| Background and objectivesTuberculosis(TB)is a chronic infectious disease caused by the pathogen of mycobacterium TB.According to the WHO global TB report 2016,there were 10.4 million people diagnosed with TB around the world in 2015,including 1.2 million patients co-infected with HIV;and 1.4 million death attributed to TB.China is a country with high TB burden,just following India and Indonesia.TB epidemic situation in China has the characteristics of high incidence,high prevalence,high drug resistance,high recurrence and low detection rate.Traditional epidemiological methods are difficult to confirm the source of infection and uncover the transmission mechanism.The development of molecular epidemiology provides TB researchers with a useful tool.It can help trace the source of infection,find the regularity of regional spread of pathogen and identify the risk population,which can provide scientific evidence for controlling TB.In this study,we used the molecular epidemiological method to genotype isolates of mycobacterium TB in Lianyungang City,with aims to describe their genetic diversity,analyze the clustering of the strains and the relation with clinical features,and explore the geographical distribution and the phylogenetic characteristics of the strains.MethodsThis study chose Lianyungang City,Jiangsu Providence as the study area.We recruited newly diagnosed sputum culture positive TB patients as study subjects since 2013 to 2014.Demographic information and clinical data were collected.This study included two parts.In the first part,we used the 15 locus VNTR-MIRU(variable number tandem repeats-mycobacterial interspersed repetitive units)genotyping method to analyze the genetic diversity and specific finger prints of mycobacterium TB isolated,as well as their relation with clinical characteristics of patients.The Hunter-Gaston discriminatory index(HGDI)was used to determine the resolution of the strain.In the second part,we applied the pheatmap package of R software to perform the clustering analysis.The minimum spanning tree was constructed using the BioNumerics7.0 software.The risk for clustering was analyzed by the Logistic regression model and expressed with odds ratio(OR)and 95%confidence interval(CI).Results(1)We genotyped 742 strains using the 15 locus VNTR-MIRU method.The total resolution of HGDI was 0.99998.The locus with the highest genetic diversity was Qub11b,with the h value of 0.763.The locus with the lowest genetic diversity was ETRC,with the h value of 0.037.(2)A total of 643 categories were found in cluster analysis.Among them,597 were categorized as the "single" one,and 145 strains were categorized as 46 clusters.The clustering ratio was 19.54%.The proportion of strains forming larger clusters(with the number of strains>5)was 35.17%.The larger clusters showed a certain regional aggregation characteristic.The specific genotype strains were clustered in the north and the south part of Lianyungang City.Most of the clusters were distributed along the main traffic route.(3)A significant association was found between the clustering and both career and treatment outcomes.Strains isolated from patients with other types of occupation rather than farmers have a higher risk for clustering(adjusted OR=2.35,95%Cl:1.33-4.50,P=0.003).Strains isolated from patients with negative outcomes were more likely to form clusters(adjusted OR=1.85,95%Cl:1.00-3.45,P=0.050).(4)There was no specific clustering phenomenon by constructing the minimum spanning tree.Conclusions(1)Mycobacterium TB in Lianyungang city showed a high genetic diversity.The proportion of clustering is similar to nearby counties,but different from distant areas.The proportion of recent transmission among patients was low,indicating the possibility of recrudescence and previous infection.(2)Spatial analysis showed that larger clusters had geographical aggregation characteristics,suggesting an endemic of these strains.(3)Career and treatment outcomes were significantly related with clustering. |
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