Determinants of drug-resistant tuberculosis in Hunan province, China: a case-control study.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is a major public health threat in Hunan Province, with an increasing clinical burden in recent years. This study aimed to identify socio-demographic and clinical factors associated with DR-TB in Hunan province, China. METHODS: A case-control study was conducted in Hunan province. Cases were all DR-TB patients who were confirmed by culture and Drug susceptibility testing (DST) and enrolled at the DR-TB treatment center of Hunan Chest Hospital from 2013 to 2018. Controls were all Drug Susceptible TB (DS-TB) patients confirmed by DST and enrolled at the same hospital during the same period. A multivariable logistic regression model was fitted to identify factors significantly associated with DR-TB. RESULTS: A total of 17,808 patients (15,534 DS-TB controls and 2274 DR-TB cases) were included in the study, with a mean age of 42.5 years (standard deviation (SD) ± 17.5 years) for cases and 46.1 years (SD ± 19.1 years) for controls. Age 15-64 years (Adjusted odds ratio (AOR = 1.5, 95% CI; 1.4, 1.8)), ethnic minorities (AOR = 1.5; 95% CI; 1.4, 1.8), and a history of previous TB treatment (AOR) = 1.84; 95% CI: 1.57, 2.15) was significantly associated with DR-TB. Being resident in a province outside Hunan was also a significant risk factor (AOR = 1.67; 1.27, 2.21) for DR-TB. CONCLUSION AND RECOMMENDATIONS: To prevent the occurrence of DR-TB in Hunan Province, interventions should be targeted at high-risk demographic groups such as ethnic minorities, individuals of productive age, and residents living outside the province. Interventions must also be targeted to previously treated cases, suggesting the appropriateness of diagnosis, treatment, and follow-up. Understanding the risk factors at the province level helps design strategies for controlling DR-TB due to variations by socioeconomic differences, quality of health care, and healthcare access.

Risk factors for diagnosis and treatment delay among patients with multidrug-resistant tuberculosis in Hunan Province, China.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a global health threat associated with high morbidity and mortality rates. Diagnosis and treatment delays are associated with poor treatment outcomes in patients with MDR-TB. However, the risk factors associated with these delays are not robustly investigated, particularly in high TB burden countries such as China. Therefore, this study aimed to measure the length of diagnosis and treatment delays and identify their risk factors among patients with MDR-TB in Hunan province. METHODS: A retrospective cohort study was conducted using MDR-TB data from Hunan province between 2013 and 2018. The main outcomes of the study were diagnosis and treatment delay, defined as more than 14 days from the date of symptom to diagnosis confirmation (i.e., diagnosis delay) and from diagnosis to treatment commencement (i.e., treatment delay). A multivariable logistic regression model was fitted, and an adjusted odds ratio (AOR) with a 95% confidence interval (CI) was used to identify factors associated with diagnosis and treatment delay. RESULTS: In total, 1,248 MDR-TB patients were included in this study. The median length of diagnosis delays was 27 days, and treatment delays were one day. The proportion of MDR-TB patients who experienced diagnosis and treatment delay was 62.82% (95% CI: 60.09-65.46) and 30.77% (95% CI: 28.27-33.39), respectively. The odds of experiencing MDR-TB diagnosis delay among patients coming through referral and tracing was reduced by 41% (AOR = 0.59, 95% CI: 0.45-0.76) relative to patients identified through consultations due to symptoms. The odds of experiencing diagnosis delay among ≥ 65 years were 65% (AOR = 0.35, 0.14-0.91) lower than under-15 children. The odds of developing treatment delay among foreign nationalities and people from other provinces were double (AOR = 2.00, 95% CI: 1.31-3.06) compared to the local populations. Similarly, the odds of experiencing treatment delay among severely ill patients were nearly 2.5 times higher (AOR = 2.49, 95% CI: 1.41-4.42) compared to patients who were not severely ill. On the other hand, previously treated TB cases had nearly 40% (AOR = 0.59, 95% CI: 0.42-0.85) lower odds of developing treatment delay compared with new MDR-TB cases. Similarly, other ethnic minority groups had nearly 40% (AOR = 0.57, 95% CI: 0.34-0.96) lower odds of experiencing treatment delay than the Han majority. CONCLUSIONS: Many MDR-TB patients experience long diagnosis and treatment delays in Hunan province. Strengthening active case detection can significantly reduce diagnosis delays among MDR-TB patients. Moreover, giving attention to patients who are new to MDR-TB treatment, are severely ill, or are from areas outside Hunan province will potentially reduce the burden of treatment delay among MDR-TB patients.

A caprylate esterase-activated fluorescent probe for sensitive and selective detection of Salmonella enteritidis.

Salmonella enteritidis is one of the most common foodborne pathogens. Many methods have been developed to detect Salmonella, but most of them are expensive, time-consuming, and complex in experimental procedures. Developing a rapid, specific, cost-effective, and sensitive detection method is still demanded. In this work, a practical detection method is presented using salicylaldazine caprylate as the fluorescent probe, which could be hydrolyzed by caprylate esterase liberated from Salmonella lysed by phage, to form strong fluorescent salicylaldazine. The Salmonella could be detected accurately with a low limit of detection of 6 CFU/mL and a broad concentration range of 10-106 CFU/mL. Moreover, this method was successfully used for the rapid detection of Salmonella in milk within 2 h through pre-enrichment by ampicillin-conjugated magnetic beads. The novel combination of fluorescent turn-on probe salicylaldazine caprylate and phage ensures this method has excellent sensitivity and selectivity.

Whole-Genome Sequencing and Epidemiological Investigation of Tuberculosis Outbreaks in High Schools in Hunan, China.

Background: Tuberculosis (TB) seriously threatens individual and public health. Recently, TB outbreaks in schools have been reported more frequently in China and have attracted widespread attention. We reported three TB outbreaks in high schools in Hunan Province, China. Methods: When a tuberculosis patient was reported in a school, we carried out field epidemiological investigations, including tuberculin skin testing (TST), chest X-ray (CXR) and laboratory test for all close contacts, and whole-genome sequencing (WGS) analyses to understand the transmission patterns, the causes and the risk factors for the outbreaks, thereby providing a foundation for the control of TB epidemics in schools. Results: A total of 49 students with TB patients were identified in the three schools where TB outbreaks occurred, including nine patients in School A, 14 patients in School B, and 26 patients in School C. In Schools A, B and C, the putative attack rates in the classes of the index case were 13.8% (8/58), 7.6% (5/66), and 40.4% (21/52), while the putative attack rates of expanding screening in the school were 0.3% (1/361), 0.2% (9/3955), and 0.2% (5/2080), respectively. Thirteen patients had patient delay, with a median delay interval of 69 days (IQR 30.5-113 days). Twelve patients had a healthcare diagnostic delay with a median delay interval of 32 days (IQR 24-82 days). Phylogenetic analysis of culture-positive patients revealed that most of them shared a small genetic distance (≤12 SNPs), with three separate genetic clusters (including one MDR-TB genomic cluster), indicating the recent transmission of Mycobacterium tuberculosis strains. Conclusion: This combination of field investigation and WGS analysis revealed the transmission of three TB outbreaks in schools. Reinforced implementation is needed to improve timely case finding and reduce diagnosis delay in routine TB control in the school population.

The impact of ethnic minority status on tuberculosis diagnosis and treatment delays in Hunan Province, China.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Risk factors associated with unsuccessful tuberculosis treatment outcomes in Hunan Province, China.

OBJECTIVES: Globally, China has the third highest number of tuberculosis (TB) cases despite high rates (85.6%) of effective treatment coverage. Identifying risk factors associated with unsuccessful treatment outcomes is an important component of maximising the efficacy of TB control programmes. METHODS: Retrospective cohort study to evaluate the outcomes of 306,860 drug-susceptible TB patients who underwent treatment in Hunan Province, China between 2013 and 2018. Univariable and multivariable logistic regression models were used to identify factors associated with unsuccessful TB treatment outcomes. RESULTS: A successful treatment outcome was recorded for 98.6% of patients, defined as the sum of patients who were cured (36.2%) and completed treatment (62.4%). An unsuccessful treatment outcome was recorded for 1.8% of patients, defined as the sum of treatment failure (1.1%), deaths (0.5%) and lost to follow up (0.2%). The odds of an unsuccessful treatment outcome showed an increasing trend in more recent years of registration (2018 adjusted odds ratio (AOR): 1.43; 95% Confidence Interval (CI) 1.31, 1.57 relative to 2013). Other significant risk factors were male sex (AOR: 1.17; 95% CI 1.10, 1.25); increasing age (AOR:1.02 per year increase; 95% CI 1.02,1.02); being severely ill (AOR: 1.50; 95% CI 1.33, 1.70); having a history of TB treatment (AOR: 2.93; 95% CI 2.69, 3.20); not being under systematic management (AOR: 16.10 (14.49, 17.88) and treatment regimens that differed from full course management. CONCLUSIONS: The increasing likelihood of an unsuccessful treatment outcome over time necessitates the need for further research.

Spatiotemporal Patterns of Tuberculosis in Hunan Province, China.

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.

Spatial clustering of drug-resistant tuberculosis in Hunan province, China: an ecological study.

OBJECTIVE: This study aimed to investigate the spatial distribution of drug-resistant tuberculosis (DR-TB) in Hunan province, China. METHODS: An ecological study was conducted using DR-TB data collected from the Tuberculosis Control Institute of Hunan Province between 2012 and 2018. Spatial clustering of DR-TB was explored using the Getis-Ord statistic. A Poisson regression model was fitted with a conditional autoregressive prior structure, and with posterior parameters estimated using a Bayesian Markov chain Monte Carlo simulation, to quantify associations with possible risk factors and identify clusters of high DR-TB risk. RESULTS: A total of 2649 DR-TB patients were reported to Hunan TB Control Institute between 2012 and 2018. The majority of the patients were male (74.8%, n=1983) and had a history of TB treatment (88.53%, n=2345). The proportion of extensively DR-TB among all DR-TB was 3.3% (95% CI 2.7% to 4.1%), which increased from 2.8% in 2012 to 4.4% in 2018. Of 1287 DR-TB patients with registered treatment outcomes, 434 (33.8%) were cured, 198 (15.3%) completed treatment, 92 (7.1%) died, 108 (8.3%) had treatment failure and 455 (35.3%) were lost to follow-up. Half (50.9%, n=655) had poor treatment outcomes. The annual cumulative incidence rate of notified DR-TB increased over time from 0.25 per 100 000 people in 2012 to 0.83 per 100 000 people in 2018. Substantial spatial heterogeneity was observed, and hotspots were detected in counties located in the North and East parts of Hunan province. The cumulative incidence of notified DR-TB was significantly associated with urban communities. CONCLUSION: The annual incidence of notified DR-TB increased over time in Hunan province. Spatial clustering of DR-TB was detected and significantly associated with urbanisation. This finding suggests that targeting interventions to the highest risk areas and population groups would be effective in reducing the burden and ongoing transmission of DR-TB.

Development of a risk score for prediction of poor treatment outcomes among patients with multidrug-resistant tuberculosis.

BACKGROUND: Treatment outcomes among patients treated for multidrug-resistant tuberculosis (MDR-TB) are often sub-optimal. Therefore, the early prediction of poor treatment outcomes may be useful in patient care, especially for clinicians when they have the ability to make treatment decisions or offer counselling or additional support to patients. The aim of this study was to develop a simple clinical risk score to predict poor treatment outcomes in patients with MDR-TB, using routinely collected data from two large countries in geographically distinct regions. METHODS: We used MDR-TB data collected from Hunan Chest Hospital, China and Gondar University Hospital, Ethiopia. The data were divided into derivation (n = 343; 60%) and validation groups (n = 227; 40%). A poor treatment outcome was defined as treatment failure, lost to follow up or death. A risk score for poor treatment outcomes was derived using a Cox proportional hazard model in the derivation group. The model was then validated in the validation group. RESULTS: The overall rate of poor treatment outcome was 39.5% (n = 225); 37.9% (n = 86) in the derivation group and 40.5% (n = 139) in the validation group. Three variables were identified as predictors of poor treatment outcomes, and each was assigned a number of points proportional to its regression coefficient. These predictors and their points were: 1) history of taking second-line TB treatment (2 points), 2) resistance to any fluoroquinolones (3 points), and 3) smear did not convert from positive to negative at two months (4 points). We summed these points to calculate the risk score for each patient; three risk groups were defined: low risk (0 to 2 points), medium risk (3 to 5 points), and high risk (6 to 9 points). In the derivation group, poor treatment outcomes were reported for these three groups as 14%, 27%, and 71%, respectively. The area under the receiver operating characteristic curve for the point system in the derivation group was 0.69 (95% CI 0.60 to 0.77) and was similar to that in the validation group (0.67; 95% CI 0.56 to 0.78; p = 0.82). CONCLUSION: History of second-line TB treatment, resistance to any fluoroquinolones, and smear non-conversion at two months can be used to estimate the risk of poor treatment outcome in patients with MDR-TB with a moderate degree of accuracy (AUROC = 0.69).

Comparison of the validity of smear and culture conversion as a prognostic marker of treatment outcome in patients with multidrug-resistant tuberculosis.

BACKGROUND: The World Health Organization (WHO) has conditionally recommended the use of sputum smear microscopy and culture examination for the monitoring of multidrug-resistant tuberculosis (MDR-TB) treatment. We aimed to assess and compare the validity of smear and culture conversion at different time points during treatment for MDR-TB, as a prognostic marker for end-of-treatment outcomes. METHODS: We undertook a retrospective observational cohort study using data obtained from Hunan Chest Hospital, China and Gondar University Hospital, Ethiopia. The sensitivity and specificity of culture and sputum smear conversion for predicting treatment outcomes were analysed using a random-effects generalized linear mixed model. RESULTS: A total of 429 bacteriologically confirmed MDR-TB patients with a culture and smear positive result were included. Overall, 345 (80%) patients had a successful treatment outcome, and 84 (20%) patients had poor treatment outcomes. The sensitivity of smear and culture conversion to predict a successful treatment outcome were: 77.9% and 68.9% at 2 months after starting treatment (difference between tests, p = 0.007); 95.9% and 92.7% at 4 months (p = 0.06); 97.4% and 96.2% at 6 months (p = 0.386); and 99.4% and 98.9% at 12 months (p = 0.412), respectively. The specificity of smear and culture non-conversion to predict a poor treatment outcome were: 41.6% and 60.7% at 2 months (p = 0.012); 23.8% and 48.8% at 4 months (p<0.001); and 20.2% and 42.8% at 6 months (p<0.001); and 15.4% and 32.1% (p<0.001) at 12 months, respectively. The sensitivity of culture and smear conversion increased as the month of conversion increased but at the cost of decreased specificity. The optimum time points after conversion to provide the best prognostic marker of a successful treatment outcome were between two and four months after treatment commencement for smear, and between four and six months for culture. The common optimum time point for smear and culture conversion was four months. At this time point, culture conversion (AUROC curve = 0.71) was significantly better than smear conversion (AUROC curve = 0.6) in predicting successful treatment outcomes (p < 0.001). However, the validity of smear conversion (AUROC curve = 0.7) was equivalent to culture conversion (AUROC curve = 0.71) in predicting treatment outcomes when demographic and clinical factors were included in the model. The positive and negative predictive values for smear conversion were: 57.3% and 65.7% at two months, 55.7% and 85.4% at four months, and 55.0% and 88.6% at six months; and for culture conversions it was: 63.7% and 66.2% at two months, 64.4% and 87.1% at four months, and 62.7% and 91.9% at six months, respectively. CONCLUSIONS: The validity of smear conversion is significantly lower than culture conversion in predicting MDR-TB treatment outcomes. We support the WHO recommendation of using both smear and culture examination rather than smear alone for the monitoring of MDR-TB patients for a better prediction of successful treatment outcomes. The optimum time points to predict a future successful treatment outcome were between two and four months after treatment commencement for sputum smear conversion and between four and six months for culture conversion. The common optimum times for culture and smear conversion together was four months.

Treatment outcomes of patients with multidrug-resistant and extensively drug resistant tuberculosis in Hunan Province, China.

BACKGROUND: 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. METHODS: 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. RESULT: 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. CONCLUSION: 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.

Incidence of active tuberculosis in individuals with latent tuberculosis infection in rural China: follow-up results of a population-based, multicentre, prospective cohort study.

BACKGROUND: The management of latent Mycobacterium tuberculosis infection is a new priority action for the WHO End Tuberculosis (TB) Strategy. However, national guidelines on latent tuberculosis infection testing and treatment have not yet been developed in China. Here, we present the results from the 2-year follow-up of a study that aimed to track the development of active disease in individuals with latent tuberculosis infection, identify priority populations for latent infection management, and explore the most suitable latent infection diagnostic approach. METHODS: A population-based multicentre prospective study was done in four sites in rural China, between 2013 and 2015. The baseline survey in 2013 measured the prevalence of latent tuberculosis infection using QuantiFERON-TB Gold In-Tube (QFT) and tuberculin skin test (TST) in eligible participants. During the follow-up phase between 2014-15, we assessed individuals who had tuberculosis infection at baseline (QFT-positivity or TST tuberculin reaction size [induration] of ≥10 mm) for the development of active disease through active case finding. Eligible participants included in follow-up survey had a birth date before June 1, 2008 (5 years or older in 2013), and continuous residence at the study site for 6 months or longer in the past year. Participants with current active tuberculosis at baseline survey were excluded. FINDINGS: Between Sept 1, 2013, and Aug 31, 2015, 7505 eligible participants (aged 5 years or older) were included in tuberculosis infection test positive cohorts (4455 were QFT positive, 6404 had TST induration ≥10 mm, and 3354 were positive for both tests) after baseline examination. During the 2-year follow-up period, 84 incident cases of active tuberculosis were diagnosed. Of participants who developed active tuberculosis, 75 were diagnosed with latent infection by QFT, 62 were diagnosed by TST, and 53 were diagnosed by both tests. An incidence rate of 0·87 (95% CI 0·68-1·07) per 100 person-years was observed for individuals who tested positive with QFT, 0·50 (0·38-0·63) per 100 person-years for those who tested positive with TST (p<0·0001), and 0·82 (0·60-1·04) per 100 person-years for those who tested positive with both tests. Male sex and a history of tuberculosis were significantly associated with increased risk of disease development with adjusted hazard ratios of 2·36 (95% CI 1·30-4·30) for male sex and 5·40 (3·34-8·71) for a history of tuberculosis. INTERPRETATION: Our results suggest that high-risk populations in communities in rural China, such as individuals at a high risk of disease reactivation from previous tuberculosis, should be targeted for latent infection screening and treatment with an interferon-γ releasing assay rather than a TST. FUNDING: National Science and Technology Major Project of China, Program for Changjiang Scholars and Innovative Research Team in University of China, CAMS Innovation Fund for Medical Sciences, and Sanming Project of Medicine in Shenzhen.

Reasons for Non-Enrollment in Treatment among Multi-Drug Resistant Tuberculosis Patients in Hunan Province, China.

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.

Annual risk of tuberculosis infection in rural China: a population-based prospective study.

Prospective population data on the incidence of tuberculosis (TB) infection has been sparsely reported in the global literature.A population-based prospective study was conducted in rural China to investigate the annual risk of TB infection, and its persistence using serial tuberculin skin tests (TSTs) and an interferon-γ release assay. In total, 13 580 eligible participants from four rural sites, identified as TST negative (<10 mm) or QuantiFERON-TB Gold In-Tube (QFT) (an interferon-γ release assay) negative from a baseline survey, were included in the first year's follow-up examination.The annual conversion rate of QFT among the study sites ranged between 2.1% and 4.9% (average 3.1%), and the incidence of TST conversion ranged between 6.0% and 31.1% (average 14.5%). During the second year's follow-up, infection persistence was investigated using 390 subjects with QFT conversions. Among them, 49.7% (164 out of 330) were found to be consistently QFT positive. Both the conversion and the persistence of QFT positivity were found to be significantly increased with increasing age.In conclusion, the annual TB infection rate was suggested to be ∼1.5% based on persistent positive results after QFT conversion in rural China. Therefore, infection control among those high-risk populations, including the elderly, should be prioritised for TB control in China.

Latent tuberculosis infection in rural China: baseline results of a population-based, multicentre, prospective cohort study.

BACKGROUND: Prophylactic treatment of individuals with latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control in some settings. In China, the prevalence of latent tuberculosis infection, and preventive interventions against this disease, have not been systematically studied. We aimed to assess the prevalence of latent tuberculosis and its associated risk factors in rural populations in China. METHODS: Between July 1, and Sept 30, 2013, we undertook a baseline survey of a population-based, multicentre, prospective cohort study of registered residents (≥5 years old) at four study sites in rural China. Eligible participants were identified by door-to-door survey with a household sampling design. We screened participants for active tuberculosis and history of tuberculosis then used a tuberculin skin test and an interferon-γ release assay (QuantiFERON [QFT]) to test for latent infection. We used odds ratios (ORs) and 95% CIs to assess variables associated with positivity of QFT and tuberculin skin tests. FINDINGS: 21,022 (90%) of 23,483 eligible participants completed a baseline survey. Age-standardised and sex-standardised rates of skin-test positivity (≥10 mm) ranged from 15% to 42%, and QFT positivity rates ranged from 13% to 20%. Rates of positivity for the tuberculin skin test and the QFT test were low in study participants younger than 20 years and gradually increased with age (p for trend <0·0001). Rates of latent tuberculosis infection were higher for men than women (p<0·0001). Overall agreement between the tuberculin skin test and the QFT test was moderate (81·06%; kappa coefficient 0·485), with skin-test-only positive results associated with the presence of BCG scar, male sex, and ages of 60 years and older, and QFT-only positive results associated with male sex and ages of 60 years and older. INTERPRETATION: On the basis of findings showing that the performance of the tuberculin skin test might be affected by various factors including BCG vaccination and age, our results suggest that the prevalence of latent tuberculosis in China might be overestimated by skin tests compared with interferon-γ release assays. FUNDING: The National Science and Technology Major Project of China, the Program for Changjiang Scholars and Innovative Research Team in University of China.