Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of th...Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.展开更多
Background Diagnosis and appropriate treatment of multidrug-resistant tuberculosis （MDR-TB） remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patien...Background Diagnosis and appropriate treatment of multidrug-resistant tuberculosis （MDR-TB） remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patients are at high risk for primary drug resistance tuberculosis and how to prevent these outbreaks. Methods We used 12-locus mycobactedal interspersed repetitive unit and 7-locus variable-number tandem repeat to identify household transmission of extensively drug resistant and multiple drug resistant Mycobacterium tuberculosis in three families admitted in Shanghai Pulmonary Hospital affiliated with Tongji University. Drug susceptibility tests were done by the modified proportion method in the MGIT 960 system in the same time. Clinical data were also obtained from the subjects＇ medical records. Results All of the six strains were defined as Beijing genotype by the deletion-targeted multiplex PCR （DTM-PCR） identification on the genomic deletion RD105. Strains from family-1 had the same minisatellite interspersed repetitive unit （MIRU） pattern （232225172531） and the same MIRU pattern （3677235）. Strains from family-2 had the same MIRU pattern （2212261553323） and the same MIRU pattern （3685134）. Strains from family-3 did not have the same MIRU pattern and they differed at only one locus （223326173533, 223325173533）, and did not have the same VNTR pattern with two locus differed （3667233, 3677234）. Conclusions Household transmission exists in the three families. A clear chain of tuberculosis transmission within family exists. Tuberculosis susceptibility should be considered when there is more than one tuberculosis patients in a familv. Household tuberculosis transmission could be prevented with adequate treatment of source Patients.展开更多
The aim of this study was to characterize rpoC gene mutations in Mycobacterium tuberculosis(MTB)and investigate the factors associated with rpoC mutations and the relation between rpoC mutations and tuberculosis(TB)tr...The aim of this study was to characterize rpoC gene mutations in Mycobacterium tuberculosis(MTB)and investigate the factors associated with rpoC mutations and the relation between rpoC mutations and tuberculosis(TB)transmission.A total of 245 MTB clinical isolates from patients with TB in six provinces and two municipalities in China were characterized based on gene mutations through DNA sequencing of rpoC and rpoB genes,phenotyping via standard drug susceptibility testing,and genotypic profiling by mycobacterial interspersed repetitive unit-variable number tandem repeat(MIRU-VNTR)typing.Approximately 36.4%of the rifampinresistant isolates harbored nonsynonymous mutations in the rpoC gene.Twenty-nine nonsynonymous single mutations and three double mutations were identified.The rpoC mutations at locus 483(11.3%)were predominant,and the mutations at V483G,W484G,I491V,L516P,L566R,N698K,and A788E accounted for 54.5%of the total detected mutations.Fifteen new mutations in the rpoC gene were identified.Rifampin resistance and rpoB mutations at locus 531 were significantly associated with rpoC mutations.MIRU-VNTR genotype results indicated that 18.4%of the studied isolates were clustered,and the rpoC mutations were not significantly associated with MIRU-VNTR clusters.A large proportion of rpoC mutation was observed in the rifampicin-resistant MTB isolates.However,the findings of this study do not support the association of rpoC mutation with compensated transmissibility.展开更多
基金funded by the National Key R&D Program of China [2022YFC2305200]Natural Science Foundation of Xinjiang Uygur Autonomous Region [2021A01D145 and 2022D01A115]Applied Technology Research and Development Programing Project of Kashgar Prefecture [KS2021031 and KS2021034]。
文摘Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking.Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns.Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023–1.954;P=0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains.Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.
文摘Background Diagnosis and appropriate treatment of multidrug-resistant tuberculosis （MDR-TB） remain major challenges. We sought to elucidate that persons who share a household with drug resistance tuberculosis patients are at high risk for primary drug resistance tuberculosis and how to prevent these outbreaks. Methods We used 12-locus mycobactedal interspersed repetitive unit and 7-locus variable-number tandem repeat to identify household transmission of extensively drug resistant and multiple drug resistant Mycobacterium tuberculosis in three families admitted in Shanghai Pulmonary Hospital affiliated with Tongji University. Drug susceptibility tests were done by the modified proportion method in the MGIT 960 system in the same time. Clinical data were also obtained from the subjects＇ medical records. Results All of the six strains were defined as Beijing genotype by the deletion-targeted multiplex PCR （DTM-PCR） identification on the genomic deletion RD105. Strains from family-1 had the same minisatellite interspersed repetitive unit （MIRU） pattern （232225172531） and the same MIRU pattern （3677235）. Strains from family-2 had the same MIRU pattern （2212261553323） and the same MIRU pattern （3685134）. Strains from family-3 did not have the same MIRU pattern and they differed at only one locus （223326173533, 223325173533）, and did not have the same VNTR pattern with two locus differed （3667233, 3677234）. Conclusions Household transmission exists in the three families. A clear chain of tuberculosis transmission within family exists. Tuberculosis susceptibility should be considered when there is more than one tuberculosis patients in a familv. Household tuberculosis transmission could be prevented with adequate treatment of source Patients.
基金supported by the National Science and Technology Major Project(No.2018ZX10103001)the National Basic Research Program of China(No.2014CB744403).
文摘The aim of this study was to characterize rpoC gene mutations in Mycobacterium tuberculosis(MTB)and investigate the factors associated with rpoC mutations and the relation between rpoC mutations and tuberculosis(TB)transmission.A total of 245 MTB clinical isolates from patients with TB in six provinces and two municipalities in China were characterized based on gene mutations through DNA sequencing of rpoC and rpoB genes,phenotyping via standard drug susceptibility testing,and genotypic profiling by mycobacterial interspersed repetitive unit-variable number tandem repeat(MIRU-VNTR)typing.Approximately 36.4%of the rifampinresistant isolates harbored nonsynonymous mutations in the rpoC gene.Twenty-nine nonsynonymous single mutations and three double mutations were identified.The rpoC mutations at locus 483(11.3%)were predominant,and the mutations at V483G,W484G,I491V,L516P,L566R,N698K,and A788E accounted for 54.5%of the total detected mutations.Fifteen new mutations in the rpoC gene were identified.Rifampin resistance and rpoB mutations at locus 531 were significantly associated with rpoC mutations.MIRU-VNTR genotype results indicated that 18.4%of the studied isolates were clustered,and the rpoC mutations were not significantly associated with MIRU-VNTR clusters.A large proportion of rpoC mutation was observed in the rifampicin-resistant MTB isolates.However,the findings of this study do not support the association of rpoC mutation with compensated transmissibility.
