Table of Content

10 November 2023, Volume 45 Issue 11

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Special Topic

Interpretation and reflection on the WHO Preferred Product Characteristics for New Tuberculosis Vaccines

Dong Jiaxin, Zhao Aihua, Xia Huanzhang, Xu Miao

Chinese Journal of Antituberculosis. 2023, 45(11):  1016-1020.  doi:10.19982/j.issn.1000-6621.20230318

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Despite significant advancements in global research, no new tuberculosis (TB) vaccine has been successfully licensed so far. Development of new TB vaccines is urgently needed to end the prevalence of TB, therefore, the World Health Organization (WHO) published the report “WHO Preferred Product Characteristics for New Tuberculosis Vaccines” in 2018. This document outlines the preferences of WHO for new TB vaccines. The authors interpret the document and analyze the direction of development for new TB vaccines, in hope to provide valuable insights for vaccine researchers and formulate new TB vaccines more adaptable to practical needs.

Original Articles

A cross-sectional study on the economic burden of pulmonary tuberculosis patients from western China

Hao Dongqing, Li Tao, Huang Fei, Xu Caihong

Chinese Journal of Antituberculosis. 2023, 45(11):  1021-1030.  doi:10.19982/j.issn.1000-6621.20230137

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Objective: To investigate the economic burden of patients with pulmonary tuberculosis (TB) in western China and provide reference for developing policies to reduce the economic burden of TB patients. Methods: This cross-sectional study employed cluster sampling to select 16 TB treatment facilities across 12 western provinces in China from October 2022 to December 2020. Face-to-face questionnaire surveys were conducted on drug-susceptive pulmonary TB patients who had undergone treatment for more than two weeks. These surveys encompassed their demographic characteristics, expenses and household income. Descriptive analysis was used to analyze the demographic characteristics, expenses and catastrophic expenditure of patients. Results: A total of 1030 patients with pulmonary TB were included in the study. The median (IQR) of the total cost for tuberculosis patients was 8703.30 (4046.00, 15715.59) yuan, comprising direct medical costs of 5823.85 (2341.01, 10852.23) yuan, direct non-medical costs of 1589.53 (675.14, 3163.45) yuan, and indirect costs of 12.03 (0.34, 720.27) yuan. A total of 52.82% (544/1030) of patients experienced household catastrophic expenditure for the treatment of pulmonary TB. Conclusion: The economic burden of pulmonary TB patients in western region of China is heavy. The total cost and direct medical cost of pulmonary TB patients are high, contributing to a heightened incidence of household catastrophic expenditure.

Analysis of economic burden and influencing factors of rifampin-resistant pulmonary tuberculosis in Yunnan Province

Lyu Tong, Yang Yunbin, Pan Ying, Cheng Yuyu, Li Zichao, Xu Lin

Chinese Journal of Antituberculosis. 2023, 45(11):  1031-1037.  doi:10.19982/j.issn.1000-6621.20230235

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Objective: To evaluate the cost burden of rifampicin-resistant pulmonary tuberculosis patients in Yunnan Province, and analyze the influencing factors, to provide a basis for reducing the economic burden of patients and improving the investment of health resources. Methods: A cross-sectional survey was conducted to collect all rifampicin-resistant pulmonary tuberculosis patients who received drug resistant treatment in designated hospitals of Kunming, Baoshan, Pu’er, Lincang, Honghe, Wenshan, Dali, and Zhaotong in Yunnan Province from January 1, 2020 to March 1, 2022. A total of 214 cases were investigated. Basic demographic characteristics, diagnosis and treatment information, and cost information of them were collected, and the economic burden and influencing factors were analyzed. Results: The median (quartile) total cost of the survey subjects from the first visit to the completion of treatment was RMB 88114.02 (70260.45, 118130.37) yuan, of which the median (quartile) direct economic burden was RMB 76164.03 (59589.27, 94893.69) yuan, accounting for 85.60% (18.3605 million/21.44899 million), and the median (quartile) direct medical cost in the direct economic burden was RMB 70999.33 (55405.57, 88420.54) yuan, accounting for 79.93% of the total expenses (17.1451 million/21.4489 million). Medical insurance reimbursement accounted for 42.75% (9.1693 million/21.4489 million) of the total expenses, followed by self-paid direct medical expenses (25.78%, 5.5285 million/21.4489 million), indirect economic burden (14.40%, 2.4454 million/21.4489 million), policy reduction (11.40%, 2.4454 million/21.4489 million), and direct non-medical expenses (5.67%, 1.2154 million/21.4489 million). The median (quartile) self-paid expenses of the survey subjects was RMB 39648.35 (26397.11, 56458.26) yuan. Of the survey subjects, 186 (86.92%) were found that the proportion of self-paid expenses to family annual income was ≥20%, which was a high economic burden for the family. Multivariate logistic analysis showed that patients who had been hospitalized twice or more during the diagnosis stage had a 18.522 times (95%CI: 1.855-184.981) higher risk of high family economic burden than those who had not been hospitalized. Patients with an annual income of over 75% of the family annual income had a 8.320 times (95%CI: 1.466-47.223) higher risk of high family economic burden than those who with an annual income of less than 25% of the family annual income. Conclusion: With existing policies, the economic burden of rifampicin-resistant pulmonary tuberculosis patients in Yunnan Province is still heavy, especially for patients who have been hospitalized twice or more during the diagnosis stage and whose annual income accounts for over 75% of their family’s annual income. It is recommended that the proportion of medical insurance reimbursement should be increased in Yunnan Province, and support measures such as social assistance to patients should be provided, to reduce their economic burden.

Analysis of recurrence and influencing factors of tuberculosis patients in Sichuan Province within 2 years

Li Jing, Gao Yuan, Lu Jia, He Jinge, Chen Chuang, Zhong Yin, Yang Ni, Xia Lan

Chinese Journal of Antituberculosis. 2023, 45(11):  1038-1044.  doi:10.19982/j.issn.1000-6621.20230193

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Objective: To understand the relapse situation and influencing factors of tuberculosis patients in Sichuan Province in the past two years, and to provide scientific basis for further adjustment and improvement of tuberculosis prevention and control strategies in Sichuan Province. Methods: A cluster random sampling method was used to select one county from 21 cities in Sichuan Province with detection capability. 1393 etiologically positive tuberculosis patients who completed treatment in 2019 were taken as research objects. In 2020 and 2021, the study subjects were followed up and re-examined using a unified method (including questionnaire surveys, symptom screening, and chest X-ray examination), to analyze the recurrence of tuberculosis in 2 years. Multivariate logistic regression was used to analyze the main influencing factors of recurrence after successful treatment of pulmonary tuberculosis. Results: 61 (4.4%) of 1393 cases of tuberculosis with previous etiology were found to have relapses. The recurrence density was 3.37/100 person years (61/1657.61). Body mass index ≥24.0 (aOR=0.30, 95%CI: 0.94-0.96), 4 and 5 correct answers to core knowledge of tuberculosis (aOR=0.28, 95%CI: 0.09-0.88; aOR=0.23, 95%CI: 0.07-0.76), good initial treatment compliance (aOR=0.42, 95%CI: 0.19-0.94) were protective factors for relapse of tuberculosis patients. The risk factors for relapse of tuberculosis patients were pulmonary cavity (aOR=3.24, 95%CI: 1.71-6.14) and HIV infection (aOR=3.26, 95%CI: 1.03-10.36) after the initial treatment. Conclusion: Tuberculosis patients in Sichuan Province had a high risk of recurrence within two years. It is necessary to strengthen the management of pulmonary cavities and newly treated tuberculosis patients with HIV infection. Targeted measures such as strengthening health education and nutritional guidance for the above high-risk population could reduce tuberculosis recurrence.

Awareness of core information on tuberculosis prevention and treatment and its influencing factors in Yunnan Province, 2020

Yang Rui, Su Zhiyang, Liu Yiping, Lu Kunyun, Xu Lin

Chinese Journal of Antituberculosis. 2023, 45(11):  1045-1051.  doi:10.19982/j.issn.1000-6621.20230209

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Objective: To understand the awareness of core information on tuberculosis prevention and treatment and its influencing factors in Yunnan Province,and to provide scientific basis for health promotion of tuberculosis prevention and control in the future. Methods: From December 1, 2020 to January 31, 2021,the multi-stage stratified cluster sampling method was used to investigate the core knowledge of tuberculosis prevention and control among local residents ≥15 years old in Yunnan Province. A total of 1440 questionnaires were distributed, and 1397 valid questionnaires were retrieved, with an effective rate of 97.01%. Descriptive analysis, Chi-square test and multivariable logistic regression analysis were used to explore the related factors influencing the public awareness. Results: The total awareness rate and overall awareness rate of tuberculosis prevention and control core knowledge were 85.27% (5956/6985) and 50.32% (703/1397) in Yunnan Province in 2020. The overall awareness rates among age groups of 15-24 (OR=2.729, 95%CI:1.404-5.305), 25-44 (OR=2.612, 95%CI:1.599-4.264), and 45-64 (OR=1.689, 95%CI:1.083-2.634) were all higher than those aged 65 and above. Rate of Han people was higher than rates of other ethnic groups (OR=1.971,95%CI:1.482-2.623), rates among people with education level of primary school (OR=2.001,95%CI:1.193-3.355), junior high school and equivalent education (OR=2.418,95%CI:1.451-4.030), high school and equivalent education (OR=2.834,95%CI:1.580-5.083), college and above (OR=2.214,95%CI:1.160-4.225) were higher than rates among illiterate and semi-illiterate people, and rates among those who received health education were higher than those who did not (OR=2.193,95%CI:1.662-2.894). 76.74% (1072/1397) of participants had received health education, mainly through television (55.69%, 597/1072). Conclusion: The awareness rate of tuberculosis prevention and control core knowledge among the public in Yunnan Province has met the requirements of the national plan, but it is still necessary to further strengthen the health promotion of tuberculosis prevention and control, especially for the elderly, people with low education level and ethnic minorities.

Study on the rapid diagnosis of bovine tuberculosis by dual-target real-time fluorescent PCR

Ou Xichao, Zhao Bing, Teng Chong, Zhang Siqi, Xu Ye, Xing Ruida, Pei Shaojun, Xia Hui, Wang Shengfen, Fan Weixing, Zhao Yanlin

Chinese Journal of Antituberculosis. 2023, 45(11):  1052-1057.  doi:10.19982/j.issn.1000-6621.20230202

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Objective: A dual-target real-time fluorescent PCR technique was developed for the detection of IS6110 and IS1081 genes of Mycobacterium tuberculosis complex (MTBC), to evaluate the feasibility of MTBC rapid detection in cow samples, and to provide basic data support for the application of molecular detection technology in the early diagnosis of bovine tuberculosis. Methods: MTBC real-time fluorescence PCR system was established with IS6110 and IS1081 as specific target genes. The limit of detection for two-target real-time fluorescent PCR system was determined by preparing and detecting bovine lung tissues containing different concentrations of Mycobacterium bovis suspensions. Using DNA of 21 common standard nontuberculous mycobacteria (NTM) strains as amplification template, the specificity of dual-target real-time fluorescent PCR detection of MTBC was determined. MGIT 960 liquid culture, Xpert MTB/RIF (Xpert), Xpert MTB/RIF Ultra (Xpert Ultra) and dual-target real-time fluorescent PCR were used to detect the tissue samples. Using liquid culture results as a reference standard, the efficacy of dual target real-time fluorescence PCR detection in detecting MTBC in dissected cow diseased materials was analyzed. Results: According to the results of dual-target real-time fluorescent PCR detecting the DNA of 21 NTM strains, no amplification curve was detected, the detection specificity of MTBC was 100.0% (21/21). The positive rates of liquid culture, Xpert, Xpert Ultra, and dual-target real-time fluorescent PCR detection were 64.0% (32/50), 56.0% (28/50), 78.0% (39/50), and 76.0% (38/50), respectively. The positive rate of dual-target real-time fluorescent PCR detection was significantly higher than that of Xpert detection (χ²=4.456, P=0.035). There was no statistically significant difference between the positive rates of dual-target real-time fluorescent PCR detection and Xpert Ultra detection (χ²=0.056, P=0.812). Based on the results of liquid culture experiments, the sensitivity and specificity of dual-target real-time fluorescent PCR for detecting MTBC were 90.3% (28/31) and 40.0% (6/15), and those of Xpert Ultra were 96.8% (30/31) and 40.0% (6/15), respectively. Conclusion: The dual-target real-time fluorescent PCR technique can be used for early diagnosis of bovine tuberculosis, which is helpful to control the epidemic and spread of zoonotic tuberculosis.

Investigation of the inconsistent results between two methods in determining fluoroquinolone resistance against Mycobacterium tuberculosis isolates

Zhan Jian, You Guoqing, He Xia, Kong Jueying, Liu Wenguo, Feng Xin, Hu Yan

Chinese Journal of Antituberculosis. 2023, 45(11):  1058-1063.  doi:10.19982/j.issn.1000-6621.20230161

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Objective: To evaluate the performance of the fluorescence PCR melting curve method in determining fluoroquinolone resistance in Mycobacterium tuberculosis isolates, and to analyze the inconsistency between the fluorescence PCR melting curve method (melting curve method) and the phenotypic drug susceptibility test (DST) in detecting the susceptibility of fluoroquinolone. Methods: A total of 126 multidrug-resistant tuberculosis (MDR-TB) isolates confirmed with identification and DST from 39 counties of Chongqing City between January 2019 and June 2020 were randomly selected using simple random sampling. Phenotypic DST by both microdilution testing and melting curve method were applied to detect the drug resistance to levofloxacin (Lfx) and moxifloxacin (Mfx). Phenotypic DST served as a reference standard to assess the detection performance. Whole genome sequencing (WGS) was used to analyze the discordant results between the phenotypic and molecular DST. Results: Taking the phenotypic DST as the standard, the sensitivity, specificity of melting curve method were 94.5% (86/91, 95%CI: 87.1%-98.0%), 100.0% (35/35, 95%CI: 87.7%-100.0%) respectively. There were 12 cases with discordant results between the two methods, and the inconsistency rate was 9.5% (12/126). Five isolates identified as FQs-resistant by phenotypic DST showed melting curve method susceptibility. Further WGS sequencing analysis showed that 2 isolates didn’t harbor any gyrA mutations, 2 isolates harbored gyrB mutations (the MIC of these 4 isolates were 1-2 μg/ml for Lfx and 0.5 μg/ml for Mfx) and 1 isolate with 15.3% FQs heteroresistance harbored gyrA_Asp94Ala mutation. Seven isolates identified as FQs-resistant by melting curve method showed phenotypic susceptibility to FQs. WGS sequencing analysis detected 5 isolates with gyrA_Ala90Val, 1 with gyrA_Asp94Ala and 1 with gyrA_Asp94Asn, the MIC of these 7 isolates were 1-2 μg/ml for Lfx and 0.25-0.5 μg/ml for Mfx. Conclusion: The melting curve method showed high detection efficiency for FQs resistance. The proportion of FQs heteroresistant populations and the low-level-resistance-associated mutations are the main reasons that affect the detection performance of melting curve method and lead to its inconsistency with phenotypic DST.

The value of GeneXpert MTB/RIF in improving the laboratory confirmed pulmonary tuberculosis and rifampicin resistance screening at district level institution in Beijing

Zhao Ailan, Yu Qin, Yu Nan, Zhang Aijie, Xia Hui, Xu Wei

Chinese Journal of Antituberculosis. 2023, 45(11):  1064-1071.  doi:10.19982/j.issn.1000-6621.20230206

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Objective: To analyze the value of GeneXpert MTB/RIF (GeneXpert) in improving the pathogenic positivity and early diagnosis of rifampicin resistance of pulmonary tuberculosis in primary tuberculosis prevention and treatment institution in Beijing. Methods: A retrospective analysis was performed on 3060 pulmonary tuberculosis suspects who visited the Tuberculosis Outpatient Department in Chaoyang District of Beijing from 2018 to 2022. The positive rates of acid-fast bacilli smear microscopy, Löwenstein-Jensen medium based solid culture for mycobacterium (solid culture), and GeneXpert among tuberculosis suspects, as well as the positive proportion of each testing method among overall laboratory confirmed patients were analyzed. The sensitivity and specificity of GeneXpert was analyzed in sputum samples using solid culture as a reference standard. The value of GeneXpert for detection of rifampicin resistance was also analyzed. Results: From 2018 to 2022, the laboratory confirmed cases in active pulmonary tuberculosis cases gradually increased from 45.07% (215/477) in 2018 to 69.39% (102/147) in 2022, with statistical significance ( {\chi }_{\mathrm{t}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{d}}^2=27.761, P<0.001). The positive rate of acid-fast bacilli smear microscopy (46.51%, 347/746), mycobacterial solid culture (83.24%, 621/746), and GeneXpert (82.71%, 617/746) among all laboratory confirmed pathogenic positive cases was statistically different (χ²=320.000, P<0.001). Among all pathogenic positive cases, the proportion of smear-negative and GeneXpert-positive cases was 36.86% (275/746), and smear-negative/solid culture-negative but GeneXpert-positive cases were 12.60% (94/746), respectively. The sensitivity and specificity of GeneXpert were 79.39% (493/621; 95%CI: 76.20%-82.56%) and 93.39% (1751/1875; 95%CI: 92.27%-94.51%), respectively. The total rifampicin resistance rate of pulmonary tuberculosis patients detected by GeneXpert was 7.46% (46/617). The frequency of each mutation probe was as follows: probe E (63.27%, 31/49) >combined mutation (AB, AD, DE and ABE, 10.20%, 5/49) >probe D (8.16%, 4/49) >probe A (6.12%, 3/49) =probe B (6.12%, 3/49) >no probe mutation (4.08%, 2/49) >probe C (2.04%, 1/49). Conclusion: In primary tuberculosis prevention and treatment institution, the application of GeneXpert combined with mixing three sputum samples can help improve the pathogenic positive rate of pulmonary tuberculosis patients, and early detect the rifampicin-resistant patients.

Analysis of the effect of GeneXpert MTB/RIF technology on early detection of bacteriologically confirmed and drug-resistant pulmonary tuberculosis in general hospitals

Ruan Yunzhou, Zhang Hongwei, Li Yuehua, Ma Yingzi, Cheng Shiming, Fan Haiying, Li Renzhong, Zhao Yanlin

Chinese Journal of Antituberculosis. 2023, 45(11):  1072-1077.  doi:10.19982/j.issn.1000-6621.20230313

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Objective: To understand the current situation of GeneXpert MTB/RIF (GeneXpert) technology in the diagnosis of bacteriologically confirmed pulmonary tuberculosis and drug-resistant pulmonary tuberculosis in general hospitals, so as to better play the role of general hospitals in the detection of pulmonary tuberculosis. Methods: A retrospective cohort study was conducted with pulmonary tuberculosis patients that from 8 tertiary general hospitals equipped with GeneXpert as the study group and those from 3 tertiary general hospitals not equipped with GeneXpert as the control group. The proportion of bacteriologically confirmed patients, the proportion of rifampicin-resistant patients, the diagnosis time of pulmonary tuberculosis patients and the diagnosis time of rifampicin-resistant patients were compared and analyzed between the two groups. Results: A total of 370 patients who were tested by GeneXpert in the study group and 342 patients who were not tested by GeneXpert in the control group were enrolled in the study. The proportion of bacteriologically confirmed patients in the study group (88.9%, 329/370) was higher than that in the control group (67.0%, 229/342; χ²=50.560, P<0.001). Among the patients with bacteriologically confirmed, the proportion of first diagnosis in the study group (96.4%, 317/329) was higher than that in the control group (75.1%, 172/229; χ²=56.228, P<0.001). The diagnosis time of pulmonary tuberculosis in the study group (1 (1,5) d) was shorter than that in the control group (4 (1,11) d; nonparametric test, P<0.001). The study group found that the proportion of patients with rifampicin resistance was 80.0% (8/10), while the proportion found in the control group was 0 (0/6; Fisher’s exact test, P=0.007). The diagnosis time of rifampicin resistance in the study group (1 (1,4) d) was significantly shorter than that in the control group (20 (11,29) d; nonparametric test, P=0.005). Among the patients in the study group who underwent both GeneXpert and sputum smear testing, the proportion of MTB detected by GeneXpert (82.0%, 242/295) was higher than that detected by sputum smear (33.6%, 99/295; χ²=142.092, P<0.001); when GeneXpert and sputum culture were tested simultaneously, the proportion of MTB detected by GeneXpert (86.3%, 107/124) was higher than that of sputum culture (63.7%, 79/124; χ²=16.860, P<0.001). Conclusion: GeneXpert technology is helpful for the early diagnosis of bacteriologically confirmed pulmonary tuberculosis and drug-resistant pulmonary tuberculosis in general hospitals. It is suggested that general hospitals should routinely carry out GeneXpert test and incorporate it into the medical insurance reimbursement catalogue to improve its efficiency.

Effect of a new treatment regimen on patients with initially retreated drug-sensitive pulmonary tuberculosis

Ge Qiping, Zhang Lijie, Huang Xuerui, Jiang Guanglu, Han Xiqin, Wang Jingping, Du Jian, Ma Yan, Gao Weiwei

Chinese Journal of Antituberculosis. 2023, 45(11):  1078-1083.  doi:10.19982/j.issn.1000-6621.20230192

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Objective: To evaluate the efficacy and safety of a new treatment regimen against a standardized regimen on patients with retreated drug-susceptible pulmonary tuberculosis (PTB). Methods: This multi-centered study adopted a prospective study design, 592 patients with initially retreated PTB (including drug-susceptible, mono-drug resistance, poly-drug resistance and a few cases of smear negative retreated PTB) whom had been randomized into the new regimen arm (4H-L₂-E-Z-Lfx/4H-L₂-E; H: isoniazid, L: rifapentine, E: ethambutol, Z: pyrazinamide, Lfx: levofloxacin; body mass <50 kg, H for 0.3 g/d, E for 0.75 g/d; body mass ≥50 kg, H for 0.4-0.5 g/d, E for 0.75-1.0 g/d; regardless of body weight, L was 0.6 g, twice a week; Z: 1.5 g/d, Lfx: 0.5-0.6 g/d), and the standardized regimen arm (3H-R-E-Z/6H-R-E using conventional doses; R: rifampicin), diagnosed and hospitalized in between Jan 2019 and Dec 2021 by 24 PTB designated hospitals across 14 provinces and 3 municipalities in China were screened at baseline. According to inclusion and exclusion criteria, only those with initially retreated drug-susceptible PTB were recruited as study subjects. The rates of treatment success, treatment failure as well as incidence of adverse events were compared, safety and efficacy of the new regimen derived. Results: The final analysis included 238 cases, of which 172 cases (72.3%) were randomized into the new regimen arm, 66 cases (27.7%) into the standardized regimen arm. The success rate of the new regimen arm was higher than that of the standardized regimen arm (77.3% (133/172) vs. 62.1% (41/66); χ²=5.609, P=0.018), and the failure rate was lower than that of the standard regimen arm (4.7% (8/172) vs. 27.3% (18/66); χ²=25.083, P=0.000). There was no significant difference in the incidence of adverse reactions between the two arms (4.7% (8/172) vs. 3.0% (2/66); Fisher test, P=0.731). Conclusion: Compare to the standardized regimen, the new retreatment regimen had improved the treatment success rate and lowered the rate of treatment failure among patients with retreated drug-sensitive PTB, demonstrated good overall safety and efficacy profile.

Research on the factors influencing tuberculosis hospitalization costs and diagnosis related grouping

Yan Xiaojing, Nie Wenjuan, Liu Haiyan, An Jun, Chi Yuqing, Chu Naihui

Chinese Journal of Antituberculosis. 2023, 45(11):  1084-1089.  doi:10.19982/j.issn.1000-6621.20230127

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Objective: Based on the research on the influencing factors of hospitalization costs, explore the scheme of diagnosis related groups (DRG) of tuberculosis under the classification of tuberculosis, determine the grouping according to the cost, and provide a basis for reasonable grouping of DRG. Methods: We collected 1812 confirmed patients from Beijing Chest Hospital affiliated to Capital Medical University from January 1, 2018 to December 31, 2020. According to the classification of pulmonary tuberculosis, the basic group level was divided into two groups: sensitive pulmonary tuberculosis and drug-resistant pulmonary tuberculosis. There were 109 cases in the sensitive pulmonary tuberculosis group and 1703 cases in the drug-resistant pulmonary tuberculosis group. Statistical description of the median and quartile of hospitalization expenses for patients under different factors was done. Kruskal Wallis H-test, Mann Whitney U-test, and multiple linear regression methods were used to analyze the factors affecting hospitalization expenses. P<0.05 indicates a statistically significant difference. Using decision trees to process data to complete the division of sub-groups. The coefficient of variation (CV) and reduction in variance (RIV) were used to evaluate intra group homogeneity and inter group heterogeneity between the groups, and the Kruskal Wallis H test was used to test the group results. Results: We analyzed the hospitalization expenses of patient groups under different factors. It was found that the median (quartile) hospitalization expenses for patients aged ≤30 years old were 20586.66 (13656.41,90163.58) yuan, 23256.47 (17490.26,82919.32) yuan for those aged 31-40 years old, 21154.19 (13615.14,76240.28) yuan for those aged 41-50 years old, 23544.59 (16325.46,87608.46) yuan for those aged 51-60 years old, 25190.27 (20528.01,78321.02) yuan for those aged 61-70 years old, and 24890.24 (18424.86,91662.89) yuan for those aged ≥71 years old. The median (quartile) hospitalization cost for drug sensitive patients was 21693.82 (16567.26,91662.89) yuan, 21866.32 (14390.17,87896.56) yuan for multidrug-resistant patients, 23703.70 (18021.55,90163.58) yuan for monodrug-resistant patients, 18846.98 (11400.11,78321.02) yuan for extensively resistant patients, and 23900.67 (16006.08,58834.03) yuan for multidrug-resistant patients. The median (quartile) hospitalization cost for patients with 0 complications was 9730.37 (5361.33,28053.18) yuan, 20378.65 (14110.72,90163.60) yuan for patients with 1-5 complications, 24072.81 (17966.19,87608.46) yuan for patients with 6-10 complications, 24953.26 (18411.59,87896.56) yuan for patients with 11-15 complications, 32530.70 (23904.41,74195.40) yuan for patients with 16-20 complications, and 29647.02 (25707.11,91662.89) yuan for patients with ≥21 complications. The median (quartile) hospitalization cost for newly treated patients was 23594.24 (17890.74,91662.89) yuan, while for re-treated patients it was 21662.63 (14369.58,87896.56) yuan. Kruskal Wallis H-test showed that there was statistical significance in hospitalization expenses between groups after grouping according to age, drug-resistance type, and different complications (H-values were 58.510, 19.556, and 92.424, respectively, P<0.05). The Mann Whitney U-test showed that there was a statistically significant difference in hospitalization expenses between groups after initial/recurrent treatment (U=-4.422, P<0.05). The presence of complications, type of initial and recurrent treatment, length of hospital stay, and age were all included in the regression model. At the sub-group level, the DRG group of pulmonary tuberculosis was divided into 5 groups: drug sensitive pulmonary tuberculosis, drug-resistant pulmonary tuberculosis with hospitalization time ≤7 days, drug-resistant pulmonary tuberculosis with hospitalization time 8-14 days, drug-resistant pulmonary tuberculosis with hospitalization time 15-20 days, and drug-resistant pulmonary tuberculosis with hospitalization time ≥21 days. The median (quartile) hospitalization cost for drug sensitive pulmonary tuberculosis group was 21693.82 (16567.26,91662.89) yuan. While for drug-resistant pulmonary tuberculosis with hospitalization time ≤7 days group, the median (quartile) hospitalization cost was 12334.88 (7141.91,59741.83) yuan. For drug-resistant pulmonary tuberculosis with hospitalization time 8-14 days, the median (quartile) hospitalization cost was 20842.28 (16459.27,80496.43) yuan. The median (quartile) hospitalization cost for drug-resistant pulmonary tuberculosis with hospitalization time 15-20 days was 26612.13 (21683.16,90163.58) yuan. The median (quartile) hospitalization cost for drug-resistant pulmonary tuberculosis with hospitalization time ≥21 days was 33326.87 (25680.93,87896.56) yuan. The Kruskal Wallis H-test results showed an H-value of 660.241, with a P<0.05, indicating a statistically significant difference between the groups. The CV values of each group were less than 1, which met the DRG grouping criteria. From the basic group divided by sensitive drug-resistance type to the sub-group level, the RIV value increased from 0.01% to 33.82%, with a significant increase in differences. Conclusion: Introducing elements of drug-resistance type and treatment type into grouping elements was conducive to closely combining clinical similarity and resource consumption similarity, improving the accuracy and scientificity of grouping. It is recommended to group according to different types of pulmonary tuberculosis and determine payment standards based on this to improve the scientificity of DRG grouping and payment.

Analysis of clinical features and influencing factors of epilepsy secondary to tuberculosis meningitis in children

Shi Jiayun, Zhou Haiyi, Wei Songqing, Jiang Jie, Wu Lei

Chinese Journal of Antituberculosis. 2023, 45(11):  1090-1096.  doi:10.19982/j.issn.1000-6621.20230183

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Objective: To analyze the clinical features and influencing factors of epilepsy secondary to tuberculous meningitis (TBM) in children. Methods: One hundred and thirty-six children diagnosed with TBM during Jan. 2018 to Jan. 2022 in Changsha Central Hospital Affiliated to the University of South China were enrolled for retrospective analysis. Univariate and multivariate logistic regression models were used to analyze the influence of clinical characteristics on secondary epilepsy in children with TBM. Results: Among 136 children with TBM, 20 (14.7%) had secondary epilepsy. Univariate analysis showed that focal symptoms in the nervous system (30.0% (6/20)), changes in consciousness (65.0% (13/20)), hydrocephalus(50.0% (10/20)), cerebral infarction (30.0% (6/20)), accompanied by tuberculoma (10.0% (2/20)), TBM phase Ⅲ (50.0% (10/20)), cerebrospinal fluid protein (1.66 (0.02, 5.60) g/L), cerebrospinal fluid adenosine deaminase (ADA)(12.74 (1.22, 63.50) U/L), blood sodium ((127.35±3.73) mmol/L) in children with secondary epilepsy were significant different from that in children without secondary epilepsy (6.9% (8/116), 30.2% (35/116), 17.2% (20/116), 9.5% (11/116), 1.7% (2/116), 11.2% (13/116), 1.01 (0.02, 5.60) g/L, 3.79 (0.00, 94.00) U/L and (132.91±5.40) mmol/L)(χ²=9.860, P=0.007; χ²=9.060, P=0.004; χ²=13.820, P=0.001; χ²=6.566, P=0.021; χ²=13.511, P=0.004; χ²=19.478, P=0.000; Z=-2.120, P=0.034; Z=-5.005, P=0.000; t=-4.424, P=0.000). Multivariate logistic regression analysis showed that cerebral infarction (OR (95%CI)=4.397 (1.152-5.837), P=0.014), increased ADA in cerebrospinal fluid (OR (95%CI)=1.044 (1.021-1.297), P=0.033), and hyponatremia (OR (95%CI)=0.814 (0.672-0.909), P=0.003) were risk factors for secondary epilepsy to TBM. Conclusion: The proportion of secondary epilepsy in children with TBM is high, which should be paid great attention in clinic. The occurrence of cerebral infarction, increase of ADA in cerebrospinal fluid and hyponatremia may be important early predictive indicators of secondary epilepsy in children with TBM. Active and standardized anti-epileptic treatment has certain value in controlling secondary epilepsy.

Review Articles

Research progress on macrophage glucose metabolism reprogramming in Mycobacterium tuberculosis infection

Nan Yue, Long Meizhen, Dong Yuhui, Wang Yuanzhi, Zhou Xiangmei

Chinese Journal of Antituberculosis. 2023, 45(11):  1097-1102.  doi:10.19982/j.issn.1000-6621.20230266

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Macrophages are important cells involved in innate immunity and also the main target of Mycobacterium tuberculosis infection. It was found that metabolic reprogramming of immune cells is closely related to their functions. In the early stage of infection, the main change of macrophages is M1 polarized, and the mode of glucose metabolism changes from mitochondrial oxidative phosphate to aerobic glycolysis (Warburg effect), which promotes the secretion of inflammatory factors; while in the late stages of infection, the mode of glucose metabolism of macrophages changes from aerobic glycolysis to mitochondrial oxidative phosphorylation, which inhibits macrophage proinflammatory and antimicrobial responses. A comprehensive understanding of the relationship between macrophage metabolism and function during Mycobacterium tuberculosis infection is help to the development of host directed therapy. In this article, the author summarized the related research on macrophage glycometabolism reprogramming during the infection of Mycobacterium tuberculosis, in order to provide new ideas for the prevention and treatment of tuberculosis.

The progress of non-tuberculous mycobacterial disease in children

Jiang Xiaoyi, Liang Qian, Xue Yi, Huang Hairong

Chinese Journal of Antituberculosis. 2023, 45(11):  1103-1107.  doi:10.19982/j.issn.1000-6621.20230243

Abstract ( 149 )   HTML ( 7 )   PDF (797KB) ( 88 )   Save

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The prevalence of non-tuberculous mycobacteria (NTM) disease in children is increasing globally. The clinical manifestations of NTM disease in children are significantly different from those in adults,although only a few related literatures have been published. This article summarizes the epidemiological characterization, the common disease type and the most pathogenic NTM species, main clinical manifestations, diagnosis and treatment of pediatric NTM diseases, so as to strength the understanding of the disease.