Table of Content

10 September 2019, Volume 41 Issue 9

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Retrospect and Prospect

The overview and prospect of tuberculosis control in China since the founding of the People’s Republic of China

Hui ZHANG,Jian-jun LIU

Chinese Journal of Antituberculosis. 2019, 41(9):  913-916.  doi:10.3969/j.issn.1000-6621.2019.09.001

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Tuberculosis is a major public health problem of great concern in China and the world. This article reviews the achievements of tuberculosis control and prevention in China since the founding of new China,analyzes the current situation of tuberculosis control and prevention in China, reveals the problems and challenges faced in the new era, and puts forward the countermeasures to be taken in the next step.

Expert View

Suggestions on infection control of active pulmonary tuberculosis patients treated at home

Xiao-ying JIANG,Shi-wen JIANG,Meng-qiu GAO,Wen ZHANG,Zhi-guo ZHANG,Zhi-dong GAO,Hong ZHANG,Jian DU,Fei-fei NIE,Hui ZHANG,Hong-fei DUAN,Feng-ling MI

Chinese Journal of Antituberculosis. 2019, 41(9):  920-925.  doi:10.3969/j.issn.1000-6621.2019.09.003

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Active pulmonary tuberculosis (APTB) patients are highly infectious before anti-TB drugs are administered, and hospitalization is ideal for patients and their families. They are the main source of TB infection. However, the article “Factors affecting the hospitalization treatment of smear positive pulmonary tuberculosis patients in Chaoyang District, Beijing” shows that 76.83% of smear-positive tuberculosis patients do not choose hospitalization, which poses a health threat to their close contacts living together. In recent years, China has done some work in tuberculosis infection control, and carried out a series of training and research. However, there are no systematic guidelines or documents on how to carry out infection control for tuberculosis patients treated at home in China or abroad. Therefore, authorized by Beijing Science and Technology Commission in 2018, we organized national and local experts in tuberculosis prevention and control, clinical, management, nursing and other fields to draft “Suggestions on infection control of active pulmonary tuberculosis patients treated at home”, which were formed through three rounds of expert consultation and one round of email expert consultation. This article briefly introduces the infection control requirements and suggestions of home treatment management for active pulmonary tuberculosis patients and their close contacts, including isolation of patients, cough etiquette, wearing of masks, infection control of patients going out, hand washing, home setting and ventilation, daily disinfection, etc. At the end of the article, the limitations of this proposal are explained, and the future development are also prospected.

Special Articles

Interpretation of key points and suggestion for the Health Management Service Specification for Tuberculosis Patients

Shi-wen JIANG,Xiao-qiu LIU

Chinese Journal of Antituberculosis. 2019, 41(9):  926-929.  doi:10.3969/j.issn.1000-6621.2019.09.004

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The author briefly introduces the main points of the Health Management Service Specification for Tuberculosis Patients, including management contents and methods, as well as evaluation indicators, and puts forward suggestions on existing problems, including the use of funds and refinement of definitions related to health management services for tuberculosis patients.

Original Articles

Survey on the treatment and management of tuberculosis patients in China in 2018

Dong-mei HU,Xue LI,Xiao-qiu LIU,Cai-hong XU

Chinese Journal of Antituberculosis. 2019, 41(9):  930-935.  doi:10.3969/j.issn.1000-6621.2019.09.005

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Objective To analyze the current situation of the treatment and management of pulmonary tuberculosis (PTB) patients in counties, townships and villages in 31 provinces (municipalities, autonomous regions) and Xinjiang production and construction corps, and to provide scientific basis for further improving the treatment and management efficiency and quality of PTB patients. Methods National Center for Tuberculosis Control and Prevention of Chinese Center for Disease Control and Prevention designed the questionnaire and conducted the investigation on the PTB patients treatment management of TB designated institutions and center for disease control and prevention (CDC) at county level and primary medical and health institutions among 2799 counties(districts) in 2018. The content of the questionnaire included the implementation of TB patient treatment and management, follow-up management, patients’ re-examination and refilling medicine, and management of treatment interrupted patients. The data were used to understand the task cohesion of patients’ treatment management in county (district), township and village. Results Among 2799 counties (districts) which were investigated, 2072 designated TB institutions were set up in hospitals (74.0%, 2072/2799), the numbers of TB designated medical institutions set up in TB dispensary, in CDC and in hospital for chronic diseases were 287 (10.3%, 287/2799), 296 (10.6%, 296/2799) and 74 (2.6%, 74/2799) respectively, 131 (4.7%, 131/2799) counties (districts) designated TB institutions didn’t transmit patients’ information to patients’ management institutions, and the proportion of non-transmission in hospitals was 5.6% (117/2072), and 1.1% (7/657) in TB dispensary, CDC and hospitals for chronic diseases. The difference was significant between the two types (χ²=24.138, P<0.01). 1016 (36.3%, 1016/2799) designated TB institutions transmitted patient information to CDC, 912 (32.6%, 912/2799) transmitted patient information to primary medical and health institutions, and 740 (26.4%, 740/2799) transmitted patient information to the above two institutions at the same time. The numbers of designated medical institutions transmitting patient information through paper, electronic, National Tuberculosis Information Management System (TBIMS) and other systems were 622 (22.2%, 622/2799), 1121 (40.1%, 1121/2799), 819 (29.3%, 819/2799) and 97 (3.5%, 97/2799), respectively, 127 (4.5%, 127/2799) CDC did not transmit patient information to primary medical and health institutions. 2430 (86.8%, 2430/2799) transmitted to township health agencies, 17 (0.6%, 17/2799) transmitted to village doctors, and 225 (8.0%, 225/2799) transmitted to both levels. The numbers of CDC transmitting patient information through paper, electronic, TBIMS and other systems were 694 (24.8%, 694/2799), 1611 (57.6%, 1611/2799), 178 (6.4%, 178/2799) and 183 (6.5%, 183/2799), respectively. The primary medical and health institutions of 1153 (41.2%, 1153/2799) counties (districts) did not send follow-up records, and the numbers of counties (districts) that sent follow-up records through paper, electronic version, TBIMS and other systems were 895 (32.0%, 895/2799), 289 (10.3%, 289/2799), 41 (1.5%, 41/2799) and 263 (9.4%, 263/2799), respectively, 158 (5.6%, 158/2799) counties (districts) sent follow-up records by other methods. If the patients were found with adverse reactions or other complications, grassroots doctors of 374 (13.4%, 374/2799) counties (districts) informed the doctor at county (district) level directly, those of 711 (25.4%, 711/2799) counties (districts) directly referred the patient to the county (district) institution, those of 1665 (59.5%, 1665/2799) counties (districts) dealt with minor adverse reactions, and those of 43 (1.5%, 43/2799) counties (districts) informed patients to the county (district) institution. The patients of 91.4% (2557/2799) county (district) took re-examination at county (district) institutions at the end of each month of treatment or at the end of the second, fifth and sixth month of treatment. The primary doctors of 1.2% (33/2799) county (district) did not remind the patients to take re-examination, and 37.8% (1058/2799) designated medical institutions at county (district) level did not remind the patients. The patients of 91.6% (2563/2799) county (district) received drugs from county (district) designated medical institutions, and the township health institutions of 84.9% (2376/2799) county (district) did not provide TB re-examination services. In 2240 (80.0%, 2240/2799) counties (districts), patients with interrupted treatment were found by primary doctors, and the primary doctors of 1382 (49.4%, 1382/2799) counties (districts) organized tracing of patients with interrupted treatment. Conclusion County (district) designated medical institutions, CDC and primary medical and health institutions have a good connection of their duties in the treatment and management of TB patients. All levels should do a good job in patient treatment management according to the requirements, and comprehensively improve TB patients’ treatment management.

Prediction models for latent tuberculosis infection among contacts of tuberculosis patients in an institutionalized population

Hong-xia FANG,Guang-rong ZHANG,Yu-bao QIN,Zhi-min XIE,Keng LAI,Cheng-zhang HUANG,Yan WANG,Wen-long HE,Kai-qiao ZHENG,Zhi-kai XIAO,Chang-wei LIU,Jian-ping LIANG,Zhi-cong CHEN

Chinese Journal of Antituberculosis. 2019, 41(9):  936-945.  doi:10.3969/j.issn.1000-6621.2019.09.006

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Objective To understand the prevalence of latent tuberculosis infection (LTBI) among TB contacts who were institutionalized for drugs in a compulsory detoxification centers; further, to analyze the factors associated with risks of TB infection and establish predictive models for LTBI.Methods A total of 13 TB cases were detected during October 2016 to November 2018. Tuberculosis skin test (TST) for TB infection were provided to all the institutionalized persons who had contacted the TB cases at the same period. Follow-up TSTs were given every 6 months to these contacts for two years until July 2019. TST positivity was defined as an induration ≥10 mm for BCG-vaccinated (with a BCG scar), or ≥5 mm for people without a BCG scar, according to the WS 288-2017 for diagnosis of tuberculosis. Prevalence of LTBI were measured. Cox regression and conditional logistic regression were applied to develop risk prediction models with and without site characteristics (drug-using time, frequency of detoxification, and no previous admission to the detoxification centers). Independent variables include age, BMI, BCG vaccination history, tuberculosis history, suspected symptoms of TB, contact degree and contacts with etiology-positive patients. Model performances were evaluated based on the area under the ROC curve (AUC) to find the optimal predictive model.Results This study included 2062 eligible subjects who had accepted TST and had contacted the 13 TB cases at the same period in detoxification centers. The prevalence of LTBI at the first TST examination was 51.4% (1060/2062). During the follow-up, another 267 contacts who were negative at first became TST positive, led to an 26.6% (267/1002) increment. Furthermore, 173 cases (64.8%, 173/267) had a TST positive conversion after those new TB cases were diagnosed in detoxification centers. In total, the 2-year positivity was 64.4% (1327/2062). Using logistic regression, if the site characteristics were adapted, the model showed that TB infection risk=0.041×age+0.373×exposure degree+0.046×BMI+0.028×drug-using time -2.285; if not, the model was that TB infection risk=0.050×age+0.372×contact degree+0.041×BMI-2.282. The AUC of these two models were 0.584 (95%CI: 0.558-0.609) and 0.625 (95%CI: 0.600-0.650), P<0.001. The predictive accuracy of TB infection were 93.6% (1242/1327) and 94.1% (1249/1327), respectively. Using Cox regression, with the site characteristics, the model was presented as that TB infection risk=0.020×age+0.133×contact degree+0.030×BMI+0.013×drug-using time, the AUC of which was 0.633 (95%CI: 0.608-0.658), P<0.001; without site characteristics, the predictive model was that TB infection risk=0.025×age+0.135×contact degree+0.028×BMI, the AUC of which was 0.625 (95%CI: 0.600-0.650), P<0.001.Conclusion Three-factor models have been constructed without site characteristics, including age, BMI, and exposure degree. Cox regression and conditional logistic regression led to similar effects. Considering site characteristics, adding the drug-using time, Cox regression will be better if the follow-up time is available. These models have a high level of accuracy in predicting LTBI risk in institutionalized population, although more studies are needed to identify potential risk factors associated with TB infection.

The effectiveness evaluation of using mobile communication for directly observed short course chemotherapy on tuberculosis patients

Jia-wen WANG,Shan-shan HUANG,Kai-yi LIU,Hong-di LIANG,Hui-ying FENG,Fang-jing ZHOU,An-qi LIANG,Liang CHEN,Lin ZHOU

Chinese Journal of Antituberculosis. 2019, 41(9):  946-950.  doi:10.3969/j.issn.1000-6621.2019.09.007

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Objective To compare conventional way of directly observed short course chemotherapy (DOTS) method and DOTS using mobile communication, to evaluate the effectiveness of TB treatment supervision under DOTS with mobile communication and to provide scientific evidence for tuberculosis control strategy development.Methods one hundred and seventy-four cases diagnosed with tuberculosis in TB control institutions and designated hospitals in Guangdong Province from January 2018 to June 2018, were randomly allocated to two groups according to the order of diagnosis using random number table. Eighty-nine cases were enrolled in conventional DOTS group and supervised following the guideline of China’s TB control program (Edition 2008); 85 cases were enrolled in the mobile communication DOTS group which adopted TB mobile communication DOTS management system to conduct the whole-course and standardized supervision. Data of those two groups were collected, regularity of drug taking, treatment outcome, status of supervision and follow-up under different DOTS models were analyzed.Results In terms of treatment compliance and outcome, the regular medication rate in mobile communication group was 97.6% (83/85), which was significantly higher than the conventional DOTS group 87.6% (78/89) (χ²=6.297,P<0.05). The median (quartile1 and quartile 3) gap time from adverse drug reactions onset to getting treated in conventional DOTS group was 6 (5,7) d, while in mobile communication DOTS group was 3 (2,4) d. The difference between those two groups was statistically significant (Z=-5.643, P<0.01). In terms of supervision and follow-up management, the supervision management rates of both groups were 100.0%. The regular supervision rate of conventional DOTS group was 88.8% (79/89), which was lower than the mobile communication DOTS group’s 92.9% (79/85), but it did not achieve statistical significance (χ²=0.909,P>0.05). The completion rate of follow-up in the intensive and consolidated phases of the mobile DOTS group were both 100.0%, compared with 98.9% (88/89) and 97.8% (87/89) in the conventional DOTS group (intensive phase:χ²=0.000, P>0.05;consolidated phase:χ²=0.461, P>0.05).Conclusion TB mobile communication DOTS management system provides comprehensive, continuous and proactive management service, which can effectively improve the regular medication rate of patients, shorten the delay for adverse drug reactions treatment and strengthen management of regular follow-up.

Evaluating the implementation effect of tuberculosis patients health management services for Basic Public Health Projects in Shaanxi Province

Hong-wei ZHANG,Jing XU,Yu MA,Ya-li DENG

Chinese Journal of Antituberculosis. 2019, 41(9):  951-956.  doi:10.3969/j.issn.1000-6621.2019.09.008

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Objective The aim of this was to evaluate the policy and implementation effect of tuberculosis patients health management services for the basic public health projects in Shaanxi Province, and provide reference for further improving and implementing the tuberculosis prevention and control mode in primary medical institutions.Methods The implementation and assessment programs of tuberculosis patients health management service for the basic public health project in Shaanxi Province issued in 2017 and 2018 by the Health Commission of Shaanxi Province were collected, and then the five contents of work objectives, tasks, workflow, budget and performance appraisal were refined. Combined with special supervision and research as well as the data of “Quarterly Report on Tuberculosis Prevention and Control in Primary Medical Institutions” and “National Tuberculosis Patient Information Management System”, this paper evaluated the specific practices, organizational implementation and effect of the tuberculosis patients health management service for the basic public health projects in Shaanxi Province. In 2018, 43816 cases of suspected symptoms of pulmonary tuberculosis were recommended to county-level designated hospital by primary medical institutions, of which 4183 cases were diagnosed as active pulmonary tuberculosis, and 21401 cases with common pulmonary tuberculosis and 318 rifampicin-resistant tuberculosis patients were managed.Results The number of recommended newly diagnosed patients by primary medical institutions accounted for 37.05% (43816/118266) of the total number of first registered in provincial designated hospitals in 2018, and the number in each quarter (Q1: 22.08% (6565/29729), Q2: 36.13% (10892/30150), Q3: 39.81% (11028/27702), and Q4: 49.96% (15331/30685); {\chi }_{\mathrm{trend}}^2 =4921.82, P=0.000) showed an upward trend. Among the suspected symptoms of tuberculosis recommended by primary medical institutions, the confirmed active pulmonary tuberculosis patients accounted for 18.00% (4183/23237) of active pulmonary tuberculosis patients in the province, which was lower than other sources of confirmed patients (including referral, follow-up, and active visits) with the rate of 25.59% (19054/74450), and the difference was statistically significant (χ ²=4498.52, P=0.000). The notification rate, management rate, and contracted rate of common pulmonary tuberculosis were 93.81% (21798/23237), 98.18% (21401/21798), and 92.49% (20161/21798), respectively, which reached the goal of 90% of the national requirements. The notification rate of rifampicin-resistant tuberculosis patients was only 60.98% (325/533), while the management rate was 97.85% (318/325), reaching the goal of 90%; and the contracted rate was 88.62% (288/325) that slightly lower than the goal of 90%.Conclusion The tuberculosis patient health management service of the basic public health project in Shaanxi Province has strengthened the recommendation of suspected tuberculosis patients in primary medical institutions, and promoted the realization of the goal on the management rate and contract rate of tuberculosis patient, which can provide reference for other areas. However, the quality of recommendation for suspected tuberculosis patients and the contracting service for rifampicin-resistant tuberculosis patients need to be further improved.

The application of electronic medicine box and mobile phone WeChat APP on the effect of drug compliance in tuberculosis patients

Xue LI,Shi-wen JIANG,Dong-mei HU,Cai-hong XU,Xiao-qiu LIU

Chinese Journal of Antituberculosis. 2019, 41(9):  957-961.  doi:10.3969/j.issn.1000-6621.2019.09.009

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Objective To evaluate the drug compliance effect of TB patients by application of intelligent electronic medicine box and mobile phone WeChat APP supervision drug management tool.Methods Since October 3,2017 to March 15, 2018, according to the purposive sampling method, Anda City and Lanxi County of Suihua City of Heilongjiang Province, Changqing District and Jiyang County of Jinan City of Shandong Province were selected as the research site by National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention. In accordance with the registration sequence and inclusion criteria for the screening, 134 cases were enrolled in the study among 234 newly registered cases since September 1, 2017. Among the 73 patients who met the inclusion criteria, 40 patients who had smart phones and could stay online during the medication period (6 months) and were willing to use WeChat APP to remind them to take the medication were included in the WeChat APP group. Of the 94 patients who did not have smart phones or had smart phones, but willing to use the medicine monitor, 80 pationts who were willing to use the medicine monitor for medication reminder were included in the medicine monitor group. Two groups of patients were prospectively monitored and administered medication for 6 months. SPSS 17.0 software was used to conduct trend Chi-square test on the drug taking rate and regular drug compliance rate of patients in different treatment months in the two groups. P<0.05 was considered as statistically significant difference.Results During the observation period, 34 patients in the two groups withdrew, and the withdrawal rate was 28.3% (34/120), in which 29 patients in the medicine monitor group and 5 patients in the WeChat APP group in addition to 10 patients in the medicine monitor group with incomplete medication data. At the end of 6 months, 41 and 35 patients in the medicine monitor group and WeChat APP group were observed effectively. The drug taking rate of the two groups was more than 93.0% in different months, while the drug taking rate decreased as the treatment month increased, the drug taking rate in the medicine monitor group (97.5% (1025/1051)-93.3% (1110/1190)) and the WeChat APP group (99.5% (994/999)-94.4% (1018/1078)). {\chi }_{\mathrm{trend}}^2 were 11.868 and 82.921, P values were 0.001 and 0.000 respectively. The overall regular medication rate was 85.4% (35/41) among the effective observation cases of the medicine monitor group and 91.4% (32/35) in the WeChat APP group.Conclusion The supervision medication management mode of WeChat APP and medicine monitor have good effect on the medication rate and compliance of patients, which can be rolled out.

Drug affordability study in drug-resistant tuberculosis patients: based on the cost of treatment

Li-jun SHEN,Yi-tong WANG,Xue LI,Zhao LIU,Fan ZHANG,Kun ZHAO,Yue-hua LIU

Chinese Journal of Antituberculosis. 2019, 41(9):  962-967.  doi:10.3969/j.issn.1000-6621.2019.09.010

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Objective The purpose of this study is to measure the cost of treatment for drug-resistant tuberculosis under different treatment options and price sources.Methods Based on the recommended treatment plans by China’s Multidrug-Resistant Pulmonary Tuberculosis Clinical Path (2012 edition) and WHO Drug-Resistant Tuberculosis Treatment Guide (2018 edition), the treatment costs of drug-resistant tuberculosis were measured under the market price in China Mainland and the WHO centralized purchase price, respectively, and the catastrophic health expenditure (refers to the proportion of household cash payment medical expenses to household consumption expenditure ≥40%) was used to evaluate drug affordability of patients.Results Under the treatment plan and market price in China (2012 edition), the total cost range of drug-resistant tuberculosis patients was 19500-12700 million yuan/person, and the self-paying interval was 5322-78482 yuan/person. Among them, under some treatment programs, only the expenditure of drugs caused catastrophic health expenditure. The proportion of health expenditure in urban residents ranged from 2.19% to 32.25%, and it ranged from 5.87% to 86.60% in rural residents. Under the same treatment plan (2018 WHO Guide), the self-paying interval of drug-resistant tuberculosis patients under the market purchase price in China Mainland was 745000-770000 yuan/person, and all treatment programs had reached catastrophic health expenditure, while the patient’s self-paying interval under the WHO centralized purchase price was 80700-95900 yuan/person.Conclusion Compared with the WHO centralized purchase price, domestic second-line anti-tuberculosis drugs are more expensive, and the drug-resistant tuberculosis treatment imposes a heavy economic burden on patients, especially in rural area.

Cost-effectiveness analysis of TB screening in patients with diabet

Juan WANG,Xiang XU,Xiao-feng CAI,Mei-xia YANG

Chinese Journal of Antituberculosis. 2019, 41(9):  968-973.  doi:10.3969/j.issn.1000-6621.2019.09.011

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Objective In order to provide reference for the relevant policy making by government, a cost-effectiveness analysis of tuberculosis (TB) screening in patients with diabetes was conducted. Methods The related data and information were collected from the patients with diabetes aged 15 years old or above and were registered by Xuhui District CDC of Shanghai in June 2014 or June 2015 respectively through the diabetes management information system which was based on a comprehensive management platform of chronic disease in Xuhui District, Shanghai. Finally, 32800 patients who were registered in 2014 and 33723 patients who were registered in 2015 were enrolled into this analysis and received TB screening free of charge. The screening date was arranged in August and September each year. One month before the screening date, the enrolled patients were informed by phone call or visiting to come to the community health service centers at the appointed time for TB screening on the spot using digital radiography (DR). SPSS 17.0 software was used for statistical analysis to the following data: TB screening cost which was considered as the total social costs, including the investment of the health sector (explicit cost) and the cost of chest X-ray film which provided by the diabetes patients (implicit cost), Social effect, Social benefit, Cost-effectiveness ratio, Benefit-cost ratio. Fisher’s exact probability method was used to compare the counting data with P<0.05 as the statistical significance. Results A total of 38617 diabetes patients (19723 cases in 2014 and 18894 cases 2015) received TB screening with DR (21030 cases received DR screening on the spot while 17587 cases provided the chest X-ray examination reports). Out of 38617 patients, 9944 patients participated in the screening in both years, so in actually 28673 patients received TB screening in two years. A total of 9 pulmonary TB patients were found during the screening in 2014 and 2015. Those detected patients aged above 50 years; the detection rate was 25.35/100000 (5/19723) and 21.17/100000 (4/18894) respectively in 2014 and 2015; the detection rate of pulmonary TB in the male diabetes patients (64.98/100000, 8/12311) was significantly higher than that in the female diabetes patients (6.11/100000, 1/16362) (Fisher’s exact probability method, P=0.006). The results of cost-effectiveness analysis showed that the total expenditure of social cost in the screening was RMB 3089400 yuan and the explicit cost investment by the health sector was RMB 1858300 yuan. The TB screening could reduce the TB death by 2.25 cases, avoid TB infection by 67.50-101.25 healthy people, reduce social medical expenses by RMB 381800-572800 yuan, avoid 85.5 DALY losses and recover the indirect social value by RMB 5756600 yuan. The social cost-effectiveness ratio was RMB 36100 yuan (3089400/85.5), and the dominant cost-effectiveness ratio was RMB 21700 yuan (1858300/85.5). The social benefit-cost ratio was 2.02 ((477300+5756600)/3089400) and the dominant benefit-cost ratio was 3.35 ((477300+5756600)/1858300). Conclusion The benefit-cost ratio of TB screening with chest X-ray in diabetic patients in Xuhui District is not high, so it is not suitable for large-scale TB screening; attention should be paid to TB screening in male and elderly patients with diabetes mellitus.

Analysis on economic burden of patients with tuberculosis and its influencing factors in Fengxian District of Shanghai

Chun-hua XU,Qing LIU,Zi-chun WANG,Yong WU

Chinese Journal of Antituberculosis. 2019, 41(9):  974-984.  doi:10.3969/j.issn.1000-6621.2019.09.012

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Objective To understand the economic burden of the patients with pulmonary tuberculosis (PTB) and its influencing factors in Fengxian District of Shanghai.Methods The study enrolled 136 initial treatment or re-treatment PTB patients, who were notified in Fengxia District CDC of Shanghai and managed by community health centers in 2018.A self-designed questionnaire was used to investigate the basic information of the patients, including sex, age, if having health insurance or not, family catastrophic health expenditure, if having complications or not, etc.; the related direct and indirect costs of the patients in the process of diagnosis and treatment were recorded. The SPSS 17.0 software was used to do the data statistical analysis and the optimal scale regression analysis.Results Two patients were excluded from the study, one died during treatment while the other was due to incomplete data on medical expenses. Finally, a total of 134 patients, who completed the whole course of anti-TB treatment and had complete information, were involved into the analysis. Among them, 88 patients had local household registration while 46 patients did not have. The average annual income per PTB patient was RMB 55181.46 yuan and the average annual income per family of the PTB patients was RMB 112937.91 yuan. The average expenses per patient was RMB 32035.99 yuan, including RMB 24363.97 yuan direct expenses and RMB 7672.02 yuan indirect expenses. The median (Q₁, Q₃) of total cost in the patients who had local household registration was RMB 25635.25 (8361.82,45314.05) yuan while it was RMB 18847.43 (9016.25,31894.65) yuan in those patients who did not have local household registration, there was no significant difference between the two groups of patients (Z=-0.984, P=0.325); however, the direct cost in the patients who had local household registration (RMB 19336.34 (7756.65,36700.57) yuan) was significantly higher than that who did not have local household registration (RMB 11658.03 (6716.38,20072.61) yuan) (Z=2.329, P=0.020), while the indirect cost in the patients who had local household registration (RMB 1000.00 (0.00,4075.00) yuan) was significantly lower than that who did not have local household registration (RMB 3000.00 (75.00,13500.00) yuan) (Z=-2.773, P=0.006). 23.75% (7607.26/32035.99) of the average overall expenses was reimbursed by medical insurance, 4.55% (1458.03/32035.99) was paid by government relief funds and 71.70% (22970.70/32035.99) was paid out of patient’s own pocket which occupied 20.34% (22970.70/112937.91) of average annual household income of the patients. The amounts of expenditures which were reimbursed by health insurance and paid by government relief funds in the patients who had local household registration were RMB 2703.00 (1024.00,10917.00) yuan and RMB 1210.50 (820.25,1721.75) yuan,while those were RMB 179.00 (0.00,1218.00) yuan and RMB 1480.50 (1328.75,1802.50) yuan in the patients who did not have local household registration, there were significant difference between the two groups of patients (Z values were -5.291 and -2.962; P values were 0.000 and 0.003, respectively). The results of optimal proportional regression analysis showed that the district-level health facilities in the patients who visited district-level health facilities (RMB 11535.48 (6622.96,22741.41) yuan), costs of standard daily medication (RMB 14147.86 (6878.47,27395.80) yuan), costs without hospitalization (RMB 6395.98 (4425.99,8878.89) yuan), costs with less-one-day hospitalization (RMB 6395.98 (4425.99,8878.89) yuan), costs never hospitalization (RMB 6395.98 (4425.99,8878.89) yuan), costs with treatment duration less than 8 months (RMB 11474.18 (6563.88,22880.65) yuan), costs with severity by self-assessment (RMB 8726.80 (4666.35,20642.64) yuan), costs without family catastrophic health expenditure (RMB 11474.18 (6818.67,22880.65) yuan), costs without medical insurance (RMB 7074.25 (4741.36,8660.69) yuan) were significantly lower than the direct medical expenses in the patients who visited municipal-level health facilities (RMB 15550.02 (8456.05,37171.31) yuan), costs with irregular medication (RMB 15107.080 (8901.53,34197.84) yuan), costs with hospitalization (RMB 19982.64 (9676.31,35013.72) yuan), costs with hospitalization days >30 days (RMB 56713.89 (37977.08,101972.01) yuan), costs with hospitalization for 3-5 times (RMB 53899.46 (36421.73,113670.87) yuan), costs with treatment duration >8 months (RMB 18925.76 (8616.10,36823.34) yuan), costs with mild illness by self-assessment (RMB 20070.70 (9456.83,44849.70) yuan), costs with family catastrophic health expenditure (RMB 35562.35 (20704.26,55516.06) yuan), costs with medical insurance (RMB 14907.71 (7335.28,29653.38) yuan). F values were 5.794, 5.983, 6.346, 11.102, 70.825, 8.087, 11.636, 31.912, 5.851, and P values were 0.044, 0.037, 0.034, 0.021, 0.000, 0.036, 0.011, 0.000, 0.039, respectively.Conclusion The economic burden of diagnosis and treatment of tuberculosis patients in Fengxian District is heavy. The costs of patients’ burden are mainly related to the health facilities that patients seek health care, daily standard medication, hospitalization, accumulated hospitalization days, number of hospitalizations, duration of treatment, medical insurance, self-assessment of the degree of illness, and catastrophic family health expenditure.

Fingerprint analysis of gut microbiota by denaturing gradient gel electrophoresis in newly diagnosed tuberculosis patients

Han YANG,Huan LI,Jun XI,Ai-fang LI,Ji-ru XU

Chinese Journal of Antituberculosis. 2019, 41(9):  985-992.  doi:10.3969/j.issn.1000-6621.2019.09.013

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Objective To analyze the difference in gut microbiota between normal and newly diagnosed tuberculosis patients.Methods From August 2017 to July 2018, 2 to 3 copies of the fecal specimens of healthy medical examinations that met the inclusion criteria were collected at the fixed time every month in the Xi’dian Group Hospital. Specimens collection was stopped after collecting 30 specimens which served as the control group. The fecal specimens of patients with newly diagnosed tuberculosis were collected from August 2017 to July 2018 in the Xi’an Chest Hospital. Similarly, inclusion was stopped once 30 specimens were collected as the tuberculosis group. The diversity and similarity of gut microbiota in the control group and the tuberculosis group were analyzed by denaturing gradient gel electrophoresis, and the proportion of the bacteria groups in the main bands after polymerase chain reaction-denaturing gradient gel electrophoresis was analyzed.Results The number of bands (13.57±3.37) and the diversity index of the bacteria (H' index; 2.55±0.27) in the control group were significantly higher than those in the tuberculosis group ((8.60±4.19) and 1.99±0.52)), respectively, with the statistically significant differences (t=12.55, P<0.001; t=6.75, P<0.001). A statistically significant difference (Z=-73.38, P<0.001) was found in the intra-group Dice similarity coefficient (Cs) between the control group (22.90% (16.20%, 29.30%)) and the tuberculosis group ((35.35% (23.73%, 44.98%)) (both indicate the median and quartile). Sequencing alignment showed that the main gut microbiota of the control group and the tuberculosis group were mainly Bacteroides, accounting for 73.96% (179/242) and 79.40% (158/199), respectively. The proportion of Prevotella (9.04%, 18/199) in the tuberculosis group was lower than that in the control group (24.38%, 59/242), and the difference was statistically significant (χ ²=17.82, P<0.001). The proportion of Uncultured bacterium genus in the tuberculosis group (11.56%, 23/199) was higher than that in the control group (0, 0/242), and the difference was statistically significant (χ ²=29.51, P<0.001). Conclusion The gut microbiota of healthy people and tuberculosis patients are different due to different immune functions. The occurrence of tuberculosis may result in the changes in the composition ratio of Prevotella and Uncultured bacterium.

Evaluation of antituberculosis activities of 14 antituberculosis drugs in macrophage

Xi CHEN,Zhong-quan LIU,Bin WANG,Hui ZHU,Lei FU,Yuan-yuan LI,Yu LU

Chinese Journal of Antituberculosis. 2019, 41(9):  993-998.  doi:10.3969/j.issn.1000-6621.2019.09.014

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Objective To determine the activities of 14 drugs against Mycobacterium tuberculosis in macrophages, and to evaluate the effect of detection the anti-tuberculosis activity in macrophages on screening of new drugs.Methods J774.1 macrophages were infected with Mycobacterium tuberculosis standard strain H37Rv to establish an in vitro macrophage infection model. Rifampicin, isoniazid, levofloxacin, pyrazinamide, bedaquiline, clofazimine, linezolid, PA-824, TBI-166, OTB-658, PBTZ-169,BTZ-043, TZY-5-84 and NTB-3119H were detected respectively to evaluate the intracellular activity. The minimal inhibitory concentration (MIC₉₀) of the above drugs was determined by MABA method. In addition, rifampicin, isoniazid, levofloxacin, bedaquiline, clofazimine, linezolid, TBI-166 and PBTZ-169 were selected to treat on J774.1 macrophages for 3 h respectively, and the concentrations of these drugs in the macrophages were determined by high performance liquid chromatography-mass spectrometry/mass spectrometry.Results Isoniazid, PBTZ-169, bedaquiline, BTZ-043, NTB-3119H, TZY-5-84 and PA-824 reduced Mycobacterium tuberculosis in macrophages by 1.60, 1.33, 1.31, 1.25, 1.13, 1.01 and 1.00 lg (CFU/ml)(CFU, colony-forming unit) at a concentration of 0.50 μg/ml, isoniazid and PBTZ-169 were the most active in the cell, followed by bedaquiline. However, pyrazinamide, linezolid, TBI-166 and OTB-658 only reduced Mycobacterium tuberculosis in macrophages by 0.65, 0.55, 0.33 and 0.31 lg (CFU/ml). Comparing the minimal inhibitory concentration (MIC₉₀) with intracellular activity, linezolid and OTB-658 had good antibacterial activity in vitro (MIC₉₀ is 0.25 and 0.05 μg/ml respectively), but at the linezolid and OTB-658 concentration of 5 μg/ml, they only reduced 0.77 and 0.50 lg (CFU/ml) in macrophages. In addition, at the concentration of 20 μg/ml in cell culture medium, the concentrations of PBTZ-169, bedaquiline, clofazimine, rifampicin, TBI-166, isoniazid, levofloxacin and linezolid in macrophages were 1.42, 2.11, 4.93, 1.65, 0.50, 0.27, 1.13 and 0.32 μg/ml. The intracellular drug concentrations were 2840.00, 70.33, 41.08, 33.00, 12.50, 5.40, 4.52, and 1.28 times that of its MIC₉₀ (0.0005, 0.03, 0.12, 0.05, 0.04, 0.05, 0.25, 0.25 μg/ml, respectively).Conclusion The ability of each drug to enter macrophages is not the same. The difference of antibacterial activity in macrophages suggests that the concentration of drugs in cells and the relationship with MIC₉₀ are the determining factors of intracellular activity.

Analysis on identification of 129 non-tuberculosis mycobacteria strains using two molecular biology techniques

Jia-wen LIU,Hong-yan LYU,Bei-chuan DING,Zhi-guo ZHANG

Chinese Journal of Antituberculosis. 2019, 41(9):  999-1003.  doi:10.3969/j.issn.1000-6621.2019.09.015

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Objective To analyze the results of strains’ identification of clinical isolates of non-tuberculosis mycobacteria (NTM) from three tuberculosis institution in Beijing using chip hybrization (chip method) and 16S rRNA gene sequencing (gene sequencing), and to provided scientific evidences for rapid and accurate diagnosis of clinical mycobacterial disease.Methods One hundred and twenty-nine strains of NTM from 3 institutes in Beijing were performed to identify using chip method and gene sequencing which the blind method was conducted among technicians. The results of two identifications were compared and evaluated.Results Of the 129 strains of NTM, 107 strains were performed by gene sequencing, the identification results were as follows: M.intracellulare in 59 strains (55.1%), M.kansasii in 29 strains (27.1%), M.chelonae/abscessus in 5 strains (4.7%), M.avium in 3 strains (2.8%), M.fortuitum and M.gordonae in each 2 strains (1.9% each), M.xenopi, M.phlei and M.scrofulaceum in each one strain (0.9% each) and other NTM in 4 strains (3.7%). Of 116 strains performed by chip method, 96 strains were performed with both methods. The coincidence rate of the two methods was 88.5% (85/96). There were three foreign strains of NTM identified by gene sequencing, which were M.minnesotense, M.kumamotonense and M.temen.Conclusion The main strains of NTM from three institutes in Beijing are M.intracellulare, M.kansasii and M.chelonae/abscessus. The consistency rate of identification of clinical isolates of NTM by chip method and gene sequencing is high.

Assessment of GeneXpert MTB/RIF test for diagnosis of tuberculous pleurisy

Su-hua MENG

Chinese Journal of Antituberculosis. 2019, 41(9):  1005-1008.  doi:10.3969/j.issn.1000-6621.2019.09.017

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Objective To evaluate the diagnostic performance of GeneXpert MTB/RIF (“Xpert”) for tuberculous pleurisy.Methods Pleural effusion samples collected with ultrasound guidance from 180 patients with suspected tuberculous pleurisy from Anshan Tuberculosis Hospital between January 2017 and December 2017 were tested with smear acid-fast bacilli testing (“smear”), liquid culture by BACTEC MGIT 960(“MGIT 960”) and GeneXpert. With clinical diagnosis results as the reference standard, sensitivity, specificity, positive prediction value, negative prediction value and consistent rate were evaluated for performances of smear test, MGIT 960 and GeneXpert test on detecting Mycobacterium tuberculosis (MTB) in those pleural effusion samples.Results Among those 180 suspected patients, 162 cases (90.00%) were confirmed as tuberculous pleurisy (TBP), 18 cases (10.00%) were excluded of TBP. Among the 162 cases of TBP, 61 cases (37.65%) were MGIT 960 culture-positive, 101 cases (62.35%) were diagnosed as TBP basing on standard clinical diagnosis criteria, including clinical symptoms, biochemical indicators of pleural effusion samples, results of chest imaging examination, and diagnostic anti-TB treatment results. Eighteen cases excluded of TBP had lung cancer pleural metastasis in 9 cases, sarcoidosis in 1 case, systematic lupus pleurisy in 1 case, pleural mesothelioma in 2 cases, nephropathy in 2 cases, cardiac insufficiency in 2 cases and hypoproteinemia in 1 case. With clinical diagnosis as the reference standard, the sensitivity of smear test, MGIT 960 and GeneXpert test were 0.00% (0/162), 37.65% (61/162) and 54.94% (89/162) separately; The specificity of three tests were all 100.00% (18/18); Positive prediction value of three tests were 0.00% (0/0),100.00% (61/61) and 100.00% (89/89); Negative prediction value of three tests were 10.00% (18/180),15.13% (18/119) and 19.78% (18/91);Consistent rate of three tests with clinical diagnosis results were 10.00% (18/180), 43.89% (79/180) and 59.44% (107/180) separately. Sensitivity of GeneXpert test was significantly higher than that of the smear and MGIT 960 culture (χ ²=119.82,P=0.000). Conclusion GeneXpert has high diagnostive value in detecting tuberculous pleurisy.

CT features analysis of Mycobacterium avium-intracellulare complex lung disease with cavities

Rong-zhen ZHOU,Xiu-li WU,Jian WANG,Hai YANG,Wen-bin JI

Chinese Journal of Antituberculosis. 2019, 41(9):  1009-1014.  doi:10.3969/j.issn.1000-6621.2019.09.018

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Objective This study aimed to explore the CT features of Mycobacterium avium-intracellulare complex (MAC) lung disease with cavities, which might be able to assist in clinical diagnosis.Methods A total of 21 patients who diagnosed as MAC lung disease and presented chest CT scan with cavities (served as the observation group) were retrospectively collected from the Taizhou Hospital affiliated to Wenzhou Medical University between June 2014 to December 2018. Meanwhile, based on 1∶1 case-control study, 21 patients with cavitary tuberculosis who met the inclusion criteria as well as matched by gender and age ±2 year were selected as the control group. Then several indicators, including types of cavities, wall thickness, diameter, bronchiectasis, consolidation, nodules or masses with a long diameter >1 cm, central nodules of the lobes (including tree buds), pleural effusion, mediastinal lymph node calcification, were compared between the two groups.Results A total of 74 cavities were detected in the observation group, among which, the median (quartile) diameter of the cavity (M(Q₁,Q₃)) was 27.9 (17.3, 39.8) mm, and the median wall thickness of the cavity was 2.7 (1.7, 4.1) mm; meanwhile, 55 cavities were detected in the control group with 20.6 (13.4, 32.0) mm of the median diameter of the cavity and 3.6 (2.5, 4.7) mm of the median wall thickness of the cavity. There were significantly statistical differences in terms of diameter and wall thickness between the two groups (Z values: -2.241, and -2.431, respectively, and all P values <0.05). The detection ratio of thin-walled cavities as well as the detection rates of bronchiectasis, and bronchiectasis accompanied with central nodules of the lobes in the observation group were 60.8% (45/74), 85.7% (18/21), and 57.1% (12/21), respectively, which were higher than those in the control group (36.4% (20/55), 38.1% (8/21), and 23.8% (5/21), respectively), with the statistically significant differences ( {\mathrm{\chi }}^2 values: 7.543, 10.096, and 4.842, respectively; all P values <0.05); the detection ratios of thick-walled cavities, surrounding satellite foci, and drainage bronchus, as well as the detection rate of lung nodules with long diameter >1 cm in the observation group were 39.2% (29/74), 58.1% (43/74), 28.4% (21/74), and 23.8% (5/21), respectively, which were lower than those in the control group(63.6% (35/55), 94.5% (52/55), 63.6% (35/55), and 76.2% (16/21), respectively), with the statistically significant differences (χ ² values: 7.543, 21.582, 15.966, and 11.524, respectively; all P values <0.05). Conclusion Patients with MAC lung disease more likely present CT scans with thin-walled cavities accompanied with bronchiectasis and small pulmonary nodules; while CT scans of tuberculosis patients more likely show thick-walled cavities accompanied with drainage bronchus, surrounding satellite foci, and pulmonary nodules with a long diameter >1 cm. The CT findings of different patients display their own characteristics, which can contribute to the early clinical diagnosis and treatment.

Review Articles

A review of research progress on the management of tuberculosis patients based on digital technology

Zhi LI,Hui ZHOU,Xiao-jun CHEN,Li-jie ZHANG,Sen-lu WANG,Hui ZHANG,Xiao-qiu LIU

Chinese Journal of Antituberculosis. 2019, 41(9):  1015-1020.  doi:10.3969/j.issn.1000-6621.2019.09.019

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Tuberculosis (TB) is a chronic respiratory infectious disease which seriously endangers human health and threatens human life. The implementation of DOTS (directly observed treatment, short course) strategy has made great achievements in TB control. One of the core elements of DOTS strategy is directly observed treatment (medication) for TB patients supervised by medical staff; however, there are still many problems in the actual implementation process, especially in countries and regions with limited resources. The advent of the network era and the prominence of mobile terminal devices have made it possible to put forward a patient-centered management strategy based on digital technology. The purpose of this paper is to introduce the application of digital technology in the management of TB patients, and provide reference for the prevention and control of TB.

Progression of preventive treatment of latent tuberculosis infection in close contacts of patients with tuberculosis

Zhe-wen REN,Jun CHENG,Cai-hong XU,Hui ZHANG

Chinese Journal of Antituberculosis. 2019, 41(9):  1021-1024.  doi:10.3969/j.issn.1000-6621.2019.09.020

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Close contacts of tuberculosis patients is one of the high-risk groups for Mycobacterium tuberculosis infection and active tuberculosis. Preventive treatment of close contacts with latent infection can decrease the incidence of tuberculosis. This study discusses the current researches on preventive treatment in close contacts with latent tuberculosis infection to clarify the research progress and existing problems of preventive treatment in this group, and to provide suggestions for further researches and explorations in the future.