Isoniazid-resistant tuberculosis: a cause for concern?

Stagg, Helen R.; Lipman, Marc; McHugh, Timothy D.; Jenkins, Helen E.

doi:10.5588/ijtld.16.0716

Cited by 77 publications

(70 citation statements)

References 82 publications

(84 reference statements)

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“…Conversely, one isolate was INH resistant but sensitive to rifampin. Thus, detection of RIF or INH resistance via analysis of either rpoB or katG genes alone may not accurately confirm MDR-TB, resulting in patients with non-MDR INH resistance at risk of being treated inadequately (35).…”

Section: Discussionmentioning

confidence: 99%

Next-Generation Sequencing for Characterizing Drug Resistance-Conferring Mycobacterium tuberculosis Genes from Clinical Isolates in the Ukraine

Daum¹,

Konstantynovska

Solodiankin

et al. 2018

J Clin Microbiol

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The Ukraine ranks among the top 20 countries with the highest number of multidrug-resistant (MDR) and extensively drug resistant (XDR) cases in the world. However, little is known of the genetic diversity, i.e., resistance signatures, in clinical isolates from this region. We analyzed seven of most prevalent MDR/XDR antibiotic resistance-conferring genes from clinical isolates ( = 75) collected from geographically diverse Ukrainian oblasts and the southern Crimean peninsula. Genomic analysis revealed that 6 (8%) were sensitive, 3 (4%) were resistant to at least one antibiotic but were not MDR, 40 (53%) were MDR, and 26 (35%) were XDR. The majority of isolates (81%) were of the Beijing-like lineage. This is the first study to use next-generation sequencing (NGS) of clinical isolates from the Ukraine to characterize mutations in genes conferring drug resistance. Several isolates harbored drug resistance signatures that have not been observed in other countries with high-burden tuberculosis. Most notably, the absence of gene promoter mutations, a diversity of mutation types in the resistance-determining region, and detection of heteroresistance provide a broader understanding of MDR/XDR from this area of the world.

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Section: Discussionmentioning

confidence: 99%

Next-Generation Sequencing for Characterizing Drug Resistance-Conferring Mycobacterium tuberculosis Genes from Clinical Isolates in the Ukraine

Daum¹,

Konstantynovska

Solodiankin

et al. 2018

J Clin Microbiol

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“…Resistance to INH is linked to all multidrug-resistant forms of TB (MDR, XDR, TDR). Several studies have shown that INH resistance is acquired first, followed by resistance to rifampin and the other anti-TB drugs (32-36), which highlights the significant impact of INH in the success of treatment in active and latent TB and warrants further efforts to understand the global burden of INH-resistant TB (37). Fig.…”

Section: Discussionmentioning

confidence: 99%

Differential Host Gene Signatures in Response toMycobacterium tuberculosisInfection

Tazi

Wang

Fornage

2020

Preprint

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24Tuberculosis (TB) represents a global public health threat and is the leading cause of morbidity 25 and mortality worldwide. Effective control of TB is complicated with the emergence of multidrug 26resistance. Yet, there is still a fundamental gap in understanding the complex and dynamic 27 interactions between different Mycobacterium tuberculosis strains and the host. In this project, we 28 investigated the host immune response to different M. tuberculosis strains, including avirulent or 29 virulent and rifampin-resistant or isoniazid-resistant strains in THP-1 cells. We identified major 30 differences in the gene response profiles in response to infection with these strains. The expression 31 of IDO1 and IL-1b in the infected cells was stronger in all virulent M. tuberculosis strains. The 32 most striking result was the overexpression of many interferon-stimulated genes (ISGs) in cells 33 infected with the isoniazid-resistant strain, compared to the rifampin-drug resistant strain and the 34 drug-sensitive strain. A transcription regulation analysis of the differentially expressed genes in 35 infected THP-1 cells implicated two major transcription factors, NF-kB and STAT1. The 36 differentially expressed ISGs in response to the isoniazid-resistant M. tuberculosis strain were 37 associated with STAT1 signaling, while the expression of many cytokines, such IL-1b, was 38 associated with NF-kB signaling. Our data suggest that the isoniazid-resistant M. tuberculosis 39 strain preferentially activates STAT1 in response to cGAS-STING activation and induces a host 40 immune response signature that is characteristic of isoniazid resistance. This study has a potential 41 to provide important new insights into TB pathogenesis and to characterize host gene signatures 42 specifically involved in isoniazid-resistant TB. 43 44 45 groups (24 h post-infection; p<0.05). The 20 highly significant differentially expressed genes in 439 each plot are indicated in the insets. 440 441 442 443 H37Rv vs H37Rv-INH-R H37Rv-Rif-R vs H37Rv-INH-R MX1,

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“…23 Development of INH resistance precedes the development of MDR-TB. 24 Initial INH resistance increases incidence rates of treatment failure and relapse compared with pan-sensitive strains (incidence rate ratio 10.9 and 1.8, respectively). 25 Research priorities include the development of a strong evidence base for the optimal use of preventive therapy in high-risk populations, determining the protective efficacy of novel vaccines, developing sensitive and rapid diagnostic tests for DR-TB (directly from sputum samples), identifying biomarkers to predict future disease risk, identifying pragmatic methods to enhance case detection, testing new models of care to reduce time to effective treatment, developing treatment regimens that are short, safe and durable and improving infection control in all high-transmission settings.…”

Section: Discussionmentioning

confidence: 99%

Progression from tuberculosis to multi drug resistance-TB in revised national tuberculosis control programme: perspectives from health system care givers

Kumar

Rana

Sundram

et al. 2019

Int J Community Med Public Health

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Background: The aims and objectives were to study the progression from tuberculosis to multi drug resistance-TB in revised national tuberculosis control programme: perspectives from health system care givers.Methods: The study was carried out in TB Sanatorium ITKI, Sadar Hospital Ranchi and RIMS Ranchi. The interview of various health personnel including SAHIYAs was taken using a semi-structured questionnaire based on programmatic management of multi drug resistant tuberculosis guidelines -2016.Results: Among Doctors knowledge level was good compared to other health personnel which had mean value 7.33 (±2.79), laboratory technician 3.45 (±2.64), STS 4.67 (±1.59), Sahiya 2.1 (±0.73). Regarding capacity enhancement level all health personnel needed refresher trainings in which doctors got 4.67 (±1.58), laboratory technician 3.45±2.64, STS 1.72±0.34, and Sahiya 0.5±0.52. Specially sahiya needs training regarding MDR-TB because they are the connecting link between health system and community. Regarding execution level, Doctors got 1.86 (±0.74), laboratory technician 1.64 (±0.56), STS 1.64 (±0.56) and Sahiya (ASHA) 2.2 (±0.44). Sahiya were better than other health personnel at execution level.Conclusions: Advocacy, communication, and social mobilization are important aspects of TB control, Policy makers and administrators should be sensitized for need of adequate and sustained funding for TB control to ensure quality capacity building. They need to provide continuous and quality training of staff at different levels and retention of trained staff and periodic reviews to identify gaps and take corrective steps.

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Isoniazid-resistant tuberculosis: a cause for concern?

Cited by 77 publications

References 82 publications

Next-Generation Sequencing for Characterizing Drug Resistance-Conferring Mycobacterium tuberculosis Genes from Clinical Isolates in the Ukraine

Next-Generation Sequencing for Characterizing Drug Resistance-Conferring Mycobacterium tuberculosis Genes from Clinical Isolates in the Ukraine

Differential Host Gene Signatures in Response toMycobacterium tuberculosisInfection

Progression from tuberculosis to multi drug resistance-TB in revised national tuberculosis control programme: perspectives from health system care givers

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