ArticleBMC pulmonary medicine2019
Frequency and patterns of second-line resistance conferring mutations among MDR-TB isolates resistant to a second-line drug from eSwatini, Somalia and Uganda (2014-2016).
Article in BMC pulmonary medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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11 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Mycobacterium tuberculosis mixed infections and drug resistance in sub-Saharan Africa: a systematic review.African health sciences · 2022Pooled it
- Genetic diversity and transmission pattern of multidrug-resistant tuberculosis based on whole-genome sequencing in Wuhan, China.Frontiers in public health · 2025Article
- Whole-genome sequencing of clinical isolates from tuberculosis patients in India: real-world data indicates a high proportion of pre-XDR cases.Microbiology spectrum · 2024Article
- 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 · 2022Article
- Beijing genotype ofNew microbes and new infections · 2021Article
- Molecular Evaluation of Fluoroquinolone Resistance in Serial Mycobacterium tuberculosis Isolates from Individuals Diagnosed with Multidrug-Resistant Tuberculosis.Antimicrobial agents and chemotherapy · 2020Article
- Prescription of Levofloxacin and Moxifloxacin in Select Hospitals in Uganda: A Pilot Study to Assess Guideline Concordance.Antibiotics (Basel, Switzerland) · 2020Article
- Detection of Resistance to Fluoroquinolones and Second-Line Injectable Drugs AmongInfection and drug resistance · 2020Article
- Frequency of first and second-line drug resistance-associated mutations among resistant Mycobacterium tuberculosis clinical isolates from São Paulo, Brazil.Memorias do Instituto Oswaldo Cruz · 2020Article
- Career development for infection and immunity research in Uganda: a decade of experience from the Makerere University - Uganda Virus Research Institute research and training programme.AAS open research · 2020Article
- Mutation and Transmission Profiles of Second-Line Drug Resistance in Clinical Isolates of Drug-ResistantFrontiers in microbiology · 2019Article
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13 authors at 6 institutions in 4 countries.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundPulmonary tuberculosis is a leading cause of morbidity and mortality in developing countries. Drug resistance, a huge problem in this contagious disease, is driven by point mutations in the Mycobacterium tuberculosis genome however, their frequencies vary geographically and this affects applicability of molecular diagnostics for rapid detection of resistance. Here, we report the frequency and patterns of mutations associated with resistance to second-line anti-TB drugs in multidrug-resistant (MDR) M. tuberculosis isolates from eSwatini, Somalia and Uganda that were resistant to a second-line anti-TB drug.
methodsThe quinolone resistance determining region (QRDR) of gyrA/gyrB genes and the drug resistance associated fragment of rrs gene from 80 isolates were sequenced and investigated for presence of drug resistance mutations. Of the 80 isolates, 40 were MDR, of which 28 (70%) were resistant to a second-line anti-TB injectable drug, 18 (45%) were levofloxacin resistant while 12 (30%) were extensively drug resistant (XDR). The remaining 40 isolates were susceptible to anti-TB drugs. MIRU-VNTR analysis was performed for M/XDR isolates.
resultsWe successfully sub-cultured 38 of the 40 M/XDR isolates. The gyrA resistance mutations (Gly88Ala/Cys/Ala, Ala90Val, Ser91Pro, Asp94Gly/Asn) and gyrB resistance mutations (Asp500His, Asn538Asp) were detected in 72.2% (13/18) and 22.2% (4/18) of the MDR and levofloxacin resistant isolates, respectively. Overall, drug resistance mutations in gyrA/gyrB QRDRs occurred in 77.8% (14/18) of the MDR and levofloxacin resistant isolates. Furthermore, drug resistance mutations a1401g and g1484 t in rrs occurred in 64.3% (18/28) of the MDR isolates resistant to a second-line anti-TB injectable drug. Drug resistance mutations were not detected in drug susceptible isolates.
conclusionsThe frequency of resistance mutations to second-line anti-TB drugs in MDR-TB isolates resistant to second line anti-TB drugs from eSwatini, Somalia and Uganda is high, implying that rapid molecular tests are useful in detecting second-line anti-TB drug resistance in those countries. Relatedly, the frequency of fluoroquinolone resistance mutations in gyrB/QRDR is high relative to global estimates, and they occurred independently of gyrA/QRDR mutations implying that their absence in panels of molecular tests for detecting fluoroquinolone resistance may yield false negative results in our setting.
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