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

Autor: Mujuni D; Makerere University, College of Health Sciences, Kampala, Uganda.; World Health Organisation Supranational Reference Laboratory, Uganda National TB Reference Laboratory, Kampala, Uganda., Kasemire DL; World Health Organisation Supranational Reference Laboratory, Uganda National TB Reference Laboratory, Kampala, Uganda., Ibanda I; Department of Pharmacology and Toxicology, School of Pharmacy, Kampala International University, Kampala, Uganda., Kabugo J; World Health Organisation Supranational Reference Laboratory, Uganda National TB Reference Laboratory, Kampala, Uganda., Nsawotebba A; World Health Organisation Supranational Reference Laboratory, Uganda National TB Reference Laboratory, Kampala, Uganda.; National Health Laboratory and Diagnostic Services, Kampala, Uganda., Phelan JE; Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK., Majwala RK; United States Agency for International Development, Defeat TB Project, Kampala, Uganda., Tugumisirize D; World Health Organisation Supranational Reference Laboratory, Uganda National TB Reference Laboratory, Kampala, Uganda.; National Tuberculosis and Leprosy Control Programme, Ministry of Health, Kampala, Uganda., Nyombi A; World Health Organisation Supranational Reference Laboratory, Uganda National TB Reference Laboratory, Kampala, Uganda.; National Tuberculosis and Leprosy Control Programme, Ministry of Health, Kampala, Uganda., Orena B; World Health Organisation Supranational Reference Laboratory, Uganda National TB Reference Laboratory, Kampala, Uganda., Turyahabwe I; World Health Organisation EPI Laboratory, Uganda Virus Research Institute, Entebbe, Uganda., Byabajungu H; World Health Organisation Supranational Reference Laboratory, Uganda National TB Reference Laboratory, Kampala, Uganda., Nadunga D; World Health Organisation Supranational Reference Laboratory, Uganda National TB Reference Laboratory, Kampala, Uganda., Musisi K; World Health Organisation Supranational Reference Laboratory, Uganda National TB Reference Laboratory, Kampala, Uganda., Joloba ML; World Health Organisation Supranational Reference Laboratory, Uganda National TB Reference Laboratory, Kampala, Uganda.; Department of Medical Microbiology, School of Biomedical Sciences, Makerere University, Kampala, Uganda., Ssengooba W; Department of Medical Microbiology, School of Biomedical Sciences, Makerere University, Kampala, Uganda. willyssengooba@gmail.com.; Makerere University Lung Institute, Makerere University College of Health Sciences, Kampala, Uganda. willyssengooba@gmail.com.
Jazyk: angličtina
Zdroj: BMC infectious diseases [BMC Infect Dis] 2022 Apr 11; Vol. 22 (1), pp. 363. Date of Electronic Publication: 2022 Apr 11.
DOI: 10.1186/s12879-022-07339-w
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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