Trends of Drug-Resistant Tuberculosis in an Urban and a Rural Area in China: A 10-Year Population-Based Molecular Epidemiological Study

Abstract

Peng Xu,1 Meng Li,1,2 Qi Jiang,3 Chongguang Yang,4 Xiangxiang Liu,1 Howard Takiff,5 Qian Gao1,2 1National Clinical Research Center for Infectious Diseases, Shenzhen Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Science, Shanghai Medical College, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, People’s Republic of China; 3Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, People’s Republic of China; 4School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen, People’s Republic of China; 5Laboratorio de Genética Molecular, CMBC, IVIC, Caracas, VenezuelaCorrespondence: Qian Gao, National Clinical Research Center for Infectious Diseases, Shenzhen Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, No. 29 Bulan Road, Longgang District, Shenzhen, Guangdong, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]: Drug resistance is the critical determinant for appropriate tuberculosis (TB) treatment regimens and an important indicator of the local TB burden. We aimed to investigate and compare trends in TB drug resistance in the urban Songjiang District of Shanghai from 2011 to 2020, and the rural Wusheng County of Sichuan Province from 2009 to 2020, to assess the effectiveness of local TB control and treatment programs.Methods: Whole-genome sequencing data of Mycobacterium tuberculosis were used to predict drug-resistance profiles and identify genomic clusters. Clustered, retreated cases of drug-resistant TB with identical resistance mutations, as well as all new resistant cases, were defined as transmitted resistance. The Cochran-Armitage trend test was used to identify trends in the proportions. Differences between groups were tested using the Wilcoxon rank sum or chi-square tests.Results: The annual proportions of rifampicin-resistant (RR), isoniazid-resistant (INH-R) and multidrug-resistant (MDR) TB cases did not change significantly in Songjiang. In Wusheng, however, the percentage of total TB cases that were RR decreased from 13.2% in 2009 to 3.7% in 2020, the INH-R cases decreased from 16.5% to 7.3%, and the MDR cases decreased from 10.7% to 3.7%. In retreated cases, the percentage of drug resistance decreased in both Songjiang and Wusheng, suggesting improved treatment programs. Transmitted resistance accounted for more than two thirds of drug-resistant cases over the entire study periods, and in recent years this proportion has increased significantly in Songjiang.Conclusion: In both urban Songjiang and rural Wusheng, drug-resistant TB is mostly the result of transmission of drug resistant strains and the percentage of transmitted resistance will likely increase with on-going improvements in the TB treatment programs. Reducing the prevalence of drug resistance depends principally upon decreasing transmission through the prompt diagnosis and effective treatment of drug-resistant TB cases.Keywords: tuberculosis, trends of drug resistance, whole-genome sequencing, urban and rural China

Keywords

• tuberculosis
• trends of drug resistance
• whole-genome sequencing
• urban and rural china