Since January 1, 2005, PTB cases are reported to the TBIMS, the national TB surveillance system, within 24 hours of diagnosis [3]. From the TBIMS database, we collected information from PTB cases on basic demographic information (sex, birth date, home address, occupation, and treatment of classification), time of illness onset and diagnosis, and laboratory outcomes (sputum smear results and sputum culture results). The percentage values of multidrug-resistant tuberculosis (MDR-TB) infections in all cases, new patients, and re-treated patients were obtained by analysis of multidrug resistance of tuberculosis. The mortality was obtained from the national disease surveillance system’s tuberculosis death analysis report and the Ministry of Health’s prevalence survey in 2010.

Descriptive statistical methods were adopted to analyze continuous variables and categorical variables. The annual incidence rates of PTB (per 100,000 people) and bacteriological-positive PTB were calculated. We used the Arc Map’s (version 10.2; ESRI Inc) ring map to show the spatiotemporal patterns of PTB incidence. In order to illustrate the seasonal patterns of PTB in different regions, we created heatmaps for the proportion of PTB cases identified during each month of the year. A hierarchical clustering method was used to identify similar regions based on the overall and bacteriological-positive PTB incidence rates, which were compared with the distribution of poverty-stricken regions in Henan province. Univariable and multivariable logistic regression models were applied in order to investigate the factors associated with bacteriological-positive PTB, and unadjusted odds ratios (OR) and adjusted odds ratios (AOR) were also estimated.

We used a dynamic compartmental model [5,7] to predict the incidence and mortality of TB epidemics, and the main parameters included natural history parameters, mortality rate or birth rate, and program parameters such as patient visit rate and long-term cure rate. We found the present background parameters values through a review of the literature [5,6], including the long-term cure rate for new cases and re-treatment cases in different medical settings. Based on experts' opinions and a local epidemiological survey from Henan Center for Disease Control and Prevention, we selected and set the local background parameters and further simulated 4 main scenarios for the future. We assumed that these scenarios would be implemented in 2018 and estimated their effect by 2025 using the model. In scenario 1 (the current status in Henan), we estimated the ranges of the decline in incidence and mortality if the current strategies are maintained until 2025. In scenario 2, we estimated the change of incidence and mortality by year if the treatment success rate for drug-susceptible tuberculosis (DS-TB) increased to 92% for new treatment and 90% for re-treatment. In scenario 3, we considered using better diagnosis technologies and increasing treatment success for MDR-TB to show the impact of the measures, and the long-term cure rate with a second-line drug for MDR-TB was 82%. In scenario 4, a combination of all conducted measures was represented; that is, scenarios 1, 2, and 3 were delivered simultaneously. A detailed description of the statistical analyses is provided in Multimedia Appendix 1.

In addition, the data of TB burden in Henan province were used to calibrate the model by adopting the Bayesian melding approach [8]. Then, the impact of intervention strategies on the epidemiology of TB was predicted using the fitted model. We predicted the incidence, mortality, and multidrug-resistant percentage for all cases and new cases for each scenario. The posterior simulations produced 95% credible intervals. Furthermore, the post-2015 global tuberculosis targets were compared with the variation in incidence and mortality that we calculated.

The ethics review committee of the Henan Tuberculosis Control Institute provided approval for this study. Additionally, patients’ information was anonymized to ensure privacy.

A total of 976,526 PTB cases were reported to TBIMS in the 2005–2018 period. Of these, 381,598 (39.08%) were cases of bacteriological-positive tuberculosis. In all PTB cases, the overall male-to-female ratio was 2.38:1; however, this pattern was not uniform across the years (Figure 1A), and the gender difference in the 0-14 years age group was the lowest (Figure 1B). The median age was 48 (IQR 28–63) years, and the median age for bacteriological-positive cases (51 years, IQR 31-65) was higher than for negative cases (47 years, IQR 28-63).

Moreover, 95.0% of patients were new cases, and 98.2% had received antituberculosis therapy (Table 1).

The annual average PTB incidence was 75.3/10⁵, and the overall incidence trend declined from 91.4/10⁵ in 2005 to 58.5/10⁵ in 2017. The annual average incidence for patients with bacteriological-positive PTB was 30.1/10⁵, and it decreased from 44.5/10⁵ in 2005 to 14.7/10⁵ in 2017 (Figure 2A).

PTB incidence showed broad age-specific variations, and patients aged ≥60 years and 15-29 years ranked first and second, respectively. In addition, the incidence in rural regions was higher than in urban areas (P<.05; Table 2).

As can be observed from the PTB’s geographical distribution across Henan in the 2005-2018 period, the high incidence areas of PTB in Henan province remained unchanged (Figure 2B). In addition, from 2005 to 2010, the overall incidence of bacteriological-positive cases remained high, except in Zhengzhou city (Figure 2C). The incidence rates of PTB, cases of bacteriological-positive tuberculosis, and poverty-stricken counties were basically the same, especially in Nanyang city, Xinyang city, Zhoukou city, and Zhumadian city (Figure 3A-C).

On the provincial scale, it can be observed that people developed PTB throughout the year, while at the city-level, the incidence did not reach a peak at the same time across Henan; nevertheless, the annual seasonal peaks were noticeable. A seasonal pattern was observed in March, April, May, and June, and the peak season occurred in March and April. Cases decreased during early June and after mid-October, and the PTB cases increased again, with transmission reaching a small peak, in November. The 2 months with the lowest PTB incidence were January and February (Figure 2D-E).

Bacteriological results showed that the proportion of bacteriological-positive cases decreased from 48.79% in 2005 to 23.64% in 2016. However, the proportion of bacteriological-positive infection rose in 2017 and 2018 to 25.20% and 32.27%, respectively (Figure 4A). Further, the proportion of males with bacteriological-positive tuberculosis was higher than that of females (Figure 4B-C). In addition, the proportion of patients with bacteriological-positive infection in the ≥60 years age group was the highest, and the proportion increased continuously from 35.42% in 2005 to 38.42% in 2018 (Figure 4D). The proportion of patients with bacteriological-negative infection across different age groups was consistent with that of patients with bacteriological-positive infection (Figure 4E).

Male sex, residence in rural areas, and re-treated cases were factors associated with the development of bacteriological-positive PTB, and the AORs for these groups were 1.32, 1.17, and 1.70, respectively. In addition, a trend of substantial increase in PTB risk with bacteriological-positive infection was observed with increasing age; the AORs were 1.91, 1.92, 1.97, and 2.17 for the 15-29, 30-44, 45-59, and ≥60 years age groups, respectively. Moreover, workers, farmers and herders, and the commercial service stratum were more susceptible to developing bacteriological-positive PTB than nursery children and students; the AORs for these groups were 3.78 (95% CI 1.93-8.54), 3.69 (95% CI 1.88-8.34), and 3.44 (95% CI 1.75-7.79), respectively (Table 3).

In scenario 1 (the current status in Henan), if the strategies are kept unchanged, the incidence and mortality are expected to gradually decline by 22.6% (95% CI 21.7%-23.6%) and 27.9% (95% CI 27.0%-28.3%), respectively, from 2015 to 2025 (Figure 5A-B, Table 4).

In scenario 2, if the treatment success rate of new and re-treatment cases is increased to 92% and 90%, respectively, the incidence and mortality will be decreased by 23.9% (95% CI 23.0%-25.0%) and 36.8% (95% CI 36.1%-38.0%), respectively, by 2025 (Figure 5A-B, Table 4).

In scenario 3, if 90% of TB smear-positive patients are tested for resistance testing, and the long-term cure rate for MDR-TB can reach 82%, the incidence and mortality was found to decline by 24.2% (95% CI 23.2%-25.3%) and 38.5% (95% CI 37.7%-39.9%), respectively (Figure 5A-B, Table 4). In addition, we observed that the proportions of MDR-TB in all patients with TB and new cases were declining slowly in Henan with the current measures. Moreover, the use of better diagnostic technologies and increasing treatment success for MDR-TB would yield the greatest percentage reduction in MDR-TB in the general population, all patients with TB, and new cases, by 26.9%, 3.6%, and 5.1%, respectively, from 2015 to 2025 (Figure 5C-E).

The greatest reduction was observed in scenario 4, where the combined strategy would yield reductions in incidence and mortality of 24.5% (95% CI 23.5%-25.6%) and 40.4% (95% CI 39.4%-42.1%), respectively, by 2025 (Figure 5A-B, Table 4).

This study has some limitations. First, all the data used in this study were obtained from the TBIMS. However, drug resistance was not fully analyzed because the system contained incomplete drug resistance data. Second, no active detection and intervention data were obtained from the TBIMS. Hence, we only determined whether the WHO’s goal could be achieved through passive strategies.

In China, from 1990 to 2020, 3 nationwide random surveys on TB were carried out to evaluate the effectiveness of the DOTS strategy. However, based on the internet-based TBIMS, we can now monitor the changes of TB epidemiological characteristics in real time while saving money, manpower, and time in the evaluation of the effect of different strategies. The local government has embarked on a series of nonfragmented TB-related intervention combinations, and the incidence of PTB and bacteriological-positive PTB has continued to decrease during the last 14 years; however, the WHO’s 2025 goal will not be reached. New active—rather than passive—strategies for detection and intervention should be formulated based on epidemiological characteristics while improving the cure rates of DS-TB and MDR-TB.