ABSTRACT
Tuberculosis (TB) has remained an ongoing concern in China. The national scale-up of the Directly Observed Treatment, Short Course (DOTS) program has accelerated the fight against TB in China. Nevertheless, many challenges still remain, including the spread of drug-resistant strains, high disease burden in rural areas, and enormous rural-to-urban migrations. Whether incident active TB represents recent transmission or endogenous reactivation has helped to prioritize the strategies for TB control. Evidence from molecular epidemiology studies has delineated the recent transmission of Mycobacterium tuberculosis (M. tuberculosis) strains in many settings. However, the transmission patterns of TB in most areas of China are still not clear. Studies carried out to date could not capture the real burden of recent transmission of the disease in China because of the retrospective study design, incomplete sampling, and use of low-resolution genotyping methods. We reviewed the implementations of molecular epidemiology of TB in China, the estimated disease burden due to recent transmission of M. tuberculosis strains, the primary transmission of drug-resistant TB, and the evaluation of a feasible genotyping method of M. tuberculosis strains in circulation.
Subject(s)
Humans , China , Epidemiology , Genotyping Techniques , Molecular Epidemiology , Mycobacterium tuberculosis , Genetics , Tuberculosis, Multidrug-Resistant , Epidemiology , Whole Genome SequencingABSTRACT
Objective To delineate the application of whole genome sequencing technology in the epidemiology of tuberculosis.Methods From 2009 to 2012,nine Mycobacterium tuberculosis that sharing identical variable number of tandem repeats genotype (VNTR) patterns were reported from two TB cases designated hospitals.Both whole-genome sequencing analysis (WGS) and epidemiologic investigations were performed to describe the transmission patterns of these Mycobacterium tuberculosis.Results By WGS analysis,two genomic clusters including 7 and 2 Mycobacterium tuberculosis were noticed,respectively.The cluster of 2 cases possessed more than 15 single nucleotide polymorphisms (SNPs) when compared to the cluster of 7 cases and suggesting that the transmission route was independent.The transmission chain based on the SNPs difference showed the process of the propagation direction and the accumulation of drug resistance mutations in each cluster.Conclusion Using a WGS-based genomic epidemiologic approach,we were able to reconstruct the tuberculosis transmission network,tracing the putative source of the transmission and determining the transmission direction or the missing links.
ABSTRACT
Objective To delineate the application of whole genome sequencing technology in the epidemiology of tuberculosis.Methods From 2009 to 2012,nine Mycobacterium tuberculosis that sharing identical variable number of tandem repeats genotype (VNTR) patterns were reported from two TB cases designated hospitals.Both whole-genome sequencing analysis (WGS) and epidemiologic investigations were performed to describe the transmission patterns of these Mycobacterium tuberculosis.Results By WGS analysis,two genomic clusters including 7 and 2 Mycobacterium tuberculosis were noticed,respectively.The cluster of 2 cases possessed more than 15 single nucleotide polymorphisms (SNPs) when compared to the cluster of 7 cases and suggesting that the transmission route was independent.The transmission chain based on the SNPs difference showed the process of the propagation direction and the accumulation of drug resistance mutations in each cluster.Conclusion Using a WGS-based genomic epidemiologic approach,we were able to reconstruct the tuberculosis transmission network,tracing the putative source of the transmission and determining the transmission direction or the missing links.
ABSTRACT
Objective To investigate the prevalence and risk factor of Ofloxacin resistance among the tuberculosis patients in Shanghai.Methods Totally 447 isolates resistant to anyone of first-line drug (Isoniazid,Rifampicin,Streptomycin and Ethambutol) and 151 randomly selected isolates susceptible to all above drugs were collected from district tuberculosis(TB) hospitals in Shanghai during 2009 to 2010.All 598 isolates were subject to Ofloxacin sensitive test.Logistic regression analysis was conducted to determine risk factors of Ofloxacin resistance.DNA sequencing was applied to study the mutation characteristics in gyrA and gyrB among Ofloxacin resistant isolates.Results Seventy-two(16.1%) of the 447 drug-resistant isolates were found resistant to Ofloxacin,and the Ofloxacin resistant rate among multiple drug-resistant (MDR) isolates was 39.6%(44/111).Ofloxacin resistance was also found in 4(2.6%) of the 151 drug sensitive isolates.Logistic regression analysis showed that first-line drug-resistance MDR(resistant to at least rifampin and isoniazid) and poly-drug resistance(resistance to two or more first-line drugs but not MDR) had significant effect on Ofloxacin resistance(OR = 19.5、5.6,95% CI:6.4 - 59.4、1.7 - 18.1,all P＜ 0.05);re-treatment(OR = 2.3,95 % CI:1.2 -4.0,P＜ 0.05),and a higher age(OR = 1.03,95 % CI:1.0 1 - 1.05,P＜ 0.05)were also significantly associated with Ofloxacin resistance.Resistance mutations in the gyrA and gyrB genes were detected in 62 of 76(81.6%) isolates with phenotypic Ofloxacin-resistance. Conclusions The Ofloxacin resistance rate in Shanghai MDR-TB patients is significantly higher than the pan-susceptible TB patients.Risk factors of ofloxacin resistance are MDR,poly-resistant,retreated patients,age.Among them,MDR has the highest strength of association.