1.Gene mutation associated with drug resistance in M.tuberculosis strains isolated from national TB prevalence survey in Mongolia
Tsetsegtuya B ; Baasansuren E ; Oyuntuya T ; Tserelmaa B ; Gundsuren Sh ; Tsolmon B ; Naranbat N ; Tsatsralt-Od B ; Buyankhishig B ; Naranzul D
Mongolian Medical Sciences 2019;187(1):3-10
Background:
According to the First National Tuberculosis (TB) Prevalence Survey in Mongolia the prevalence of
bacteriologically-confirmed pulmonary TB among adults was 559.6 (95% CI: 454.5–664.7) per 100000
population in 2014–2015. This was three times as high as previously estimated. Nationwide anti-tuberculosis (TB) drug resistance survey was conducted in 1999 and 2007 in Mongolia. Share of multidrug resistant TB (MDR-TB) cases among newly notified TB cases increased from 1.0% in 1999 to 1.4% in 2007. Accordingly, we aimed to perform drug susceptibility test on strains isolated from TB Prevalence Survey and to determine the prevalence of drug resistant TB.
Material and Methods:
All 242 MTB strains isolated from the survey TB cases were tested GenoTypeMTBDRplus test and conventional 1st line DST on solid medium.
Result:
Conventional DST and GenoTypeMTBDRplus tests done for 93.8% (227/242) of them and 6.2% (15/242) were tested by GenoTypeMTBDRplus only. A 61.6% (95%CI 55.3-67.4) of all cases were susceptible to first line anti-TB drugs, any drug resistance and MDR-TBdetected as 38.4% (95% CI 32.5-44.7)and 9.5% (95% CI 6.4-13.9), respectively. Prevalence of MDR-TB was7.8% (95% CI 4.9-12.4) among new and 17.9% (95% CI 9.0-32.7) among previously treated cases. The 64 strains were identified as a resistant to isoniazid, 32.8% (42/64) and 65.6% (21/64) were katG, and inhAmutation, respectively. One isolate (1.6%) was mutations in both the inhAand katGgenes.The predominant mutations detected in therpoB were S531L (91.3%) among rifampicin resistant isolates and the mutation in inhAwas C–15T (100%) and katG mutation was S315T1 (100%) among isoniazid-resistant isolates.
Conclusion
Prevalence of cases with DR-TB is high among prevalent TB cases, especially prevalence of MDR-TB among new cases. In comparison to previous studies, DR-TB cases seem to be increased. Rifampicin resistant strains have a mutation of the rpoBand resistance to isoniazid is predominantly associated with the inhA mutation.
2.The results of genotype and drug resistance analysis of M. tuberculosis strains circulating in Mongolia, compared over a 10-year interval
Oyuntuya T ; Tsetsegtuya B ; Baasansuren B ; Akiko T ; Naranzul D ; Gantungalag G ; Mitarai S ; Buyankhishig B ; Sarantuya J
Mongolian Journal of Health Sciences 2025;85(1):67-73
Background:
Tuberculosis (TB) is a preventable and usually curable disease. Yet in 2022, TB was the world’s second
leading cause of death from a single infectious agent, after coronavirus disease (COVID-19)1.
Aim:
By reviving strains isolated at specific years over a 10-year interval and performing next-generation sequencing,
we can analyze their strain genotype, epidemiology, drug resistance, and dynamicsTherefore, this study was conducted
to examine the historical trends and dynamics of strain genotype, variants, and drug resistance of tuberculosis preserved
in the culture bank.
Materials and Methods::
Using a retrospective, laboratory-based research approach, 200 strains were randomly selected from over 1,000 diagnostic isolates preserved in the NTRL culture collection from 2010 and 2020. Whole-genome
sequencing (WGS) was performed using GridION from Oxford Nanopore Technologies (ONT, Oxford, UK) to analyze
these strains. The FastQ file was submitted to the International Mycobacterial Database. Strain genotypes, subtypes, gene
mutations of drug resistance, and resistance profiles were identified using TBprofiler, MTBseq, IQ-Tree (version 1.6.12),
and EPI2me software.
Results:
Of the tuberculosis strains selected for the study, 66.5% were from eight out of nine districts of Ulaanbaatar,
while 33.5% were sampled from 16 out of 21 provinces. Out of the strains analyzed, 83.9% (95% CI 78.7–89.1) belonged
to lineage 2 or the Beijing genotype, while 16.1% (95% CI 10.9–21.3) were lineage-4 or Euro-American genotype. While
the proportion of Beijing lineage strains was slightly higher and the Euro-American lineage strains slightly lower in rural
populations compared to urban populations, the difference in strain distribution between urban and rural areas was not
statistically significant (p=0.485). Among the Beijing lineage strains, only the modern Beijing sublineage (100%) was
identified. In contrast, the Euro-American lineage exhibited various sublineages: 4 (0.5%), 4.5 (1%), 4.1.2.1 (Haarlem,
3%), Latin American-Mediterranean (LAM, 7.5%), mainly T (3.5%), and S type (0.5%). Notably, the proportion of Lineage 2 strains increased from 80% in 2010 to 86% in 2020.
The overlap of the confidence intervals for 2010 (72.16%–87.84%) and 2020 (79.20%–92.80%) indicates that there has
been no significant change in the distribution of Mycobacterium tuberculosis lineages over time. The study revealed that
among the selected Mycobacterium tuberculosis strains, resistance rates to first-line anti-tuberculosis drugs were as follows: isoniazid (39%), rifampicin (21%), ethambutol (19%), and streptomycin (34%). Genotypic analysis indicated that
the Beijing lineage was predominantly associated with drug-resistant tuberculosis cases, including multidrug-resistant
(MDR), poly-drug-resistant, and mono-drug-resistant TB. Notably, the Beijing lineage accounted for 100% of pre-extensively drug-resistant (pre-XDR) TB cases. Within the Haarlem lineage, 33% were MDR-TB.
In the Latin American-Mediterranean (LAM) lineage, 13.3% were MDR-TB, 6.6% were poly-drug-resistant, and 13.3%
were mono-drug-resistant. Among the mainly T lineage, 42.8% exhibited mono-drug resistance. These findings suggest
that the distribution of M. tuberculosis lineages in the Mongolian population has remained relatively stable over time,
with no significant temporal changes.
Conclusion
The distribution of M. tuberculosis genotypes circulating among the population of Mongolia has remained
relatively stable over time, with no significant time-dependent changes. Additionally, no mutations associated with resistance to newly introduced anti-TB drugs were detected.