Tuberculosis Group Research Articles

Diagnostic value of chemiluminescence for urinary lipoarabinomannan antigen assay in active tuberculosis: insights from a retrospective study.

This study aimed to assess the efficacy of chemiluminescence-based urinary lipoarabinomannan (LAM) antigen assay as a diagnostic tool for identifying active tuberculosis. A retrospective study was conducted on 166 Tuberculosis (TB), 22 Non-Tuberculous Mycobacteria (NTM), 69 Non-TB cases, and 73 healthy controls from Zhangjiagang First Peoples Hospital between July 2022 and November 2022. Clinical and laboratory data were collected, including urine samples for LAM antigen detection, sputum samples and pleural effusion for GeneXpert, TB-DNA, and culture. TB group exhibited a higher LAM positivity rate (P < 0.001). CD4 count and diabetes as independent factors influencing the diagnostic accuracy of LAM. The LAM assay showed a sensitivity of 50.6% and a specificity of 95.65%. Notably, LAM's sensitivity was superior to TB-DNA (50.60% vs. 38.16%, P < 0.05). LAM's PTB detection rate was 51.7%, superior to TB-DNA (P = 0.047). Moreover, in EPTB cases, the LAM detection rate was 42.11%, surpassing Gene Xpert (P = 0.042), as well as exceeding the detection rates of TB-DNA and sputum culture. LAM antigen detection using chemiluminescence has demonstrated outstanding clinical diagnostic value for active TB, especially in the diagnosis of extrapulmonary TB. The convenience of sample collection in this diagnostic approach allows for widespread application in the clinical diagnosis of active tuberculosis, particularly in cases of EPTB and sputum-negative patients.

Analysis of Risk Factors for Developing Tuberculosis in Patients Who Received Prophylactic Latent Tuberculosis Infection Treatment with Experience of Biologic Medications.

Biologic medications have dramatically improved the treatment outcomes of immunological inflammatory diseases, but their immunosuppressive effects put patients at risk for tuberculosis (TB). We investigated the risk factors for developing TB in patients treated for latent tuberculosis infection (LTBI) who also had experience of using biologic medications. At Keio University Hospital, we retrospectively investigated patients treated with anti-mycobacterial drugs before or concurrently with biologic medications from January 2012 to August 2020. Patients in the 'follow-on cases group' who had a positive TB screening test after initiating biologic medications and subsequently started LTBI treatment were excluded. We researched and compared the patient characteristics for TB and non-TB patient groups. Of the 146 eligible patients, 5 (3.4%) developed TB. The incidence rate was 600/100000 person-years. There were no significant differences between TB and non-TB patient groups in the history of TB, interferon-gamma release assay (IGRA), duration of biologic medication therapy, LTBI treatment periods, concomitant use of calcineurin inhibitors or anti-rheumatic drugs. The percentage of patients who received prednisolone at a dose of ≥15 mg for more than 1 month was higher in those who developed TB than in those who did not (40.0 vs. 7.1%, p = 0.054); however, this difference was not statistically significant. Regular monitoring of TB is necessary for long-term concomitant use of high prednisolone doses during and after the administration of biologic medications.

Microbiome Alteration in Lung Tissues of Tuberculosis Patients Revealed by Metagenomic Next-Generation Sequencing and Immune-Related Transcriptional Profile Identified by Transcriptome Sequencing.

This study explored alterations in the respiratory microbiome and transcriptome after Mycobacterium tuberculosis infection in tuberculosis (TB) patients. Metagenomic next-generation sequencing (mNGS) was adopted to reveal the microbiome in lung tissues from 110 TB and 25 nontuberculous (NonTB) patients. Transcriptome sequencing was performed in TB tissues (n = 3), tissues adjacent to TB (ParaTB, n = 3), and NonTB tissues (n = 3) to analyze differentially expressed genes (DEGs) and functional pathways. The microbial β diversity (p = 0.01325) in TB patients differed from that in the NonTB group, with 17 microbial species distinctively distributed. Eighty-three co-up-regulated DEGs were identified in the TB versus NonTB and the TB versus ParaTB comparison groups, and six were associated with immune response to Mtb. These DEGs were significantly enriched in the signaling pathways such as immune response, NF-κB, and B cell receptor. Data in the lung tissue microbiome and transcriptome in TB patients offer a sufficient understanding of the pathogenesis of TB.

Distributed lag effects and vulnerable groups of PM and active pulmonary TB in Qingdao, China.

There has been a gap regarding current knowledge of the effect of PM on pulmonary TB, such as the exposure-time-response between them. This study aimed to explore the distributed lag effects of particulate matter (PM) on active pulmonary tuberculosis (TB) and identify the vulnerable groups. A generalized additive mixed model combined with a distributed lag non-linear model was applied to quantify the association between PM and active pulmonary TB with adjustment for potential confounders. Relative risk (RR) and cumulative RR with 95% confidence interval (CI) were calculated to quantify the exposure-time-response. A total of 16,486 cases of active pulmonary TB were notified. Results suggested that a unit 10µg/m3 increase of daily PM2.5 concentration was positively associated with active pulmonary TB morbidity at 36-115 lag day and RR reached maximum at 66 lag day (1.0076; 95%CI, 1.0031-1.0122), and the cumulative RR was 2.1940 (95%CI, 1.2292-3.9161). For PM10, this association was significantly positive at 73-117 lag day, and RR reached maximum at 100 lag day (1.0036; 95%CI, 1.0003-1.0067), and the cumulative RR was not significant. This study provides evidence that PM significantly associate with active pulmonary TB. Vulnerability to PM2.5 was identified in male, female, 0-18 ages, 19-64 ages, workers, and students. Our findings have significant implications for developing local strategies to prevent and reduce health impact in PM polluted areas.

A dual-process of targeted and unbiased Nanopore sequencing enables accurate and rapid diagnosis of lower respiratory infections

Nanopore metagenomics has been used for infectious disease diagnosis for bacterial pathogens. However, this technology currently lacks comprehensive performance studies in clinical settings for simultaneous detection of bacteria, fungi, and viruses. We developed a dual-process of Nanopore sequencing for one sample, with unbiased metagenomics in Meta process and target enrichment in Panel process (Nanopore Meta-Panel process, NanoMP) and prospectively enrolled 450 respiratory specimens from multiple centers. The filter system of pathogen detection was established with machine learning and receiver operator characteristic (ROC) curve to optimize the detection accuracy based on orthogonal test of 21 species. Antimicrobial resistance (AMR) genes were identified based on the Comprehensive Antibiotic Resistance Database (CARD) and single-nucleotide polymorphism matrix. Our approach showed high sensitivity in Meta process, with 82.9%, 88.7%, and 75.0% for bacteria, fungi (except Aspergillus), and Mycobacterium tuberculosis groups, respectively. Moreover, target amplification improved the sensitivity of virus (>80.0% vs. 39.4%) and Aspergillus (81.8% vs. 42.3%) groups in Panel process compared with Meta process. Overall, NanoMP achieved 80.2% sensitivity and 98.8% specificity compared with the composite reference standard, and we were able to accurately detect AMR genes including blaKPC-2, blaOXA-23 and mecA and distinguish their parent organisms in patients with mixed infections. We combined metagenomic and enriched Nanopore sequencing for one sample in parallel. Our NanoMP approach simultaneously covered bacteria, viruses and fungi in respiratory specimens and demonstrated good diagnostic performance in real clinical settings. National Key Research and Development Program of China and National Natural Science Foundation of China.

Outbreaks of COVID-19 in a tuberculosis treatment sanatorium on the Thailand-Myanmar border: a retrospective cohort analysis

Background Tuberculosis (TB) is a chronic condition, with overlapping symptoms to those of coronavirus disease 2019 (COVID-19). There has been inconsistent evidence on whether TB is a predisposing factor for developing severe COVID-19. The aim of this report is to explore whether TB influences the severity of COVID-19. Methods COVID-19 cases at two TB sanatoria on the Thailand-Myanmar border were reviewed. Demographic, clinical and laboratory data including TB treatment and co-morbidities, were analyzed. Characteristics and COVID-19 clinical outcomes were compared between two groups of patients: TB and those without TB (the caretakers and the medical personnel). Multivariable ordered logistic regression was conducted to compare the risk of severe COVID-19 between the two groups. Results Between September 2021 and March 2022, 161 COVID-19 cases were diagnosed. Over half of the COVID-19 patients were infected with TB (n= 104, 64.6%), and the rest were not (n=57, 35.4%). The median (interquartile range) age was 48 (33.5-57.0) and 27 (23-33) years in the TB and in the non-TB COVID-19 patients, respectively. Before COVID-19 infection, 67.1% (106/158) of patients had received at least one dose of COVID-19 vaccine. The median cycle threshold value at diagnosis was not different between TB (18.5, IQR 16.1-32.3) and non-TB patients (18.8, 15.1-30.0). Fever, gastrointestinal symptoms and ageusia were more common in non-TB patients. Six patients (3.8%, 6/156) all from the TB group became severe of which five (3.2%, 5/156) required oxygen therapy. One TB patient died (1/104, 0.96%) of lung cancer. After adjustment for potential confounders, the final clinical severity was not different between the two groups (adjusted odds ratio 1.40, 95% confidence interval 0.16–12.39). Conclusions TB was not associated with severe outcomes in the two TB sanatoria. The high uptake of COVID-19 vaccination and active screening could have impacted on disease progression and prevented unfavorable outcomes.

Renal Transplantation in Patients With Tuberculosis: A Single-center Experience From an Endemic Region.

Despite being a common infection in end-stage kidney disease patients, there are no evidence-based guidelines to suggest the ideal time of transplantation in patients on antitubercular therapy (ATT). This study aimed to examine the outcome of transplantation in patients while on ATT compared with those without tuberculosis (TB). This was a retrospective study. Renal transplant recipients transplanted while on ATT were compared with a 1:1 matched group (for age, sex, diabetic status, and type of induction agent) of patients without TB at the time of transplant. Patient outcomes included relapse of TB and graft and patient survival. There were 71 patients in each group. The mean duration for which ATT was given pretransplant was 3.8 ± 2.47 mo. The average total duration of ATT received was 12.27 ± 1.25 mo. Mortality in both the groups was similar (8.4% in the TB group versus 4.5% in the non-TB group; P = 0.49). None of the surviving patients had recurrence of TB during the follow-up. Death-censored graft survival (98.5% in the TB group versus 97% in the non-TB group; P = 1) and biopsy-proven acute rejection rates (9.86% in the TB group versus 8.45% in the non-TB group; P = 1) were also similar in both the groups. Successful transplantation in patients with end-stage kidney disease on ATT is possible without any deleterious effect on patient and graft survival and no risk of disease recurrence. Multicentric prospective studies are needed.

Three years’ experience of tuberculosis versus non-tuberculosis cases of bronchopleural fistula repair at Dr. Soetomo General Academic Hospital Surabaya

Link of Video Abstract: https://youtu.be/DVqGIPOyWR0 Background: Tuberculosis (TB) continues to be a significant health issue and causes various complications, especially in developing countries. Bronchopleural fistula (BPF) is a rare and potentially life-threatening complication of pulmonary tuberculosis that needs to be treated by surgical procedure. This research aimed to compare the outcome of post-operative BPF repair caused by Tuberculosis and non-Tuberculosis cases. Methods: In this retrospective review, we include patients from post-operative repair of BPF with Tuberculosis and non-Tuberculosis cases from January 2020 to December 2022 who were admitted to our primary center. Preoperative, operative and postoperative data were collected from medical records. We identified 36 patients and analyzed the differences between TB and non-TB groups. Results: There were 36 patients with BPF who underwent surgery. The mean age of the subjects was 47.940±15.288 years. Out of these, 25 subjects (69.4%) had TB, while 11 (30.6%) subjects did not. Among the subjects, 14 TB patients (38.9%) and 2 non-TB patients (56%) experienced recurrent pneumothorax before surgery. Statistical analysis showed a significant association between comorbid TB and the occurrence of secondary attack BPF before surgery (p = 0.035). Regarding the duration of post-operative drain placement, 22 TB patients (61.1%) had the drain placed for less than 7 days, while 3 subjects (8.3%) had it for more than 7 days. Among the non-TB patients, 10 subjects (27.8%) had the drain placed for less than 7 days, and only 1 subject (2.8%) had it for more than 7 days. The statistical analysis showed no association between the TB group and the duration of post-operative drain placement (p=0.798). Conclusion: There are numerous post-operative complications and morbidities following BPF repair surgery. Patients with TB who undergo BPF repair surgery are significantly associated with secondary attack BPF before surgery.

Prevalence of bacteriologically-confirmed pulmonary tuberculosis in urban Blantyre, Malawi 2019-20: Substantial decline compared to 2013-14 national survey.

Recent evidence shows rapidly changing tuberculosis (TB) epidemiology in Southern and Eastern Africa, with need for subdistrict prevalence estimates to guide targeted interventions. We conducted a pulmonary TB prevalence survey to estimate current TB burden in Blantyre city, Malawi. From May 2019 to March 2020, 115 households in middle/high-density residential Blantyre, were randomly-selected from each of 72 clusters. Consenting eligible participants (household residents ≥ 18 years) were interviewed, including for cough (any duration), and offered HIV testing and chest X-ray; participants with cough and/or abnormal X-ray provided two sputum samples for microscopy, Xpert MTB/Rif and mycobacterial culture. TB disease prevalence and risk factors for prevalent TB were calculated using complete-case analysis, multiple imputation, and inverse probability weighting. Of 20,899 eligible adults, 15,897 (76%) were interviewed, 13,490/15,897 (85%) had X-ray, and 1,120/1,394 (80%) sputum-eligible participants produced at least one specimen, giving 15,318 complete cases (5,895, 38% men). 29/15,318 had bacteriologically-confirmed TB (189 per 100,000 complete-case (cc) / 150 per 100,000 with inverse weighting (iw)). Men had higher burden (cc: 305 [95% CI:144-645] per 100,000) than women (cc: 117 [95% CI:65-211] per 100,000): cc adjusted odds ratio (aOR) 2.70 (1.26-5.78). Other significant risk factors for prevalent TB on complete-case analysis were working age (25-49 years) and previous TB treatment, but not HIV status. Multivariable analysis of imputed data was limited by small numbers, but previous TB and age group 25-49 years remained significantly associated with higher TB prevalence. Pulmonary TB prevalence for Blantyre was considerably lower than the 1,014 per 100,000 for urban Malawi in the 2013-14 national survey, at 150-189 per 100,000 adults, but some groups, notably men, remain disproportionately affected. TB case-finding is still needed for TB elimination in Blantyre, and similar urban centres, but should focus on reaching the highest risk groups, such as older men.

Association of Cytokine Gene Polymorphisms and Their Impact on Active and Latent Tuberculosis in Brazil's Amazon Region.

Some genetic variations in cytokine genes can alter their expression and influence the evolution of Mycobacterium tuberculosis (Mtb) infection. This study aimed to investigate the association of polymorphisms in cytokine genes and variability in plasma levels of cytokines with the development of tuberculosis (TB) and latent tuberculosis infection (LTBI). Blood samples from 245 patients with TB, 80 with LTBI, and healthy controls (n = 100) were included. Genotyping of the IFNG +874A/T, IL6 -174G/C, IL4 -590C/T, and IL10 -1082A/G polymorphisms was performed by real-time PCR, and cytokine levels were determined by flow cytometry. Higher frequencies of genotypes AA (IFNG +874A/T), GG (IL6 -174G/C), TT (IL4 -590C/T), and GG (IL10 -1082A/G) were associated with an increased risk of TB compared to that of LTBI (p = 0.0027; p = 0.0557; p = 0.0286; p = 0.0361, respectively) and the control (p = <0.0001, p = 0.0021; p = 0.01655; p = 0.0132, respectively). In combination, the A allele for IFNG +874A/T and the T allele for IL4 -590C/T were associated with a higher chance of TB (p = 0.0080; OR = 2.753 and p < 0.0001; OR = 3.273, respectively). The TB group had lower levels of IFN-γ and higher concentrations of IL-6, IL-4, and IL-10. Cytokine levels were different between the genotypes based on the polymorphisms investigated (p < 0.05). The genotype and wild-type allele for IFNG +874A/T and the genotype and polymorphic allele for IL4 -590C/T appear to be more relevant in the context of Mtb infection, which has been associated with the development of TB among individuals infected by the bacillus and with susceptibility to active infection but not with susceptibility to latent infection.

Tuberculosis and Sudden Death in Lithuania.

Tuberculosis is one of the most common infectious diseases in the world. 10.6 million people fell ill in 2021 and 1.6 million died from the disease. Lithuania has the third-highest tuberculosis incidence rate per 100,000 and the second-highest mortality rate per 100,000 in EU/EEA countries. During 2015-2021 years, there were 799 deaths of pulmonary tuberculosis in Lithuania. However, the presence of pulmonary tuberculosis is often unknown before death and is only revealed during autopsy. The aim of the study is to review current literature on this topic and present statistical analysis on evaluated socioeconomical, epidemiological indicators, as well as autopsy findings that may suggest pulmonary tuberculosis infection. This research was designed as a retrospective study focusing on full forensic pathology autopsies between 2015 and 2021. Of these, 100 cases were randomly selected where the cause of death was tuberculosis diagnosed during post-mortem examination and compared to a control group consisting of 415 cases of sudden death. The study revealed that out of 100 pulmonary tuberculosis cases, 90% were male with the mean age of 53.48 ± 11.12 years old. In the case of sudden death where tuberculosis was found, a significant portion of the sample (91%) was not followed up at any medical institution. Regarding socioeconomic factors, a moderate negative correlation between Lithuania's gross domestic product and tuberculosis distribution was observed, as well as a weak negative correlation between alcohol consumption (l per capita) in the general population and tuberculosis distribution. The lung weight of the pulmonary tuberculosis group was statistically significantly higher than that of the control group. Tuberculosis remains a major problem in Lithuania and the combination of socioeconomic indicators determines the prevalence of tuberculosis in the country. In cases of sudden death, autopsy helps to identify tuberculosis cases that have not been clinically detected and ensures tuberculosis monitoring. Therefore, the person who performs autopsy remains at high risk of contracting tuberculosis. Furthermore, extreme caution is advised if higher lung weight or hardenings are seen during autopsy because of the possibility of tuberculosis.

Role of serum adenosine deaminase (ADA) in the diagnosis of tuberculosis &amp; other respiratory diseases

: The WHO Tuberculosis (TB) statistics for India in 2021 gave an estimated incidence figure of 25,90,000 cases, i.e., about 40% of Indian population is infected with TB. There are different investigative methods available for TB diagnosis like ZN-staining of ., which lacks sensitivity &amp; another method of Mycobacterial culture takes around 6-8 weeks to isolate . in culture which results in delayed diagnosis &amp; treatment and meanwhile further progression of disease. Other sensitive methods like PCR &amp; CBNAAT are costly &amp; they require skilled personnel &amp; lots of equipment. Therefore, there is a need of simple, cost-effective, rapid &amp; reliable test which can be easily carried out in the clinical laboratories of resource limited countries. In some previous studies, the level of ADA in effusion fluids was used for the diagnosis of TB, but it is not always possible to access effusion fluid &amp; it requires skilled personnel. Thus, the aim of the present study is to evaluate the usefulness of measuring the serum level of ADA as noninvasive biochemical marker in early diagnosis of TB.The present cross-sectional study was conducted on 200 serum ADA samples. Patient samples were divided into four groups based on their diagnosis, i.e., 50 patients with pulmonary TB, 50 patients with extra-pulmonary TB, 50 patients with respiratory infections other than TB &amp; 50 healthy people not having TB. The ADA level for each group was presented as mean + SD &amp; compared by applying post hoc Bonferroni test which showed that the pulmonary TB group was significantly different from the other 3 groups with p&amp;#60;0.001. According to ROC curve analysis, the best cutoff point was 21.8 IU/L at which sensitivity &amp; specificity were 88% &amp; 87% respectively.Serum ADA activity with high sensitivity &amp; specificity percentage can be used as a reliable marker in the diagnosis of TB &amp; to differentiate TB from other respiratory illness.

The effects of etiological factors on timing of decortication

Aim: Tube drainage is the primary method in the treatment of empyema with 80-90% cure rates. In patients with empyema who have not received adequate treatment, the result is pleural fibrosis. Decortication is the only treatment option for chronic empyema that has caused fibrothorax that prevents lung expansion. In our study, we aimed to determine the relations between etiological base of the disease, the consequences and the decision of decortication timing. Methods: The patients who were admitted and hospitalized with pleural effusion between 1994 and 2000 were included in the study. We examined the duration of pretreatment, pleural thickness and the duration of postoperative hospital stay of these cases, with who have undergone decortication surgery. Results: A total of 82 cases of decortication were enrolled, which consisted of 61 male (74.3%) and 21 female (25.6%). The cases were examined in two groups: tuberculosis [12 (25%) empyema, 27 (56.3%) tuberculous pachypleuritis, 9 (18.8%) pleurisy + parenchymal involvement] and non-tuberculosis [2 (5.9%) trauma, 5 (14.7%) pneumonia + empyema, 23 (%) 67.6% empyema, 4 (11.8%) hydatid cyst]. The effects of preoperative treatment durations on the thickness of the decortication materials and the duration of postoperative hospital stay were investigated. The preoperative treatment period of the tuberculosis group was significantly higher, the decortication pleural thicknesses were found to be greater. (p&lt;0.01) There was no statistically significant difference in the duration of postoperative hospital stay between the tuberculosis and other group (p&gt;0.05). Conclusion: In cases that do not respond to closed tube drainage and appropriate antibiotic therapy, decortication should be performed without delay considering the etiological factors. If decortication is performed earlier than 2 weeks, the visceral pleura can be easily separated; parietal decortication is rarely needed which might be an advantage of the procedure.

Differential Expression of miR-146 and miR-155 in Active and Latent Tuberculosis Infection.

Tuberculosis (TB) is one of the leading causes of death worldwide. Besides, one-third of the world population is infected with Mycobacterium tuberculosis (MTB) while staying clinically asymptomatic; the situation is called latent TB infection (LTBI). MiR-21, miR-31, miR-146a, and miR-155 play an important role in many immune and inflammatory pathways. In the present study the expression levels of MiR-21, miR-31, miR-146a, and miR-155 in peripheral blood mononuclear cells (PBMCs) from patients with active TB, latently infected individuals (LTBI), and healthy controls (HC) were investigated. Participants were recruited at the Bouali Hospital, Zahedan University of Medical Sciences, Zahedan, Iran from 2010 to 2011. PBMCs were stimulated with PPD before RNA extraction. TaqMan RT-qPCR assay was used to analyze the expression levels of miRNAs. The results indicated no significant differences in the expression of miR-21 and miR-31 between different groups; however, in patients with active TB, the expression of miR-21 (P=0.03) and miR-31 (P=0.04) were significantly increased after stimulation with PPD compared to the unstimulated condition. The expression of miR-146 in response to PPD in both LTBI (P=0.02) and TB (P=0.03) groups compared to the HC group was increased. No significant differences were found in the expression level of miR-155 in response to PPD between LTBI and HC groups. However, the fold change was significantly higher in the TB group in comparison with the HC (P=0.03) and LTBI (P=0.05) groups. The results confirm the main role of miR-146 and miR-155 in TB infection and suggest a role for miR-146 and miR-155 as infection and activation markers in tuberculosis infection, respectively.

A high proportion of caseous necrosis, abscess, and granulation tissue formation in spinal tuberculosis.

The special blood circulation, anatomy, and tissue structure of the spine may lead to significant differences in pathological features and drug resistance between spinal tuberculosis and pulmonary tuberculosis. Here, we collected 168 spinal tuberculosis cases and 207 pulmonary tuberculosis cases, and compared their clinical and pathological features as well as drug resistance. From the anatomical location, the highest incidence was of lumbar tuberculosis, followed by thoracic tuberculosis. PET-CT scans showed increased FDG uptake in the diseased vertebrae, discernible peripheral soft tissue shadow, visible internal capsular shadow, and an abnormal increase in FDG uptake. MRI showed infectious lesions in the diseased vertebral body, formation of paravertebral and bilateral psoas muscle abscess, and edema of surrounding soft tissues. As with control tuberculosis, the typical pathological features of spinal tuberculosis were chronic granulomatous inflammation with caseous necrosis. The incidence of granulomas was not statistically different between the groups. However, the proportions of caseous necrosis, acute inflammation, abscess, exudation, and granulation tissue formation in the spinal tuberculosis group were all significantly increased relative to the control tuberculosis group. Compared to the control tuberculosis group, the incidences of resistance to rifampicin (RFP) + isoniazid (INH) + streptomycin (STR) and INH + ethambutol (EMB) were lower in the spinal tuberculosis group, while the incidences of resistance to RFP + INH + EMB and RFP + EMB were higher. Moreover, we also found some differences in drug-resistance gene mutations. In conclusion, there are noticeable differences between spinal Mycobacterium tuberculosis and pulmonary tuberculosis in pathological characteristics, drug resistance, and drug resistance gene mutations.

Association between a single nucleotide polymorphism of the ALOX5 gene and susceptibility to multisystem tuberculosis in a Chinese Han population

BackgroundHost genetic single nucleotide polymorphisms can exert an influence susceptibility to tuberculosis infection. Previous investigations have demonstrated an association between the polymorphism in the ALOX5 gene and a range of diseases, encompassing not only noninfectious conditions like asthma, acute myocardial infarction, and cerebral infarction but also infections caused by various pathogens. However, the relationship between ALOX5 gene polymorphism and susceptibility to tuberculosis has received limited research attention. The ALOX5 gene encodes arachidonic acid 5-lipoxygenase(5-LO), which serves as the initiating catalyst in the generation of the inflammatory mediator leukotriene.Leukotrienes, products derived from the 5-LO pathway, are potent proinflammatory lipid mediators that assume a pivotal role in tuberculosis infections.Consequently, ALOX5 gene variants may be intricately associated with the pathogenesis of tuberculosis. In instances where the host exhibits immunocompromisation, infection with Mycobacterium tuberculosis can impact multiple systems. The involvement of multiple systems significantly augments the complexity of treatment and escalates patient mortality rates. Regrettably, the underlying mechanisms driving multisystem tuberculosis pathogenesis remain enigmatic, with clinicians paying scant attention to this aspect. Although the protein encoded by the ALOX5 gene represents a pivotal enzyme that catalyzes the metabolism of arachidonic acid into LXA4, and thereby plays a significant role in the inflammatory response during tuberculosis infection, studies investigating ALOX5 gene polymorphism and its association with susceptibility to multisystem tuberculosis in the Chinese Han population are exceptionally scarce. Therefore, the primary objective of this study is to comprehensively examine the correlation between ALOX5 gene polymorphisms and susceptibility to tuberculosis within the Chinese Han population, with particular emphasis on multisystemic tuberculosis. MethodsA case‒control study design was employed, encompassing 382 individuals with pulmonary tuberculosis and 367 individuals with multisystemic tuberculosis as the case groups, along with 577 healthy controls.Whole blood DNA was extracted from all patients and healthy controls. Subsequently, three tag polymorphisms (rs2029253, rs7896431, rs2115819) within the ALOX5 gene were selectively identified and genotyped. ResultsAfter adjusting for age and sex, the presence of allele A at rs2029253 exhibited a pronounced association with an elevated risk of TB susceptibility when compared to the tuberculosis group and healthy control group. (ORa: 2.174, 95% CI: 1.827–2.587; Pa<0.001, respectively). Notably, the rs2029253 AG genotype and AA genotype displayed a significantly increased susceptibility to tuberculosis (ORa: 2.236, 95% CI: 1.769–2.825; Pa <0.001 and ORa: 4.577, 95% CI: 2.950–7.100; Pa <0.001, respectively) compared to the GG genotype. Moreover, in the analysis utilizing genetic models, rs2029253 also exhibited a markedly heightened susceptibility to tuberculosis in additive models, dominant models, and recessive models (Pa <0.001). Conversely, no significant association was observed between rs7896431, rs2115819, and tuberculosis. In the subgroup analysis, when comparing the pulmonary tuberculosis group with the healthy control group, we observed no significant disparities in the distribution frequencies of alleles, genotypes, and gene models (additive model, dominant model, and recessive model) for the three tag SNPs, with P-values were >0.05 after adjusting for age and sex. Additionally, we noted that the presence of allele A at rs2029253 was linked to an increased susceptibility to tuberculosis in the multisystemic tuberculosis group relative to the healthy control group (ORa: 2.292, 95% CI: 1.870–2.810; Pa<0.001). Similarly, the rs2029253 AG genotype, AA genotype, and gene models, including the additive model, dominant model, and recessive model, demonstrated a significantly elevated risk of tuberculosis susceptibility. ConclusionsThe polymorphism in the ALOX5 gene is associated with susceptibility to multisystemic tuberculosis in the Chinese Han population.

Pengetahuan, Sikap dan Dukungan Keluarga terhadap Niat Memeriksakan Dahak pada Presumtif TBC

This study aims to determine the relationship between knowledge, attitudes, and family support on the intention to have sputum examined in a group suspected of having tuberculosis in the Margoyoso II Health Center. The research method used in this research is quantitative. The design in this study is analytic with a cross sectional approach. The results showed that of the 113 respondents who had low knowledge about tuberculosis, 44 (67.7%) had a low attitude towards sputum examination, 47 (65.3%), and 55 (85.9%) had a low level of family support. Results The knowledge variable has a p value of 0.003, attitude has a p value of 0.006, family support has a p value &lt;0.0001. The results of the probability variables of knowledge, attitudes, and family support are smaller than the significant level of 5% (0.05), meaning that it can be concluded that there is a relationship related to knowledge, attitudes, and family support on the intention to check sputum in the suspected tuberculosis group in the Work Area of ​​the Margoyoso II Health Center .&#x0D; Keywords: Attitude, Family Support, Knowledge, Sputum Examination, Tuberculosis

Construction and Validation of a Diagnostic Scoring System for Predicting Active Pulmonary Tuberculosis in Patients with Positive T-SPOT Based on Indicators Associated with Coagulation and Inflammation: A Retrospective Cross-Sectional Study.

Tuberculosis (TB) is a life-threatening single infectious disease, which remains a major global public health concern. This study was to establish and validate a clinically practical diagnostic scoring system for predicting active pulmonary tuberculosis (APTB) in patients with positive tuberculosis T cell spot test [T-SPOT] using indicators associated with coagulation and inflammation. A single-center retrospective cross-sectional study was performed to include patients with positive T-SOPT registered and hospitalized at Wuhan Jinyintan Hospital between January 2017 and December 2019. All patients were separated into the active pulmonary tuberculosis (APTB) group and the inactive pulmonary tuberculosis (IPTB) group, according to the diagnostic criteria from China's Expert Consensus for APTB and IPTB. Subsequently, the patients were randomized into a training set and a validation set at a ratio of 2:1. Indicators associated with coagulation and inflammation, including prothrombin time activity (PTA), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen concentration (Fbg-C), C-reactive protein/albumin ratio (CAR), C-reactive protein/prealbumin ratio (CPR), neutrophils count/lymphocyte count ratio (NLR), platelet count/lymphocyte count ratio (PLR), monocyte count/lymphocyte count ratio (MLR), and erythrocyte sedimentation rate (ESR) were obtained from electronic medical record system (EMRS). Stepwise logistic regression was performed in the training set to build a diagnostic model for predicting APTB, which was transformed into an easily applicable scoring system via nomogram. Receiver operating characteristic (ROC) analysis, calibration curve (CC), and decision curve analysis (DCA) were conducted to evaluate the predictive performance of the established diagnostic scoring system. A total of 508 patients [training set (211 cases of APTB and 116 cases of IPTB) and validation set (103 cases of APTB and 78 cases of IPTB)] with positive T-SPOT were recruited in the study. Stepwise logistic regression showed that CPR, MLR, ESR, APTT and Fbg-C were independent predictors for APTB. The scoring system was subsequently formulated based on the abovementioned predictors, which correspond to scores of 10, 6, 7, 5, and 5, respectively. In addition, patients are more likely to be diagnosed as APTB when the cut-off score was ≥16 scores, while patients with <16 scores are more likely to be diagnosed as IPTB. The scoring system showed good predictive efficacy in both the training set [area under the curve (AUC): 0.887] and the validation set (AUC: 0.898). Furthermore, both CC and DCA confirmed the clinical utility of the scoring system. The data suggest that the combination of indicators associated with coagulation and inflammation could serve as biomarkers to identify APTB in patients with positive T-SPOT. In addition, patients with positive T-SPOT were more prone to be diagnosed with APTB when having a combined total of scores ≥16 in the scoring system.

Association between a single nucleotide polymorphism of the IL23R gene and tuberculosis in a Chinese Han population: a case‒control study

BackgroundSevere tuberculosis constitutes a significant menace to human safety and well-being, with a considerable mortality rate. The severity of tuberculosis can be impacted by genetic variations in host genes, particularly single nucleotide polymorphisms (SNPs).MethodsA case‒control study was undertaken, encompassing a cohort of 1137 tuberculosis patients (558 with severe tuberculosis and 579 with mild tuberculosis), alongside 581 healthy controls within the age range of fifteen to forty-five years. Whole blood DNA was extracted from all participants, and three tag polymorphisms (rs1884444, rs7518660, rs7539625) of the IL23R gene were selectively identified and genotyped.ResultsNo significant correlation was observed between the IL23R gene polymorphisms (rs1884444, rs7518660, and rs7539625) and tuberculosis. Upon comparing the tuberculosis group with the healthy control group, the mild tuberculosis group with the healthy control group, and the severe tuberculosis group with the healthy control group, the obtained P-values were> 0.05. However, in the comparison between severe tuberculosis and mild tuberculosis, the presence of rs1884444 G alleles exhibited a significantly increased risk of severe tuberculosis after adjusting for age and sex (ORa: 1.199, 95% CI: 1.009–1.424; Pa=0.039, respectively). In subgroup analysis, after accounting for confounding factors, including age and sex, rs1884444 G alleles continued to demonstrate a significantly heightened risk of severe tuberculosis. Nonetheless, the comparison between the multisystemic tuberculosis group and the mild tuberculosis group was no significant difference. Notably, rs1884444 of the IL23R gene exhibited a noteworthy association with the risk of severe tuberculosis in the comparison between severe tuberculosis and mild tuberculosis before and after adjusting for age and sex (ORa: 1.301, 95% CI: 1.030–1.643; Pa=0.027, respectively). Furthermore, the presence of the rs1884444 G allele exhibited a significantly increased risk of severe tuberculosis after adjusting for age and sex in the comparison between tuberculous meningitis and mild tuberculosis (ORa: 1.646, 95% CI: 1.100-2.461; Pa=0.015, respectively).ConclusionsThe present study suggests that there is no significant association between IL23R gene polymorphism and tuberculosis susceptibility in the Chinese Han population. However, it does indicate a potential link between IL23R polymorphism and an increased risk of developing severe tuberculosis.

Enhancing the interferon-γ release assay through omission of nil and mitogen values

PurposeTo address the limited utility of the interferon (IFN)-γ release assay (IGRA) caused by its variability and inconsistency.MethodsThis retrospective cohort study was based on data obtained between 2011 and 2019. QuantiFERON-TB Gold-In-Tube was used to measure IFN-γ levels in nil, tuberculosis (TB) antigen, and mitogen tubes.ResultsOf 9,378 cases, 431 had active TB. The non-TB group comprised 1,513 IGRA-positive, 7,202 IGRA-negative, and 232 IGRA-indeterminate cases. Nil-tube IFN-γ levels were significantly higher in the active TB group (median = 0.18 IU/mL; interquartile range: 0.09–0.45 IU/mL) than in the IGRA-positive non-TB (0.11 IU/mL; 0.06–0.23 IU/mL) and IGRA-negative non-TB (0.09 IU/mL; 0.05–0.15 IU/mL) groups (P < 0.0001). From receiver operating characteristic analysis, TB antigen tube IFN-γ levels had higher diagnostic utility for active TB than TB antigen minus nil values. In a logistic regression analysis, active TB was the main driver of higher nil values. In the active TB group, after reclassifying the results based on a TB antigen tube IFN-γ level of 0.48 IU/mL, 14/36 cases with negative results and 15/19 cases with indeterminate results became positive, while 1/376 cases with positive results became negative. Overall, the sensitivity for detecting active TB improved from 87.2 to 93.7%.ConclusionThe results of our comprehensive assessment can aid in IGRA interpretation. Since nil values are governed by TB infection rather than reflecting background noise, TB antigen tube IFN-γ levels should be used without subtracting nil values. Despite indeterminate results, TB antigen tube IFN-γ levels can be informative.