Inferring Mycobacterium Tuberculosis Drug Resistance and Transmission using Whole-genome Sequencing in a High TB-burden Setting in China

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.

The Epidemiological Characteristics of Pulmonary Tuberculosis——Kashgar Prefecture,Xinjiang Uygur Autonomous Region,China,2011-2020

Introduction:National Notifiable Disease Reporting System(NNDRS)plays an important role in the early detection and control of tuberculosis(TB)in China.This study analyzed the epidemiological characteristics of pulmonary tuberculosis(PTB)in Kashgar Prefecture,Xinjiang Uygur Autnomous Region,China from 2011 to 2020 to provide a scientific basis for developing TB control strategies and measures in Kashgar.Methods:The data were collected from the NNDRS,which included the geographical distribution,age,sex,occupation,and pathogenic classification of reported PTB cases in 12 counties/cities of Kashgar Prefecture from 2011 to 2020.Descriptive statistics were used to describe the characteristic of PTB epidemic in Kashgar.Results:There were 189,416 PTB cases reported during 2011–2020,with a mean annual PTB case notification rate(CNR)of 451.29/100,000.A rising trend in the rate of reported PTB between 2011 and 2017(χ2 trend=26.09,P<0.01)and a declining trend between 2018 and 2020(χ2 trend=314.44,P<0.01)were observed.The months with the highest reported number of PTB cases were March to May and November to December.The mean annual rate of reported PTB was 451.88/100,000 for males and 450.67/100,000 for females.In addition,19.76%of patients were bacteriologically-confirmed(Bac+)cases(37,425/189,416),and the mean annual Bac+CNR was 89.17/100,000,rising from 64.76/100,000 in 2011 to 139.12/100,000 in 2020(χ^(2)_(trend)=74.44,P<0.01).Conclusions:The CNR of reported PTB in Kashgar showed a significant declining trend in the past three years.Males,elderly population,winter and spring,and farmers as an occupation were the main factors associated with high incidence of tuberculosis in Kashgar.Targeted prevention and treatment of TB should be strengthened in key groups in this region.