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International scientific-online conference
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INTEGRATION OF WHOLE-GENOME SEQUENCING INTO NATIONAL
STRATEGIES FOR THE CONTROL OF DRUG-RESISTANT
TUBERCULOSIS
Saifutdinov Zayniddin Asamutdinovich
Department of Microbiology, Immunology and
Fundamentals of Molecular Genetics
Parpieva Nargiza Nusratovna
director of the republican scientific and practical medical center of phthisiology
and pulmonology, chief phthisiologist of the republic, head of the department of
phthisiology of the TMA, doctor of medical sciences, professor
https://doi.org/10.5281/zenodo.15473942
Abstract
This study evaluates the integration of whole-genome sequencing (WGS)
into the national tuberculosis (TB) control strategy to detect and monitor drug-
resistant
Mycobacterium tuberculosis
strains. A total of 280 clinical isolates from
MDR and XDR-TB patients were sequenced and analyzed for resistance-
associated mutations. The most frequent mutations were found in
katG
,
rpoB
,
gyrA
, and
rrl
. Beijing lineage dominated the population, accounting for 62% of all
isolates. WGS reduced the time to resistance detection by 10–14 days compared
to phenotypic methods. The findings demonstrate WGS as a reliable and rapid
tool to support precision treatment and strengthen national TB surveillance
systems.
Keywords:
Mycobacterium tuberculosis
, whole-genome sequencing, MDR-TB, XDR-TB,
resistance mutations, Beijing lineage, molecular diagnostics, TB surveillance.
Relevance
The growing prevalence of multidrug-resistant (MDR) and extensively
drug-resistant (XDR) tuberculosis represents a critical challenge for TB control,
especially in high-burden regions. Conventional diagnostic tools often fail to
detect resistance quickly and comprehensively, delaying effective treatment.
Whole-genome sequencing (WGS) has emerged as a transformative approach,
enabling rapid identification of mutations responsible for resistance to both
first-line and second-line drugs. The integration of WGS into national TB
programs offers a powerful solution to improve early diagnosis, guide
appropriate therapy, and monitor the spread of resistant strains. In addition to
its diagnostic advantages, WGS can provide epidemiological insights into the
genetic structure and transmission dynamics of
M. tuberculosis
. Understanding
which genotypes dominate and how resistance emerges can help develop
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targeted interventions. This study highlights the strategic value of WGS in
modern TB surveillance, proposing its incorporation into diagnostic protocols to
enhance national capacity in managing drug-resistant TB and to support global
goals for TB elimination.
Objective:
To assess the effectiveness of whole-genome sequencing for the detection of
drug resistance and epidemiological monitoring of
Mycobacterium tuberculosis
within a national TB control framework.
Materials and Methods
A total of 280
M. tuberculosis
isolates were collected from patients
diagnosed with MDR and XDR-TB across five high-burden regions between 2022
and 2024. Whole-genome sequencing was performed using the Illumina MiSeq
platform. Sequence data were analyzed using TB-Profiler to detect resistance-
associated mutations in
katG
,
rpoB
,
gyrA
,
rrl
, and
Rv0678
. Phylogenetic analysis
identified major lineages and transmission clusters. Results were compared to
phenotypic drug susceptibility testing (DST) data for validation. Turnaround
time, diagnostic accuracy, and concordance between phenotypic and genotypic
methods were calculated. Statistical analysis was performed using SPSS 26.0 and
R software for SNP-based clustering.
Results
Of the 280 isolates, 62% belonged to the Beijing lineage, followed by LAM
(21%) and CAS (10%). Resistance-associated mutations were most frequently
observed in
katG S315T
(78%),
rpoB S450L
(71%), and
gyrA D94G
(39%). WGS
detected resistance mutations with 95% sensitivity and 93% specificity,
reducing the average diagnostic delay by 12 days compared to phenotypic DST.
A total of 14 genomic clusters were identified, with strong geographic
correlations. Concordance between WGS and DST was high (κ = 0.87). These
results demonstrate that WGS provides both diagnostic and epidemiological
benefits and can serve as a cornerstone of TB resistance monitoring systems.
Conclusion
The study confirms that whole-genome sequencing is an effective tool for
detecting drug resistance and monitoring the genetic structure of
M. tuberculosis
in national TB programs. The technology provides rapid, accurate, and
comprehensive information on resistance mutations and strain transmission.
Integration of WGS significantly reduces diagnostic delays and enhances
treatment precision. Given the dominance of the Beijing lineage and the
clustering of resistant strains, genomic data are essential for informed public
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health responses. The findings support the adoption of WGS in routine TB
diagnostics and surveillance, reinforcing its role in modernizing national
strategies to control drug-resistant TB.
Literature:
1.
Парпиева Н. Н. и др. Характеристика лекарственной устойчивости
микобактерий туберкулеза у ВИЧ-инфицированных //Туберкулез и
болезни легких. – 2011. – Т. 88. – №. 5. – С. 101-102.
2.
Сайфутдинов З. А. СОВРЕМЕННЫЕ ПОДХОДЫ К ЛЕЧЕНИЮ БОЛЬНЫХ
ТУБЕРКУЛЕЗОМ, УСТОЙЧИВЫХ К НОВЫМ ПРОТИВОТУБЕРКУЛЕЗНЫМ
ПРЕПАРАТАМ // Журнал гуманитарных и естественных наук. – 2023. – №.
5. – С. 191-193.
3.
Сайфутдинов З. А. СОВРЕМЕННЫЕ ПОДХОДЫ К ЛЕЧЕНИЮ БОЛЬНЫХ
ТУБЕРКУЛЕЗОМ, УСТОЙЧИВЫХ К НОВЫМ ПРОТИВОТУБЕРКУЛЕЗНЫМ
ПРЕПАРАТАМ // Журнал гуманитарных и естественных наук. – 2023. – №.
5. – С. 191-193.
4.
Трауэр Дж. М. и др. Моделирование эффекта краткосрочного лечения
туберкулеза с множественной лекарственной устойчивостью в
Каракалпакстане, Узбекистан //BMC медицина. — 2016. — Т. 14. — С. 1-11.
