Incidence of pulmonary tuberculosis under the regular COVID-19 epidemic prevention and control in China

Tuberculosis (TB) is a serious threat to global public health, with about 10 million people suffering from pulmonary tuberculosis (PTB) and nearly 2 million people will die of this disease each year [1, 2]. Since 2007, PTB has become the leading cause of death from a single infectious agent [1]; despite the substantial achievements made under some expanded programs to strengthen the delivery of high-quality TB treatment [3‐5] and improve the level of TB care and prevention [6, 7]. Further strengthening of efforts are required to provide better disease control. From 2000 to 2018, the average decline in TB incidence was 1.6% per year, and the cumulative reduction in TB incidence between 2015 and 2018 was only 6.3% [1]. In 2015, the World Health Organization launched the End TB Strategy to end the global TB epidemic by 2030 [8].

China, despite having achieved great progress in TB prevention and care over the past two decades [9], remains the second-largest contributor to the global burden of new TB cases, accounting for 8.5% of the global total, second only to India (26%) [1]. Moreover, TB incidence between 2015 and 2018 almost did not decrease in China, which is a cumulative reduction far below the average level worldwide. Multiple models have shown that, in addition to active case finding and effective treatment for an active case, prevention remains the key component of an intervention strategy [10‐13]. However, existing intervention strategies for controlling TB, such as the enhancement of TB services, would be insufficient to eliminate TB [14]. Bacillus Calmette–Guérin (BCG), the only available TB vaccine, can only protect young children. BCG has been demonstrated to prevent severe extrapulmonary tuberculosis and also plays a weaker role in preventing PTB [15]. The pipeline for new TB-related diagnostics, drugs, and vaccines is progressing but at a slow pace [16]. Thus, new strategies must be developed to reduce TB incidence and mortality and fulfill the goals set in the End TB Strategy.

The urgent response mounted as a result of the COVID-19 outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through social intervention strategies provide a perfect reference for improving the effectiveness of PTB prevention [17, 18]. By the end of 2020, the outbreak had resulted in over 83 million COVID-19 infections and over 1,800,000 deaths [19]. To contain the outbreak, China implemented unprecedented strict intervention strategies on 23 January 2020. The entire city of Wuhan was quarantined, strict measures limiting travel and public gatherings were introduced, public spaces were closed, rigorous temperature monitoring was implemented, and people were asked to maintain social distance, wear masks, and frequently wash hands nationwide. After over 2 months of unremitting efforts, the transmission of COVID-19 had been effectively controlled in China, and the lockdown in Wuhan was lifted on 8 April 2020 [20]. Nevertheless, scattered outbreaks of COVID-19 occurred in some areas, and cases imported from abroad were recorded. Accordingly, the same strategies, i.e., maintaining social distancing, wearing masks, and washing hands frequently, have been implemented as the regular COVID-19 epidemic prevention and control protocol. Interestingly, a remarkable decrease in PTB incidence in China was simultaneously observed during the COVID-19 outbreak. In addition, the PTB incidence in China had been effectively controlled under the regular COVID-19 epidemic prevention and control for the next 8 months. Thus, the interventional strategies conducted during the COVID-19 pandemic likely played a role in reducing PTB incidence as both diseases spread through the air.

The effectiveness of various measures to lower or control PTB incidence could potentially be fitted into an interventional model, which in turn could be further used to forecast future trends of PTB incidence according to previous data. To explore the availability of some COVID-19 interventional strategies, such as maintaining social distance, wearing masks, and regular handwashing, for the control of PTB incidence, we analyzed and estimated the observed impact of intervention effects on PTB incidence in China. Both a non-interventional model and an interventional model with different levels were constructed to predict the future development of PTB incidence. These results can guide reasonable policies for strengthening the control of PTB and other infectious diseases.

COVID-19 is primarily a respiratory disease, and its causal virus (SARS-CoV-2) is mainly transmitted between people via respiratory droplets and contact routes. Limiting close contact between infected people and others is central to breaking the transmission of the virus [32]. Since January 2020, some of the strict strategies to prevent COVID-19 and reduce its spread in the public include wearing masks, living in rooms with good ventilation, having good hand hygiene, keeping physical distance, and avoiding crowded indoor gatherings. With strong government intervention, the COVID-19 outbreak has been well controlled in China [33], and the regular COVID-19 epidemic prevention and control protocol has been implemented since April 2020. Clinicians and researchers can apply knowledge from experiences with effective prevention and control of COVID-19 to prevent other infectious diseases, especially respiratory diseases. For example, the ultimate goal of public health interventions should be to reduce PTB burden through early detection and disruption of the chain of transmission [34]. Unfortunately, a study in China estimated that the current strategy has had a limited impact on the reduction of PTB incidence and mortality [12]. Nevertheless, as of June 2020, the average monthly mortality due to PTB in 2020 has dropped by 32.43% compared with that in the past 5 years in China [21]. In theory, effective strategies, such as maintaining social distance, wearing masks, and regular handwashing to prevent COVID-19, which are based on limiting close contact between infected people and uninfected people, could be helpful to control the spread of respiratory infectious diseases. Moreover, no definitive quantitative studies have been conducted to systematically assess the effects of other respiratory diseases that are transmitted from humans to humans via respiratory droplets and air, such as PTB. Our study provides a good avenue to quantify the potential effects of intervention strategies for preventing COVID-19 on PTB incidence. The modeling results indicated that if the implementation of some of the aforementioned measures are continued post-COVID-19, there may be positive effects in preventing other infectious diseases, such as PTB.

The potential effects of various intervention strategies on PTB were quantified using the ARIMA model, which is the most common time-series prediction model in statistical modeling. The ARIMA model has also been previously used in the field of infectious diseases [35, 36]. However, when the linear time series under study is disturbed by some external events known as an intervention, the forecasting performance of the ARIMA model may be affected. Model performance after such a disturbance can be improved by employing appropriate techniques, such as ARIMA intervention modeling. Intervention modeling is utilized to account for the impact of any unprecedented events in the time-series data. In this study, two models, namely, non-intervention and interventional models, were constructed to evaluate the impact of control measures implemented during the COVID-19 outbreak on PTB. If there had been no COVID-19 outbreak in China, according to the ARIMA model, PTB incidence from January 2020 to December 2020 would have been significantly higher than the actual PTB incidence observed during the COVID-19 outbreak (Table 1 and Additional file 3). These findings might be explained by the positive effect of China’s intervention strategies for stopping the public spread of SARS-CoV-2 on breaking the chains of transmission of Mycobacterium tuberculosis. Although the PTB incidence has been on a decreasing trend year by year in recent years and reached the lowest level in history in 2021 (Fig. 4), assuming China maintained these strict intervention strategies in 2020 and 2021, monthly PTB incidence would decrease at an average of 1.03 per 100,000 each month compared with the absence of interventions. Meanwhile, the annual incidence estimated with the non-interventional model was 64.71 per 100,000 in 2021, the annual incidence was 59.15 with the interventional model under regular intervention conditions, and the value would decline to 50.65 with the interventional model under strict intervention conditions. Considering that strict intervention is difficult to implement continuously, the regular intervention strategies are more conducive to promotion and implementation.

This study has several limitations. First, the analysis was based on the ARIMA model that was fitted with the epidemic data in China only. The model and the results must be validated with further prospective studies using large cohorts. Secondly, the incubation period for PTB is about three months or even longer, intervention strategies may cause the symptoms to appear later. Therefore, the prediction results should be comprehensively considered according to the actual situation. Finally, this study focused on the mixed effects of intervention measures. However, many confounding factors could have contributed to the reduction in PTB incidence. For example, recent research suggests that the COVID-19 pandemic has dramatically impacted TB diagnosis and case finding and has artificially decreased the number of TB cases in some countries including India, a country with a large number of PTB cases [22, 37, 38]. Therefore, the PTB cases used in this research were a measure of diagnosis instead of actual TB burden. Thus, these interventional measures would only affect those who would have had contracted PTB without the intervention, and the intervention is not effective for the treatment of patients with tuberculosis and for the prevention of reinfection of those with reactivation [39, 40].

Identifying any single-factor effect on preventing the development of the TB epidemic in China is challenging. Therefore, additional efforts are warranted to precisely evaluate the prevention effects of COVID-19-related social interventions on tuberculosis in China and other countries.

Interruption in the transmission of TB remains an important concern in China, a country with a high TB burden. Our data and modeling results suggested that the regular strategies implemented to control COVID-19 have also helped control the incidence of tuberculosis in China.

In summary, our findings have important implications for clinical and public health policies for tuberculosis prevention via the disruption of the chain of tuberculosis transmission. We recommend several strategies for the regular prevention of TB, including wearing of masks in endemic regions, provision of government-subsidized masks for crowded public places, maintaining good hand hygiene, avoiding large crowded indoor gatherings, and controlling the number of people in gatherings.

With the ARIMA prediction model, the knock-on effects of intervention strategies for COVID-19 on PTB incidence were successfully estimated. If the same intervention strategy for controlling the spread of COVID-19 were maintained in 2020, the monthly PTB incidence would have decreased on average by about 1.03 per 100,000 people each month compared with the incidence predicted by the non-interventional model. The annual incidence estimated without intervention was 64.71 per 100,000 in 2021, and the annual incidence was 59.15 under regular intervention. This value would decline to 50.65 with strict intervention. Combined with the feasibility of these strategies, these results suggested that continuous regular interventions may play important roles in the future prevention and control of PTB.