Abstract
BackgroundMultidrug-resistant tuberculosis (MDR-TB) has become a major public health problem in China, with mounting evidence suggesting that recent transmission accounts for the majority of MDR-TB. Here we aimed to reveal the transmission pattern of an MDR-TB outbreak in the Jing'an District of Shanghai between 2010 and 2015.MethodsWe used whole-genome sequencing (WGS) to conduct genomic clustering analysis along with field epidemiological investigation to determine the transmission pattern and drug resistance profile of a cluster with ten MDR-TB patients in combining field epidemiological investigation.ResultsThe ten MDR-TB patients with genotypically clustered Beijing lineage strains lived in a densely populated, old alley with direct or indirect contact history. The analysis of genomic data showed that the genetic distances of the ten strains (excluding drug-resistant mutations) were 0–20 single nucleotide polymorphisms (SNPs), with an average distance of 9 SNPs, suggesting that the ten MDR-TB patients were infected and developed the onset of illness by the recent transmission of M. tuberculosis. The genetic analysis confirmed definite epidemiological links between the clustered cases.ConclusionsThe integration of the genotyping tool in routine tuberculosis surveillance can play a substantial role in the detection of MDR-TB transmission events. The leverage of genomic analysis in combination with the epidemiological investigation could further elucidate transmission patterns. Whole-genome sequencing could be integrated into intensive case-finding strategies to identify missed cases of MDR-TB and strengthen efforts to interrupt transmission.
Highlights
According to the global tuberculosis report [1], there are an estimated 465,000 rifampicin-resistant tuberculosis (RR-TB) patients in 2019 worldwide, of which about 78% were multidrug-resistant tuberculosis (MDR-TB)
Previous methods used for M. tuberculosis molecular epidemiology that have provided useful insight to understand transmission and differentiate between endogenous onset and exogenous reinfection of drug-resistant strains include insertion sequence 6110-restriction fragment length polymorphism (IS6110), spoligotyping, and variable numbers of tandem repeats (VNTR) techniques [3, 4]
The whole-genome sequencing (WGS) can confirm the variation of genetic diversity among clustered strains to construct a relatively accurate transmission chain may provide insight into source cases and potential missing cases, an advantage compared to the traditional epidemiological investigation and genotyping methods. [5,6,7,8]
Summary
According to the global tuberculosis report [1], there are an estimated 465,000 rifampicin-resistant tuberculosis (RR-TB) patients in 2019 worldwide, of which about 78% were multidrug-resistant tuberculosis (MDR-TB). Previous methods used for M. tuberculosis molecular epidemiology that have provided useful insight to understand transmission and differentiate between endogenous onset and exogenous reinfection of drug-resistant strains include insertion sequence 6110-restriction fragment length polymorphism (IS6110), spoligotyping, and variable numbers of tandem repeats (VNTR) techniques [3, 4]. The resolution of the genotyping tool has been improved as the development of high-throughput whole-genome sequencing (WGS) in the studies of molecular epidemiology of TB transmission. The WGS can confirm the variation of genetic diversity among clustered strains to construct a relatively accurate transmission chain may provide insight into source cases and potential missing cases, an advantage compared to the traditional epidemiological investigation and genotyping methods. Multidrug-resistant tuberculosis (MDR-TB) has become a major public health problem in China, with mounting evidence suggesting that recent transmission accounts for the majority of MDR-TB. We aimed to reveal the transmission pattern of an MDR-TB outbreak in the Jing’an District of Shanghai between 2010 and 2015
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