The worldwide emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has posed additional challenges for global tuberculosis (TB) control efforts, as limited treatment options are available and treatment outcomes are often sub-optimal. This study determined treatment outcomes among a cohort of MDR-TB and XDR-TB patients in Hunan Province, China, and identified factors associated with poor treatment outcomes. We conducted a retrospective study using data obtained from medical records of TB patients in Hunan Chest Hospital, and from the internet-based TB management information system managed by the Tuberculosis Control Institute of Hunan Province, for the period 2011 to 2014. Treatment outcomes were assessed for patients diagnosed with MDR-TB (TB resistant to at least isoniazid and rifampicin) and XDR-TB (MDR-TB plus resistance to any fluoroquinolone and at least 1 second-line injectable drug). Cumulative incidence functions were used to estimate time to events (i.e. poor treatment outcomes, loss to follow-up, and unfavourable treatment outcomes); and a competing-risks survival regression model was used to identify predictors of treatment outcomes. Of 481 bacteriologically-confirmed patients, with a mean age of 40 years (standard deviation SD ± 13 years), 10 (2%) had XDR-TB and the remainder (471; 98%) had MDR-TB. For the entire cohort, treatment success was 57% (n = 275); 58% (n = 272) for MDR-TB and 30% (n = 3) for XDR-TB. Overall, 27% were lost to follow-up (n = 130), 27% (n = 126) for MDR-TB and 40% (n = 4) for XDR-TB; and 16% had a poor treatment outcome (n = 76), 15% for MDR-TB and 30% (n = 3) for XDR-TB. Of the 10 XDR-TB patients, 3 (30%) completed treatment, 3 (30%) died and 4 (40%) were lost to follow-up. Of the 471 MDR-TB patients, 258 (57%) were cured, 16 (3%) completed treatment, 13 (3%) died, 60 (13%) experienced treatment failure, and 126 (27%) were lost to follow-up. Resistance to ofloxacin was an independent predictor of poor (AHR = 3.1; 95%CI = 1.5, 6.3), and unfavourable (AHR = 1.7; 95%CI = 1.07, 2.9) treatment outcomes. Patients who started treatment during 2011–2012 (AHR = 2.8; 95% CI = 1.5, 5.3) and 2013 (AHR = 2.1; 95% CI = 1.2, 3.9) had poorer treatment outcomes compared to patients who started treatment during 2014. Patients with MDR-TB and XDR-TB had low rates of treatment success in Hunan Province, especially among patients who started treatment during 2011 to 2013, with evidence of improved treatment outcomes in 2014. Resistance to ofloxacin was an independent predictor of poor treatment outcomes.

Background: In the context of decreasing tuberculosis prevalence in China, we examined the effectiveness of screening household contacts of tuberculosis patients. Methods: A tuberculosis survey was conducted in 2008. All 3,355 household contacts of notified tuberculosis cases were examined with a questionnaire interview, chest X-ray and three sputum smear tests. The effectiveness was examined by comparing the prevalence of pulmonary tuberculosis in household contacts with or without presenting clinical symptoms against the respective notification rates. Regression models were used to evaluate the factors associated with pulmonary tuberculosis. Results: Of the 3,355 household contacts, 92 members (2.7%) had pulmonary tuberculosis, among which 46 cases were asymptomatic. The prevalence of pulmonary tuberculosis and smear positive cases in household contacts without symptoms were 20 and 7 times higher than the notification rates in 2008, while those in household contacts with symptoms were 247 and 108 times higher than notification rates, respectively. The patients detected were mainly Index Cases’ spouses, sisters/brothers and those who were in contact with female Index Cases. Conclusions: The present study provides convincing evidence that household contacts of notified tuberculosis cases are at higher risk of developing tuberculosis. Routine screening for household contacts without any symptoms is recommended for sustained tuberculosis control in China as well as in the world.

Tuberculosis (TB) is the leading cause of death from a bacterial pathogen worldwide. China has the third highest TB burden in the world, with a high reported burden in Hunan Province (amongst others). This study aimed to investigate the spatial distribution of TB and identify socioeconomic, demographic, and environmental drivers in Hunan Province, China. Numbers of reported cases of TB were obtained from the Tuberculosis Control Institute of Hunan Province, China. A wide range of covariates were collected from different sources, including from the Worldclim database, and the Hunan Bureau of Statistics. These variables were summarized at the county level and linked with TB notification data. Spatial clustering of TB was explored using Moran’s I statistic and the Getis–Ord statistic. Poisson regression models were developed with a conditional autoregressive (CAR) prior structure, and with posterior parameters estimated using a Bayesian approach with Markov chain Monte Carlo (MCMC) simulation. A total of 323,340 TB cases were reported to the Hunan TB Control Institute from 2013 to 2018. The mean age of patients was 51.7 years (SD + 17.6 years). The majority of the patients were male (72.6%, n = 234,682) and had pulmonary TB (97.5%, n = 315,350). Of 319,825 TB patients with registered treatment outcomes, 306,107 (95.7%) patients had a successful treatment outcome. The annual incidence of TB decreased over time from 85.5 per 100,000 population in 2013 to 76.9 per 100,000 population in 2018. TB case numbers have shown seasonal variation, with the highest number of cases reported during the end of spring and the beginning of summer. Spatial clustering of TB incidence was observed at the county level, with hotspot areas detected in the west part of Hunan Province. The spatial clustering of TB incidence was significantly associated with low sunshine exposure (RR: 0.86; 95% CrI: 0.74, 0.96) and a low prevalence of contraceptive use (RR: 0.88; 95% CrI: 0.79, 0.98). Substantial spatial clustering and seasonality of TB incidence were observed in Hunan Province, with spatial patterns associated with environmental and health care factors. This research suggests that interventions could be more efficiently targeted at locations and times of the year with the highest transmission risk.

Concerns about specificity of the Xpert MTB/RIF (Xpert) assay have arisen as false positive errors in the determination of Mycobacterium tuberculosis complex (MTBC) infection and rifampin (RIF) resistance in clinical practice have been reported. Here, we investigated 33 cases where patients were determined to be RIF susceptible using the Bactec MGIT 960 (MGIT) culture system but RIF resistant using the Xpert assay. Isolates from two of these patients were found not to have any mutations in the RRDR region of rpoB and had good treatment outcomes with first-line anti-TB drugs. The remaining 31 patients included five new cases and 26 previously treated patients. A large number of well-documented disputed mutations, including Leu511Pro, Asp516Tyr, His526Asn, H526Leu, His526Cys and Leu533Pro were detected, and previously unreported mutations, including a 508-509 deletion and His526Gly, were described here as disputed mutations for the first time. Twenty-one (81%) of the 26 previously treated patients had poor treatment outcomes, and isolates from 19 (90%) of these 21 patients, were resistant to isoniazid (INH) as determined using the MGIT culture system. Twenty-seven of the 31 isolates with disputed rpoB mutations were phenotypically resistant to INH, 21 (78%) being predicted by GenoType MTBDRplus to have a high-level of INH resistance. Most (77.4%) of the isolates with disputed mutations were of the Beijing lineage. These findings have implications for the interpretation of false-positive and disputed rifampin resistant Xpert MTB/RIF results in clinical samples, and provide guidance on how clinicians should manage patients carrying isolates with disputed rpoB mutations.

In 2015, only 49% of notified multi-drug resistant tuberculosis (MDR-TB) patients in China were estimated to have initiated treatment, compared with 90% of those worldwide. A case-control study was conducted to identify the reasons for non-enrollment in treatment among MDR-TB patients in Hunan province, China. All detected MDR-TB patients registered in designated MDR-TB hospitals in Hunan province from 2011 to 2014 were included and followed until June 2015 to determine their treatment status. Approximately 33.8% (482/1425) of patients were not enrolled in standardized treatment. Factors associated with lower enrollment rate were: age greater than 60 years, living in rural area, unemployed or occupation unreported. Of those who were not enrolled in MDR-TB treatment, the primary reasons for non-enrollment included economic hardship (23.0%), out-migration for work (18.0%), concerns about work and studies (13.7%), and the belief that they were cured after undergoing drug-sensitive TB treatment (12.4%). Therefore, comprehensive strategies targeting priority populations, especially those enhancing treatment affordability and availability, need to be implemented to improve MDR-TB control.

Tuberculosis (TB) continues to be a major public health challenge in China. Understanding TB management delays within the context of China’s unique ethnic diversity may be of value in tackling the disease. This study sought to evaluate the impact of ethnic minority status on TB diagnosis and treatment delays. This retrospective cohort study was conducted on patients diagnosed with TB in Hunan Province, China between 2013 and 2018. Diagnosis delay was defined as the time interval between the onset of symptoms and the date of diagnosis. Treatment delay was defined as the time interval between diagnosis and treatment commencement. Univariable and multivariable logistic regression models were used to identify factors associated with TB diagnosis and treatment delay, including ethnic minority status. Adjusted odds ratios (AOR) with 95% confidence intervals (CI) were calculated to assess the strength of association between the dependant and independent variables. A total of 318,792 TB patients were included in the study with a mean age of 51.7 years (SD 17.7). The majority of patients were male (72.6%) and Han ethnicity (90.6%). The odds of experiencing diagnosis delay (> 21 days) were significantly higher for Tujia (AOR: 1.46, 95% CI: 1.41, 1.51), Miao (AOR: 1.31, 95% CI: 1.26, 1.37), Dong (AOR: 1.97, 95% CI: 1.85, 2.11), Yao (AOR: 1.27, 95% CI: 1.17, 1.37), and Bai (AOR: 1.45, 95% CI: 1.22, 1.74) ethnic minorities compared to the Han majority. The odds of experiencing treatment delay (> 15 days) were significantly lower for five of the seven ethnic minority groups relative to the Han majority: Tujia (AOR 0.92, 95% CI 0.88, 0.96), Miao (AOR 0.74, 95% CI 0.70, 0.79), Dong (AOR 0.87, 95% CI 0.81, 0.95), Yao (AOR 0.20, 95% CI 0.17, 0.24) and ‘other’ (ethnic minorities that individually represented < 0.1% of the patient population) (AOR 0.70, 955 CI 0.51, 0.97). This study shows ethnic minority status to be a significant risk factor in diagnosis delay, but for it to reduce the odds of treatment delay. Further research is required to determine the underlying causes of diagnosis delay within ethnic minority populations.