Addressing the Burden and Detection Gap of Latent Tuberculosis Infection in Schoolchildren and Adolescents in China: A Cross-sectional Study

doi:10.21203/rs.3.rs-4320976/v1

Download PDF

Research Article

Addressing the Burden and Detection Gap of Latent Tuberculosis Infection in Schoolchildren and Adolescents in China: A Cross-sectional Study

https://doi.org/10.21203/rs.3.rs-4320976/v1

This work is licensed under a CC BY 4.0 License

Journal Publication

published 16 Sep, 2024

Read the published version in BMC Infectious Diseases →

You are reading this latest preprint version

Background

The latent tuberculosis infection (LTBI) burden is still unclear in schoolchildren and adolescents in China. Previous study and daily surveillance data indicate a LTBI detection gap. The research objective was to evaluate the LTBI burden and detection gap among schoolchildren and adolescents in China.

Methods

A cross-sectional study was conducted among 69667 schoolchildren and adolescents in Chongqing, China between September 2022 and December 2023 implemented by Chongqing Municipal Institute of Tuberculosis using tuberculin skin test (TST) and creation tuberculin skin test (C-TST). To evaluate the LTBI detection gap, the pulmonary tuberculosis (PTB) screening data implemented by Chongqing Municipal Institute of Tuberculosis have been compared with the data in 2021 implemented by community-level medical and health care institutions.

Results

the LTBI prevalence rate using TST and C-TST implemented by Chongqing Municipal Institute of Tuberculosis was 12.7% (95%CI, 12.5%-13%) and 6.4% (95%CI, 6%-6.8%) respectively. The LTBI prevalence rate by Chongqing Municipal Institute of Tuberculosis was 9.6% higher than that by community-level medical and health care institutions (χ² = 2931.9, P < 0.001).

Conclusions

The LTBI detection gap existed among schoolchildren and adolescents in Chongqing, and it also may exist in other similar countries and regions. National screening strategy needs improvement. Regular training and quality assurance could improve the performance of TST and C-TST and close the detection gap of LTBI.

Tuberculosis

Child

Adolescent

Latent tuberculosis

Tuberculin Test

Tuberculosis (TB) is the major cause of death in children and adolescents in infectious diseases worldwide. Children and adolescents with LTBI are a large reservoir for active TB, and proactive intervention of LTBI is a key part of the WHO End TB Strategy [1].

The cumulative number of children treated between 2018 and 2021 was 1.9 million, which was 54% of the five-year target of 3.5 million set at the UN high level meeting in 2018, and preventive treatment target has only been achieved by 42% [2]. LTBI is defined as a state of being infected with Mycobacterium TB without clinical evidence of active TB [3]. Sufficient detection of LTBI is the basis of TB prevention and control, especially for schoolchildren and adolescents.

China is one of the 30 high TB burden countries, and has the third largest numbers of cases accounting for 7.1% of the global total [2]. The LTBI burden is still unclear in schoolchildren and adolescents in China. Three national tuberculosis prevalence surveys done in 1990, 2000, and 2010 excluded children under 14 years [4]. A study has been conducted to estimate the LTBI burden in China in 2021, and the prevalence of LTBI in people five years old and above was 18.1% [5], but the study did not provide complete LTBI burden in schoolchildren and adolescents.

In China, PTB screening in schoolchildren and adolescents is widely carried out at schools. The majority of PTB screening are carried out by community-level medical and health care institutions, which have not received regular standardized training and quality control. This issue has not received adequate attention in provincial tuberculosis prevention and control policies. It was also found that there may be a LTBI detection gap from daily surveillance system and previous investigation. The LTBI burden and detection gap among schoolchildren and adolescents needs comprehensive investigations.

Study design

This was a cross-sectional study using stratified cluster random sampling, which was conducted among schoolchildren and adolescents in Chongqing, China between September 2022 and December 2023 by Chongqing Municipal Institute of Tuberculosis. A standardized quality control system for active PTB screening was developed. On this basis, we evaluated the LTBI burden and detection gap among schoolchildren and adolescents.

According to the local policy of Chongqing, Junior One, Senior One and Senior Two students should be screened for active PTB. The participants were tested using TST or novel skin tests for tuberculosis infection (TBST). TST remains the most widely used tool at a global scale. According to China national diagnostic criteria for TB [6], the results of TST are divided into four levels: negative(the induration average diameter < 5mm), generally positive(5mm ≤ the induration average diameter < 10mm), moderately positive(10mm ≤ the induration average diameter < 15mm), and strongly positive(the induration average diameter ≥ 15mm). Bacillus Calmette-Guérin (BCG) vaccination at birth is a national policy in China, and coverage has been at a high level, which might interfere with TST reactivity. Considering this, the TST induration cut-off point of ≥ 15mm was used to indicate TB infection in school [7, 8].

C-TST is a type of TBST, which uses a new type of recombinant fusion protein that only contains Mycobacterium TB early secretory antigen target six (STAT-6) and culture filtrate protein ten (CFP10), and exposure to previous BCG vaccine will not interfere with the C-TST reactivity. The C-TST induration or erythema cut-off point of ≥ 5mm has been commonly recommended for TB infection. TST or C-TST has been selected according to the wishes of local health department and schools.

The annual risk of tuberculous infection (ARTI) was evaluated, which was the probability of acquiring new tuberculous infection over a period of one year. In the classical approach, the annual rate of infection was estimated using the equation:

P is the TST strongly positive rate or C-TST positive rate, and age is the mean age of the cohort [9].

Sample Size

According to the the previous PTB screening investigation in schoolchildren and adolescents by Chongqing Municipal Institute of Tuberculosis, the LTBI prevalence rate is about 15%. The sample size was estimated at 13401 schoolchildren and adolescents using the following formula, based on the expected LTBI prevalence rate of 15%, the allowable error of 1%, and the significance level of 5%.

Randomisation and Cluster Selection

This study used stratified cluster random sampling. According to the division of local government, there were four regions in Chongqing including: the Central Urban Districts, New West Urban Development Districts, Northeast Districts and Southeast Districts. These regions were different in terms of socioeconomic development. Clusters were defined as middle schools located in the four districts. Each cluster had at least 500 participants registered between September 2022 and December 2023.

Study participants

The inclusion criteria were as follows: (1) participants in school at least ten years old, and (2) participants who can participate in the entire PTB screening process. The exclusion criteria were as follows: (1) participants with allergic constitution, (2) participants with acute infectious diseases or other diseases judged by doctors that TST or C-TST can not be performed, (3) participants who have been vaccinated in the last month, (4) previous TB patients, and (5) TST or C-TST has been implemented in the last three months.

According to the inclusion and exclusion criteria, participants were continuously selected from the selected clusters until they were fully enrolled.

Procedures

Standardized training was provided for all medical workers involved in this study, including public health and clinical theory, as well as TST and C-TST practical skill. The trainees were assessed, and only those who pass the assessment can implement PTB screening.

For each enrolled participant, socio-demographic information was collected, including age, gender and educational level.

PTB screening mainly includes a consultation on close contact history with PTB patients and suspicious symptoms of PTB, a TST test/C-TST test, and a chest X-ray examination.

TST and C-TST were was performed according to the Mantoux technique. When performing TST (Purified Protein Derivative of Tuberculin; Xiang Rui, China or Chengdu Institute of Biology, China), 0.1 mL (5IU) purified protein derivative of tuberculin was injected on the volar surface of the left forearm intradermally. The induration was measured in millimeter after 72 hours at injection sites.

When performing C-TST (Recombinant Mycobacterium Tuberculosis Fusion Protein; Zhifei Longcom Biologic Pharmacy Company, Anhui, China), 0.1 mL (5U) recombinant mycobacterium TB fusion protein was injected on the volar surface of the left forearm intradermally. The induration or erythema was measured in millimeter after 48 hours at injection sites.

Digital chest radiography was performed on each participant with suspected symptoms of PTB, who was TST strong positive or C-TST positive, and who met the exclusion criteria. Those with abnormal digital chest radiography went to designated medical institutions for further examination.

The LTBI detection gap

To evaluate LTBI detection gap, we collected PTB screening data implemented by community-level medical and health care institutions in the same schools selected in this study in 2021, which have been compared with the data implemented by Chongqing Municipal Institute of Tuberculosis between September 2022 and December 2023.

Statistical analysis

We calculated the proportion and 95% CI for the LTBI prevalence rate, which was the proportion of schoolchildren and adolescents with LTBI excluding active PTB. Different LTBI prevalence rates were tested using chi-square test. The trend of rate was tested using chi-square test for linear trend. Some participants were unable to verify the TST or C-TST results due to leave or other reasons, resulting in missing data. To evaluate the impact of missing data, we compared the distribution of gender, grade, region and school type between participants with and without the TST or C-TST results by chi-square test. A two-sided P < 0.05 was taken as statistically significant. Statistical analyses were performed with the SPSS 22.0 software (SPSS, Inc., Chicago, IL, USA).

The screening process for participants

There were 69667 participants in 51 schools in Chongqing between September 2022 and December 2023, and 4786 (6.9%) were excluded for various reasons leaving 64881 (93.1%) participants with TST or C-TST result (Fig. 1).

There are 41 schools using TST (48583 participants with results), and ten schools using C-TST (16298 participants with results). Participants who were unable to verify the TST or C-TST results due to leave or other reasons were excluded from statistical analysis considering that these missing data were completely random and had a low proportion of 0.4% (279/65160). In addition, there was no difference in the distribution of gender, grade, region and school type between participants with and without the TST or C-TST results (appendix p 2).

PTB screening results

The LTBI prevalence rate using TST and C-TST was 12.7% (95%CI, 12.5%-13%) and 6.4% (95%CI, 6%-6.8%) respectively (Tables 1 and 2). The LTBI prevalence rate using TST was significantly higher than that using C-TST (χ² = 492.7, P < 0.001).

Table 1

Schoolchildren and adolescents PTB screening results using TST by our PTB screening team between September 2022 and December 2023 in Chongqing
Characteristics	Subgroup	TST
Characteristics	Subgroup	Participants with TST implemented	Participants without result	TST Strongly Positive	Active PTB	LTBI prevalence rate	95% CI
Gender	Male	25295	94	2969	8	11.8%	11.4%-12.2%
	Female	23487	105	3240	8	13.8%	13.4%-14.3%
Grade	Junior One	6921	30	575	1	8.3%	7.7%-9%
	Senior One	20700	88	2475	3	12%	11.6%-12.4%
	Senior Two	21161	81	3159	12	14.9%	14.5%-15.4%
Region	Central Urban Districts	18778	84	2382	2	12.7%	12.3%-13.2%
	New West Urban Development Districts	13875	63	1800	1	13%	12.5%-13.6%
	Northeast Districts	6755	24	469	3	6.9%	6.3%-7.5%
	Southeast Districts	9374	28	1558	10	16.6%	15.8%-17.3%
School type	Public school	33868	150	4096	13	12.1%	11.8%-12.5%
	Private school	14914	49	2113	3	14.2%	13.6%-14.8%
Total		48782	199	6209	16	12.7%	12.5%-13%

Table 2

Schoolchildren and adolescents PTB screening results using C-TST by by our PTB screening team between September 2022 and December 2023 in Chongqing
Characteristics	Subgroup	C-TST
Characteristics	Subgroup	Participants with C-TST implemented	Participants without result	C-TST Positive	Active PTB	LTBI prevalence rate	95% CI
Gender	Male	8897	45	603	8	6.7%	6.2%-7.2%
	Female	7481	35	454	3	6.1%	5.5%-6.6%
Grade	Junior One	746	5	36	0	4.9%	3.3%-6.4%
	Senior One	7410	45	448	4	6%	5.5%-6.6%
	Senior Two	8222	30	573	7	6.9%	6.4%-7.5%
Region	Central Urban Districts	4255	21	162	1	3.8%	3.2%-4.4%
	New West Urban Development Districts	-	-	-	-	-	-
	Northeast Districts	2664	14	147	0	5.5%	4.7%-6.4%
	Southeast Districts	9449	35	748	10	7.8%	7.3%-8.4%
School type	Public school	11837	54	864	10	7.3%	6.8%-7.7%
	Private school	4541	26	193	1	4.3%	3.7%-4.8%
Total		16378	80	1057	11	6.4%	6%-6.8%

The detection rate of active PTB in participants using TST was 32.9 cases per 100000 population (16/48583), and the detection rate of active PTB in participants using C-TST was 67.5 cases per 100000 population (11/16298). There was not a significant difference in detection rate of active PTB in participants using TST or C-TST (χ² = 3.5, P = 0.06).

The TST strongly positive rate has increased significantly from 8.3% in Junior One to 15% in Senior Two (χ² trend = 223.6, P < 0.001) .The C-TST positive rate has also increased significantly from 4.9% in Junior One to 7% in Senior Two (χ² trend = 8.6, P = 0.003) .

The LTBI detection gap

There were 47320 participants with TST result in the same schools of this study in 2021. The LTBI prevalence rate using TST by community-level medical and health care institutions was 3.2% (95%CI, 3.1%-3.4%) in 2021 (Table 3).

Table 3

Schoolchildren and adolescents PTB screening results using TST by community-level medical and health care institutions in 2021 in Chongqing
Characteristics	Subgroup	TST
Characteristics	Subgroup	Participants with result	TST Strongly Positive	Active PTB	LTBI prevalence rate	95% CI	χ²	P^‡
Grade	Junior One	7233	201	1	2.8%	2.4%-3.1%	211	< 0.001
	Senior One	24397	629	1	2.6%	2.4%-2.8%	1545.8	< 0.001
	Senior Two	15690	702	0	4.5%	4.2%-4.8%	1050.2	< 0.001
Region	Central Urban Districts	5901	104	0	1.8%	1.4%-2.1%	594.4	< 0.001
	New West Urban Development Districts	20659	969	0	4.7%	4.4%-5%	778.7	< 0.001
	Southeast Districts	12174	133	2	1.1%	0.9%-1.3%	473.7	< 0.001
	Northeast Districts	6718	149	0	2.2%	1.9%-2.6%	857.5	< 0.001
School type	Public school	37025	1319	2	3.6%	3.4%-3.7%	1831.8	< 0.001
	Private school	10295	213	0	2.1%	1.8%-2.3%	1067.4	< 0.001
Total		47320	1532	2	3.2%	3.1%-3.4%	2931.9	< 0.001

The LTBI prevalence rate by Chongqing Municipal Institute of Tuberculosis was 9.6% higher than that by community-level medical and health care institutions(χ² = 2931.9, P < 0.001), and there were also similar trends in LTBI prevalence rate in each subgroup (Fig. 2). The risk factors associated with LTBI were analyzed, and the LTBI prevalence rate in Southeast Districts by Chongqing Municipal Institute of Tuberculosis was the highest (appendix p 3). The LTBI detection gap in Southeast Districts was also the greatest, reaching 15.5%.

The ARTI of schoolchildren and adolescents

the ARTI using TST and C-TST was 0.9% (95%CI, 0.8%-1%) and 0.4% (95%CI, 0.3%-0.5%) respectively ( Table 4).

Table 4

ARTI in schoolchildren and adolescents between September 2022 and December 2023 in Chongqing
Subgroup	TST					C-TST
Subgroup	mean age ± s	ARTI	95% CI	χ²	P	mean age ± s	ARTI	95% CI	χ²	P
Male	15.6 ± 1.4	0.8%	0.7%-0.9%	3.4	0.07	15.9 ± 1.1	0.4%	0.3%-0.6%	0.14	0.81
Female	15.5 ± 1.5	1.0%	0.8%-0.11%	3.4	0.07	15.8 ± 1.1	0.4%	0.3%-0.5%	0.14	0.81
Junior One	12.7 ± 0.9	0.7%	0.5%-0.9%	6.2	0.04	13 ± 1.6	0.4%	0.1%-0.9%	0.1	0.95
Senior One	15.5 ± 0.7	0.8%	0.7%-0.9%			15.6 ± 0.8	0.4%	0.3%-0.6%
Senior Two	16.5 ± 0.8	1%	0.8%-1.1%			16.3 ± 0.7	0.4%	0.3%-0.6%
Central Urban Districts	15.2 ± 1.7	0.9%	0.8%-1%	23.8	< 0.001	15.9 ± 0.8	0.2%	0.1%-0.4%	6.14	0.04
New West Urban Development Districts	16.1 ± 0.9	0.9%	0.7%-1.1%			-	-	-
Northeast Districts	15.9 ± 0.9	0.5%	0.3%-0.6%			16.1 ± 1.1	0.4%	0.1%-0.6%
Southeast Districts	15.3 ± 1.6	1.2%	1%-1.6%			15.8 ± 1.2	0.5%	0.4%-0.7%
Public school	15.1 ± 1.5	0.9%	0.8%-1%	0.65	0.43	15.9 ± 1.1	0.5%	0.4%-0.6%	3.4	0.08
Private school	16.4 ± 0.8	0.9%	0.8%-1%	0.65	0.43	15.8 ± 1	0.3%	0.1%-0.4%	3.4	0.08
Total	15.6 ± 1.5	0.9%	0.8%-1%			15.9 ± 1.1	0.4%	0.3%-0.5%

There was a significant difference in ARTI using TST among different grades (χ² = 6.2, P = 0.04), and the ARTI in Senior Two was the highest. There was also a significant difference in ARTI using TST in different regions (χ² = 23.8, P < 0.001), and the ARTI in Southeast Districts was the highest. There was also a significant difference in ARTI using C-TST in different regions (χ² = 6.1, P = 0.04), and the ARTI in Southeast Districts was the highest.

One key challenge in TB prevention and control is to accurately find students infected with TB among schoolchildren and adolescents. Through this study, we have obtained accurate LTBI burden among them in Chongqing.

In this study, the LTBI prevalence rate conducted by Chongqing Municipal Institute of Tuberculosis using TST between September 2022 and December 2023 was 9.6% higher than the results conducted by community-level medical and health care institutions in the same schools in 2021. The quality of PTB screening implemented by community-level medical and health care institutions may be poor. The reduction of the reported number of TST strong positive schoolchildren and adolescents has significantly decreased the detection of active PTB and LTBI, which may result in more community transmission. According to Statistical Bulletin on National Economic and Social Development in Chongqing of 2021, the total number of middle school students in Chongqing was 1.77 million, which may mean a LTBI detection gap of 0.17 million middle school students who were not detected and intervened timely in Chongqing.

This detection gap may not happen only in Chongqing. A study found that the TST strong positive rate was 2.69% among 16795 freshmen in senior high schools and boarding junior high schools in 2019 in Ningbo, Zhejiang Province, China [10], and the TST strong positive rate was 1.45% among 78102 freshmen in the same population of the same area in 2021 [11]. The PTB screening among 220269 freshmen in senior high schools and boarding junior high schools showed that the TST strong positive rate was 1.70% from 2016 to 2020 in Liuzhou, Guangxi Province, China [12]. The TST strong positive rate was 0.36% among 20153 students in Longgang District, Shenzhen, China in 2021 [13]. Two studies in Beijing showed that the TST strong positive rate was 2.59% among 6187 freshmen in 2018, and 1.86% among 12562 freshmen in 2020 respectively [14, 15]. The TST strong positive rates in these studies were lower than our results, which may be due to the lower PTB burden in these regions or the existence of a LTBI detection gap. The reported incidence rate of active PTB was about 48 cases per 100000 population in Chongqing, which currently ranks 13th among all provinces in 2023 in China according to national TB surveillance system, and the reported PTB incidence rate of the above provinces was about 23–68 cases per 100000 population. It was unreasonable to explain such a low TST strong positive rate using the reason that the PTB burden in these regions was far lower than that in Chongqing.

Our study conducted standardized training for medical workers. During the training process, it was found that the reasons for this detection gap may include non-standard TST administration and inaccurate TST result reading, and inaccurate TST reading may have the greatest impact on this detection gap, which may be due to the reader's incorrect understanding of the operation rules and rusty practical skills.

Research on TST quality control is rare. A study has noticed the limitations of TST quality, which included reader variability and the need for trained personnel to read the results [16]. A study has found that TST reading results vary very much between readers [17]. Although a large number of schoolchildren and adolescents underwent TST every year, the TST quality might be seriously underestimated. With the development of information technology, intelligent software for TST or TBST result reading may also be developed to improve the accuracy. Regular training and quality assurance are needed to establish, and maintaining proficiency is equally important. A study has found that mhealth approach using smartphone may be a method that could serve as a TST training and quality control tool in many settings [18].

This study used two skin test methods, TST and C-TST. However, C-TST was approved for TB diagnosis in China in 2020, and has not been widely used in China. This study obtained the LTBI prevalence rate using C-TST, and the C-TST positive rate was lower than the TST strong positive rate. BCG vaccination might have accounted for a considerable proportion of positive TST [19]. A study using C-TST showed that the positive rate was 10.14% (14/157) in 2022 in a high school in southeast of Chongqing [20]. YANG Zhen et al [21] have found that C-TST positive rate was 9.1% among 1924 college students in 2022 in Beijing, China. MU Tingmei et al [22] showed that C-TST positive rate was 0.97% among 7416 junior middle school students and 1.1% among 2555 high school students respectively in 2021 in Yaan City, Sichuan Province, China. There were still differences in the C-TST positive rates conducted in different regions, and there was also a possibility of LTBI detection gap.

The TST strongly positive rate and C-TST positive rate has increased significantly from Junior One to Senior Two in Chongqing. Other studies have also shown that the TST positive rate has increased with age in schoolchildren and adolescents [10, 11, 12, 14]. Most provinces of China do not implement PTB screening for Senior Two in high school, and it is important to add a PTB screening in Senior Two, so as to prevent students from being unable to participate in the college entrance examination because of PTB.

In 2022, the reported PTB incidence rate of schoolchildren and adolescents aged 10–19 of Chongqing was 23.77 cases per 100000 population per year according to the national TB surveillance system, which was less than the actual incidence rate. In this study, the overall prevalence of LTBI using TST was 12.7% (95% CI, 12.5%-13%) with a corresponding ARTI of 0.9% (95% CI, 0.8%-1%). If we assume 5% rapid progression from recent infection to active TB [23], and 0.05% annual progression rate from remote infection to active TB [24], incidence rate can be measured: 0.9%×5%+12.7%×0.05%=51.4 cases per 100000 population per year [9]. According to a study in Chongqing in 2021, the PTB screening proportion of freshmen in middle school is only 42.4%, indicating that there were still some PTB patients who have not been found in time [25]. Under these assumptions, the ARTI obtained in this study using TST may reflect the current situation.

Using the same method, estimated incidence rate using C-TST was 23.2 cases per 100000 population per year. The estimated incidence rate using C-TST may be underestimated using the Styblo’s rule [23, 26]. Considering the universal vaccination of BCG in China and the lower false positive rate of C-TST, the progression rate should be higher than 5% in LTBI using C-TST [26].

This study has limitations. There were no schools in Northeast Districts that conducted C-TST. The PTB screening in schoolchildren and adolescents has not been systematically implemented before 2022, resulting in the data from routine surveillance system were limited. Lack of gender and some information in routine surveillance system before 2022 made it impossible to conduct related analysis.

This study obtained accurate LTBI burden using TST and C-TST in schoolchildren and adolescents in Chongqing, China. The LTBI detection gap existed among schoolchildren and adolescents in Chongqing, and it also may exist in other similar countries and regions, which may lead to more TB infections and morbidity. This situation must attract high attention from decision-makers. The staff of community-level medical and health care institutions need to receive regular standardized training and quality control to maintain the skill proficiency. These measures should be included in national tuberculosis prevention and control policies. Intelligent software for the result reading of TST and TBST should be developed, along with the development of mhealth systems capable of conducting quality control, which could help to enhance the PTB screening capabilities in areas with limited medical resources.

In conclusion, obtaining accurate LTBI burden in schoolchildren and adolescents is crucial to develop effective TB prevention and control policies. Taking necessary measures could significantly improve the quality of TST and TBST, and close the detection gap of LTBI.

WHO World Health Organization

LTBI Latent Tuberculosis Infection

TST Tuberculin Skin Test

C-TST Creation Tuberculin Skin Test

TB Tuberculosis

PTB Pulmonary Tuberculosis

TBST Novel Skin Tests for Tuberculosis Infection

BCG Bacillus Calmette-Guérin

STAT-6 Secretory Antigen Target Six

CFP10 Culture Filtrate Protein Ten

ARTI The Annual Risk of Tuberculous Infection

Ethics approval and consent to participate

The study was approved by the ethics committees of Chongqing Municipal Institute of Tuberculosis (202202, 26 September 2022). As we were carrying out a data analysis based on mandatory physical examinations and all individual information was removed before analysis, we were not required to obtain written informed consent from participants.

Consent for publication

Not applicable.

Availability of data and materials

The PTB screening data of this study has been stored in the the provincial TB surveillance system but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the corresponding author upon reasonable request and with permission of the provincial TB surveillance system.

Competing interests

The authors declare that they have no competing interests.

Funding

The data collection and data analysis of the study was supported by Chongqing Science and Health Joint Research Project (2023ZDXM027 and 2023MSXM143), Chongqing Health Commission Medical Science Research Project (2024WSJK08), and Chongqing Public Health Key Specialties (Disciplines) Construction Fund.

Authors' contributions

JF, JYZ, BW, and YY designed the study. CGW, YLS, YL, JY, QS, ZZ, XH, and MW were involved in conducting the study. BW, YY, JY, QS and YP were involved in data analysis. BW and YY wrote the draft manuscript. BW, YY, JY, and QS had access to and verified the existence of the raw data. All authors read and approved the final manuscript before submission. JF was responsible for the decision to submit the manuscript.

Acknowledgments

We thank the field workers and the study nurses Jinshan Qian, Jia Luo, Xianhui Feng, Xuemei Feng, Jin Wu, Yanping Feng, Cuimei Yue, Shanshan Liu, Huli Pan, and Yanjun Feng.

Uplekar M, Weil D, Lonnroth K, Jaramillo E, Lienhardt C, Dias HM, et al. WHO’s new end TB strategy. Lancet. 2015;385(9979):1799-801.
World Health Oragnization. Global tuberculosis report 2023. Geneva, Switzerland: World Health Organization. 2023. https://www.who.int/publications/i/item/9789240083851. Accessed March 10, 2024.
World Health Organization. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva, Switzerland: World Health Organization. 2018. https://www.who.int/publications/i/item/9789241550239. Accessed March 10, 2024.
Wang L, Zhang H, Ruan YZ, DP Chin, Y Xia, S Cheng, et al. Tuberculosis prevalence in China, 1990-2010; a longitudinal analysis of national survey data. Lancet. 2014;383(9934):2057-2064.
Gao L, Zhang H, Hu MG, Xu CD, Xia YY, Li T, et al. Estimation of the national burden on latent tuberculosis infection based a multi-center epidemiological survey and the space statistics model. Chinese Journal of Antituberculosis. 2022;2022(01):54-59.
National Health Commission of the People's Republic of China. Diagnosis for pulmonary tuberculosis. Beijing, China: National Health Commission of the People's Republic of China; 2017.
National Health Commission of the People's Republic of China. Technical Specifications for Tuberculosis Prevention and Control in China (2020 Edition). Beijing, China: National Health Commission of the People's Republic of China; 2020.
National Health Commission of the People's Republic of China, Ministry of Education of the People's Republic of China. Guidelines for Tuberculosis Prevention and Control in Chinese Schools (2020 Edition). Beijing, China: National Health Commission of the People's Republic of China, Ministry of Education of the People's Republic of China; 2020.
David WD, Marcel AB. Are we underestimating the annual risk of infection with Mycobacterium tuberculosis in high-burden settings? Lancet Infect Dis. 2022;22(9):e271-e278.
Chen T, He TF, Yu M, Che Y, Lin X. Analysis on tuberculin skin test results in 16795 freshmen in Ningbo, Zhejiang. Disease Surveillance. 2023;38(9):1043-1047.
Lin X, Yu M, He TF, Che Y, Lin L, Cheng T. Tuberculin skin test results among new middle and high school students in Ningbo in 2021. Chinese Preventive Medicine.2023;02:135-138.
Huang BY, Wei GL. Tuberculosis screening among freshmen and incidence of tuberculosis among students in Liuzhou from 2016 to 2020. Chinese Youjiang Medical Journal. 2020;10:790-793.
Li ML, Liu JY, Zhang XQ, Qiu YH, Huang DH, Zheng TH. Analysis of tuberculosis health examination results in schools in Longgang District, Shenzhen in 2021. Journal of Medical Pest Control. 2023;05:465-469.
Ma CX, Xu W, Liang YR, Liang RY, Zhang XZ, Wang M. Tuberculosis screening results among new students in Chaoyang district of Beijing in 2020. Disease Surveillance. 2022;37(7):949-953.
Meng WL, Li SY, Wang FH, Li HY, Lang Y, Guo JL, et al. Tuberculosis screening results of freshmen in 138 primary and secondary schools. China Tropical Medicine. 2019;19(8):781-783.
Gina G, Paola M, Francesco NL, Fabrizio P, Sayoki M, Peter M. Tuberculin skin test-Outdated or still useful for Latent TB infection screening? Int J Infect Dis. 2019;80S:S20-S22.
Keiko N, Kiminori S, Yuko S, Akimitsu S, Hidetoshi I, Keiichi N. Problems about tuberculin skin test raised from consultations and countermeasures--influence to the interpretation of tuberculin skin test in case of the stoppage of BCG revaccination abolition and the introduction of induration measurement. Kekkaku. 2002;77(10):639-645.
Saeedeh MN, Leila B, Olivia O, Chantal V, Mei-Xin L, Jonathon RC. The mTST-An mHealth approach for training and quality assurance of tuberculin skin test administration and reading. PLoS One. 2019;14(4):e0215240. doi: 10.1371/journal.pone.0215240.
Ben JM. Mycobacterium tuberculosis infection burden in poor urban communities. Lancet Child Adolesc Health. 2018;2(1):7-8.
Su Q, Wang QY, Zhang T, Liu Y. Comparison of recombinant Mycobacterium tuberculosis fusion protein skin test and tuberculin skin test for screening latent tuberculosis infection in school students. Chinese Journal of Infection Control. 2023;22 (5):547-551.
Yang Z, Sun Q, Han L, Bao C, Wang X, Zhang ZG. Analysis of recombinant mycobacterium tuberculosis fusion protein in screening for latent tuberculosis infection in college students. Chinese Journal of the Frontiers of Medical Science. 2022;14(07):51-54.
Mu TM, Hu QY, Li W, Feng Y, Wang XG. Analysis of recombinant mycobacterium tuberculosis fusion protein in screening for latent tuberculosis infection in college students. Parasitoses and Infectious Diseases. 2022;3:166-170.
Styblo K. The relationship between the risk of tuberculous infection and the risk of developing infectious tuberculosis. Bull Int Union Tuberc Lung Dis. 1985;60:117-119.
Horsburgh CJ, O’Donnell M, Chamblee S, Moreland JL, Johnson J, Marsh BJ, et al. Revisiting rates of reactivation tuberculosis: a population-based approach. Am J Respir Crit Care Med. 2010;182:420-425.
Pang Y, Wu CG, Wang QY, Zhang T. Screening results of tuberculosis among new students in Chongqing Municipality, 2021. Practical Preventive Medicine. 2023;30(02):165-168.
Dye C. Breaking a law: tuberculosis disobeys Styblo’s rule.Bull World Health Organ. 2008;86:4.

No competing interests reported.

Download PDF

Journal Publication

published 16 Sep, 2024

Read the published version in BMC Infectious Diseases →

Editorial decision: Revision requested
29 Apr, 2024
Submission checks completed at journal
27 Apr, 2024
Editor assigned by journal
27 Apr, 2024
First submitted to journal
24 Apr, 2024

You are reading this latest preprint version

Addressing the Burden and Detection Gap of Latent Tuberculosis Infection in Schoolchildren and Adolescents in China: A Cross-sectional Study

Status:

Journal Publication

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

Background

Methods

Study design

Sample Size

Randomisation and Cluster Selection

Study participants

Procedures

The LTBI detection gap

Statistical analysis

Results

The screening process for participants

PTB screening results

The LTBI detection gap

The ARTI of schoolchildren and adolescents

Discussion

Abbreviations

Declarations

References

Additional Declarations

Status:

Journal Publication

Version 1