Honghuan Song

Jiangsu Provincial Center for Disease Control and Prevention

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Limei Zhu

Jiangsu Provincial Center for Disease Control and Prevention

Yan Shao

Jiangsu Provincial Center for Disease Control and Prevention

Guoli Li

Nanjing General Hospital of Nanjing Military Command

Wei Lu

Jiangsu Provincial Center for Disease Control and Prevention

Cheng Chen

Soochow University

Qiao Liu

Hunan Provincial Maternal and Child Health Hospital

Dandan Yang

Jiangsu Provincial Center for Disease Control and Prevention

Xinsong Hu

Nanjing Medical University

Cheng Chen

Fujian Medical University

Weiguo Xu

Mianyang Central Hospital

Cooperative Institutions

Jiangsu Provincial Center for Disease Control and Prevention

Nanjing Medical University

Chinese Academy of Medical Sciences & Peking Union Medical College

Chinese Center For Disease Control and Prevention

Ministry of Agriculture and Rural Affairs

Sun Yat-sen University

Center for Disease Control

National Institute for Communicable Disease Control and Prevention

Wenzhou Medical University

Fudan University

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Long non-coding RNA expression in PBMCs of patients with active pulmonary tuberculosis

Frontiers in Microbiology (2023)

Guoli Li Zhelong Feng Honghuan Song Y Wang Limei Zhu

Purpose Mycobacterium tuberculosis (Mtb) infection is the primary cause of the chronic infectious illness tuberculosis (TB). Long non-coding RNAs (lncRNAs) are functional RNA molecules that cannot be translated into proteins and play a crucial role in regulating the immune system’s innate and adaptive responses. It has been demonstrated that the dysregulation of lncRNA expression is associated with various human diseases. However, the mechanism underlying the involvement of so many lncRNAs in the immune response to TB infection remains unclear. The objective of our current study was to identify a number of significantly differentially expressed lncRNAs in peripheral blood mononuclear cells (PBMCs) from TB patients and to select the most indicative lncRNAs as potential biomarkers for active pulmonary tuberculosis. Methods Microarray analysis was performed to determine the lncRNA and mRNA expression profiles in TB patients using a case-control model. The differentially expressed lncRNAs were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to investigate potential roles and pathways associated with the pathogenesis of TB infection, and to screen lncRNAs specifically linked to TB infection. Using real-time fluorescence quantitative PCR (QRT-PCR), specific lncRNAs were identified in TB patients and latent infections. Results Our findings revealed that various signaling pathways were differentially expressed in TB-infected individuals, suggesting a potential role for lncRNAs in the immunological responses driven by TB infection. This study provides crucial guidelines for future functional research. Upregulated lncRNAs were mainly enriched in Neutrophil extracellular trap formation and Chemokine signaling pathways, while downregulated lncRNAs were enriched in Neuroactive ligand-receptor interaction and Cushing syndrome in TB PBMCs. Furthermore, we found that lnc-XPNPEP1-5, lnc-CASKIN2-2, lnc-HSPA13-6, lnc-CLIC5-1, and LINC02502 were significantly downregulated in TB-infected patients, while LINC00528, lnc-SLC45A4-3, and LINC00926 were significantly upregulated in TB patients and latent infections. These eight lncRNAs, identified as novel biological marker candidates for diagnosing TB infection, were validated by real-time fluorescence quantitative PCR (QRT-PCR). Conclusion The abnormally expressed lncRNAs identified in this research may provide crucial information for understanding the pathophysiological characteristics of TB patients and the dysfunction of PBMCs. Our findings reveal potential targets for early TB diagnosis and therapy, as well as offer new insights into the mechanisms underlying TB infection.

Active tuberculosis

10.3389/fmicb.2023.1257267

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Rates and risk factors for drug resistance tuberculosis in Northeastern China

BMC Public Health (2013)

Qiao Liu Limei Zhu Yan Shao Honghuan Song Guoli Li

Abstract Background Drug-resistant tuberculosis (TB) has emerged as a major challenge toward TB control and prevention. In Lianyungang city, the extent and trend of drug resistant TB is not well known. The objective of the survey was to assess drug resistance pattern of MTB and risk factors for drug resistant TB, including multidrug resistance tuberculosis (MDR-TB) in this area. Methods We performed drug susceptibility testing on Mycobacterium tuberculosis (MTB) isolates with first- and second-line anti-tuberculosis drugs of 1012 culture positive TB cases by using the proportion method, who were consecutively enrolled from January 2011 to December 2012 in Lianyungang city, China. The patterns of drug resistance in MTB were investigated and multiple logistic regression analysis was performed to assess the risk factors for drug resistant TB. Results Among the 1012 strains tested, 308 (30.4%) strains were resistant to at least one first-line drug; the prevalence of MDR-TB was 88 (8.7%), 5 (0.5%) strains were found to be extensively drug-resistant tuberculosis (XDR-TB). Female gender was a risk factor for MDR-TB (adjusted odds ratio (aOR) 1.763, 95% CI (1.060-2.934). The aged 28–54 years was significantly associated with the risk of MDR-TB with an aOR: 2.224, 95% CI (1.158-4.273) when compared with those 65 years or older. Patients with previous treatment history had a more than 7-fold increased risk of MDR-TB, compared with those never previously treated. Conclusions The burden of drug resistant TB cases is sizeable, which highlights an urgent need to reinforce control, detection and treatment strategies for drug resistant TB.

Biostatistics

10.1186/1471-2458-13-1171

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Incidence, Outcomes, and Risk Factors for Isoniazid-Resistant Tuberculosis from 2012 to 2022 in Eastern China

Antibiotics (2024)

Yan Shao Wenlei Song Honghuan Song Guoli Li Limei Zhu

Background: Isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) is the most frequent drug-resistant tuberculosis (DR-TB) in the world, and unfavorable outcomes of Hr-TB are more common compared to drug-susceptible TB. Considering there is no optimal regimen accepted worldwide, we undertook a retrospective cohort study in eastern China to estimate incidence trends and risk factors associated with unfavorable outcomes of Hr-TB. Methods: Between January 2012 and December 2022, all Hr-TB patients’ information was extracted from the Tuberculosis Information Management System (TIMS), which is a national electronic information platform, to record TB patients’ clinical information in this study. The incidence of Hr-TB was determined by the mid-year population according to census data published by the government. We categorized treatment regimens depending on fluoroquinolone (FQ) use, and potential risk factors were analyzed using multivariable logistic regression. Results: A total of 3116 Hr-TB patients fulfilled the inclusion criteria and were enrolled in this study. The average annual rate of Hr-TB in the 11 years under investigation was 0.34 per 100,000 and increased to 0.53 per 100,000 until 2019. In total, six different treatment regimens were utilized in the study sites, and less than 1% of regimens adopted FQ. There was no difference in the unfavorable outcomes between the FQ-included and FQ-excluded groups (p = 0.22). The average treatment duration was 7.06 months, and the longest treatment was 26 months. Approximately 20% (637/3116) of Hr-TB patients had unfavorable outcomes, and 60.13% (383/637) of them proceeded to multidrug-resistant tuberculosis (MDR-TB). Treatment duration and a positive smear at the end of the 5th month were significantly associated with unfavorable outcomes (p < 0.001). Conclusion: The unfavorable treatment outcomes of Hr-TB are still high in eastern China, and the efficacy of FQ-containing regimens needs to be validated for Hr-TB treatment.

Regimen

Multi-drug-resistant tuberculosis

10.3390/antibiotics13040378

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Genotypes of Mycobacterium tuberculosis isolates in rural China: Using MIRU-VNTR and spoligotyping methods

Scandinavian Journal of Infectious Diseases (2013)

Wei Lu Bing Lü Qiao Liu Haiyan Dong Yan Shao

Background: The genotypes of Mycobacterium tuberculosis (MTB) have been found to be related to the risk of transmission and the development of drug resistance of this pathogen. Thus, exploring the molecular characteristics of MTB is helpful for understanding and controlling the spread of strains in areas with a high incidence of tuberculosis. Methods: We recruited 512 sputum smear-positive tuberculosis patients from 30 counties from 1 April to 30 June 2010; 503 MTB strains were isolated and 497 were successfully genotyped. We genotyped the strains based on a new 15-locus mycobacterial interspersed repetitive unit–variable number of tandem repeats (MIRU-VNTR) method in combination with spacer-oligonucleotide typing (spoligotyping) technology. Results: Based on spoligotyping, 487 strains displayed known patterns, and 10 were absent from the current global spoligotyping database (SpolDB4). The predominant spoligotypes belonged to the Beijing or Beijing-like family (81.1%). When we used the new 15-locus (MIRU-15) set for the MIRU-VNTR analysis, 388 different patterns were identified, including 46 clusters and 342 unique patterns. The combination of spoligotyping and MIRU-15 demonstrated a high discriminatory power. The proportion of clusters varied significantly between the Beijing and non-Beijing family strains, but no significant association was observed between multidrug resistance and Beijing family strains. Conclusions: The present study demonstrated that the Beijing family strains are the most prevalent in rural China. Spoligotyping in combination with the new MIRU-15 technique is useful for the epidemiological analysis of MTB transmission and could be used as a first-line method for the large-scale genotyping of MTB.

Molecular Epidemiology

10.3109/00365548.2013.858182

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The Epidemiology and Geographic Distribution of Nontuberculous Mycobacteria Clinical Isolates from Sputum Samples in the Eastern Region of China

PLoS neglected tropical diseases (2015)

Yan Shao Cheng Chen Honghuan Song Guoli Li Qiao Liu

Background Nontuberculous mycobacteria (NTM) have been reported to be increasing worldwide and its geographic distribution differs by region. The aim of this study was to describe the epidemiology and distribution of NTM in the eastern part of China. Methods Sputum samples were collected from 30 surveillance sites for tuberculosis drug resistance test from May 1, 2008 to December 31, 2008. Identification was performed using a biochemical test, multiplex PCR and GenoType Mycobacterium CM/AS assay. Results A total of 1779 smear positive clinical isolates were obtained, of which 60 (3.37%) were NTM. Five species/complex of NTM were identified; M. intracellulare was the predominated species (68.33%), followed by M. abscessus-M. immunogenum (13.33%), Mycobacterium spec. (10.00%), M. Kansasii (6.67%) and M. peregrinum-M. alvei-M. septicum (1.67%). Conclusion M. intracellulare was the main species of NTM in the eastern part of China and clinical physicians should pay more attention to NTM induced pulmonary disease.

Nontuberculous Mycobacteria

10.1371/journal.pntd.0003623

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The association between diabetes status and latent-TB IGRA levels from a cross-sectional study in eastern China

Frontiers in Cellular and Infection Microbiology (2023)

Cheng Chen Xinsong Hu Yan Shao Honghuan Song Guoli Li

Background There is a debate regarding the sensitivity of the QuantiFERON-TB Gold In-Tube (QFT) among people with diabetes, and prior studies have shown heterogeneous results. We evaluated whether the QFT TB antigen was modified among persons with differing diabetes status and other related risk factors. Methods A cross-sectional study of 5,302 people was conducted to screen latent tuberculosis infection (LTBI) in eastern China. The QFT assay was performed as an indicator of LTBI. Fasting plasma glucose (FPG) was collected from each participant; the definition of diabetes followed the guidelines from the American Diabetes Association. Participants were classified into normoglycemia, prediabetes, undiagnosed diabetes, and previously diagnosed diabetes to evaluate the relationship between the QFT TB antigen and distinct diabetes status. Results TB antigen values from the QFT were statistically different among participants with differing diabetes status ( P = 0.008). Persons with undiagnosed diabetes had a higher TB antigen value (0.96 ± 0.20) than persons with normoglycemia (0.50 ± 0.02, P < 0.05). However, the TB antigen values demonstrated no significant difference among the four different diabetic groups when stratified by the standard cutoff for the QFT ( P = 0.492 for the positive group and P = 0.368 for the negative group). In a linear regression model, we found that FPG, age, and smoking were positively associated with the QFT TB antigen value ( P = 0.017, P < 0.001, and P < 0.001). Conclusions Diabetes status had little influence on the level of QFT TB antigen response among IGRA-positive persons. However, FPG, old age, and smoking were important risk factors for increasing levels of QFT TB antigen.

Prediabetes

Cross-sectional study

10.3389/fcimb.2022.1057298

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Tuberculosis Infection Control in MDR-TB designated hospitals, Jiangsu Province of China

medRxiv (Cold Spring Harbor Laboratory) (2024)

Honghuan Song Guoli Li Zhuping Xu Feixian Wang Xiaoping Wang

Background Hospital-acquired TB (Tuberculosis) infection among healthcare workers (HCWs) and patients is a severe problem due to the increased attributable risk of TB infection among these groups. Methods A standardized tool was applied. The assessment was conducted by direct observation, document review, and interviews with the facility heads. Baseline evaluation of TBIC (Tuberculosis infection control) in TB outpatient , inpatient departments, and laboratories was completed by January 2019. Based on the results, we implemented a comprehensive package of interventions, including administrative, environmental engineering, and respiratory protection (PPE) three-level hierarchy of controls. Subsequent monitoring was finalized quarterly and improvement measures should be formulated accordingly. More than two years of follow-up data was collected until August 31, 2021, by hospitals, municipality CDCs, and Jiangsu provincial CDC. Results At baseline, the implementation rate of administrative, environmental engineering and PPE IC was 57.29%, 59.21%, and 66.63%, respectively. After evaluation and implementation, priority way for cough patients was established, mechanical ventilation and the use of masks were improved, UV and UVGI lights were settled in need. The implementation rate of administrative, environmental and PPE IC were significantly increased to 86.27%, 87.41%, and 98.42% P<0.05 , respectively. Conclusions After more than one and a half years of intervention, TBIC in the designated hospitals has significantly improved. However, the availability of separate TB wards remains suboptimal. TB IC measures must be strengthened to reduce TB transmission among HCWs and non-TB patients. This method was practical and suitable to be popularized in countries with high TB burden

Tuberculosis control

10.1101/2024.09.11.24313499

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Relapse or Re-Infection, the Situation of Recurrent Tuberculosis in Eastern China

Frontiers in Cellular and Infection Microbiology (2021)

Yan Shao Honghuan Song Guoli Li Li Yan Yishu Li

Purpose Recurrent tuberculosis (TB) is defined by more than one TB episode per patient and is caused by re-infection with a new Mycobacterium tuberculosis (Mtb) strain or relapse with the previous strain. Recurrence of TB is one important obstacle for End TB strategy in the world and elucidating the triggers of recurrence is important for the current TB control strategy in China. This study aimed to analyze the sources of recurrent TB by the molecular genotyping method. Method A population-based surveillance was undertaking on all culture-positive TB cases in Jiangsu province, China from 2013 to 2019. Phenotypic drug susceptibility test (DST) by proportion method and mycobacterial interspersed repetitive units-variable number of tandem repeat (MIRU-VNTR) were adopted for drug resistance and genotype detection. Results A total of 1451 culture-positive TB patients were collected and 30 (2.06%, 30/1451) TB cases had recurrent TB episodes. Except 7 isolates were failed during subculture, 23 paired isolates were assessed. After genotyping by MIRU-VNTR, 12 (52.17%, 12/23) paired recurrence TB were demonstrated as relapse and 11 (47.83%,11/23) paired cases were identified as re-infection. The average interval time for recurrence was 24.04 (95%CI: 19.37-28.71) months, and there was no significant difference between relapse and re-infection. For the relapsed cases, two paired isolates exhibited drug resistance shifting, while four paired isolates revealed inconsistent drug resistance among the re-infection group including two multidrug-resistant tuberculosis (MDR-TB) at the second episode. Conclusion Relapse and re-infection contributed equally to the current situation of recurrence TB in Jiangsu, China. Besides, more efficient treatment assessment, specific and vigorous interventions are urgently needed for MDR-TB patients, considering obvious performance among re-infection cases.

10.3389/fcimb.2021.638990

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Citations (18)

Risk factors associated with TB, a case-control study in a Chinese population

Journal of Public Health and Emergency (2017)

Cheng Chen Limei Zhu Dandan Yang Yan Shao Honghuan Song

Background: Tuberculosis (TB) remains one of the leading communicable diseases in the world, and this case-control study was conducted to explore potential risk factors for TB. Methods: A total of 104 new TB patients were collected in 2011, and each 2 cases were matched with one healthy control. A standardized questionnaire was applied for risk factors collection. Multivariate logistic regression analysis was employed for multi-factors analysis, and the association between related factors and TB risk were estimated by odds ratio (OR) and 95% confidence intervals (95% CI). Results: Multivariate logistic regression showed that frequent fruits intake and physical activity, high body mass index (BMI) were associated with decreased risk of TB (OR =0.20, 95% CI: 0.08–0.53; OR =0.41, 95% CI: 0.17–1.00; OR =0.86, 95%CI: 0.76–0.97; respectively), while diabetes mellitus (DM) and no ventilation of working place were related to increased risk of TB (OR =12.99, 95% CI: 1.30–129.58; OR =3.39, 95% CI: 1.24–9.26; respectively). Conclusions: Lower BMI might be susceptible to TB, and frequent fruits consumption and more physical activity would low the risk of TB. Meanwhile, ventilation of working place and DM treatment will be in the necessity for TB control.

Chinese population

10.21037/jphe.2017.05.09

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Smoking Exposure and the Risk of Latent Tuberculosis Infection: Results from NHANES 2011–2012

Toxics (2024)

Xinsong Hu Jiongya Liu Yan Shao Guoli Li Honghuan Song

The association between smoking exposure and latent tuberculosis infection (LTBI) has been investigated in a few studies; however, further investigation is needed. In this study, the 2011–2012 NHANES population was used to evaluate smoking exposure and LTBI risk. A total of 7042 participants with available LTBI results and without active tuberculosis were included for analysis. Smoking was defined as participants who smoked at least 100 cigarettes in their life. Both univariable and multivariable analysis were adopted to evaluate smoking exposure, as well as related factors on the risk of LTBI. LTBI rates among current smokers (12.1%) and former smokers (9.9%) were higher than non-smokers (5.9%). However, current smokers and former smokers were not significantly associated with LTBI risk when compared to non-smokers after adjusting by age and sex in the multivariable analysis. Meanwhile, we found that passive smoking was not associated with LTBI (adjusted odds ratio (AOR), 0.85; 95%CI, 0.66–1.09). In multivariable analysis, current smoking was associated with LTBI (OR, 1.67; 95%CI, 1.28–2.19), while former smokers had an increased OR of LTBI, but the OR did not reach statistical significance (OR, 1.15; 95%CI, 0.90–1.48). Household tuberculosis (TB) contact was also related to LTBI (OR, 1.93; 95%CI, 1.25–2.99). However, BMI and diabetes were not found to be associated with LTBI. Smoking, especially current smoking, was significantly associated with LTBI. LTBI screening should be recommended for active smokers. Former smoking and passive smoking exposure were not found to have a significant relationship with LTBI risk. However, the high LTBI rate among quitters indicated we should pay more attention to former smokers with LTBI.

10.3390/toxics12010094

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Citations (3)