷  Dianah Linda Kasemire⁷  Abdunoor Nyombi⁷  Moses Lutakoome Joloba⁷  Henry Byabajungu⁷  Kenneth Musisi⁷  Andrew Nsawotebba⁷  Joel Kabugo⁷ 

[1] Department of Medical Microbiology, School of Biomedical Sciences, Makerere University;Department of Pharmacology and Toxicology, School of Pharmacy, Kampala International University;Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine;Makerere University, College of Health Sciences;United States Agency for International Development, Defeat TB Project;World Health Organisation EPI Laboratory, Uganda Virus Research Institute;World Health Organisation Supranational Reference Laboratory, Uganda National TB Reference Laboratory;

关键词: Mycobacterium tuberculosis;    Drug-resistant tuberculosis;    Drug susceptibility testing;    Second line probe assay;   

DOI  :  10.1186/s12879-022-07339-w

来源: DOAJ

【 摘 要 】

Abstract Background Second-line drug resistance (SLD) among tuberculosis (TB) patients is a serious emerging challenge towards global control of the disease. We characterized SLD-resistance conferring-mutations among TB patients with rifampicin and/or isoniazid (RIF and/or INH) drug-resistance tested at the Uganda National TB Reference Laboratory (NTRL) between June 2017 and December 2019. Methods This was a descriptive cross-sectional secondary data analysis of 20,508 M. tuberculosis isolates of new and previously treated patients’ resistant to RIF and/or INH. DNA strips with valid results to characterise the SLD resistance using the commercial Line Probe Assay Genotype MTBDRsl Version 2.0 Assay (Hain Life Science, Nehren, Germany) were reviewed. Data were analysed with STATAv15 using cross-tabulation for frequency and proportions of known resistance-conferring mutations to injectable agents (IA) and fluoroquinolones (FQ). Results Among the eligible participants, 12,993/20,508 (63.4%) were male and median (IQR) age 32 (24–43). A total of 576/20,508 (2.8%) of the M. tuberculosis isolates from participants had resistance to RIF and/or INH. These included; 102/576 (17.7%) single drug-resistant and 474/576 (82.3%) multidrug-resistant (MDR) strains. Only 102 patients had test results for FQ of whom 70/102 (68.6%) and 01/102 (0.98%) had resistance-conferring mutations in the gyrA locus and gyrB locus respectively. Among patients with FQ resistance, gyrAD94G 42.6% (30.0–55.9) and gyrA A90V 41.1% (28.6–54.3) mutations were most observed. Only one mutation, E540D was detected in the gyrB locus. A total of 26 patients had resistance-conferring mutations to IA in whom, 20/26 77.0% (56.4–91.0) had A1401G mutation in the rrs gene locus. Conclusions Our study reveals a high proportion of mutations known to confer high-level fluoroquinolone drug-resistance among patients with rifampicin and/or isoniazid drug resistance. Utilizing routinely generated laboratory data from existing molecular diagnostic methods may aid real-time surveillance of emerging tuberculosis drug-resistance in resource-limited settings.

【 授权许可】

Unknown