“Xinjiang Model” for tuberculosis prevention and control | IDR

Introduction

Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis that poses a serious health risk to humans and can involve almost all organs of the body, but pulmonary tuberculosis (PTB) is the most common. Tuberculosis is the leading cause of death from infectious diseases among adults worldwide, with more than 10 million new cases of tuberculosis each year.¹ China is one of the 30 high tuberculosis burden countries in the world, and according to the Global Tuberculosis Report 2023,² China accounted for 7.1% of the total global tuberculosis cases in 2022, after India (27%) and Indonesia (10%). China has made great efforts in the prevention and control of tuberculosis and has achieved some success, but TB prevention and management remains a challenging task.³ Xinjiang is one of the regions with the most serious tuberculosis hazards in the country, and according to the 2022 China Health and Health Statistics Yearbook, the incidence and mortality rates of tuberculosis in Xinjiang were 87.85/100,000 and 0.55/100,000, respectively,⁴ which are among the highest in the country. In order to curb the epidemiological trend of tuberculosis in Xinjiang, a series of measures such as active screening for tuberculosis, hospitalization of patients with infectious stage, and “nutritional breakfast” began to be comprehensively implemented in 2018 under the comprehensive coordination and policy support of the Xinjiang health department, forming a new model of tuberculosis prevention and control with Xinjiang’s characteristics, namely the “Xinjiang Model”.⁵

The “Xinjiang model” policy allows for the early detection of more tuberculosis patients through active case finding, avoiding further spread of the disease; inpatient management effectively controls the source of infection and ensures that medication is taken in full, regularly, in the right amount, and in combination, and with further nutritional support effectively improves the success rate of tuberculosis patient treatment. However, the implementation of this policy requires a certain amount of human and financial resources, which has had an impact on the financial expenditure and workload of local health departments. In the implementation of the “Xinjiang model” policy, it is important to summarize and analyze the determinants of the effectiveness of the implementation in order to guide the continuation of the policy.

In a previous study, it was found that the “Xinjiang model” policy had a significant effect on controlling the tuberculosis epidemic in Xinjiang.⁶ To promote sustainable and effective implementation of the “Xinjiang model”, it is important to promptly identify the factors affecting its effectiveness. Based on the previous study, this study analyzed the effectiveness of the Xinjiang model in Kashgar, a region with a high burden of tuberculosis in Xinjiang,^7,8 and its counties and cities, and further explored the factors influencing the effectiveness of the model based on two counties with poor and good implementation. Identifying and improving the factors affecting the effectiveness of the “Xinjiang model” will provide information for the continuous improvement and high quality of the new model of tuberculosis control in Xinjiang.

Materials and Methods

Study Design

We conducted a cross-sectional study divided into two phases. The first phase of the study was to retrospectively collect data on tuberculosis registrations in Kashgar before and after the implementation of the “Xinjiang model” policy, analyze the temporal trends in PTB registration incidence in Kashgar from 2012 to 2021, and evaluate and compare the effectiveness of the new model based on the rate of decline in registered incidence (the percentage of decline in registered incidence in 2021 compared to the average registered incidence before implementation) as well as the annual percentage of change. Phase 2: On the basis of comparing the implementation effect of the policy in 12 counties and cities in Kashgar, a county with better implementation effect (Zepu County) and a county with poorer implementation effect (Shache County) were selected as the investigation sites, and on-site questionnaire surveys were carried out on tuberculosis patients who had completed the tuberculosis treatment, to collect and analyze the factors that influenced the implementation effect in the two counties. The workflow of the study is shown in Figure 1.

Based on a large number of related literature, questionnaires and consulting experts in the field of tuberculosis prevention and control, the researchers designed the Questionnaire on Treatment Effect and Influencing Factors of Tuberculosis Patients. The questionnaire included: ① Individual information of PTB patients: gender, age, education level, type of medical insurance, distance between health service institution and residence; ② Treatment and outcome: whether anti-tuberculosis treatment is carried out according to doctor’s advice, whether “nutritional breakfast” is taken, whether there are side effects of drugs, and the effect of current health status compared with that before treatment; ③ Knowledge of TB prevention and treatment: according to the doctor’s requirements, the vast majority of tuberculosis can be cured, tuberculosis can be prevented and cured, and the state has a cost reduction policy for tuberculosis treatment (100% reimbursement for outpatient services and 90% reimbursement for hospitalization); ④ Treatment burden: discomfort caused by medication or injection of drugs, taking tuberculosis drugs on time every day, efforts to remember medication, etc. The 11 items of treatment burden in the questionnaire were derived from the Burden of Treatment Questionnaire developed by TRAN et al,9 which involves four dimensions: doctor visits and follow-ups, medication, healthcare-related behaviors and health issues, with each item scored from 0 to 10, with higher scores representing a higher degree of treatment burden, and scores ≥5 were considered to be a heavy burden of treatment for the purposes of this study.

Survey Method

Firstly, the tuberculosis specialists of each township health hospital or community health service centers in Shache and Zepu Counties verified whether the PTB patients included in the study were currently in the local area, and those who were in the local area were informed of the time and place of the on-site survey after obtaining their informed consent. After arriving at the designated survey site, PTB patients were surveyed face-to-face by uniformly trained investigators, who provided on-site guidance for filling out the questionnaires and verified the contents in a timely manner after the questionnaires were completed to ensure the accuracy and completeness of the data.

Statistical Processing

The database was established using EpiData 3.1 software, and the questionnaire was double-entered; Excel 2019 and SPSS 26.0 were used to collate and analyze data. Temporal trends in registered incidence were analyzed using Joinpoint Regression Software 4.9.0, and APC was calculated to quantify changes in annual registered incidence.^10,11 Qualitative data was described using the number of cases and the composition ratio (%), and the analysis of variance between groups was performed using χ² test. The test level was α=0.05.

Result

Temporal Distribution of PTB Registered Incidence in Kashgar Prefecture

2012–2021 PTB registered incidence in Kashgar Prefecture showed a trend of first rising and then decreasing, among which, it showed a significant upward trend from 2012 to 2018 (APC>0, PPFigure 2 and Table 1.

Table 1 Temporal Distribution of PTB Registered Incidence in Kashgar Prefecture, 2012–2021

Figure 2 Temporal trends in registered incidence in Kashgar Prefecture.

Temporal Distribution of PTB Registered Incidence in Counties and Cities of Kashgar Prefecture

Kashgar City and Bachu, Maigaiti, Shache, Shufu, Shule, Yecheng, Yingjisha, Yuepuhu, and Zepu Counties all showed a significant upward trend from 2012 to 2018 (APC>0, PPTable 2.

Table 2 Temporal Distribution of PTB Registered Incidence in Counties and Cities of Kashgar Prefecture, 2012–2021

Compared with the average registered incidence from 2012–2017, the registered incidence in 2021 in all counties and cities in Kashgar Prefecture decreased in all counties and cities except Shache County, among which, Shufu, Maigaiti, and Zepu Counties had a larger decline rate in 2021, which was 58.68%, 57.16%, and 54.02%, respectively, and registered incidence in 2021 in Shache County increased by 6.32%, as shown in Figure 3.

Figure 3 Decline rate of registered incidence before and after the implementation of the policy in the counties and cities of Kashgar Prefecture.

Analyze the Factors Influencing the Effect of Policy Implementation

Individual Information of Survey Subjects

Shache and Zepu Counties were selected to represent the areas with poor and good policy implementation effect, and PTB patients who completed the treatment were investigated by questionnaire. 338 PTB patients were investigated in Shache County, 163 of them were male (48.2%), 169 of them were aged ≥65 years (50.0%); 194 PTB patients were investigated in Zepu County, 104 of them were male (53.6%), 101 of them were aged ≥65 years (52.1%), no significant difference in gender and age distribution between the two areas (P>0.05). There was no statistically significant difference in the distribution of education level, type of medical insurance participation, and distance between health service institutions and places of residence between survey subjects in Shache and Zepu County (P>0.05), as shown in Table 3.

Table 3 Comparison of Individual Information of Survey Subjects in Shache and Zepu Counties n(%)

Treatment and Outcome of Survey Subjects

In Shache and Zepu County, 95.0% and 97.0% of the patients received anti-tuberculosis treatment according to the doctor’s advice, 99.1% and 99.5% of the patients took nutritional breakfast, and 25.1% and 23.7% of the patients had drug side effects during anti-tuberculosis treatment (P>0.05); the proportion of patients whose current health status was significantly improved compared with that before treatment was 36.4% and 63.9% respectively, which was significantly higher in Zepu County than in Shache County (PTable 4.

Table 4 Comparison of Treatment and Outcome for Survey Subjects in Shache and Zepu Counties n (%)

Knowledge of Tuberculosis Treatment Among Survey Subjects

In the tuberculosis treatment knowledge items, patients in Shache and Zepu Counties knew less than 90% about “adverse effects of tuberculosis medicines taken”, “irregular drug use may lead to incomplete cure of the disease or even relapse into drug-resistant tuberculosis”, and “irregular review may result in damage caused by drug side effects not being observed in time”. The awareness rates of patients in Shache County on “taking methods and precautions of tuberculosis drugs taken”, “adverse reactions of anti-tuberculosis drugs taken”, “irregular medication may lead to incomplete cure or even relapse into drug-resistant tuberculosis”, and “tuberculosis patients need regular reexamination during treatment” were 85.5%, 72.5%, 76.3% and 88.2% respectively, which were significantly lower than those in Zepu County (PTable 5.

Table 5 Comparison of Knowledge of Tuberculosis Treatment Among Survey Subjects in Shache and Zepu Counties n(%)

Treatment Burden of Survey Subjects

The factors with larger proportions of patients with heavy treatment burden in both Shache and Zepu Counties were discomfort caused by taking or injecting drugs, accounting for 12.8% and 8.7%, respectively; the differences in the proportions of patients with heavy burden of medical costs, examinations and tests required in tuberculosis treatment, and regular appointments for outpatient clinics and examinations in tuberculosis treatment were statistically significant between Shache and Zepu County (PTable 6.

Table 6 Comparison of Treatment Burden Among Survey Subjects in Shache and Zepu Counties n(%)

Discussion

The PTB registered incidence in Kashgar Prefecture increased significantly in the year when the “Xinjiang Model“ policy was implemented, and then decreased, reflecting that “Xinjiang Model” has a good effect in detecting and managing patients,3,12 which is helpful to control the epidemic situation of tuberculosis in Kashgar Prefecture. There are differences in the effect of policy implementation among different counties and cities in Kashgar Prefecture. The decline rate of registered incidence in Shufu and Zepu Counties is relatively large and presents a significant downward trend, while registered incidence in Shache County decreases slowly. From the overall point of view, considering that Shache County is the most populous county in Xinjiang, with a high population density and high population mobility, which may increase the risk of tuberculosis transmission; at the same time, Shache County also leads the region in the number of incidence cases of tuberculosis patients, and compared to other counties and cities, it may be more difficult to implement measures for the detection and management of patients in the process of implementing “Xinjiang model”, and the challenges faced may be more complex. These may be the reasons why the effect of policy implementation is not as obvious as in other counties and cities.

In order to explore the local factors affecting the effectiveness of “Xinjiang Model”, the study further compared the factors of difference between Zepu County, where the policy has been implemented more effectively, and Shache County, where it has been implemented less effectively. According to the treatment status of PTB in Zepu and Shache counties, the proportion of PTB patients who followed the doctor’s prescription for tuberculosis treatment and the proportion of PTB patients who took the “Nutritional Breakfast” were both ≥95.0%, which reflected that the “Xinjiang Model” policy was implemented better in the two regions. However, the proportion of patients in Zepu County who self-assessed that their current health status had significantly improved compared with that before treatment was greater than that in Shache County, which may suggest that the effectiveness of treatment was better in Zepu County than in Shache County, a difference that may stem from factors such as the allocation of healthcare resources, the level of healthcare technology, and the overall health awareness of patients. Therefore, it is necessary to rationalize the allocation of medical resources in different regions, improve the level of medical technology and strengthen health education.

Based on the knowledge of TB treatment, it was found that patients in Shache County were significantly less aware than those in Zepu County of how to take tuberculosis drugs, precautions, adverse reactions, and regular review during treatment. Related studies have shown that there is an inextricable relationship between tuberculosis patients’ knowledge of treatment and the risk of developing tuberculosis and treatment outcomes.^13–15 In addition, a study by Westerlund et al¹⁶ showed that low levels of tuberculosis-related knowledge independently predicted more than double the risk of tuberculosis relapse. Patients’ knowledge of tuberculosis treatment affects their attitudes and adherence to treatment, and when patients have a good understanding of the dangers of tuberculosis and the need for treatment, they can be motivated to be more active in receiving treatment and to follow medical advice more closely. At the same time, increased awareness of tuberculosis will also encourage patients and their families to take active preventive and curative measures to reduce the spread of tuberculosis. Given that the World Health Organization has proposed “building strong alliances with social organizations and communities” as one of the principles of the End the Tuberculosis Epidemic Strategy,¹⁷ a systematic review has shown that community engagement interventions can be effective in promoting infectious disease control in low- and lower-middle-income countries.¹⁸ Therefore, healthcare institutions should join forces with the community to strengthen publicity and education on tuberculosis, and radio and television can be used to provide tuberculosis education specifically to urban and rural residents, in order to improve patients’ and community residents’ knowledge of tuberculosis, especially to enhance patients’ understanding of how to take tuberculosis drugs, adverse reactions, precautions, and so on, which can help improve patients’ treatment compliance and reduce the spread of the disease. There is also a need for training and continuous retraining of healthcare workers, especially community and rural healthcare workers, so that they can educate the public about tuberculosis at every opportunity.^19,20

Studies have shown that treatment burden is another important factor affecting the effectiveness of policy implementation, and treatment burden refers to the amount of work that patients must cope with in order to take care of their health and its impact on their daily lives.^21,22 The factors that make the treatment burden of tuberculosis patients in Shache and Zepu Counties relatively large are the side effects of drugs, some anti-tuberculosis drugs may cause serious adverse reactions, such as liver function damage, neurological damage and so on, and these side effects will affect the patient’s adherence to the treatment and even lead to interruption of treatment, which affects the effectiveness of the prevention and treatment of tuberculosis. The study of Pradipta et al²³ mentioned that a reasonable way to address this burden by involving pharmacists directly in tuberculosis management, educating, monitoring and evaluating drug use according to the principles of pharmaceutical care. In addition, the cost of treatment is another important burden of care for tuberculosis patients in Shahe County. Tuberculosis is a disease associated with poverty, and most tuberculosis patients are from poor families.²⁴ Although patients are entitled to 90% reimbursement of medical expenses during hospitalization, the hospitalization period of two months or more, during which they are unable to work and thus reduce or lose their source of income, and the 10% out-of-pocket payment of medical expenses are still unaffordable for some patients with limited financial status, which leads to a decrease in the motivation of and cooperation with the patients in treatment, and thus affects the continuity and effectiveness of the treatment. Studies have shown that increasing social protection coverage is one of the key measures to reduce the incidence of tuberculosis,^25–27 and that socioeconomic support for tuberculosis is effective in improving tuberculosis treatment outcomes.²⁸ Therefore, the government and healthcare organizations should also provide more support and assistance, including providing more healthcare subsidies, reducing or waiving part of the treatment costs or establishing a special fund to support these patients, and further increasing the coverage of social security.

This study is of great practical value in sustaining and improving the tuberculosis control model in Xinjiang, as well as in achieving the goal of ending tuberculosis, but there are still some shortcomings. Firstly, the COVID-19 pandemic has led to a reduction or restriction in the provision of anti-tuberculosis services to a certain extent,²⁹ for example, due to the crowding out of healthcare resources and social isolation measures, which led to the slowing down or delaying of active case-finding measures, and the impossibility of implementing inpatient treatment for some patients with infectious stage tuberculosis, thus affecting registered incidence of tuberculosis. Secondly, this study is a quantitative study based on a questionnaire to collect factors influencing the implementation of the “Xinjiang model”, which may have missed some potential influences. Considering that the results of the combined qualitative study could be useful for the development of interventions and policies,³⁰ the research team will continue to conduct qualitative studies to supplement and explain the results of the quantitative study.

Conclusions

The “Xinjiang model” can effectively control the current situation of tuberculosis epidemic in Kashgar, and there are differences in the effectiveness of policy implementation among different regions. The knowledge of tuberculosis treatment, adverse reactions to tuberculosis drugs, and treatment costs are the main factors affecting the effectiveness of the “Xinjiang model”. It is recommended that regions where the policy has not been well implemented take targeted improvement measures, including strengthening publicity about tuberculosis prevention and treatment; and improving the level of medical treatment in tuberculosis sentinel hospitals, especially in the handling of adverse reactions to medication and the ability to adjust medication. In addition, government needs to further increase its support for tuberculosis prevention and treatment, so as to reduce the financial burden of tuberculosis patients in their treatment and provide them with better medical protection and services.

Abbreviations

PTB, Pulmonary tuberculosis; APC, Annual percentage change.

Data Sharing Statement

The datasets used and analyzed during the current study are not publicly available, but they are available from the corresponding author upon reasonable request.

Ethics Approval and Consent to Participate

The study was approved by the Ethics Committee of Xinjiang Medical University (XJYKDXR20230303016) and was conducted in accordance with the guiding principles of the Declaration of Helsinki. Informed consent was obtained from participants and all personal data were kept confidential.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

This research was supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region (grant number 2023D01C57), National Natural Science Foundation of China (grant number 82060622), and open Project of State Key Laboratory of Causes and Prevention of High Incidence in Central Asia Co-constructed by Province and Ministry (grant number SKL-HIDCA-2023-16).

Disclosure

The authors declare that they have no competing interests in this work.

References

1. Furin J, Cox H, Pai M. Tuberculosis. Lancet. 2019;393(10181):1642–1656. doi:10.1016/S0140-6736(19)30308-3

2. World Health Organization. Global tuberculosis report 2023; 2023. Available from: https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2023. Accessed June 17, 2024.

3. Hu M, Feng Y, Li T, et al. Unbalanced risk of pulmonary tuberculosis in china at the subnational scale: spatiotemporal analysis. JMIR Public Health Surveill. 2022;8(7):e36242. doi:10.2196/36242

4. National, Health, Commission. 2022 China Health Statistics Yearbook. Beijing: Peking Union Medical College Press; 2022.

5. Wang S, Liu N, Wang X, Cao M, Wang L, Wang X. Development and effectiveness of “xinjiang model” for tuberculosis prevention and control. Chin J Antitubercul. 2024;2:1–7.

6. Zhang Y, Wang X, Liu N, Wang S, Wang X, Cao M. Intervention effect of new tuberculosis control model on tuberculosis incidence in Xinjiang. Infect Drug Resist. 2023;2023:7485–7496. doi:10.2147/IDR.S441899

7. Tusun D, Abulimiti M, Mamuti X, et al. The epidemiological characteristics of pulmonary tuberculosis – Kashgar Prefecture, Xinjiang uygur autonomous region, China, 2011–2020. China CDC Wkly. 2021;3(26):557–561. doi:10.46234/ccdcw2021.144

8. Chen X, Emam M, Zhang L, Rifhat R, Zhang L, Zheng Y. Analysis of spatial characteristics and geographic weighted regression of tuberculosis prevalence in Kashgar, China. Prev Med Rep. 2023;35:102362. doi:10.1016/j.pmedr.2023.102362

9. Tran VT, Harrington M, Montori VM, Barnes C, Wicks P, Ravaud P. Adaptation and validation of the Treatment Burden Questionnaire (TBQ) in English using an internet platform. BMC Med. 2014;12:109. doi:10.1186/1741-7015-12-109

10. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017;390(10114):2769–2778. doi:10.1016/S0140-6736(17)32448-0

11. Desai MM, Cacciamani GE, Gill K, et al. Trends in incidence of metastatic prostate cancer in the US. JAMA Network Open. 2022;5(3):e222246. doi:10.1001/jamanetworkopen.2022.2246

12. Zhen-jiang L, Yi H, Wei S; Diermulati·Tu-sun, MAIWEILANJIANG·A-bu-li-mi-ti. Analysis of the epidemiological characteristics of pulmonary tuberculosis in Kashgar, Xinjiang UygulAutonomous Region from 2011 to 2020. J Trop Dis Parasitol. 2023;21(02):93–97+101.

13. Vericat-Ferrer M, Ayala A, Ncogo P, et al. Knowledge, attitudes, and stigma: the perceptions of tuberculosis in Equatorial Guinea. Int J Environ Res Public Health. 2022;19(14):8227. doi:10.3390/ijerph19148227

14. Gautam N, Karki RR, Khanam R, Hasnain SE. Knowledge on tuberculosis and utilization of DOTS service by tuberculosis patients in Lalitpur District, Nepal. PLoS One. 2021;16(1):e0245686. doi:10.1371/journal.pone.0245686

15. Kigozi NG, Heunis JC, Engelbrecht MC, Janse van Rensburg AP, van Rensburg H. Tuberculosis knowledge, attitudes and practices of patients at primary health care facilities in a South African metropolitan: research towards improved health education. BMC Public Health. 2017;17(1):795. doi:10.1186/s12889-017-4825-3

16. Westerlund EE, Tovar MA, Lönnermark E, Montoya R, Evans CA. Tuberculosis-related knowledge is associated with patient outcomes in shantytown residents; results from a cohort study, Peru. J Infect. 2015;71(3):347–357. doi:10.1016/j.jinf.2015.05.010

17. World Health Organization. Guidance on engagement of communities and civil society to end tuberculosis. Available from: https://www.who.int/publications/i/item/9789240080294. Accessed October 10, 2023.

18. Questa K, Das M, King R, et al. Community engagement interventions for communicable disease control in low- and lower- middle-income countries: evidence from a review of systematic reviews. Int J Equity Health. 2020;19(1):51. doi:10.1186/s12939-020-01169-5

19. Bashorun AO, Linda C, Omoleke S, et al. Knowledge, attitude and practice towards tuberculosis in Gambia: a nation-wide cross-sectional survey. BMC Public Health. 2020;20(1):1566. doi:10.1186/s12889-020-09685-3

20. Guo G, Zheng Y, Ma X, et al. eDOTS: improving the treatment of pulmonary tuberculosis in Xinjiang, China. Infect Drug Resist. 2023;16:7497–7505. doi:10.2147/IDR.S438962

21. Ting NCH, El-Turk N, Chou MSH, Dobler CC, Gopichandran V. Patient-perceived treatment burden of tuberculosis treatment. PLoS One. 2020;15(10):e0241124. doi:10.1371/journal.pone.0241124

22. Dobler CC, Harb N, Maguire CA, Armour CL, Coleman C, Murad MH. Treatment burden should be included in clinical practice guidelines. BMJ. 2018;363:k4065. doi:10.1136/bmj.k4065

23. Pradipta IS, Idrus LR, Probandari A, et al. Barriers and strategies to successful tuberculosis treatment in a high-burden tuberculosis setting: a qualitative study from the patient’s perspective. BMC Public Health. 2021;21(1):1903. doi:10.1186/s12889-021-12005-y

24. Huang Y, Huang J, Su X, et al. Analysis of the economic burden of diagnosis and treatment on patients with tuberculosis in Bao’an district of Shenzhen City, China. PLoS One. 2020;15(8):1.

25. Carter DJ, Glaziou P, Lönnroth K, et al. The impact of social protection and poverty elimination on global tuberculosis incidence: a statistical modelling analysis of sustainable development goal 1. Lancet Glob Health. 2018;6(5):e514–e522. doi:10.1016/S2214-109X(18)30195-5

26. Ling Z, Changfeng L, Xia S, Xu W, Shijing F. Survey on socio-economics of tuberculosis in Sanya area of Hainan province and analysis of factors affecting cure. Chin J Health Statist. 2023;40(05):762–764.

27. Nidoi J, Muttamba W, Walusimbi S, et al. Impact of socio-economic factors on Tuberculosis treatment outcomes in north-eastern Uganda: a mixed methods study. BMC Public Health. 2021;21(1):2167. doi:10.1186/s12889-021-12056-1

28. Klein K, Bernachea MP, Irribarren S, Gibbons L, Chirico C, Rubinstein F. Evaluation of a social protection policy on tuberculosis treatment outcomes: a prospective cohort study. PLoS Med. 2019;16:4.

29. Long Q, Huang F, Huan ST, Zhao YL. Scale-up of a comprehensive model to improve tuberculosis control in China: lessons learned and the way forward. Infect Dis Poverty. 2021;10(1):41. doi:10.1186/s40249-021-00828-1

30. de Vries SG, Cremers AL, Heuvelings CC, et al. Barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review of qualitative literature. Lancet Infect Dis. 2017;17(5):e128–e143. doi:10.1016/S1473-3099(16)30531-X