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GENETIC TYPING AND TREATMENT ALGORITHMS FOR XDR-
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.15473615
Abstract
This study aims to investigate the genetic characteristics of
Mycobacterium
tuberculosis
strains responsible for extensively drug-resistant tuberculosis
(XDR-TB) and to propose optimized treatment algorithms. A total of 280 clinical
isolates from XDR-TB patients across Uzbekistan were subjected to whole-
genome sequencing (WGS). Mutations in key resistance-associated genes (
katG
,
rpoB
,
gyrA
,
rrl
,
Rv0678
) were identified. High-resolution genotyping revealed the
predominance of the Beijing lineage. Correlation analysis between genotypic
profiles and clinical response enabled the development of individualized
treatment algorithms. The findings highlight the importance of integrating
molecular diagnostics into national TB control strategies to improve treatment
outcomes and limit the spread of XDR-TB.
Keywords:
XDR-TB,
Mycobacterium tuberculosis
, whole-genome sequencing, genetic
mutations, Beijing lineage, resistance, treatment algorithm, Uzbekistan.
Relevance
Extensively drug-resistant tuberculosis (XDR-TB) represents a serious
threat to global health, especially in high-burden regions such as Central Asia.
Conventional treatment approaches are often ineffective due to complex
resistance profiles. Uzbekistan has witnessed a growing prevalence of XDR-TB
cases, necessitating urgent improvements in diagnostic and treatment
strategies. Genetic typing using WGS offers a powerful approach for detecting
resistance-associated mutations rapidly and accurately. This molecular insight
enables clinicians to tailor drug regimens based on the genetic makeup of the
pathogen rather than relying solely on time-consuming culture-based methods.
Furthermore, understanding the distribution of genotypes such as the Beijing
lineage provides valuable epidemiological data for controlling transmission.
Developing treatment algorithms based on genetic markers and lineage
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associations may significantly enhance clinical outcomes. This study addresses
the critical need to integrate genotypic data into clinical protocols for effective
management of XDR-TB in Uzbekistan and similar settings.
Objective:
To perform genetic typing of
M. tuberculosis
strains in XDR-TB cases and develop
genotype-informed treatment algorithms for personalized therapy in
Uzbekistan.
Materials and Methods
This study included 280
M. tuberculosis
isolates collected from XDR-TB
patients between 2022 and 2024 across seven regions of Uzbekistan. Drug
resistance was confirmed by BACTEC MGIT 960 and Line Probe Assays. Whole-
genome sequencing was performed using the Illumina MiSeq platform.
Mutations were analyzed in genes associated with resistance:
katG
,
inhA
,
rpoB
,
gyrA
,
gyrB
,
rrl
,
Rv0678
, and
fbiA
. Genotypic lineages were determined using TB-
Profiler and SNP-based classification. Statistical analysis included logistic
regression and correlation tests to identify associations between mutation
patterns, lineages, and treatment response. Bioinformatic tools were used for
phylogenetic reconstruction and clustering analysis.
Results
Out of 280 isolates, 66% belonged to the Beijing lineage, 19% to LAM, and
10% to CAS lineages. High-frequency mutations included
katG S315T
(84%),
rpoB S450L
(78%),
gyrA D94G
(45%), and
rrl A1401G
(29%). Mutations in
Rv0678
were present in 34% of isolates, indicating reduced susceptibility to
bedaquiline. A strong correlation (r = 0.82, p < 0.001) was found between
specific mutation profiles and poor treatment response. Based on the genetic
and clinical data, a treatment algorithm was developed, incorporating mutation-
specific drug selection. The algorithm showed improved predictive value in
simulated case applications, supporting its clinical utility.
Conclusion
The study confirmed a high prevalence of the Beijing lineage and key
resistance mutations among XDR-TB strains in Uzbekistan. Whole-genome
sequencing proved to be a reliable method for identifying resistance patterns,
facilitating early and precise treatment planning. The proposed treatment
algorithm, based on genotypic profiles, allows for more effective and
individualized therapy. Incorporating genetic data into clinical decision-making
can reduce treatment failure, shorten time to effective therapy, and prevent
further transmission. These findings support the integration of molecular
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diagnostics and genetic typing into the national tuberculosis program as a
cornerstone of modern XDR-TB management strategies in high-burden regions.
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