Tuberculosis (TB) is an infectious disease of major public health concern. The disease has demonstrated large space-time variations. This study aims to explore the space-time dynamics of TB cases in an economically and geographically dynamic province in China with specific references of TB control for policy makers. Data on all reported TB cases from 2009 to 2012 were collected from the TB program at the Zhejiang Provincial Center for Disease Control and Prevention. We employed time series and exploratory spatial data analyses, including Moran’s I, Local Getis’s G i * , and Kulldorff’s space-time scan statistics, to identify the temporal trends and spatial patterns of TB at a county level. A total of 147,941 TB cases were reported during 2009–2012 in Zhejiang. A higher proportion of TB cases were younger, male, and registered permanent residents among all TB cases notified in the province. TB cases were reported most frequently in April with small peaks in June, July, and October. This disease was spatially clustering with Moran’s I values ranged from 0.29 to 0.32 (p < 0.001). A most likely cluster and ten secondary clusters were identified, mainly concentrated in the southeast and west counties of the province. This study identified seasonal patterns and significant space-time clusters of TB cases in Zhejiang, China. Poverty, migration, and seasonal effects may play important roles in potential clusters.

The problem of population aging is a critical public health concern in modern China, and more tuberculosis (TB) control efforts are needed to reach elderly people at high priority. In this study, we aim to determine the prevalence and identify the risk factors of TB among elderly people in China. A multistage cluster-sampled cross-sectional survey was conducted in 2013, and 27 clusters were selected from 10 counties of 10 provinces in China. All consenting participants greater than or equal to 65 years of age were screened for pulmonary TB with a chest X-ray (CXR) and a symptom questionnaire. Three sputum specimens for bacteriological examination by microscopy and culture were collected from those whose screening was positive. Prevalence was calculated, a multiple logistic regression model was performed to confirm the risk factors, and population attributable fraction (PAF) of each risk factor was calculated to indicate the public health significance. Of 38 888 eligible people from 27 clusters, 34 269 participants finished both questionnaire and physical examination. There were 193 active pulmonary TB cases, 62 of which were bacteriologically confirmed. The estimated prevalence of active pulmonary TB and bacteriologically confirmed TB in those 65 years of age and older was 563.19 per 100 000 (95% CI: 483.73–642.65) and 180.92 per 100 000 (95% CI: 135.89–225.96), respectively. Male sex, older age, living in rural areas, underweight, diabetes, close contact of pulmonary TB (PTB) and previous TB history are all risk factors for TB. The risk of TB increased with increasing age and decreasing body mass index (BMI) after adjusting for other factors, and there is a positive dose–response relationship. In China, active case finding (ACF) could be implemented among elderly people aged 65 and above with underweight, diabetes, close contact history and previous TB history as a priority, which will get significant yields and be cost-effective.

Recent biochemical studies suggest that exogenous sulfur dioxide (SO2) at low concentrations may have been beneficial in inhibiting mycobacteria tuberculosis (TB) growth. However, there is a dearth of population-based studies. To examine the association of ambient SO2 levels and initial TB outpatient visits. In Ningbo, China, we collected all daily initial outpatient visits for TB and routinely air pollution monitoring data between January 2009 and December 2013. A time-series study was conducted by using generalized additive regression (GAM) with log-linear Poisson models to estimate the associations between daily initial TB outpatient visits and daily average concentration of SO2. Other traffic-related co-pollutants were adjusted. Sensitivity analyses were conducted to examine the relationship when 1% extreme SO2 concentrations excluded or if related to the early onsets of TB symptoms. SO2 concentrations in Ningbo were low with a daily average of 25 μg/m3 (i.e. 0.0089 ppm). Negative associations were identified between ambient SO2 concentrations and daily initial TB outpatient visits. A 10 μg/m3 increase in SO2 at lag3 and lag0-3 days were associated with -2.0% (95%CI, -3.2, -0.8) and -4.6% (95%CI, -6.8, -2.4) changes, respectively, in initial TB outpatient visits according to single-pollutant models. The negative association became stronger when nitrogen dioxide (NO2) or particulate matter with aerodynamic diameter less than 10 μm (PM10) was adjusted in two-pollutant models. This association was higher in males vs. females and in middle-aged adults vs. the elderly. We found a stronger negative association between SO2 concentration and the initial symptom occurrence. Short-term exposure to ambient SO2 was associated with reduced risk of initial TB outpatient visits, suggesting acute protective effects of low-level ambient SO2 exposure on bacteria-induced pulmonary infections.

Purpose: Cycloserine has been used in multidrug-resistant tuberculosis (MDR-TB) treatment since the 1950s. We evaluated the efficacy and safety of cycloserine and sought to clarify the role of cycloserine for treatment of simple MDR-TB, pre-extensively drug-resistant tuberculosis (pre-XDR-TB), and extensively drug-resistant tuberculosis (XDR-TB). Materials and methods: A retrospective observational study was performed in Zhejiang Province, China. We enrolled 144 cycloserine-treated and 181 cycloserine-nontreated patients consecutively and determined the treatment outcome as the primary outcome. The proportion of patients with sputum culture conversion and the frequency of adverse drug reactions were also assessed. Results: One-hundred (69.4%) out of 144 patients in the cycloserine group successfully completed treatment. The HR of any unfavorable treatment outcome after the introduction of cycloserine was 0.58 (95% CI: 0.38–0.86, P=0.008). Subgroup analysis showed that cycloserine could benefit simple MDR-TB cases reducing the risk of unfavorable treatment outcomes (HR: 0.43, 95% CI: 0.24–0.76, P=0.004), but not pre-XDR-TB (HR: 0.65, 95% CI: 0.30–1.38, P=0.263) or XDR-TB (HR: 0.73, 95% CI: 0.22–2.37, P=0.589). The culture conversion rate at the intensive phase was similar whether cycloserine was administered or not (P=0.703). Of the 144 patients treated with cycloserine, a total of 16 (11.1%) patients experienced side effects attributed to cycloserine. Conclusion: Cycloserine is an attractive agent for the treatment of MDR-TB, and its safety profile warrants its use in most MDR-TB cases. Cycloserine significantly improved the chance of a favorable outcome for patients with simple MDR-TB but not pre-XDR-TB and XDR-TB. Thus, more aggressive regimens might be required for pre-XDR-TB or XDR-TB patients.

Background: More than 1 million tuberculosis (TB) patients are receiving the standard anti-TB treatment provided by China National Tuberculosis Prevention and Control Scheme (CNTS) in China every year. Adverse reactions (ADRs) induced by anti-TB drugs could both do harm to patients and lead to anti-TB treatment failure. The ADACS aimed to explore ADRs' incidences, prognoses, economical and public health impacts for TB patients and TB control, and build a DNA bank of TB patients. Methods/Design: Multiple study designs were adopted. Firstly, a prospective cohort with 4488 sputum smears positive pulmonary tuberculosis patients was established. Patients were followed up for 6-9 months in 52 counties of four regions. Those suspected ADRs should be checked and confirmed by Chinese State Food and Drug Administration (SFDA). Secondly, if the suspected ADR was anti-TB drug induced liver injury (ATLI), a nested case-control study would be performed which comprised choosing a matched control and doing a plus questionnaire inquiry. Thirdly, health economical data of ADRs would be collected to analyze financial burdens brought by ADRs and cost-effectiveness of ADRs' treatments. Fourthly, a drop of intravenous blood for each patient was taken and saved in FTA card for DNA banking and genotyping. Finally, the demographic, clinical, environmental, administrative and genetic data would be merged for the comprehensive analysis. Discussion: ADACS will give an overview of anti-TB drugs induced ADRs' incidences, risk factors, treatments, prognoses, and clinical, economical and public health impacts for TB patients applying CNTS regimen in China, and provide suggestions for individualized health care and TB control policy.

Tuberculosis, a severe infectious disease caused by the Mycobacterium tuberculosis, arouses huge concerns globally. In this study, a total of 331,594 TB cases in Zhejiang Province were notified during the period of 2009–2018 with the gender ratio of male to female 2.16:1. The notified TB incidences demonstrated a continuously declining trend from 75.38/100,000 to 52.25/100,000. Seasonally, the notified TB cases presented as low in January and February closely followed an apparent rise in March and April. Further stratification analysis by both genders demonstrated the double peak phenomenon in the younger population (“15–35”) and the elders (“>55”) of the whole group. Results from the rate difference (RD) analysis showed that the rising TB incidence mainly presented in the young group of “15–20” and elder group of “65–70”, implying that some implementations such as the increased frequency of checkup in specific student groups and strengthening of elder health examination could be explored and integrated into available health policy. Finally, the SARIMA (2,0,2) (0,1,1)12 was determined as the optimal prediction model, which could be used in the further prediction of TB in Zhejiang Province.