Molecular Epidemiology and Genetic Diversity of Multidrug-Resistant Mycobacterium tuberculosis Isolates in Bangladesh

Rahman, Sezanur; Rahman, Ananna; Nasrin, Rumana; Ather, Md. Fahim; Ferdous, Sara Sabrina; Ahmed, Shahriar; Uddin, Mohammad Khaja Mafij; Khatun, Razia; Sarker, Mohammad Shahnewaz; Mahmud, Asif; Rahman, Md. Munsur

doi:10.1128/spectrum.01848-21

Cited by 8 publications

(12 citation statements)

References 42 publications

(78 reference statements)

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“…Meehan et al 14 reported that clusters based on spoligotyping could encompass transmission events that occurred almost 200 years prior to sampling, while 24-locus MIRU-VNTR typing often represented three decades of transmission and WGS based genotyping applying low SNP or cgMLST allele thresholds allows for determination of recent transmission events, eg in timespans of up to 10 years for a 5 SNP/allele cut-off. In 11 out of the 29 clusters by the VNTR-15 China typing in the present study, we found that the isolates from the same cluster were from different geographical locations, similar phenomena have also been found in some earlier studies, 41,53 further proving that clusters by MIRU-VNTR typing could not represent recent transmission and remote transmission maybe identified in a cluster. When classical genotyping methods are employed, contact tracing and/or WGS were suggested to imply to investigate potential transmission hotspots.…”

Section: Discussionsupporting

confidence: 89%

“…The association between Beijing genotype and MDR has been shown in many settings. [39][40][41] Study from Hunan, China reported that Beijing genotype had a significantly higher proportion of MDR than the non-Beijing genotype (OR 3.28, 95% CI: 1.01-10.37), and also showed a higher risk for developing drug resistance to all four first-line drugs (OR 5.97, 95% CI 1.05-44.33). 39 Studies from Nepal 40 and Bangladesh 41 found that the Beijing genotype had an important role in transmitting MDR-TB.…”

Section: Discussionmentioning

confidence: 99%

“…[39][40][41] Study from Hunan, China reported that Beijing genotype had a significantly higher proportion of MDR than the non-Beijing genotype (OR 3.28, 95% CI: 1.01-10.37), and also showed a higher risk for developing drug resistance to all four first-line drugs (OR 5.97, 95% CI 1.05-44.33). 39 Studies from Nepal 40 and Bangladesh 41 found that the Beijing genotype had an important role in transmitting MDR-TB. Another systematic review also found that in Pakistan and Iran the Beijing genotype exhibited a strong and statistically significant association with drug resistance.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Epidemiology of Clinical Mycobacterium tuberculosis Isolates from Southern Xinjiang, China Using Spoligotyping and 15-Locus MIRU-VNTR Typing

Yin¹,

Mijiti²,

Liu³

et al. 2023

IDR

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In the last decades, the molecular epidemiological investigation of Mycobacterium tuberculosis has significantly increased our understanding of tuberculosis epidemiology. However, few such studies have been done in southern Xinjiang, China. We aimed to clarify the molecular epidemic characteristics and their association with drug resistance in the M. tuberculosis isolates circulating in this area. Methods: A total of 347 isolates obtained from southern Xinjiang, China between Sep, 2017 and Sep, 2019 were included to characterize using a 15-locus MIRU-VNTR (VNTR-15 China ) typing and spoligotyping, and test for drug susceptibility profiles. Then the lineages and clustering of the isolates were analyzed, as well as their association with drug resistance. Results: Spoligotyping results showed that 60 spoligotype international types (SITs) containing 35 predefined SITs and 25 Orphan or New patterns, and 12 definite genotypes were found, and the top three prevalent genotypes were Beijing genotype (207, 59.7%), followed by CAS1-Delhi (46, 13.6%), and Ural-2 (30, 8.6%). The prevalence of Beijing genotype infection in the younger age group (≤30) was more frequent than the two older groups (30~59 and ≥60 years old, both P values <0.05). The Beijing genotype showed significantly higher prevalence of resistance to isoniazid, rifampicin, ethambutol, multi-drug or at least one drug than the non-Beijing genotype (All P values ≤0.05). The estimated proportion of tuberculosis cases due to transmission was 18.4% according to the cluster rate acquired by VNTR-15 China typing, and the Beijing genotype was the risk factor for the clustering (OR 9.15,. Conclusion: Our data demonstrated that the Beijing genotype is the dominant lineage, associated with drug resistance, and was more likely to infect young people and contributed to tuberculosis transmission in southern Xinjiang, China. These findings will contribute to a better understanding of tuberculosis epidemiology in this area.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Molecular Epidemiology of Clinical Mycobacterium tuberculosis Isolates from Southern Xinjiang, China Using Spoligotyping and 15-Locus MIRU-VNTR Typing

Yin¹,

Mijiti²,

Liu³

et al. 2023

IDR

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“…The availability of effective RR/MDR-TB treatment in the Bangladesh Damien Foundation MDR-TB project area may explain the relatively low percentage of isolates that clustered. In a nationwide drug-resistant TB (DR-TB) surveillance study conducted in Bangladesh between 2011 and 2017, 38.4% of MDR-TB isolates were found in a cluster [30]. Our results are in line with these findings, despite the use of different transmission cluster estimation techniques (spoligotyping and 24-locus Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat vs WGS).…”

Section: Discussionsupporting

confidence: 83%

“…Our results suggest that known differences in transmissibility between M. tuberculosis lineages also apply to MDR-TB strains. In the DR-TB surveillance study in Bangladesh mentioned above, a significantly higher clustering rate was found in modern lineage isolates (49.3%) compared to ancient lineage isolates (9.6%) [30]. In an MDR-TB cohort in Saudi Arabia consisting of isolates belonging to lineage 1-4, no difference in clustering proportion was found between lineages [32].…”

Section: Discussionmentioning

confidence: 99%

BorderlinerpoBmutations transmit at the same rate as commonrpoBmutations in a tuberculosis cohort in Bangladesh

Lempens

Deun²,

Aung

et al. 2023

Preprint

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The spread of multidrug-resistant tuberculosis (MDR-TB) is a growing problem in many countries worldwide. Resistance to one of the primary first-line drugs, rifampicin, is caused by mutations in the Mycobacterium tuberculosis rpoB gene. While some of these infrequent mutations show lower fitness in vitro than more common mutations, their in vivo fitness is currently unknown. We used a dataset of 394 whole genome sequenced MDR-TB isolates from Bangladesh, representing around 44% of notified MDR-TB cases over 6 years, to look at differences in transmission clustering between isolates with borderline rpoB mutations and those with common rpoB mutations. We found a relatively low percentage of transmission clustering in the dataset (34.8%) but no difference in clustering between different types of rpoB mutations. Compensatory mutations in rpoA, rpoB, and rpoC were associated with higher levels of transmission clustering as were lineages 2, 3, and 4 relative to lineage 1. Young people as well as patients with high sputum smear positive TB were more likely to be in a transmission cluster. Our findings show that although borderline rpoB mutations have lower in vitro growth potential this does not translate into lower transmission potential or in vivo fitness. Proper detection of these mutations is crucial to ensure they do not go unnoticed and spread MDR-TB within communities.

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Resistance patterns and transmission of mono- and polyresistant TB: clinical impact of WGS

Dohál,

Dvořáková,

Šperková

et al. 2023

JAC-Antimicrobial Resistance

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Objectives Rapidly diagnosing drug-resistant TB is crucial for improving treatment and transmission control. WGS is becoming increasingly accessible and has added value to the diagnosis and treatment of TB. The aim of the study was to perform WGS to determine the rate of false-positive results of phenotypic drug susceptibility testing (pDST) and characterize the molecular mechanisms of resistance and transmission of mono- and polyresistant Mycobacterium (M.) tuberculosis. Methods WGS was performed on 53 monoresistant and 25 polyresistant M. tuberculosis isolates characterized by pDST. Sequencing data were bioinformatically processed to infer mutations encoding resistance and determine the origin of resistance and phylogenetic relationship between isolates studied. Results The data showed the variable sensitivity and specificity of WGS in comparison with pDST as the gold standard: isoniazid 92.7% and 92.3%; streptomycin 41.9% and 100.0%; pyrazinamide 15% and 94.8%; and ethambutol 75.0% and 98.6%, respectively. We found novel mutations encoding resistance to streptomycin (in gidB) and pyrazinamide (in kefB). Most isolates belonged to lineage 4 (80.1%) and the overall clustering rate was 11.5%. We observed lineage-specific gene variations encoding resistance to streptomycin and pyrazinamide. Conclusions This study highlights the clinical potential of WGS in ruling out false-positive drug resistance following phenotypic or genetic drug testing, and recommend this technology together with the WHO catalogue in designing an optimal individualized treatment regimen and preventing the development of MDR TB. Our results suggest that resistance is primarily developed through spontaneous mutations or selective pressure.

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Molecular Epidemiology and Genetic Diversity of Multidrug-Resistant Mycobacterium tuberculosis Isolates in Bangladesh

Cited by 8 publications

References 42 publications

Molecular Epidemiology of Clinical Mycobacterium tuberculosis Isolates from Southern Xinjiang, China Using Spoligotyping and 15-Locus MIRU-VNTR Typing

Molecular Epidemiology of Clinical Mycobacterium tuberculosis Isolates from Southern Xinjiang, China Using Spoligotyping and 15-Locus MIRU-VNTR Typing

BorderlinerpoBmutations transmit at the same rate as commonrpoBmutations in a tuberculosis cohort in Bangladesh

Resistance patterns and transmission of mono- and polyresistant TB: clinical impact of WGS

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