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

Mujuni, Dennis; Kasemire, Dianah Linda; Ibanda, Ivan; Kabugo, Joel; Nsawotebba, Andrew; Phelan, Jody; Majwala, Robert Kaos; Tugumisirize, Didas; Nyombi, Abdunoor; Orena, Beatrice; Turyahabwe, Irene; Byabajungu, Henry; Nadunga, Diana; Musisi, Kenneth; Joloba, Moses; Ssengooba, Willy

doi:10.1186/s12879-022-07339-w

Cited by 10 publications

(13 citation statements)

References 34 publications

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“…These results were relatively concordant to another study conducted in India on 90 M. tuberculosis clinical isolates to correlate rrs and eis promoter mutations with phenotypic susceptibility levels toward the injectables of the second-line using GenoType MTBDRsl assay (Hain LifeScience GmbH, Germany), the agreement of results was 97% for AMK, 96% for KM and 86% for CM 21 . Our results exceeded the results of another Line Probe Assay (LPA) currently proposed by WHO for the early drug resistance screening of sputum smear-positive samples; GenoType MTBDRplus VER2.0, which displays inconstant sensitivity and specificity for the screening of resistance to injectable SLDs 22, 23 . The overall specificity ranging from 59 to 100% and sensitivity from 83 to 87% for identifying XDR isolates 24, 25 .…”

Section: Discussioncontrasting

confidence: 58%

Detection of Mutations Associated with Resistance to Second-line Drugs in Isolates of Mycobacterium tuberculosis

Fathi

Kamal²,

Attallah³

et al. 2023

Egyptian Journal of Medical Microbiology

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Background: Mycobacterium tuberculosis (M. tuberculosis) develops resistance toward second-line anti-tuberculous drugs, mostly through mutations of the chromosome. The mechanism of resistance is complicated and accompanies several genes as rrs and eis promoter mutations. Objective: To assess the validity of the Real-time PCR (Rt-PCR) in recognizing the mutations of the resistance to second-line injectable agents (capreomycin, amikacin and kanamycin) in multidrug resistant tuberculosis (MDR-TB) clinical isolates in comparison with the gold standard proportion method (PM) using Lowenstein-Jensen (LJ) media. Methodology: This study was conducted on 48 MDR-TB clinical isolates (from sputum and bronchioalveolar lavage samples) obtained from the Egyptian National Central Laboratory of the Ministry of Health, Egypt. The isolates obtained were resistant to a minimum one of the second-line anti-tuberculous drugs (ofloxacin, capreomycin, amikacin, and kanamycin) identified by PM using LJ media. Isolates were tested by Rt-PCR to track mutations in rrs and the eis promoter. Results: isolates were positive for rrs, and 32 isolates for the promoter of eis using Rt-PCR. Comparing the results to the gold standard PM, an agreement of 100%, and 69% were found to rrs, and the eis promoter, respectively. Conclusion: Using the Real-time PCR for recognizing mutations related to second-line anti-tuberculous drugs highly agrees with the PM. This could help in MDR-TB early detection and screening for extensively drug-resistant TB (XDR-TB) strains.

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Section: Discussioncontrasting

confidence: 58%

Detection of Mutations Associated with Resistance to Second-line Drugs in Isolates of Mycobacterium tuberculosis

Fathi

Kamal²,

Attallah³

et al. 2023

Egyptian Journal of Medical Microbiology

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“…44 In our study, a single isolate was detected in the gyrA gene with a common mutation at codon D94G associated with FQ-resistant isolates, but the high prevalence of gyrA mutations has been well described in different regions. 2,7,34,45 This could be due to the low prevalence of FQ-resistant isolates in our study because of the insufficient sample size used. Besides, no mutations in the gyrB gene conferring resistance to FQs, rrs, or eis genes causing SLIDs were observed in our study.…”

Section: Discussionmentioning

confidence: 91%

Molecular characterization of genetic mutations with fitness loss in pulmonary tuberculosis patients associated with HIV co-infection in Northwest Amhara, Ethiopia

Seid,

Kassa,

Girma

et al. 2023

SAGE Open Medicine

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Objectives: Molecular approaches to identifying resistance-conferring mutations suggest a revolution in the field of tuberculosis. The aim of the study was to determine the association between resistance-conferring mutations with fitness loss in Mycobacterium tuberculosis clinical isolates and HIV co-infection in the Amhara region of Ethiopia. Methods: A laboratory-based cross-sectional study was conducted between September 2022 and June 2023. A line probe assay was performed on 146 culture-positive clinical isolates. Logistic regression analysis was used to measure the strength of the association between the drug-resistance-conferring mutations with fitness loss in M. tuberculosis isolates and tuberculosis/HIV co-infection. A p-value ⩽ 0.05 was considered statistically significant. Results: A total of 11 distinct mutations at four genetic loci among 19 resistant isolates were detected. The frequency of rifampicin, isoniazid, and fluoroquinolones resistance-conferring mutations was identified in 12 (8.2%), 17 (11.6%), and 2 (1.4%) of the isolates, respectively. The most prominent specific mutations were S450L (5/9, 55.6%), S315T (11/11, 100%), C-15T (4/4, 100%), and D94G (1/1, 100%). Double mutations were observed in 10 (52.6%) multidrug-resistant tuberculosis isolates; the most common were detected in both the rpoB and katG genes (8/10, 80.0%). The HIV-co-infected tuberculosis patients carried a higher proportion of low fitness of non- rpoB S450L variants than those tuberculosis patients without HIV (80.0% vs 14.3%) and showed a significant association (cOR = 0.042, 95% CI: 0.002–0.877, p = 0.041), but not with the low fitness of non- katG S315T variants (cOR = 3.00, 95% CI: 0.348–25.870, p = 0.318). Conclusion: This study provides valuable information on the genetic variants with fitness loss associated with HIV co-infection, but requires further whole-genome-based mutation analysis.

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“…23 It was also realized that MTBDRsl could aid in real-time surveillance of emerging DR-TB, both pulmonary and EPTB, in endemic country like India. 24 The present study, to the best of our knowledge, is the first to evaluate the performance of MTBDRplus and MTBDRsl for detecting presence and pattern of drug resistance in a decent cohort of 30 cases of GITB. Both MTBDRplus and MTBDRsl, in the current study, gave positive band for M. tuberculosis in all 30 specimens, and no false negative or invalid results were obtained.…”

Section: Discussionmentioning

confidence: 93%

“…Prior studies on pulmonary TB revealed that MTBDR assays reduced the proportion of “empirical therapy” patients and boosted up targeted therapy with improvement in DR‐TB management 23 . It was also realized that MTBDRsl could aid in real‐time surveillance of emerging DR‐TB, both pulmonary and EPTB, in endemic country like India 24 . The present study, to the best of our knowledge, is the first to evaluate the performance of MTBDRplus and MTBDRsl for detecting presence and pattern of drug resistance in a decent cohort of 30 cases of GITB.…”

Section: Discussionmentioning

confidence: 99%

MTBDRplus and MTBDRsl for simultaneous diagnosis of gastrointestinal tuberculosis and detection of first‐line and second‐line drug resistance

Sharma

et al. 2023

J of Gastro and Hepatol

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Background and Aim: Emergence of drug resistance, especially to second-line drugs, hampers tuberculosis elimination efforts. The present study aimed to evaluate MTBDRplus and MTBDRsl assays for detecting first-line and second-line drug resistance, respectively, in gastrointestinal tuberculosis (GITB). Methods: Thirty ileocecal biopsy specimens, processed in the Department of Microbiology between 2012 and 2022, that showed growth of Mycobacterium tuberculosis on culture were included in the study. DNA, extracted from culture, was subjected to MTBDRplus and MTBDRsl (Hain Lifescience GmbH, Nehren, Germany), following manufacturer's instructions. Their performance was compared against phenotypic drug susceptibility testing (pDST) and gene sequencing. Results: Out of the 30 specimens, 4 (13.33%) were mono-isoniazid resistant, 4 (13.33%) were multidrug resistant (MDR), 2 (6.67%) were pre-extensively drug resistant (pre-XDR), and 2 (6.67%) were mono-fluoroquinolone resistant. The results were 100% concordant with pDST and gene sequencing. Conclusions: In the wake of growing drug resistance in all forms of extrapulmonary tuberculosis, including GITB, MTBDRplus and MTBDRsl are reliable tools for screening of resistance to both first-line and second-line drugs.

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

Cited by 10 publications

References 34 publications

Detection of Mutations Associated with Resistance to Second-line Drugs in Isolates of Mycobacterium tuberculosis

Detection of Mutations Associated with Resistance to Second-line Drugs in Isolates of Mycobacterium tuberculosis

Molecular characterization of genetic mutations with fitness loss in pulmonary tuberculosis patients associated with HIV co-infection in Northwest Amhara, Ethiopia

MTBDRplus and MTBDRsl for simultaneous diagnosis of gastrointestinal tuberculosis and detection of first‐line and second‐line drug resistance

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