Table of Content

10 February 2018, Volume 40 Issue 2

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WHO Series of Dovuments Interpretation

Changes of pediatric tuberculosis control and prevention strategies

Lin SUN,A-dong SHEN

Chinese Journal of Antituberculosis. 2018, 40(2):  128-134.  doi:10.3969/j.issn.1000-6621.2018.02.003

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In response to the current situation of pediatric tuberculosis (TB), a series of guidelines and re-commendations have been published by World Health Organization (WHO) and Ministry of Health in various countries, which provide important guidance to regulate the diagnosis, treatment, prevention and management of pedia-tric TB. The management of children with TB is an important aspect of global TB control. The summary of pediatric TB teased from the publications of WHO since DOTS strategy proposed in 1991, including 4 guidelines, 10 recommendations, 2 statements, 2 handbooks, 2 roadmaps and 1 review, is useful to understand the changes in the prevention and control strategies for children with TB, promote the early diagnosis and treatment, solve current problems, and facilitate the popularization of the guidelines.

Trends in development of treatment guidelines for multidrug-resistant tuberculosis

Yi ZHANG,Feng SUN,Wen-hong. ZHANG

Chinese Journal of Antituberculosis. 2018, 40(2):  135-139.  doi:10.3969/j.issn.1000-6621.2018.02.004

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The global incidence of tuberculosis has declined marginally from 2000 to 2017, but it is still under poor control in parts of Africa and Asia. Multidrug-resistant tuberculosis (MDR-TB) has become a major concerned issue in the global public health system, and the optimum medications and treatment regimens for MDR-TB remain controversial. This review summarizes the treatment guidelines for MDR-TB in recent years and analyzes the background, specific recommendations, implementations and trends of these guidelines.

Expert Note

The thinking of chemotherapy for patients with spinal tuberculosis

Rui-hua JIANG,He-ping. XIAO

Chinese Journal of Antituberculosis. 2018, 40(2):  140-144.  doi:10.3969/j.issn.1000-6621.2018.02.005

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Spinal tuberculosis is one of the most common types of extra-pulmonary tuberculosis. With the progress of the modern imaging and laboratory diagnostic techniques, the confirmed diagnosis rate of spinal tuberculosis is increased year by year. The principles of the spinal tuberculosis treatment are as follows: anti-tuberculosis chemotherapy is the basic method of treatment; nutrition support and surgical treatment are the supplemental me-thods. In order to provide a reference for the clinical treatment of the patients with spinal tuberculosis, in this study, we described the characteristics of the anti-tuberculosis chemotherapy to the patients with spinal tuberculosis, time of the chemotherapy initiation, design of the treatment regimens selection of the anti-tuberculosis drugs and the treatment duration, as well as the local anti-tuberculosis chemotherapy, indications for stopping anti-tuberculosis chemotherapy.

Thinking on the disposal of tuberculosis outbreak in schools

Jun CHENG,Yin-yin XIA,Er-yong LIU,Lin. ZHOU

Chinese Journal of Antituberculosis. 2018, 40(2):  145-148.  doi:10.3969/j.issn.1000-6621.2018.02.006

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In recent years, the incidence of tuberculosis in schools has been decreasing. However, the aggregated epidemic still occurs. Up to now, nearly 80 tuberculosis epidemic cases have been reported in the country since 2006. Most happened in boarding schools, about 70% in high school or secondary school, and about 20% in private schools. Common misunderstandings for the disposal of tuberculosis in schools (1) reduce or blindly expand the scope of close contact screening. At the beginning, there was a lack of screening range, which caused the patients to find untimely, and after the aggravation of the epidemic, the scope of screening was expanded blindly, resulting in the waste of resources. (2) the screening method for close contacts is not standardized. The guidelines for tuberculosis prevention and control in schools require that close contacts should be screened by symptom screening, tuberculin skin test and chest X-ray examination. Part epidemic sites only provide chest fluoroscopy rather than chest X ray examination for people over 15 years old or only provide chest X ray examination resulting in untimely detection. Some sites were screened for close contacts by chest CT examination because of abundant resources or epidemic pressure. Many inactive or active small nodules lesions were found due to increased sensitivity, causing panic among people and increasing the pressure of outbreaks. (3) the intervention of close contact with tuberculin test strong positive was not effective. In most areas, tuberculosis preventive treatment was not performed on those with strong positive tuberculin test, and some of the epidemic occurred repeatedly. (4) non-standard anti-tuberculosis treatment and unnecessary adjuvant therapy. No reasonable selection of second-line anti-tuberculosis drug treatment often occurs; low-dose or overdose of medication in children patients with tuberculosis; intravenous medication; anti-infection drug abuse and treatment without combined infection evidence, unnecessary immune enhanced treatment, excessive liver protection treatment. The prevention and control of tuberculosis in schools should take educational system and schools as the main body of responsibility, and work under the guidance of education and health administration departments according to the requirements of school tuberculosis prevention and control work (2017 edition).

Expert Forum

Progress in the application of whole genome sequencing in tuberculosis research

Xin-chang CHEN,Wen-hong ZHANG

Chinese Journal of Antituberculosis. 2018, 40(2):  149-152.  doi:10.3969/j.issn.1000-6621.2018.02.007

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With the development of technology and the reduction of cost, whole genome sequencing has been widely used in the research of Mycobacterium tuberculosis (M.tuberculosis) in various respects, including micro-evolution and transmission, macro-evolution and phylogeny, and drug resistance detection. According to the existing research results, genome-wide sequencing has solved many problems that can not be solved by traditional molecular research methods, such as identification of transmission chain, differentiation of recurrent and re-infection, analysis of the evolution of M.tuberculosis, rapid diagnosis of tuberculosis resistance, and diagnosis of mixed infection. Nonetheless, there are still many problems that need to be solved urgently. In this paper, the current research directions and achievements of whole genome sequencing are reviewed, the limitations are proposed, and the future applications are prospected.

Original Articles

Evaluation of next generation sequencing for the diagnosis of active tuberculosis infection

Xian ZHOU,Jing-wen AI,Peng CUI,Qiao-ling RUAN,Yao-jie SHEN,Sen WANG,Yong-jun LI,Wen-hong. ZHANG

Chinese Journal of Antituberculosis. 2018, 40(2):  153-156.  doi:10.3969/j.issn.1000-6621.2018.02.008

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To evaluate the diagnostic value of next-generation sequencing (NGS) in active tuberculosis infection.

The clinical suspicion of active tuberculosis with sample submitted for NGS platform in Huashan Hospital was prospectively enrolled in the period from March 1, 2017 to September 1, 2017. All the cases were followed up for final clinical diagnosis. The submission samples (4 cases of bronchial lavage fluid, 18 cases of cerebrospinal fluid, pleural effusion in 4 cases, 3 cases of pus, ascites, liver tissue in 2 cases, 1 case of synovial fluid) were all sequenced on the BGISEQ-100 platform, and the final result was obtained by comparing the pathogenic sequences to the pathogen database. A positive result for NGS was defined as detection of the single matching sequence of Mycobacterium tuberculosis complex. At least one of tuberculosis culture, pathologically diagnosed tuberculosis infection, Xpert MTB/RIF positive and tuberculosis nucleic acid test is positive for the diagnosis of definite active tuberculosis infection. There are other etiological evidence or clinical exclusion of active tuberculosis infection as non-tuberculosis infection. Then we analyze the sensitivity and specificity of NGS in the diagnosis of tuberculosis.

Among them, 9 cases was definite TB cases, including Xpert MTB/RIF positive in 6 cases, pathological diagnosis in 4 cases, 3 cases of culture positive, tuberculosis nucleic acid PCR positive in 1 case; clinical diagnosis of active tuberculosis in 10 cases, non-tuberculosis infection in 15 cases. Among the definite and clinically diagnosed cases, 11 cases of Mycobacterium tuberculosis complex were detected by NGS. The sensitivity and specificity were 57.9% (11/19) and 100.0% (15/15) respectively. In confirmed cases, the NGS sensitivity was 66.7% (6/9). Among the 31 specimens sent in parallel for Xpert MTB/RIF and NGS, the clinical diagnosis was the gold standard, with a specificity of 100.0% (15/15) and a sensitivity of 37.5% (6/16) and 50.0% (8/16), respectively, with no significant difference (McNemar test, P=0.727).

The second-generation sequencing can detect Mycobacterium tuberculosis complex in multiple samples more rapidly. Its sensitivity and specificity are comparable to those of Xpert MTB/RIF and can be used as a diagnostic test for the early diagnosis of active TB.

The relationship between plasma concentrations of the first-line anti-tuberculosis drugs and sputum negative conversion at early stage

Qi-hui LIU,Feng SUN,Tao SUN,Xiao-fang JIA,Fei-fei SU,Ji-chan SHI,Li-jun ZHANG,Xian-gao JIANG,Wen-hong. ZHANG

Chinese Journal of Antituberculosis. 2018, 40(2):  157-160.  doi:10.3969/j.issn.1000-6621.2018.02.009

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To study the pharmacokinetics of the first-line anti-tuberculosis drugs including rifampicin, isoniazid, and ethambutol in a cohort of Chinese patients with tuberculosis and to determine the relationship between the pharmacokinetic parameters of these anti-tuberculosis drugs and the clinical treatment outcomes.

A prospective study was conducted to recruit patients diagnosed with pulmonary tuberculosis from the Inpatient Department of the Wenzhou Central Hospital from October 1, 2015 to January 31, 2016. A total of 72 patients were enrolled. Subjects were initially treated or retreated once, and both bacteriologically confirmed and clinically diagnosed cases were eligible. Plasma samples were collected 0.5h before and 2h, 4h, 6h, 8h after taking standard quadruple drugs for one week doses. Plasma concentrations were determined using LC-MS/MS. Patients were followed up 2 months after the initiation of treatment to assess the relationships between sputum negative conversion and plasma concentrations.

Among the 72 patients, one patient was confirmed to have multidrug-resistant tuberculosis and one patient was lost to follow up. Thus, 70 patients were analyzed at last, among whom 16 patients were bacteriologically negative and 54 patients were bacteriologically positive at initial diagnosis. The plasma exposures at steady state after one week of drug administration were analyzed. 25.7% (18/70) patients had a plasma peak concentration (C_max) of rifampicin lower than the recommended range (<8μg/ml), 38.6% (27/70) cases had a C_max of isoniazid lower than the recommended range (<3μg/ml), whereas 65.7% (46/70) patients had a C_max of ethambutol lower than the recommended range (<2μg/ml). After 2-month of treatment, among the 54 patients who were sputum bacteria positive at initial diagnosis, 48 patients conversed to sputum bacteria negative, while sputum bacteria were still detected in 6 patients. The C_2h, C_max, and AUC_0-8 of ethambutol were significantly higher in patients who got sputum conversion after 2-month of treatment ((1.81±0.91)μg/ml, (1.81±0.85)μg/ml, and (7.67±3.25)μg·h·ml ^-1) compared with those who failed to get sputum conversion ((0.93±0.32)μg/ml, (1.06±0.25)μg/ml, and (4.93±0.72)μg·h·ml ^-1) (t=4.74, P<0.01; t=4.93, P<0.01; and t=4.95, P<0.01, respectively). The C_2h and C_max of isoniazid were significantly higher in patients who got sputum conversion after 2-month of treatment ((3.67±1.64)μg/ml and (3.85±1.59)μg/ml) compared with those who failed to get sputum conversion ((2.11±1.14)μg/ml and (2.11±1.14)μg/ml) (t=2.60, P=0.012; t=2.25, P=0.029, respectively).

The C_max of drugs below the recommended reference ranges, especially isoniazid and ethambutol, were observed in some patients with pulmonary tuberculosis. The dosage of isoniazid and ethambutol may need to be modified. In addition, the sputum negative conversion after 2-month of treatment was shown to be related with the serum concentration of isoniazid and ethambutol.

Treatment outcomes of the standardized regimens for patients with multildrug-resistant pulmonary tuberculosis in Wenzhou during 2013 to 2015

Gui-qing HE,Feng SUN,Fei-fei SU,Ji-chan SHI,Hai-yan ZHU,Jian-yi DAI,Shou-feng YANG,Hong-ye NING,Xiao-ya CUI,Qun-hua LI,Xian-gao JIANG,Wen-hong. ZHANG

Chinese Journal of Antituberculosis. 2018, 40(2):  161-167.  doi:10.3969/j.issn.1000-6621.2018.02.010

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To study the treatment outcomes of multidrug-resistant pulmonary tuberculosis and analyze the factors associated with treatment outcome in Wenzhou.

Data of 198 MDR-TB patients diagnosed from August 2013 to December 2015 were retrospectively collected. Among them, 10 patients refused to accept treatment, 3 patients died and 2 patients were lost to follow-up before treatment, the chemotherapy regimens and treatment outcomes of 43 patients were unknown, the baseline strain of 1 patient was confirmed as sensitive by the drug sensitivity test three times, the baseline strains of 7 patients were identified as non-tuberculous mycobacteria by 16S rRNA and hsp65 gene, and 16 patients received non-standardized multidrug-resistant tuberculosis regimens. Finally 116 patients received standardized regimens for MDR-TB. We recorded their baseline clinical characteristics, baseline drug susceptibility results, sputum culture conversion, clinical symptom and imaging changes. The primary endpoint was cure, treatment completed, treatment failure, death, or default (lost to follow-up) at the end of the treatment period.

Of 116 patients enrolled into the standardized regimens for MDR-TB, the number of new patients and previously treated patients were 39 (33.6%) and 77 (66.4%), respectively. There were 83 male patients accounting for 71.6% and 33 female patients accounting for 28.4%. The average age was (48.7±12.6) years old and the age ranged from 15 to 77 years old. Of the 116 MDR-TB patients, 59 (50.9%) were cured or completed treatment, 19 (16.4%) experienced treatment failure, 5 (4.3%) died, and 33 (28.4%) were lost to follow-up. The success rate of new patients was higher than that of previously treated patients (69.2% vs 41.6%), and the difference was statistically significant (χ ²=7.932, P=0.005). The success rate of MDR-TB (67.7%, 21/31) was higher than that of pre-XDR-TB (42.6%, 20/47) and XDR-TB (15.4%, 2/13), the differences were statistically significant (χ ²=4.753,P=0.029 and χ ²=10.064,P=0.002). The loss rate of MDR-TB (25.8%, 8/31) was respectively compared with that of pre-XDR-TB (27.7%, 13/47) and XDR-TB (23.1%, 3/13), while there was no statistically significant difference among them (χ ²=0.033, P=0.857; χ ²=0.036, P=0.849). Of the 91 patients with baseline second-line drug susceptibility, 34.1% (31/91), 51.6% (47/91) and 14.3% (13/91), respectively, was simple MDR-TB, pre-XDR-TB, and XDR-TB. And the resistant proportion of ofloxacin accounted for 63.7% (58/91). Simple MDR-TB (87.1%, 27/31) was higher than the pre- XDR-TB (66.0%, 31/47) and XDR-TB (38.5%, 5/13) in terms of sputum culture conversion rates, the difference were statistically significant (log-rank trend test, χ ²=14.500, P<0.001).

The low success rates of MDR-TB treatment in Wenzhou may be related to the high proportion of Pre-XDR-TB and XDR-TB and the high default rates.

Investigation on application of cycloserine in chemotherapy for multidrug-resistant tuberculosis

Yang LI,Fei WANG,Li-min WU,Min ZHU,Gui-qing HE,Feng SUN,Xiao-meng WANG,Wen-hong. ZHANG

Chinese Journal of Antituberculosis. 2018, 40(2):  168-172.  doi:10.3969/j.issn.1000-6621.2018.02.011

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To evaluate the application of cycloserine in the treatment of multidrug-resistant tuberculosis (MDR-TB) and to provide a basis for further optimization of the chemotherapy for MDR-TB patients in China.

The clinical data, including treatment outcomes, of 143 MDR-TB patients in Hangzhou Red Cross Hospital and Wenzhou Central Hospital from 2014 to 2016 were collected. All patients received cycloserine-containing standard treatment according to the World Health Organization Treatment Guidelines for Drug-resistant Tuberculosis, 2016 Update. The data such as treatment outcome, sputum negative conversion rate, and adverse events associated with drug were summarized.

Among the 143 patients treated with cycloserine-containing regimen, the overall treatment success rate achieved 69.2% (99/143). 81.1% (116/143) of patients had sputum culture conversion in the intensive phase. A total of 13 cases (9.1%, 13/143) reported adverse events that were considered to be related with cycloserine, including 7 cases who complained of dizziness or headache, 3 cases of limb numbness, 2 cases of limb twitch and 1 case of depression. All adverse events were relieved by dose reduction or symptomatic treatment.

Cycloserine-containing standard therapy has high overall success rate and well tolerance for MDR-TB patients, which is worth to be applied in clinical.

Study on the value of three kinds of detection techniques for the diagnosis of pulmonary tuberculosis

Xiang SHI,Hong-yun YIN,Wei SHA,He-ping. XIAO

Chinese Journal of Antituberculosis. 2018, 40(2):  173-176.  doi:10.3969/j.issn.1000-6621.2018.02.012

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To evaluate the diagnostic value of sputum simultaneous amplification and testing (SAT) for tuberculosis (TB), peripheral blood T-SPOT.TB and serum TB-Ab in patients with pulmonary tuberculosis.

By reviewing the clinical data and tests results (T-SPOT.TB, SAT and serum TB-Ab) of 980 patients hospitalized in Shanghai Pulmonary Hospital (689 patients with pulmonary tuberculosis and 291 patients with non-tuberculosis lung diseases) from Nov 2014 to Oct 2015, the diagnostic sensitivity and specificity of the three methods were compared. Taking the clinical diagnosis of pulmonary tuberculosis as the gold standard, we calculated the diagnostic efficiency indexes of the three methods, while they were separately or jointly tested in these patients, and drew the receiver operating characteristic (ROC) curves to evaluate their diagnostic value for tuberculosis. As to joint testing, patients were diagnosed as pulmonary tuberculosis if one of the involved tests showed positive results, whereas patients were judged as non-pulmonary tuberculosis if all involved tests showed negative results.

The sensitivity of T-SPOT.TB was 90.67% (593/654), while the specificity was 68.09% (192/282). The sensitivity of SAT was 30.43% (133/437), while the specificity was 100.00% (87/87). The sensitivity of TB-Ab was 43.95% (298/678), while the specificity was 78.82% (227/288). The sensitivity of the co-detection of the three methods was 93.14% (285/306), while the specificity was 53.41% (47/88). The sensitivity of T-SPOT.TB combined with TB-Ab was 92.83% (440/474), while the specificity was 52.11% (148/284). After drawing the ROC curves to evaluate T-SPOT.TB and SAT detections’ performances in diagnosing pulmonary tuberculosis, T-SPOT.TB and SAT-TB tests achieved the areas under the curve (AUC) of 0.798 and 0.652, respectively; and the AUC for T-SPOT.TB+SAT+TB-Ab and T-SPOT+TB-Ab were 0.865 and 0.843, respectively.

The co-detection of the three methods, T-SPOT.TB, SAT and TB-Ab, was the most valuable method for the diagnosis of pulmonary tuberculosis. Combining detection of T-SPOT.TB and TB-Ab could be the second choice. If we only tested one of the three, T-SPOT.TB was the highest valuable detection for the diagnosis of pulmonary tuberculosis, and the highest specificity belonged to sputum SAT detection.

Analysis of mutation in pyrazinamide-resistance gene among the multidrug-resistant Mycobacterium tuberculosis strains isolated from Chongqing municipality

Da-mian ZHU,Dai-yu HU,Jie LIU,Yu PANG,Ming LUO,Jing SHEN,Lin. CHEN

Chinese Journal of Antituberculosis. 2018, 40(2):  177-182.  doi:10.3969/j.issn.1000-6621.2018.02.013

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To investigate the mutation characteristics in pncA and rpsA genes and its correlation with pyrazinamide (PZA) resistance in multidrug-resistant Mycobacterium tuberculosis (MDR-MTB) strains isolated from Chongqing.

A total of 133 MDR-MTB clinical isolates were collected from Chongqing from November 2014 to February 2016. PZA susceptibility was determined by BACTEC MGIT 960 TB system. The pncA and rpsA genes were amplified by PCR and the products were analyzed by DNA sequencing in order to identify the mutations in pncA and rpsA genes and the correlations with PZA resistance.

Among the 133 MDR-TB clinical strains, 83 isolates were resistant to PZA, yielding a resistance rate of 62.4%. Sequence analysis revealed that 73 out of 83 (87.9%) MDR-MTB strains harbored a mutation located in the pncA gene. Four out of 50 (8.0%) PZA-sensitive isolates occurred pncA gene mutation. The PZA-resistant strains showed higher mutation rate than the PZA-sensitive strains (χ ²=81.82, P=0.000). Most of the pncA gene mutations in the genomes of PZA-resistant strains were base substitution mutation, especially the G395A substitution (9 isolates). The identified mutations were dispersed along the pncA gene, distributing in the region from nucleotide -11 to nucleotide 515. The pncA gene mutations centralized in the regions of 20-40, 136-146, 185-226, and 392-408. Eighteen novel mutation sites of pncA gene were observed including T2C, T37G, T94G, C206T, G319A, C437T, T488C, GCC insertion at 52, C insertion at 130, CA insertion at 139, C insertion at 232, T insertion at 243, A insertion at 288, GGT insertion at 393, CA insertion at 408, ACGCC deletion at 341, GCCAC deletion at 342, and GATGAGGTC deletion at 376. The pncA gene mutations in the genomes of PZA-sensitive strains were only the substitution mutations, and the sites were different from those of PZA-resistant strains. While no genetic mutation associated with PZA resistance was found in the rpsA gene.

The MDR-MTB strains showed higher resistance rate to PZA in Chongqing. Mutation in pncA gene might be one of the major mechanisms of resistance to PZA in MDR-MTB isolates in Chongqing.

Analysis of drug susceptibility testing results of 881 patients with suspected multidrug-resistant pulmonary tuberculosis

Xin-yu YANG,Jun-li YI,Qing XING,Li-li TIAN,Xiao-wei DAI,Jie ZHANG,Nen-han WANG,Yan-feng ZHAO,Su-min WANG,Bei-chuan DING

Chinese Journal of Antituberculosis. 2018, 40(2):  183-188.  doi:10.3969/j.issn.1000-6621.2018.02.014

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To analyze the drug resistance situation of patients with suspected multidrug-resistant pulmonary tuberculosis (MDR-PTB) in TB control institutes and TB designated hospitals in Beijing, to provide suggestions for clinical diagnosis, treatment, and control.

We made a retrospective analysis, including preliminary bacteria identification and drug susceptibility testing of the bacteria isolated from the positive sputum specimens of the 881 suspected MDR-PTB patients from 14 TB control institutes and 6 TB designated hospitals in Beijing between January 2014 and December 2016. We collected their drug susceptibility testing results against INH, RFP, Sm, EMB, Lfx, Am, Cm, Pto, and PAS. SPSS 17.0 was used for statistical analysis. We analyzed and summarized the drug resistance situation of suspected MDR-PTB patients in those 3 years.

In the 881 suspected MDR-PTB patients, the isolation rate of Mycobacterium tuberculosis complex group was 88.6% (781/881). The isolation rate of non-tuberculous mycobacterium (NTM) was 11.4% (100/881). The total drug resistant rate of the clinical isolates of Mycobacterium tuberculosis complex group was 33.3% (260/781). The multidrug-resistance (MDR) rate was 17.2% (134/781). The proportion of high-level of resistance rates (defined as >67.0%) against the four first-line TB drugs (INH, RFP, Sm and EMB) was 69.0% (127/184), 57.1% (92/161), 60.5% (107/177) and 31.7%(19/60) respectively.

It is very necessary to carry out a drug sensitive test for the suspected MDR-PTB patients in Beijing, and the epidemic situation of TB resistance faced in Beijing is still very severe.

Epidemiological characteristics of newly registered smear positive pulmonary tuberculosis in Heilongjiang province from 2008 to 2015

Yan-fu WANG,Zheng QI,Wei YANG,Chang LIU,Hong-hai LI,Xin. WANG

Chinese Journal of Antituberculosis. 2018, 40(2):  189-193.  doi:10.3969/j.issn.1000-6621.2018.02.015

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The epidemiological characteristics of tuberculosis patients in 13 prefecture-level cities (districts) in Heilongjiang province from 2008 to 2015 were analyzed, in order to disclose the epidemic situation of tuberculosis in Heilongjiang province and to provide reference for future tuberculosis prevention and control.

From January 2008 to December 2015, the National Tuberculosis Information Management System reported 93383 new smear positive patients in Heilongjiang province. By descriptive statistical analysis, the epidemiological characteristics of these newly registered smear positive pulmonary tuberculosis patients in the 13 prefecture-level cities (districts) during the 8 years were analyzed, including average incidence rate, gender, age, and occupation distribution.

(1) From 2008 to 2015, the average annual reported incidence rate was 30.25/100000 (93383/308700000). (2) Among the newly registered smear positive pulmonary tuberculosis patients in Heilongjiang province from 2008 to 2015, the male registered incidence was 42.62/100000 (66537/156100000), whereas the female registered incidence was 17.59/100000 (26846/152580000); there was significant difference (χ ²=6086.28, P<0.05). (3) The incidence of pulmonary tuberculosis increased with age. Majority patients were in the 35-44 years old (20.78%, 19405/93383) and 45-54 years old (23.28%, 21741/93383) age group. The difference among age groups was statistically significant ( {\chi }_{\mathrm{trend}}^2 =46828.26, P<0.05). (4) Farmer was the most common occupation of patients, accounting for 46.58% (43500/93383) of the total registered incidence; followed by domestic worker, house worker and job seeker, accounting for 28.67% (26771/93383).

The statistical results of newly registered smear positive pulmonary tuberculosis in Heilongjiang during 2008-2015 showed that the elderly (aged from 35 to 54 years), male and farmer are the key targets in the future tuberculosis prevention and control work.

Investigation and analysis on the performance of tuberculosis related examinations in secondary and above medical institutions in Inner Mongolia Autonomous Region

Fang-fang GAO,Shuo ZHANG,Yun-kai SU,Li-ping REN,Fei GAO

Chinese Journal of Antituberculosis. 2018, 40(2):  194-199.  doi:10.3969/j.issn.1000-6621.2018.02.016

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To understand and evaluate the performance of tuberculosis (TB) related examinations in secondary and above medical institutions in Inner Mongolia Autonomous Region.

Questionnaire survey was conducted in 265 secondary and tertiary medical institutions all around Inner Mongolia from July to November, 2015. The questionnaire concerned hospital category and scale, TB laboratory test items and quantity in 2014. Effective questionnaires from 154 hospitals were received, including 41 (82.0%, 41/50) tertiary and 113 (52.6%, 113/215) secondary medical institutions, and the overall response rate was 58.1% (154/265).

The performance rate of TB LAB tests in tertiary medical institutions was better than that in secondary ones. The performance rates of AFB test, culture test, molecular biological detection and interferon-gamma release assay carried out in tertiary medical institutions were 87.8% (36/41), 24.4% (10/41), 12.2% (5/41) and 31.7% (13/41) respectively, and those in secondary medical institutions were 31.9% (36/113), 9.7% (11/113), 1.8% (2/113) and 1.8% (2/113) respectively. The differences were significant (χ ²=37.83, P=0.000; χ ²=5.49, P=0.019; χ ²=7.54, P=0.006; χ ²=30.67, P=0.000). The performance of culture test in non-general hospital including 8 infectious disease hospitals (23.4%, 11/47) was better than that in general hospitals (9.3%, 10/107) with significant difference (χ ²=5.48, P<0.05). The situation of TB LAB tests performed in eight infectious diseases hospitals (3 secondary and 5 tertiary ones) was relatively better. The performance rates of AFB test, culture test, molecular biological detection and interferon-gamma release assay were 8/8, 7/8, 3/8 and 6/8 respectively.

As the foremost position for TB case finding, the performance of TB LAB in general hospitals should be improved further, no matter detection items, quantity or the application of new techniques.

Analysis on influencing factors of tracking failure among reported pulmonary tuberculosis cases in internet-based reporting system from 2011 to 2016 in Hefei

Hong CAO,Li-li WANG,Ji-xiang. DENG

Chinese Journal of Antituberculosis. 2018, 40(2):  200-206.  doi:10.3969/j.issn.1000-6621.2018.02.017

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To explore the reasons and influencing factors of tracking failure among reported pulmonary tuberculosis (PTB) cases from Internet-based report by non-TB control institution (NTI)in Hefei, in order to improve the overall arrival rate.

The data of 37854 PTB and suspected PTB patients, who should be referred, reported by NTI of Hefei in 2011-2016 the TB information management system were collected from TB Information Management System. All analysis (e.g. collation, summary and statistical analysis) was performed using Excel and SPSS (version 19.0). The constituent ratio was the main evaluation index. Logistic regression was used to analyze the related factors and P values less than 0.05 was considered statistically significant.

Among the PTB and suspected PTB patients who should be referred reported by all kinds of NTI in 2011-2016, 36286 (95.86%) referral cases arrived. A total of 16484 cases should be tracked, 14916 (90.49%) cases arrived and 1561 (9.47%) cases didn’t arrived, and 7 (0.04%) cases had no track information. The reasons for 1561 cases did not arrive included factors of patients (45.04%, 703/1561), factors of NTI (29.34%, 458/1561) and factors of TB control institution (25.62%, 400/1561). Single factor analysis showed that the age of the patient, the type of reported hospital, location of the present address, occupation, and the classification of patients had different level of effects on whether the patients could be tracked (χ ² values were 33.19, 938.83, 206.13, 26.71, 24.64, Ps<0.001). Multivariate logistic regression analysis showed that the age of the patient, the type of reported hospital, location of the present address, and occupation played important roles in tracking failure (Wald χ ² values were 39.65, 621.62, 288.81 and 25.65, Ps<0.001).

The age of the patient, the type of reported hospital, the location of the present address and occupation are important factors of tracking failure. We should increase the communication of TB control institution with NTI and strengthen the training and monitor of NTI on TB Centralized Management in order to improve the overall arrival rate of TB patients.

Analysis on treatment costs of pulmonary tuberculosis patients and their satisfaction with the government derating policy for tuberculosis treatment in Zhabei district of Shanghai

Jing YAO,Hong CHEN,Zhi-hong LI

Chinese Journal of Antituberculosis. 2018, 40(2):  207-212.  doi:10.3969/j.issn.1000-6621.2018.02.018

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To understand the treatment costs of pulmonary tuberculosis (PTB) patients in Zhabei district, Shanghai, and their satisfaction with the derating policy, so as to provide evidences for improving TB derating policy and reducing economic burden of the patients.

Two hundred and sixty-five PTB patients registered for derating treatment fees at Zhabei District Center for Disease Control and Prevention from July 2015 to July 2016 were recruited to participate in this study. The invoices of non-derated medical costs were collected and questionnaire survey on satisfaction with the derating policy was conducted. A total of 265 questionnaires were sent out and 213 valid questionnaires were collected (all 213 patients were aware of the derating policy). The effective response rate was 80.4%. Basic characteristics including demographic data, treatment and medication data were collected; Ranksum test was used to compare the costs supported by government financial between patients with different characteristics; the costs at patients’ own expense on the related examinations and medicines were calculated; and the satisfaction with the derating policy were also analyzed by using questionnaire.

The median exempted costs of the total medical expenses for the 213 patients was 1766 (1020, 2411) RMB (quartile (Q₁, Q₃)), of which 655 (377, 900) RMB for medical examinations, 325 (165, 493) RMB for first-line anti-TB drugs, 293 (85, 733) RMB for second-line anti-TB drugs, and 800 (156, 800) RMB for hepatoprotective drugs, respectively. Among the non-exempted costs, the times of kidney function test and blood routine examination were 6.4 and 6.6 per patient, resulting in average fees of 156.8 (33388/213) and 79.6 (16954/213) RMB, respectively; the average cost at patients’ own expense on auxiliary drugs (such as anti-TB Traditional Chinese Medicine Patent Prescription) was 684.8 RMB. The overall satisfaction rate of patients with derating policy was 77.5% (165/213). With regard to first-line anti-TB drugs, hepatoprotective drugs, medical examinations and process of derating, the satisfaction rates were 90.1% (192/213), 77.9% (166/213), 83.1% (177/213) and 90.6% (193/213), respectively. 65.3% (139/213) of the patients believed that hepatoprotective drugs account for the majority of the total treatment costs. For the current derating policy, the proportion of patients who chose “The items that can be derated were limited” or “The costs that can be derated were low” were 51.2% (109/213) and 34.7% (74/213), respectively. The most expected item to be implemented on the basis of current policy was derating the expenses when treating at designated hospital (45.5%, 97/213).

The overall satisfaction rate of the patients with derating policy is low in Zhabei district. Considering the actual treatment situation of patients in this district, we should increase derated costs of some examinations and medicines.

Study on knowledge of pulmonary tuberculosis complicated by diabetes mellitus among nurses from the department of tuberculosis

Hui-zhen LI,Jiang-gui WU,Xiao-hua ZHUO,Luo-yang ZHONG,Ai-qiong HUANG,Jing. ZOU

Chinese Journal of Antituberculosis. 2018, 40(2):  213-217.  doi:10.3969/j.issn.1000-6621.2018.02.019

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To investigate the knowledge of pulmonary tuberculosis complicated by diabetes mellitus among the nurses from tuberculosis department, and analyze the associated factors, so as to provide scientific basis for relevant training.

Using a self-designed questionnaire on knowledge of pulmonary tuberculosis with diabetes, a random sampling method was used to randomly select two tertiary 3A hospitals from the five tertiary 3A hospitals in Hunan province which had TB departments (Hunan Chest Hospital and Changsha Central Hospital). Afterwards, based on the inclusion criteria, 280 eligible nurses from the TB departments were surveyed by cluster sampling. A total of 280 questionnaires were sent out and 269 valid questionnaires were collected, with an effective response rate of 96.07% (269/280). The results of the questionnaires were analyzed with SPSS 20.0. F test was used to analyze the data with normal distribution, and multiple group comparison was done with LSD test. The non-normal data were analyzed with Welch test and Tamhane’s T ² test, P<0.05 indicated the difference was statistically significant.

The average score of knowledge of pulmonary tuberculosis complicated by diabetes mellitus among the nurses inform tuberculosis department was (26.13±6.15), and the correct rate was 65.32% (26.13/40). The average scores of the different groups with different professional titles were as followed:(22.33±3.97) among the nurses group;(24.47±4.49) among the senior nurses group; (32.08±4.90) among the nurse-in-charge group; and (35.05±3.93) among the group with deputy directors or above. The difference between the groups was statistically significant (F=87.947,P<0.05). The average scores of the different groups with different highest educational attainment were as followed:(20.90±5.51) among those with technical secondary school degree;(23.17±4.01) among the group with associate-degree; (31.64±3.97) among the group with bachelor’s degree;(37.20±2.28) among the group with master’s degree or above. The difference between the groups was statistically significant (F=106.016,P<0.05). The average scores of the different groups with different contracts were as followed:(24.73±6.04) among the group with temporary contracts;(27.05±6.21) among the group with nurses on the payroll of manning quotas, and (27.45±5.70) among the group with long term contracts. The dif-ference between the groups was statistically significant (F=5.410,P<0.05). The average scores of the different groups with different years or nursing experience were as followed:(22.79±4.87) among the group with 0-5 years of nursing experience;(28.89±5.17) among the group with 5-10 years of nursing experience; (31.22±4.45) among the group with 10-20 years of nursing experience; and (34.00±4.69) among the group with 20 or more years nursing experience. The difference between the groups was statistically significant (F=53.029,P<0.05).

Department of tuberculosis nurses’ knowledge on pulmonary tuberculosis complicated by diabetes needs to be improved; the professional titles, the highest degree attainment, the contract types and work experience are the main factors affecting the knowledge of pulmonary tuberculosis complicated by diabetes mellitus.

Review Articles

The role of macrophages in anti-tuberculosis infection

Ya WANG,Chuan-you LI,Wei WANG,Shen-jie TANG

Chinese Journal of Antituberculosis. 2018, 40(2):  218-221.  doi:10.3969/j.issn.1000-6621.2018.02.020

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Macrophages play key roles in tuberculosis pathogenesis and host’s anti-tuberculosis immune defense. They represent an important component of innate immunity and are also major antigen presenting cells, functioning in both innate and acquired immunity. Tuberculosis, caused by Mycobacterium tuberculosis, is one of the main infectious diseases that are seriously harmful to human health. Mycobacterium tuberculosis can interfere with the immune response of macrophages in many ways. This review aims to elaborate the mechanisms of macrophages in various anti-tuberculosis immune responses after the infection of host by Mycobacterium tuberculosis.

ESMPE: a combined strategy for school tuberculosis prevention and control proposed by Dalian,China. PLoS One

X Wang,H Jiang,X Wang

Chinese Journal of Antituberculosis. 2018, 40(2):  221-221.  doi:10.3969/j.issn.1000-6621.2018.02.021

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Short Articles

Analysis of impact factors of medication adherence among patients with sputum smear-positive pulmonary tuberculosis in Wuhan

Zhan LIAN,Ting-ping WANG,Juan DU

Chinese Journal of Antituberculosis. 2018, 40(2):  222-225.  doi:10.3969/j.issn.1000-6621.2018.02.022

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A questionnaire survey with simple random sampling was conducted by trained questionnaire surveyors to 356 sputum smear-positive pulmonary TB patients of Wuhan Tuberculosis Prevention and Cure Institute during November 2013 to May 2015. The effective recovery of the questionnaire was 342 with the recovery rate of 96.07%. The status of medication adherence and its impact factors were analyzed. Of 342 patients, 39 patients had poor medication adherence (11.40%), 303 patients had good medication adherence (88.60%). Logistic regression analysis revealed that, compared with the patients joining in the medical insurance for urban workers, patients in medical insurance for urban residents (Wald χ ²=4.37, P=0.044,OR=1.64,95%CI=1.12-3.45), patients in new rural cooperative medical insurance (Wald χ ²=8.13, P=0.013,OR=2.13,95%CI=1.59-3.38) had poorer medication compliance. Patients with poor knowledge of TB had poorer medication compliance (Wald χ ²=5.10, P=0.009,OR=2.70,95%CI=1.65-3.67). This study revealed that insurance type and knowledge of TB are impact factors for TB medication compliance.