Analysis of tuberculosis epidemiological characteristics and drug resistance among the floating population in Beijing in 2019 / 中华流行病学杂志

Objective: To analyze the epidemic characteristics and drug resistance of pulmonary tuberculosis among the floating population in Beijing and to provide a scientific basis for formulating strategies for the prevention and control of tuberculosis among the floating population. Methods: Data of tuberculosis patients who were positive for Mycobacterium tuberculosis culture was collected from 16 districts and one municipal institution of tuberculosis control and prevention in Beijing in 2019. The strain samples were tested for drug sensitivity by the proportional method. According to household registration location, patients were divided into the floating population and Beijing registration. SPSS 19.0 software analyzed tuberculosis patients' epidemic characteristics and drug resistance in the floating population. Results: In 2019, there were 1 171 culture-positive tuberculosis patients in Beijing, among the floating population, 593 (50.64%) patients were identified, with a male-to-female sex ratio of 2.2∶1 (409∶184). Compared to patients under household registration as Beijing residents, a higher proportion of young adults aged 20-39 years (65.09%,386/593) were noticed, with 55.65% (330/593) reported from the urban areas and 96.80% (574/593) were reported the first time. The differences were statistically significant (all P<0.05). After completing the drug sensitivity test, 37 cases were with multiple drug-resistant tuberculosis, accounting for 6.24% (37/593). The rates of isoniazid resistance (42.11%,8/19) and multidrug resistance (21.05%,4/19) in floating population patients after retreatment were significantly higher than those in newly treated patients (11.67%, 67/574 and 5.75%, 33/574), and the differences were statistically significant (all P<0.05). Conclusions: Most patients with tuberculosis in the floating population in Beijing in 2019 were young males aged 20-39 years. The reporting areas were urban areas and the newly treated patients mainly. The patients with tuberculosis in the re-treated floating population were more likely to suffer from multidrug and drug resistance, which should be taken as the key population for prevention and control.

Screening of Serum Biomarkers for Distinguishing between Latent and Active Tuberculosis Using Proteome Microarray / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To identify potential serum biomarkers for distinguishing between latent tuberculosis infection (LTBI) and active tuberculosis (TB).</p><p><b>METHODS</b>A proteome microarray containing 4,262 antigens was used for screening serum biomarkers of 40 serum samples from patients with LTBI and active TB at the systems level. The interaction network and functional classification of differentially expressed antigens were analyzed using STRING 10.0 and the TB database, respectively. Enzyme-linked immunosorbent assays (ELISA) were used to validate candidate antigens further using 279 samples. The diagnostic performances of candidate antigens were evaluated by receiver operating characteristic curve (ROC) analysis. Both antigen combination and logistic regression analysis were used to improve diagnostic ability.</p><p><b>RESULTS</b>Microarray results showed that levels of 152 Mycobacterium tuberculosis (Mtb)-antigen- specific IgG were significantly higher in active TB patients than in LTBI patients (P < 0.05), and these differentially expressed antigens showed stronger associations with each other and were involved in various biological processes. Eleven candidate antigens were further validated using ELISA and showed consistent results in microarray analysis. ROC analysis showed that antigens Rv2031c, Rv1408, and Rv2421c had higher areas under the curve (AUCs) of 0.8520, 0.8152, and 0.7970, respectively. In addition, both antigen combination and logistic regression analysis improved the diagnostic ability.</p><p><b>CONCLUSION</b>Several antigens have the potential to serve as serum biomarkers for discrimination between LTBI and active TB.</p>

Interleukin 8 Gene Polymorphisms Are Not Associated with Tuberculosis Susceptibility in the Chinese Population / 生物医学与环境科学（英文）

Interleukin 8 (IL8) is an important chemokine that elicits host immune response against tuberculosis (TB). However, whether there is an association between IL8 gene polymorphism and TB susceptibility in the Chinese population is unknown. IL8 gene was amplified and sequenced to search for nucleotide polymorphisms among the Chinese population. Four single nucleotide polymorphisms (SNPs) were identified, selected, and analyzed in a cohort of 438 patients with TB and 536 healthy controls. Allelic, genotypic, and haplotypic analysis demonstrated that the distribution of the four IL8 SNPs between patients with TB and healthy controls was not significantly different (P>0.05). The four IL8 SNPs detected in this study were not associated with TB susceptibility in the Chinese population. Secretion of IL8 by peripheral blood cells was greatly stimulated upon exposure to Mycobacterium tuberculosis whole cell extract, but such enhanced secretion was not associated with the IL8 rs4073 alleles.

Clinical isolates of Mycobacterium abscessus in Guangzhou area most possibly from the environmental infection showed variable susceptibility / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mycobacterium abscessus (M. abscessus) can cause a variety of human infections, involving the lung, skin and soft tissues, and is generally believed to be acquired from environmental sources. The aim of this study was to investigate the molecular diversity and antibiotic susceptibility of M. abscessus isolates as the basis for strategies to improve control and management of infection.</p><p><b>METHODS</b>Seventy M. abscessus isolates from patients attending the Guangzhou Thoracic Hospital were identified from 2003 to 2005 by biochemical tests, gas chromatography, polymerase chain reaction (PCR)-restriction analysis (PRA) of heat shock protein gene hsp65, and sequencing of the quinolone resistance determining regions (QRDRs) of gyrA. Susceptibilities to six antibiotics were determined by micro-broth dilution. Isolates were genotyped using randomly amplified polymorphic DNA (RAPD) analysis.</p><p><b>RESULTS</b>Most isolates (63/70; 90%) were susceptible to amikacin but rates of susceptibility to other antibiotics varied from moderate, clarithromycin (60%) and imipenem (43%), to low for ciprofloxacin and ofloxacin (3%), and 87% of isolates had intermediate susceptibility to cefoxitin. RAPD analysis showed that the 70 clinical isolates displayed 69 unique RAPD patterns.</p><p><b>CONCLUSIONS</b>The high genetic diversity of isolates suggests that they are not transmitted from person to person but, presumably, are acquired independently from environmental sources. M. abscessus isolates displayed variable levels of susceptibility to all antibiotics tested, other than amikacin, indicating a need for routine susceptibility testing to guide treatment.</p>

Differences in the population of genetics of Mycobacterium tuberculosis between urban migrants and local residents in Beijing, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Currently, migration has become one of the risk factors of high burden of tuberculosis in China. This study was to explore the influence of mass migration on the dynamics of Mycobacterium (M.) tuberculosis in Beijing, the capital and an urban area of China.</p><p><b>METHODS</b>Three hundred and thirty-six M. tuberculosis strains from the Changping district, where the problem of urban migrants was more pronounced than in other Beijing regions, were genotyped by Spoligotyping, large sequence polymorphisms (LSPs 105 and 181), and variable number tandem repeat (VNTR) typing. Based on the genotype data, the phylogeny of the isolates was studied.</p><p><b>RESULTS</b>In Changping district, the proportion of Beijing lineage M. tuberculosis isolates amounted to 89.0% (299/336), among which 86.6 % (252) belonged to the modern lineage. The frequency of modern Beijing lineage strains is so high (around 75% (252/336)) that associated risk factors affecting the tuberculosis epidemic cannot be determined. The time to the most recent common ancestor (TMRCA) of the Beijing lineage strains was estimated to be 5073 (95% CI: 4000-6200) years. There was no significant difference in the genetic variation of Beijing isolates from urban migrants and local residents.</p><p><b>CONCLUSIONS</b>The clone of modern Beijing lineage M. tuberculosis, which is dominant in the Beijing area, most likely started to expand with the five thousand-year-old Chinese civilization. In the future, with the urbanization in the whole of China, modern Beijing lineage M. tuberculosis may gain the larger geographical spread.</p>

Influences of Mycobacterium tuberculosis on the levels of human acute monocytic leukemia cell line THP-1 apoptosis and death / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the influences of Mycobacterium tuberculosis on the levels of human acute monocytic leukemia cell line THP-1 apoptosis and death.</p><p><b>METHODS</b>Human acute monocytic leukemia cell line THP-1 were infected with Mycobacterium tuberculosis strains H37Ra, H37Rv, or Beijing genotype (BJTB), respectively, to construct the infection models. Cell apoptosis was detected using flow cytometry. The distribution of the apoptotic proteins was detected using immunofluorescent staining assays. The cells late apoptosis was detected using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining assays. The change of cell death was determined by Tyrpan blue staining assays.</p><p><b>RESULTS</b>THP-1 apoptosis was induced by Mycobacterium tuberculosis strains H37Ra, H37Rv, and BJTB. H37Ra strongly induced THP-1 apoptosis, H37Rv weakly induced THP-1 apoptosis, and BJTB induced THP-1 apoptosis at the lowest level among these three Mycobacterium tuberculosis strains. On the contrary, BJTB strongly induced THP-1 death, H37Rv weakly induced THP-1 death, and H37Ra induced THP-1 death at the lowest level.</p><p><b>CONCLUSIONS</b>Mycobacterial strains with different virulence induce different levels of apoptosis and death of THP-1 cells. Compared with highly virulent strains, attenuated strains induce more apoptosis and less death.</p>

Rapid testing on drug susceptibility of Mycobacterium tuberculosis with nitrate reducrase assay / 中华流行病学杂志

<p><b>OBJECTIVE</b>To establish a rapid method for testing drug sussceptibility on Mycobacterium tuberculosis.</p><p><b>METHODS</b>Taking absolute Concentration method for drug susceptibility testing of M. tuberculosis as the "gold standard", we examined the drug-resistant of M. tuberculosis strain with nitrate reducrase assay (NRA) and the drug-resistant of M. tuberculosis germ in sputum with NRA.</p><p><b>RESULTS</b>NRA and absolute concentration method was basically comparable with NRA susceptibility as 96.5% and the specificity was 100%, When comparing with traditional absolute concentration method, NRA could shorten the time about 3 weeks. Using NRA to test the drug-resistant of M. tuberculosis germ in sputum, its susceptibility was more than 66.7% and specificity was 100%, within 10-20 days.</p><p><b>CONCLUSION</b>NRA could be used as a rapid drug susceptibility testing on M. tuberculosis.</p>

The identification of Mycobacterium tuberculosis isolates by DNA typing technique / 中华流行病学杂志

<p><b>OBJECTIVE</b>To assess the application of IS6110-restriction fragment length polymorphism (RFLP), Spoligotyping and mycobacterial interspersed repetitive unit (MIRU) in epidemiological studies of tuberculosis and to discuss the characteristics of Mycobacterium tuberculosis strains in different regions in China.</p><p><b>METHODS</b>Mycobacterium tuberculosis strains, with a total number of 158 isolates, were subjected to IS6110-RFLP, Spoligotyping and MIRU.</p><p><b>RESULTS</b>The numbers of patterns produced by IS6110-RFLP, Spoligotyping, and MIRU typing were 118, 20 and 105 respectively. The discriminatory power of IS6110-RFLP was higher than that of Spoligotyping. However, when the copies of IS6110 were lower than 10, the discriminatory power of Spoligotyping improved obviously. The discriminatory power of MIRU typing was close to that of IS6110-RFLP for typing of Mycobacterium tuberculosis. In MIRU loci, there were four loci (loci 4, 10, 26, 40) with higher diversity. Significant differences among the Mycobacterium tuberculosis between Guangdong and other regions in clustered rate and the proportion of Beijing genotype (P < 0.05) were found. The clustered rates and the proportion of Beijing genotype in Guangdong were lower than that in other regions.</p><p><b>CONCLUSION</b>The results of this study indicated that either IS6110-RFLP, Spoligotyping or MIRU technique was useful for epidemiological studies on tuberculosis in China and the strains in different regions had different characterishes in China.</p>