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Tuberculosis (TB) remains a major public health threat in China, which has the second largest number of TB patients worldwide. The incidence of TB had been declining, but with China’s rapid pace of ageing, the incidence began to plateau, and the annual decline in TB after 2015 was half of what it was during the previous two decades (1). People are getting older. In 2018, 1.9% of the population was 65 years or above; by 2035, 20.7% of the population will be 65 or older, and by 2050, 26.1% will be (2). In addition to ageing, the coronavirus disease 2019 (COVID-19) pandemic has also brought great challenges to TB control — older people are at the highest risk of severe disease and adverse outcomes from both TB and COVID-19. A better understanding of age-specific TB incidence will provide reference points for improving targeted strategies. According to the China’s law of infectious diseases control, pulmonary TB (PTB) must be reported to the national TB Management Information System (TBIMS), which provides a profile of the PTB epidemic.
In this study, we analyzed age-specific PTB rates reported in TBIMS from 2008 to 2018 and conducted a joinpoint regression analysis to evaluate the impact of ageing on the potential to achieve the World Health Organization (WHO) End TB Strategy targets. We found an overall decline of 27.7% during the study period with an annual crude percentage change of −3.4% and an annual age-adjusted change of −4.3%. The rates of decline were greater among older people and were lower in central and western China compared with eastern China. In 2016, there was an inflection point in which the decline plateaued, potentially cancelling tuberculosis control progress in China. Targeted responses, including enhanced surveillance, age-sensitive analysis, and early screening and preventative therapy, are recommended.
The study data came from all 31 provincial-level administrative divisions (PLADs) in the mainland of China. Annual population data were collected from the China Statistical Yearbook. We determined annual crude and age-adjusted notification rates using the 2008 population as a reference. We determined the average crude and age-adjusted annual percentage change (APC) using exponential linear regression and joinpoint regression. Comparison of declines by subgroup was based on both crude and age-adjusted APCs. Joinpoint regression identified a joinpoint that divided the crude and age-adjusted notification rates into two periods that we used in subsequent analyses. A trend was defined as an increase or decrease if it had a statistically significant difference (P<0.01), and as stable if it had a non-significant difference (P≥0.01). Statistical analyses were done with R (version 3.6.0, R Development Core Team, Vienna, Austria) and Joinpoint Regression Program, (version 4.7.0, Statistical Research and Applications Branch, National Cancer Institute, Bethesda, MD, USA).
Between 2008 and 2018, a total of 9,242,525 PTB cases were notified to TBIMS, for an average notification rate of 62.1 cases per 100,000. Notification rates were higher for males, increased with age, and were disproportionately distributed by geographical region (Table 1). A total of 42% of PTB cases were smear-positive.
Group Number of total notified cases Average notification rate (1/100,000) Annual notification rate (1/100,000) Change between 2008 and 2018 Trend analysis 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 Absolute change Relative change Average annual percentage change (95% CI) P value Trend Total 9,242,525 62.1 75.6 71.4 67.9 65.7 64.5 60.9 58.6 56.6 54.6 53.8 54.7 −21.0 −27.7% −3.4%
(−3.9 to −3.0)<0.01 Decrease Sex Male 6,441,130 84.4 103.1 97.1 92.4 89.8 87.8 82.6 79.6 76.9 74.0 73.3 73.6 −29.5 −28.6% −3.5%
(−4.0 to −3.1)<0.01 Decrease Female 2,801,395 38.6 46.4 44.3 42.2 40.3 40.0 38.1 36.4 35.3 34.2 33.4 34.8 −11.6 −24.9% −3.2%
(−3.8 to −2.6)<0.01 Decrease Age (years) 0–14 59,017 2.3 3.3 3.3 2.5 2.4 2.3 1.9 1.6 1.6 1.8 1.9 2.4 −0.9 −26.9% −5.2%
(−8.6 to −1.6)<0.01 Decrease 15–24 1,425,718 58.1 71.2 69.9 68.1 65.6 61.9 56.8 53.4 48.3 47.7 46.4 46.5 −24.7 −34.7% −5.0%
(−5.7 to −4.2)<0.01 Decrease 25–34 1,318,915 62.2 77.0 72.4 69.5 65.7 62.8 59.8 58.2 56.6 55.6 54.0 53.5 −23.5 −30.5% −3.7%
(−4.2 to −3.1)<0.01 Decrease 35–44 1,331,405 51.9 67.6 64.8 61.8 58.1 55.2 50.1 49.2 44.3 41.0 38.5 37.5 −30.1 −44.6% −6.0%
(−6.5 to −5.6)<0.01 Decrease 45–54 1,543,716 70.5 88.9 80.3 75.1 72.0 70.6 68.3 64.6 64.9 65.5 65.4 64.8 −24.1 −27.1% −2.8%
(−3.8 to −1.8)<0.01 Decrease 55–64 1,616,223 99.8 126.8 116.5 108.6 104.7 105.1 101.5 93.7 90.0 86.3 83.8 89.3 −37.5 −29.6% −3.7%
(−4.5 to −2.9)<0.01 Decrease 65–74 1,275,541 147.7 189.0 172.9 161.5 141.2 153.9 146.4 142.9 144.8 126.5 130.2 130.8 −58.2 −30.8% −3.4%
(−4.5 to −2.3)<0.01 Decrease 75– 671,990 129.7 185.8 172.8 163.8 142.0 132.8 126.9 118.4 121.4 104.2 106.0 106.4 −79.4 −42.7% −5.7%
(−6.8 to −4.7)<0.01 Decrease TB category New pulmonary tuberculosis 9,130,914 61.3 74.2 70.1 66.8 64.8 63.7 60.3 58.1 56.2 54.2 53.4 54.2 −20.0 −26.9% −3.3%
(−3.8 to −2.9)<0.01 Decrease Smear-positive pulmonary tuberculosis 3,856,327 25.9 40.0 38.3 36.3 31.6 26.6 23.0 19.8 17.5 16.4 16.3 20.5 −19.5 −48.8% −9.7%
(−12.5 to −6.8)<0.01 Decrease Region Eastern 2,910,810 47.9 61.0 58.2 55.6 51.3 49.7 46.1 44.8 43.2 41.2 40.0 38.5 −22.6 −37.0% −4.7%
(−5.1 to −4.3)<0.01 Decrease Central 3,255,461 69.5 84.4 80.8 76.8 73.9 73.1 69.1 66.7 64.5 61.1 58.7 56.4 −28.0 −33.2% −3.9%
(−4.2 to −3.7)<0.01 Decrease Western 3,076,254 75.6 90.3 82.6 78.3 78.9 77.7 74.5 69.7 67.4 67.1 68.7 76.9 −13.4 −14.8% −2.2%
(−3.5 to −0.9)<0.01 Decrease Abbreviation: CI=confidential interval. Table 1. Notified pulmonary tuberculosis cases, rates, and change and trend analysis of rates in China, 2008–2018.
Among individuals 15 years or older, annual notification rates for males were significantly higher than for females, particularly among older adults (Table 1). A significant decrease was observed in PTB notification rates, with an absolute change of −21.0 cases per 100,000 during the study period — a relative change of −27.7% and an average annual percentage change of −3.4% (95% confidential interval, CI: −3.9 to −3.0). Decreases were observed in all groups, but were faster among males, people younger than 45, smear-positive patients, eastern China, and central China (Table 1).
Among children (<15 years), the average annual percentage change was significantly greater in males, in central China, and in western China compared with the overall average. Among 15 to 64-year-olds, changes were greater in 35 to 44-year-olds, 15 to 24-year-olds except in western China, 25 to 34-year-old females, and people in central China and western China. Among people 65 years and older, the average annual percentage change was greater in males, in eastern China, and in central China. Children 0 to 14 years old in eastern China and 65 to 74-year-olds in western China were the only groups without a significantly decreasing trend (Figure 1).
Figure 1.Average annual percentage change of pulmonary tuberculosis notification rates by age group in China, 2008–2018. (A) PTB; (B) PTB in male; (C) PTB in female; (D) Smear-positive PTB; (E) Smear-positive PTB in male; (F) Smear-positive PTB in female; (G) PTB in eastern; (H) PTB in central; (I) PTB in western.
Note: Dots and shaded areas represent the annual percentage change (% per year) and 95% CIs in pulmonary tuberculosis notification rates by age group in China during 2008–2018. The dashed line represents the average annual percentage change in all age groups in pulmonary tuberculosis (−3.4%) and smear-positive pulmonary tuberculosis (−9.7%). PTB is pulmonary tuberculosis.
Abbreviation: PTB=pulmonary tuberculosis; CI=confidential interval.
The year 2016 was an inflection point between decreasing and stable incidences. Before 2016, the crude annual percentage change showed a faster decline in smear-positive PTB (−11.7%, 95% CI: −13.7 to −9.6) than in PTB (−3.9%, 95% CI: −4.3 to −3.5) and a faster decline in eastern China (−5.3%, 95% CI: −5.9 to −4.8) than in central China (−3.7%, 95% CI: −4.2 to −3.3) and western China (−3.5%, 95% CI: −4.5 to −2.5). After 2016, no statistically significant change was identified. Trends in central and eastern China were different from national level and western China trends. In central China, TB declined rapidly after 2015, while in eastern China the rate of decline slowed but didn’t stop. Age-adjusted joinpoint analyses showed consistent regression patterns but with faster declines. The annual percentage change of age-adjusted rates were −4.3% (95% CI: −4.8 to −3.8) at the national level, −5.5% (95% CI: −6.1 to −4.9) in eastern China, −5.0% (95% CI: −5.2 to −4.8) in central China, and −3.1% (95% CI: −4.4 to 1.8) in western China (Table 2).
Group Joinpoint regression Annual percentage change (95% CI) from 2008 to 2018 Trend 1: decrease Trend 2: stable and decrease Period Annual percentage change (95% CI) Trend Period Annual percentage change (95% CI) Trend Crude rate 2008–2016 −3.9%
(−4.3 to −3.5)*Decrease 2016–2018 0.2%
(−3.8 to 4.3)Stable –3.4%
(−3.9 to −3.0)Sex Male 2008–2016 −4.0%
(−4.4 to −3.6)*Decrease 2016–2018 −0.1%
(−4.2 to 4.2)Stable −3.5%
(−4.0 to −3.1)Female 2008–2016 −3.8%
(−4.2 to −3.4)*Decrease 2016–2018 0.9%
(−3.1 to 5.2)Stable −3.2%
(−3.8 to −2.6)TB category New pulmonary tuberculosis 2008–2016 −3.8%
(−4.2 to −3.4)*Decrease 2016–2018 −0.0%
(−4.0 to 4.2)Stable −3.3%
(−3.8 to −2.9)Smear-positive pulmonary tuberculosis 2008–2016 −11.7%
(−13.7 to −9.6)*Decrease 2016–2018 11.1%
(−13.6 to 42.9)Stable −9.7%
(−12.5 to −6.8)Region Eastern 2008–2013 −5.4%
(−6.0 to −4.8)*Decrease 2013–2018 −3.8%
(−4.5 to −3.0)*Decrease −4.7%
(−5.1 to −4.3)Central 2008–2015 −3.7%
(−4.2 to −3.3)*Decrease 2015–2018 −4.3%
(−6.2 to −2.5)*Decrease −3.9%
(−4.2 to −3.7)Western 2008–2016 −3.5%
(−4.5 to −2.5)*Decrease 2016–2018 7.5%
(−2.2 to 18.2)Stable −2.2%
(−3.5 to −0.9)Age-adjusted rate 2008–2016 −4.8%
(−5.2 to −4.4)*Decrease 2016–2018 −0.3%
(−4.6 to 4.1)Stable −4.3%
(−4.8 to −3.8)Sex Male 2008–2016 −4.9%
(−5.3 to −4.5)*Decrease 2016–2018 −0.6%
(−4.9 to 4.0)Stable −4.4%
(−4.9 to −3.9)Female 2008–2016 −4.5%
(−4.9 to −4.1)*Decrease 2016–2018 0.3%
(−3.9 to 4.7)Stable −3.9%
(−4.5 to −3.4)TB category New pulmonary tuberculosis 2008–2016 −4.6%
(−5.0 to −4.2)*Decrease 2016–2018 −0.5%
(−4.7 to 4.0)Stable −4.1%
(−4.6 to −3.7)Smear-positive pulmonary tuberculosis 2008–2016 −12.6%
(−14.6 to −10.6)*Decrease 2016–2018 10.4%
(−14.3 to 42.3)Stable −10.2%
(−12.6 to −7.8)Region Eastern 2008–2013 −6.5%
(−7.8 to −5.2)*Decrease 2013–2018 −4.1%
(−5.6 to −2.6)*Decrease −5.5%
(−6.1 to −4.9)Central 2008–2015 −4.7%
(−5.1 to −4.4)*Decrease 2015–2018 −5.2%
(−6.9 to −3.6)*Decrease −5.0%
(−5.2 to −4.8)Western 2008–2016 −4.4%
(−5.3 to −3.5)*Decrease 2016–2018 6.7%
(−2.6 to 16.9)Stable −3.1%
(−4.4 to 1.8)* P<0.01, an average annual percentage change had significant difference from zero.
Abbreviation: CI=confidential interval.Table 2. Joinpoint analysis of crude and age-adjusted pulmonary tuberculosis notification rates in China, 2008–2018.
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Our study found that the pulmonary tuberculosis notification rate declined by 27.7% in China between 2008 and 2018, with an annual decline of 3.4% until 2016, when the decline plateaued. Age, sex, and regional disparities had significant impacts on distribution and notification trends. Age-specific analyses showed the highest notification rate in people 65 years and above. As noted, joinpoint analysis showed an inflection in the declining trend in 2016. Given few proactive strategies, China may face a slower decline or a plateau in PTB incidence in the coming years, or possibly a resurgence like some countries experienced during the 1990s. Great attention should be paid to trends and demographic characteristics of TB patients.
China is rapidly moving toward an ageing society, with high-paced economic development and achievement of universal health coverage. According to a World Population Prospects 2019 estimate, China’s fertility rate was approximately 1.7 — lower than the regeneration rate of 2.1. The percentage of the population over 65 years increased from 8.3% in 2008 to 11.9% in 2018 (3) and may exceed 20% in 2035 (2). This rapid ageing has brought great challenges to TB control in China. The TB notification rate in people 65 years and above was more than twice that of the entire population. Although the rate of decline in older people seems higher, age standardization reduced the annual decline rate by 0.9% in 2008 to 2016 and 0.5% in 2016 to 2018. Standardization impact may be even greater over the longer term due to the acceleration of population ageing.
Western China changed from decrease to plateau (and close to increase) in TB notifications, which contributed to the national plateau after 2016. Economic disparities and consequential disparities in health awareness and health service accessibility could be important reasons. According to JP Janssen and colleague’s analysis, TB incidence is linearly related to per capita gross domestic product (4). During recent decades, large-scale population flow has occurred from western and central China into eastern China because of unbalanced economic development. Considering most migrant populations are under 40 years of age (5), interregional migration may aggravate demographic, and consequently TB, disparities in the different regions.
Many factors may be responsible for a faster decline in the notification rate of smear-positive PTB patients. In 2008, China launched national guidelines (6) and standardized diagnostic criteria (7), which strengthened diagnosing, reporting, and treating of smear-negative TB patients. Enhancement programs such as health education and patient-awareness augmentation also contributed greatly to shortening diagnosis time and lessening TB patients’ symptoms. Meanwhile, the reform of China’s TB service delivery model from traditional TB-specific facilities to designated general hospitals may have influenced the examination and detection of smear-positive patients (8).
The End TB Strategy requires a decline in the TB incidence rate of at least 10% before 2025. Based on our analysis, achieving the End TB 2020/2025 milestones and the National Tuberculosis Program 13th Five Year Plan targets is on pace. However, the current rate of decline is too slow to achieve the End TB 2035 milestone. While the scientific community looks for new vaccines and drugs to accelerate this process, we must also proactively address new challenges like population ageing and regional disparities.
The annual rate of decline rate that we found is similar to modeling results from the Global Burden Disease study (1990–2017) (9), but higher than average levels in Western Pacific countries or worldwide (10). China is shifting from a high to a moderate epidemic of TB, similar to what was seen in developed countries in the 1950s. At that stage, in addition to implementation of standardized chemotherapy and treatments, most developed countries implemented various policies such as large-scale active screening, active targeted screening in key populations, and preventive treatment. For example, the United States (11) and Japan (12) both launched active screening strategies for elderly people during this period, as highlighted in the WHO End TB Strategy relevant guidelines. China has started exploring active screening pilot projects in key populations. Successful experiences will help spread these good practices to other regions.
There are limitations to our study. We did not consider HIV and drug-resistance in our analyses. The impact of COVID-19 on the TB epidemic could not be evaluated at the time of the study. Other studies showed that COVID-19 temporarily decreased the TB notification rate in China (13). Whether COVID-19 will profoundly influence TB notification will need to be evaluated in a future study.
Our dynamic analysis and monitoring of surveillance data demonstrated demographic changes and TB epidemiological trends in China. Age-specific transitions and decreased pace of TB case notifications due to population ageing and geographic disparities may significantly influence TB control progress in the future. Maintenance of the current strategy will have limited impact on reducing future TB incidence; only additional screening and preventative therapy for older people will enable China to reach its targets on time.
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No conflicts of interest reported.
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