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Objectives: This study aimed to describe the lineage-specific transmissibility and epidemiological migration of Mycobacterium tuberculosis in China. Methods: We curated a large set of whole-genome sequences from 3204 M. tuberculosis isolates, including thousands of newly sequenced genomes, and applied a series of metrics to compare the transmissibility of M. tuberculosis strains between lineages and sublineages. The countrywide transmission patterns of major lineages were explored. Results: We found that lineage 2 (L2) was the most prevalent lineage in China (85.7%), with the major sublineage 2.2.1 (80.9%), followed by lineage 4 (L4) (13.8%), which comprises major sublineages 4.2 (1.5%), 4.4 (6.2%) and 4.5 (5.8%). We showed evidence for frequent cross-regional spread and large cluster formation of L2.2.1 strains, whereas L4 strains were relatively geographically restricted in China. Next, we applied a series of genomic indices to evaluate M. tuberculosis strain transmissibility and uncovered higher transmissibility of L2.2.1 compared with the L2.2.2 and L4 sublineages. Phylogeographic analysis showed that southern, eastern, and northern China were highly connected regions for countrywide L2.2.1 strain spread. Conclusions: The present study provides insights into the different transmission and migration patterns of the major M. tuberculosis lineages in China and highlights that transmissible L2.2.1 is a threat to tuberculosis control.

Abstract Background Tuberculosis (TB) is one of the main infectious diseases that seriously threatens global health, while diagnostic delay (DD) and treatment dramatically threaten TB control. Methods Between 2005 and 2017 in Shandong, China, we enrolled pulmonary tuberculosis (PTB) patients with DD. DD trends were evaluated by Joinpoint regression, and associations between PTB patient characteristics and DD were estimated by univariate and multivariate logistic regression. The influence of DD duration on prognosis and sputum smear results were assessed by Spearman correlation coefficients. Results We identified 208,822 PTB cases with a median DD of 33 days (interquartile range (IQR) 18–63). The trend of PTB with DD declined significantly between 2009 and 2017 (annual percent change (APC): − 4.0%, P = 0.047, 2009–2013; APC: − 6.6%, P = 0.001, 2013–2017). Patients aged > 45 years old (adjusted odds ratio (aOR): 1.223, 95% confidence interval (CI) 1.189–1.257, 46–65 years; aOR: 1.306, 95% CI 1.267–1.346, > 65 years), farmers (aOR: 1.520, 95% CI 1.447–1.596), and those with a previous treatment history (aOR: 1.759, 95% CI 1.699–1.821) were prone to developing long DD (> 30 days, P

Abstract Background Drug-resistant tuberculosis (DR-TB), obesity, and malnutrition are growing public health problems in the world. However, little has discussed the impact of different BMI status on the emergence of TB drug resistance. We aimed to explore the drug-resistant profiles of DR-TB and its clinical predictors among underweight, overweight or obesity population. Methods 8957 newly diagnosed TB cases with drug susceptibility results and BMI data in Shandong China, from 2004 to 2019 were enrolled. Multivariable and univariable logistic regression models were applied to investigate the impact of BMI on different drug-resistance. Clinical predicators and drug-resistant profiles of DR-TB among obesity, underweight, normal TB group were also described. Results Among 8957 TB cases, 6417 (71.64%) were normal weight, 2121 (23.68%) were underweight, 373 (4.16%) were overweight, and 46 (0.51%) were obese. The proportion of drug resistance and co-morbidity among normal weight, underweight, overweight, obese TB groups were 18.86%/18.25%/20.38%/23.91% (DR-TB), 11.19%/11.74%/9.65%/17.39% (mono-resistant tuberculosis, MR-TB), 3.41%/3.06%/5.36%/0.00% (multidrug resistant tuberculosis, MDR-TB), 4.21%/3.39%/5.36%/6.52% (polydrug resistant tuberculosis, PDR-TB), 10.57%/8.44%/19.57%/23.91% (co-morbidity), respectively. Compared with normal weight group, underweight were associated with lower risk of streptomycin-related resistance (OR 0.844, 95% CI 0.726–0.982), but contributed to a higher risk of MR-TB (isoniazid) (odds ratio (OR) 1.347, 95% CI 1.049–1.730; adjusted OR (aOR) 1.31, 95% CI 1.017–1.686), P

Objectives To investigate the independent and collective impact of alcohol drinking and tobacco smoking on the drug-resistance of newly diagnosed tuberculosis (TB).Design This was a retrospective cohort study.Setting Shandong, China.Participants Patients with newly diagnosed TB from 1 January 2004 to 31 December 2020 were collected. Exclusive criteria: retreated cases; extrapulmonary tuberculosis; without information on drug susceptibility testing results, smoking or drinking habits; bacteriological identification as non-tuberculous mycobacteria.Primary and secondary outcome measures Patients were classified into four groups including smokers only (G1), drinker only (G2), smoker +drinker (G3), non-smoker +non-drinker group (G0). We described the drug-resistant profiles, clinical factors and calculated the ORs of different drug-resistance among G1, G2, G3, compared with G0 through univariate and multivariate logistics regression models.Results Of the 7996 TB cases enrolled, the proportions of G1, G2, G3 and G0 were 8.25%, 3.89%, 16.46% and 71.40%, respectively. The rates of drug-resistant (DR)-TB, mono-resistant TB, multidrug resistant (MDR)-TB, polydrug resistant TB in G1, G2, G3 and G0 were 19.24%/16.4%/17.33%/19.08%, 11.52%/8.68%/10.94%/11.63%, 3.03%/2.57%/2.96%/3.66% and 4.70%/4.82%/3.34%/ 4.08%, respectively. G3 had a higher risk of MDR1: isoniazid +rifampin (adjusted OR (aOR)=1.91, 95% CI: 1.036 to 3.532), but had a lower risk of DR-TB (aOR=0.84, 95% CI: 0.71 to 0.99), rifampin-related resistance (aOR=0.68, 95% CI: 0.49 to 0.93), streptomycin-related resistance (aOR=0.82, 95% CI: 0.68 to 0.99), ethambutol-related resistance (aOR=0.57, 95% CI: 0.34 to 0.95), MDR3: isoniazid +rifampin+streptomycin (aOR=0.41, 95% CI: 0.19 to 0.85), any isoniazid +streptomycin resistance (aOR=0.85, 95% CI: 0.71 to 1.00). However, there were no significant differences between G1 and G0, G2 and G0 in all drug-resistant subtypes. Those patients with cavity had a higher risk of DR-TB among G3 (OR=1.35, 95% CI: 1.01 to 1.81).Conclusion Although we did not found an independent impact of alcohol drinking or tobacco smoking on TB drug-resistance, respectively, these two habits had a combined effect on TB drug-resistance.