Active Tuberculosis Infection Research Articles

Management of Isoniazid Monoresistant Tuberculosis

lsoniazid (INH) is one of the main first-line drugs used for the treatment of active tuberculosis (TB) and latent TB infection because it has bactericidal capabilities and a good level of safety. The presence of TB germs that are resistant to INH will reduce the effectiveness of TB treatment. The treatment mix for INH monoresistant TB patients is a combination of rifampicin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E), and levofloxacin (Lfx) or R-H-Z-E-Lfx given for 6 months. If a health facility provides loose TB medication, the patient can be given a combination of treatment without INH (R-Z-E-Lfx). In conditions where the Lfx drug cannot be used because there is severe intolerance (serious adverse events) or there are contra indications, the treatment given is the R-H-Z-E combination for 6 months. Clinical monitoring for patients with INH monoresistant TB follows the same principles as treatment of drug-sensitive TB. In conclusion, the treatment guide for INH monoresistant TB patients is a combination of rifampicin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E), and levofloxacin (Lfx) or R-H-Z-E-Lfx for 6 months.

Izoniazidom navodené poškodenie pečene sprevádzané ikterom

Summary: Isoniazid belongs to the first line antituberculosis drugs and can be used for the treatment of both active and latent tuberculosis infections. It is a part of combined regimens, for the preventive treatment of tuberculosis isoniazid can be used in monotherapy as well. Even though elevations in serum aminotransferases levels during isoniazid therapy are seen frequently, the development of symptomatic hepatitis is rare, according to specialised literature. This article describes a case of a patient who developed drug-induced liver injury accompanied by jaundice during the isoniazid preventive treatment of tuberculosis. It also provides a summary of the currently known risk factors, pathogenesis, and incidence of hepatotoxicity observed throughout therapy with this antituberculosis drug. We also illustrate the process of diagnosing drug--induced liver injury in clinical practice settings with the utilisation of the updated RUCAM score. Key words: jaundice – isoniazid – drug-induced liver injury – tuberculosis preventative therapy – updated RUCAM score.

Understanding the complexities of post-tuberculosis lung disease: Implications for global health

Post-tuberculosis lung disease (PTLD) presents a significant challenge in the management of tuberculosis patients, with far-reaching implications for global health. This editorial explores the multifaceted nature of PTLD, encompassing its pathophysiology, clinical manifestations, diagnostic complexities, and implications for public health. PTLD arises from pulmonary damage due to an active tuberculosis infection, leading to inflammation, scarring, and fibrosis within the lungs. Clinical manifestations vary widely, ranging from chronic respiratory symptoms to severe respiratory failure, often resembling chronic obstructive pulmonary disease or restrictive lung disease. The diagnosis of PTLD is hindered by its heterogeneous presentation and overlap with other respiratory conditions, necessitating a comprehensive evaluation through pulmonary function tests and radiological imaging. PTLD imposes a substantial burden on global health systems, particularly in regions with high tuberculosis prevalence, contributing to increased morbidity and mortality rates. Management strategies focus on alleviating symptoms, preserving lung function, and preventing disease progression through pharmacological interventions, pulmonary rehabilitation, and, in select cases, surgical interventions. Preventive measures include effective tuberculosis control measures, vaccination against respiratory pathogens, and addressing social determinants of health. Overall, a comprehensive understanding of PTLD is essential for improving patient outcomes and reducing disease burden, highlighting the importance of concerted efforts to raise awareness, enhance diagnostic capabilities, and develop effective management strategies for this complex condition.

Late Tuberculosis Reactivation After Severe Covid-19.

Although there is no specific therapy for COVID-19, it is recommended that patients with severe SARS-CoV-2 infection are treated with corticosteroids and anti-IL-6 receptor monoclonal antibodies. Both COVID-19 itself and the treatment modalities mentioned above have suppressive effects on the immune system which may lead to an increased susceptibility to other infections. In patients with latent tuberculosis (TB) reactivation of TB infection after recovery from severe COVID-19 has been described. Most of these cases have occurred in parts of the world where tuberculosis is endemic. The patient is a female in her 70s who was born and raised in Southeast Asia and has lived in the Netherlands for more than 30 years. She was treated for a severe COVID-19 requiring mechanical ventilation for several weeks and pharmaceutical treatment with corticosteroids and anti-IL-6 receptor monoclonal antibodies (Sarilumab). She recovered well. Two years later she was readmitted with symptoms of a serious pulmonary infection and meningitis. Her condition deteriorated in a short time. An active TB infection was diagnosed. Despite adequate antibiotic treatment and supportive therapy her condition worsened and four days after admission to the ICU she deceased. Reactivation of latent TB after recovery from a severe COVID-19 has been described several times and may occur several months after the SARS-CoV-2 infection. In this case the reactivation presented two years after COVID-19. This case illustrates that long-term follow-up of patients with latent TB that recover from a severe COVID-19 may be indicated. Reactivation of latent tuberculosis infection in patients treated for a severe COVID-19 may occur even two years after recovery from SARS-CoV-2 infection.Most cases of reactivation of tuberculosis after COVID-19 are described in regions where tuberculosis is endemic. However, it may also occur in countries with a relatively low prevalence of tuberculosis infection. The exact incidence of tuberculosis reactivation after COVID-19 is unknown and probably underestimated.A long-term follow-up of patients after severe COVID-19 treated with corticosteroids and/or anti-IL-6 receptor monoclonal antibodies with a history of tuberculosis or patients migrated from countries where tuberculosis is endemic seems to be important.

Construction of Immune-Related Diagnostic Model for Latent Tuberculosis Infection and Active Tuberculosis.

Tuberculosis (TB) is one of the most infectious diseases caused by Mycobacterium tuberculosis (M. tb), and the diagnosis of active tuberculosis (TB) and latent TB infection (LTBI) remains challenging. Gene expression files were downloaded from the GEO database to identify the differentially expressed genes (DEGs). The ssGSEA algorithm was applied to assess the immunological characteristics of patients with LTBI and TB. Weighted gene co-expression network analysis, protein-protein interaction network, and the cytoHubba plug-in of Cytoscape were used to identify the real hub genes. Finally, a diagnostic model was constructed using real hub genes and validated using a validation set. Macrophages and natural killer cells were identified as important immune cells strongly associated with TB. In total, 726 mRNAs were identified as DEGs. MX1, STAT1, IFIH1, DDX58, and IRF7 were identified as real hub immune-related genes. The diagnostic model generated by the five real hub genes could distinguish active TB from healthy controls or patients with LTBI. Our study may provide implications for the diagnosis and drug development of M. tb infections.

Comprehension of Calcitriol Levels in Pregnant Women With Latent Tuberculosis and Immune Function in their Newborns.

Pregnant women with latent tuberculosis infection (LTBI) may develop active tuberculosis infection and could infect their neonates, which could impair the child's immune system due to infection-mediated immunological responses. In order to develop a preventative TB program in this study, we desired to understand the impact of calcitriol in LTBI pregnant women and immunological responses in neonates. In three hospitals in Medan, North Sumatra, we implemented a case-control design with 84 pregnant women in their third trimester and their newborns. We determined the levels of calcitriol, cathelicidin, and interferon gamma (IFN-γ) in women between December 2021 and July 2022. These measurements were then compared to the newborns' levels of calcitriol, cathelicidin, IFN-γ, and Toll-Like Receptor (TLR) 2. Analyses were performed using the Chi-squared and Fisher's tests, while Spearman correlations were employed to assess for correlations. 42 pregnant women with LTBI (interferon gamma release assay (IGRA) positive) and 42 pregnant women without LTBI (IGRA negative) participated in the study. The findings demonstrated that pregnant women with LTBI were at increased risk for calcitriol deficiency (Odds Ratio (OR) = 3.667, p = 0.006), which had an impact on the calcitriol levels of their unborn children (p = 0.038). TLR2 levels and calcitriol levels were substantially associated with LTBI pregnant women and their healthy neonates (p = 0.048; p = 0.005). Cathelicidin levels in the newborns of non-LTBI pregnant women were influenced by their higher calcitriol levels (p = 0.043). Pregnant women with LTBI had higher levels of cathelicidin and IFN-γ than those without it (p = 0.03; p = 0.001). Pregnant LTBI women's calcitriol levels had an impact on the calcitriol levels of their newborns. Mother's immunological responses and babies' calcitriol levels affected the levels of cathelicidin, IFN-γ, and TLR2 in newborns.

Tetrad metal ion mediated molecular switch aptamer sensor for fluorescence assay of plasma IP-10 in clinical tuberculosis

Interferon-γ-inducible protein 10 (IP-10) has demonstrated enormous potential as a novel biomarker for tuberculosis (TB), particularly in the monitoring of patient progression for active or latent tuberculosis infection (LTBI). Herein, we established a tetrad metal ion-mediated molecular switch aptamer sensor for the convenient detection of IP-10 in plasma and the diagnosis of TB. The simple sensor relied on the partially complementary IP-10 aptamer and four DNA hairpin strands rich in cytosine (C), which can form a relatively stable tetrad C-Ag+-C structure when combined with Ag+ without additional modification. Based on the specific recognition of IP-10 and aptamer, a large amount of Ag+ could be released in a short time. Combining with cadmium telluride quantum dots (CdTe QDs) as the signal reporter, we achieved superior analytical performance, with the limits of detection (LOD) reaching 3 fg/mL for IP-10 analysis in 1 h. Clinical practicality was confirmed by evaluating 38 clinical samples (19 TB-positive patients, 14 non-TB patients, and 5 latent TB infection patients). The results showed that the detected IP-10 levels were significantly different between the non-TB and TB/LTBI groups, and the results aligned with clinical computed tomography (CT) results, indicating that the method could represent a reliable diagnostic technique for TB.

Tuberculosis screening in the European migrant population: a scoping review of current practices.

Responding to a surge in new tuberculosis (TB) cases among migrants from high-incidence countries, low-incidence European nations have heeded World Health Organization recommendations by implementing TB screening in this population. This review aims to synthesise evidence on current screening strategies for active TB and latent tuberculosis infection (LTBI) in European high-income countries, and their main barriers and interventions. PubMed, Web of Science and Scopus were searched from March to April 2023, including articles in English, published in the last decade, pertaining to screening strategies for active TB or LTBI in Europe focused on migrants, excluding those exclusively composed of refugees, asylum seekers or other migrant populations. 32 studies fit the criteria. Screening in migrants varies between countries regarding timing, population, screening location and diagnosis. Furthermore, some barriers prevent migrants from benefiting from screening, namely physical, cultural and professional barriers. Additional research is needed to determine the patterns through which regular migrants adhere to current screening strategies in European countries.

Candidate Blood MicroRNAs as Potential Biomarkers in Patients with Active and Latent Pulmonary Tuberculosis Infection

Infection with tuberculosis (TB) has been a leading cause of death worldwide. The accurate detection of Mycobacterium tuberculosis (M. tuberculosis) is integral for the prevention and control programs for TB disease. Host-encoded microRNAs (miRNAs) are known to be triggered upon TB infection, raising possibilities of their utility as biomarkers. Here, we investigated the value of miRNAs in pointing active TB (ATB) and predicting the progression from latent TB (LTB) to ATB infection. We then constructed signaling pathways predicted to be involved in TB disease pathobiology. Our analyses identified miR-21-5p, miR-29a-3p and miR-361-5p as being down regulated in ATB and upregulated in LTB compared to healthy subjects with an area under the curve (AUC) of > 0.9, indicating potentially promising biomarker. Pathways related to estrogen signaling, TNF and apoptosis signaling were enriched targets for those miRNAs. This study provides evidence for the significance of miRNA as diagnostic and prognostic markers for ATB and LTB infections in humans. These results could be extrapolated and validated using future large-scale studies.

Total Hip Arthroplasty for Acetabular Protrusion in a Patient with Active Tuberculosis Infection: A Case Report

Background: After the spine, the hip is the most common site that can be infected with extrapulmonary tuberculosis (TB). In the early stages, patients present with complaints of pain around the hip, and after a while, they might experience deformities, shortening, and limited movements. Because hip TB mimics the symptoms of other hip diseases like rheumatoid arthritis (RA) and osteoarthritis, diagnosis is difficult. Here, we aimed to report a rare case of hip TB secondary to pulmonary TB and the result of the total hip arthroplasty (THA).
 Case Report: A 41-year-old man presented to the orthopedic clinic with a complaint of progressive pain in the right hip. After laboratory tests, imaging, and sputum culture, active TB infection and advanced arthritis of the hip joint were detected. A subluxation/ dislocation stage of arthritis and an acetabular protrusion were present, leading to the restriction of movements. After receiving medical therapy, we performed THA for the patient
 Conclusion: The patient’s right hip reached a normal range of motion (ROM) without pain in the 18-month follow-up. Since TB can mimic the symptoms of many common diseases, considering hip TB along with other diagnoses can aid in reducing possible complications and improving patients' lives.

IgG glycosylation associates with risk of progression from latent to active tuberculosis

Glycosylation motifs shape antibody structure, stability and antigen affinity and play an important role in antibody localization and function. Serum IgG glycosylation profiles are significantly altered in infectious diseases, including tuberculosis (TB), but have not been studied in the context of progression from latent to active TB. We performed a longitudinal study of paired bulk IgG glycosylation and transcriptomic profiling in blood from individuals with active TB (ATB) or latent TB infection (LTBI) before and after treatment. We identified that a combination of two IgG1 glycosylation traits were sufficient to distinguish ATB from LTBI with high specificity and sensitivity, prior to, and after treatment. Importantly, these two features positively correlated with previously defined cellular and RNA signatures of ATB risk in LTBI, namely monocyte to lymphocyte ratio and the expression of interferon (IFN)-associated gene signature of progression (IFN-risk signature) in blood prior to treatment. Additional glycosylation features at higher prevalence in LTBI individuals with high expression of the IFN-risk signature prior to treatment included fucosylation on IgG1, IgG2 and IgG3. Together, our results demonstrate that bulk IgG glycosylation features could be useful in stratifying the risk of LTBI reactivation and progression to ATB.

IP-10 for the Diagnosis and Treatment Monitoring of Tuberculosis in Children.

To determine the utility of interferon-gamma-inducible protein 10 (IP-10) for identifying active tuberculosis (TB) and TB infection (TBI) in children in BCG-vaccinated populations, establish its diagnostic performance characteristics, and evaluate changes in IP-10 level during anti-TB chemotherapy. Concentrations of IP-10 and IFN-γ were measured in QuantiFERON-TB Gold (QFT) supernatants in children with suspected TB or due to recent TB contact. A total of 225 children were investigated: 33 with active TB, 48 with TBI, 83 TB contacts, 20 with suspected TB but other final diagnoses, and 41 controls. In 60 children, cytokine responses were evaluated at a follow-up visit after 2 months of anti-TB treatment. IP-10 expression was significantly higher in infected children (active TB and TBI cases) than in uninfected individuals. IP-10 proved effective in identifying TB infection at its optimal cut-off (>1084.5 pg/mL) but was incapable of differentiating between children with active TB and TBI. Combining IP-10 and IFN-γ increased the QFT sensitivity. IP-10 but not IFN-γ decreased significantly during anti-TB treatment in children with active TB (p = 0.003). IP-10 identifies TB infection and declines during anti-TB chemotherapy in children. Incorporating IP-10 into new immunodiagnostic assays could improve TB diagnosis and allow for treatment monitoring.

Latent and active tuberculosis development in patients with rheumatoid arthritis receiving biologic disease-modifying antirheumatic drugs: A single-center prospective study.

Biologics have revolutionized the treatment of rheumatoid arthritis (RA) in recent years. However, data from clinical trials and actual clinical practice have shown that biologics currently in use may constitute a risk factor for reactivation of tuberculosis (TB) in patients with latent TB infection. Therefore, screening for latent and active TB infection is mandatory before initiating biologic therapy in patients with RA. This prospective study aimed to analyze the clinical characteristics of patients with RA receiving biologic disease-modifying antirheumatic drugs at Bach Mai Hospital, Vietnam, between 2017 and 2022, and to identify factors affecting the occurrence of active and latent TB infection among these patients. Over a 12-month follow-up period, latent TB infection was confirmed in 20% of the total 180 included patients, while 3 (1.7%) patients developed active TB (one case of pulmonary, pleural, and gluteal TB each). History of TB risk factor exposure and lack of education were significantly associated with the occurrence of active and latent TB infection, with odds ratios (95% confidence intervals [CIs]) of 1.98 (1.78; 2.2) and 1.45 (1.31; 1.6), respectively. Follow-up duration and number of X-ray, computed tomography, bronchoscopy, and sputum acid-fast bacteria examinations were identified as factors that can aid in the early diagnosis of latent TB, with odds ratios (95% CIs) of 1.00 (1; 1.01), 1.02 (1; 1.05), 1.12 (1.11; 1.2), 1.11 (1.09; 1.2), and 1.13 (1.09; 1.17), respectively. Our study showed that, in countries with high TB burden like Vietnam, latent TB infection has high prevalence among patients with RA. We also provide useful information for the screening, monitoring, and treatment of latent and active TB infection in patients with RA.

Incidence, risk factors for active tuberculosis infection and changes of IGRA in patients with Takayasu arteritis: a prospective cohort study

ABSTRACT There is limited evidence to support the association between tuberculosis (TB) and the occurrence of Takayasu arteritis (TAK). To investigate the incidence of active TB (ATB) in TAK and explore the impact of anti-rheumatic therapy on the occurrence of ATB or reactivation of Latent TB infection (LTBI) and their effect on interferon-γ release assay (IGRA) results, we conducted a prospective study based on the Chinese Registry for Systemic Vasculitis cohort. The standard incidence ratio (SIR) was calculated and stratified by age. Kaplan–Meier analysis was used to determine the effect of variables on ATB or LTBI reactivation in patients with TAK. Data from 825 patients with TAK in the registry were analysed. During a median follow-up of 5 years, 5 patients developed ATB with a crude incidence of 154 (95%CI:57–381) person-years/100,000. The SIR was 5.59 (95%CI:1.81–13.04). Glucocorticoids and conventional disease-modifying anti-rheumatic drugs (cDMARDs) did not increase the risk of ATB or LTBI reactivation (P > 0.05). However, the use of tumour necrosis factor inhibitor (TNFi) increased the risk of ATB in patients with LTBI (P < 0.001). Furthermore, the value of the IGRA assay decreased after treatment (P < 0.05). In conclusion, the incidence of TB infection is markedly increased in patients with TAK and patients with TAK are at high risk of developing ATB. Treatment with glucocorticoids and cDMARDs does not significantly increase the risk for ATB in patients with TAK. Moreover, IGRA may have limited effectiveness in monitoring ATB infection or LTBI reactivation in patients with TAK.

Patients hospitalized with active tuberculosis and Covid-19 coinfection: A matched case-control from the Brazilian Covid-19 Registry.

Although control of Covid-19 has improved, the virus continues to cause infections, such as tuberculosis, that is still endemic in many countries, representing a scenario of coinfection. To compare Covid-19 clinical manifestations and outcomes between patients with active tuberculosis infection and matched controls. This is a matched case-control study based on data from the Brazilian Covid-19 Registry, in hospitalized patients aged 18 or over with laboratory confirmed Covid-19 from March 1, 2020, to March 31, 2022. Cases were patients with tuberculosis and controls were Covid-19 patients without tuberculosis. From 13,636 Covid-19, 36 also had active tuberculosis (0.0026%). Pulmonary fibrosis (5.6% vs 0.0%), illicit drug abuse (30.6% vs 3.0%), alcoholism (33.3% vs 11.9%) and smoking (50.0% vs 9.7%) were more common among patients with tuberculosis. They also had a higher frequency of nausea and vomiting (25.0% vs 10.4%). There were no significant differences in in-hospital mortality, mechanical ventilation, need for dialysis and ICU stay. Patients with TB infection presented a higher frequency of pulmonary fibrosis, abuse of illicit drugs, alcoholism, current smoking, symptoms of nausea and vomiting. The outcomes were similar between them.

Development and Evaluation of a Promising Biomarker for Diagnosis of Latent and Active Tuberculosis Infection

Abstract Background Diagnosing latent tuberculosis (TB) infection (LTBI) and active TB (ATB) is crucial for preventing disease progression and transmission. However, current diagnostic tests have limitations in terms of accuracy and sensitivity, making it challenging to diagnose these different infection states. Therefore, this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic tests. Methods We developed a novel multiepitope-based diagnostic biomarker (MEBDB) from LTBI region of differentiation antigens using bioinformatics and immunoinformatics. Immune responses induced by MEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead assays. This study was conducted from April 2022 to December 2022 in the Senior Department of Tuberculosis at the 8th Medical Center of PLA General Hospital, China. Blood samples were collected from participants with ATB, individuals with LTBI, and healthy controls (HCs). The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic curves. Results A novel MEBDB, designated as CP19128P, was generated. CP19128P comprises 19 helper T lymphocyte epitopes, 12 cytotoxic T lymphocyte epitopes, and 8 B-cell epitopes. In silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune responses. CP19128P generated significantly higher levels of tumor necrosis factor (TNF-α), interleukin 4 (IL-4), and IL-10 in ATB patients (n = 7) and LTBI (n = 8) individuals compared with HCs (n = 62) (P &lt; 0.001). Moreover, CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and specificity. Combining IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs (the area under the receiver operating characteristic curve [AUC], 0.976 [95% confidence interval [CI], 0.934–1.000] or 0.986 [0.956–1.000]), whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from HCs (AUC, 0.887 [0.782–0.993] or 0.984 [0.958–1.000]). Conclusions Our study revealed that CP19128P is a potential MEBDB for the diagnosis of LTBI and ATB. Our findings suggest a promising strategy for developing novel, accurate, and sensitive diagnostic biomarkers and identifying new targets for TB diagnosis and management.

Analysis of the Outcomes of Tuberculosis Treatment and Factors Associated with Successful Treatment at the Bamenda Regional Hospital: A 10-year Retrospective Study

Abstract Background: Tuberculosis (TB) remains a global public health issue, impacting millions of people worldwide. This study determined the outcomes of TB treatment managed within a 10 year period at the Bamenda Regional Hospital in Cameroon. Methods: A retrospective study was carried out among 2428 patients diagnosed and treated for active TB infection from 2013 to 2022, at the Bamenda Regional Hospital. Data collection was done from March to April 2023 using a data extraction form. Bivariate and multivariate logistic regression models were used to identify factors associated with successful TB treatment outcomes. Data was analyzed using SPSS software version 26. Results: Of the 2428 patients with TB, 1380 (56.8%) were cured, 739 (30.4%) completed treatment, treatment failures were recorded in 10 (0.4%) patients, and 200 (8.2%) died during or after receiving treatment. Treatment default was the outcome in 99 (4.1%). Successful treatment outcomes were reported in 2119 (87.3%). Patients within age groups 41–50 (P = 0.010), 51–60 (P = 0.041), and &gt;60 years (P = 0.006), male (P = 0.004), and human immunodeficiency virus-positive patients (P &lt; 0.001) had decreased odds of successful treatment outcomes. Conclusion: The outcomes of treatment within a 10 year period showed that the treatment success was 2.7% below the World Health Organizations target. Prioritizing vulnerable patient groups in TB management and implementing public health interventions such as financial assistance and nutritional support will go a long way in improving treatment outcomes.

The performance of VCS(volume, conductivity, light scatter) parameters in distinguishing latent tuberculosis and active tuberculosis by using machine learning algorithm

BackgroundTuberculosis is a chronic infectious disease caused by mycobacterium tuberculosis (MTB) and is the ninth leading cause of death worldwide. It is still difficult to distinguish active TB from latent TB,but it is very important for individualized management and treatment to distinguish whether patients are active or latent tuberculosis infection.MethodsA total of 220 subjects, including active TB patients (ATB, n = 97) and latent TB patients (LTB, n = 113), were recruited in this study .46 features about blood routine indicators and the VCS parameters (volume, conductivity, light scatter) of neutrophils(NE), monocytes(MO), and lymphocytes(LY) were collected and was constructed classification model by four machine learning algorithms(logistic regression(LR), random forest(RF), support vector machine(SVM) and k-nearest neighbor(KNN)). And the area under the precision-recall curve (AUPRC) and the area under the receiver operating characteristic curve (AUROC) to estimate of the model’s predictive performance for dentifying active and latent tuberculosis infection.ResultsAfter verification,among the four classifications, LR and RF had the best performance (AUROC = 1, AUPRC = 1), followed by SVM (AUROC = 0.967, AUPRC = 0.971), KNN (AUROC = 0.943, AUPRC = 0.959) in the training set. And LR had the best performance (AUROC = 0.977, AUPRC = 0.957), followed by SVM (AUROC = 0.962, AUPRC = 0.949), RF (AUROC = 0.903, AUPRC = 0.922),KNN(AUROC = 0.883, AUPRC = 0.901) in the testing set.ConclusionsThe machine learning algorithm classifier based on leukocyte VCS parameters is of great value in identifying active and latent tuberculosis infection.

Prevalence of Latent Tuberculosis Infection Among Rheumatology Patients and Management Practices in the United Arab Emirates: A Single-Center Retrospective Cohort Study.

Introduction Prior to immunosuppression, rheumatology patients are routinely screened for latent tuberculosis (TB) infection using interferon-gamma release assays (IGRAs). Variability in the management of latent and indeterminate IGRA results across institutionslimited long-term outcome data. A retrospective study was conducted at Tawam Hospital, United Arab Emirates, to investigate the incidence and management protocols associated with positive and indeterminate IGRAresults, as well as TBinfection, among patients with rheumatic conditions. Methods A single-center retrospective observational study was performed at Tawam Hospital, Abu Dhabi, UAE. Ethical approval for this study was obtained from the Tawam Human Research Ethics Committee. Laboratory records and the hospital's electronic medical system were used to obtain information about IGRA results over a 12-year period (April 2010-April 2022). The hospital's electronic medical system was used to obtain patient information and subsequent management approaches of positive and indeterminate IGRAs.Moreover, long-term follow-up data were collected to determine the risk of TB reactivation in the cohort. Results We found a total of 1,012 positive and 223 indeterminate IGRA test results within the 12-year period. Within the rheumatology department, 123 positive and 39 indeterminate IGRA results were identified. In the indeterminate IGRA group, the majority were women (n = 24, 61.5%) and UAE nationals (n = 22, 56.4%), and their mean age was 38.6 years. Systemic lupus erythematosus was the most prevalent rheumatologic condition (n = 21, 53.8%). Thirteen (33.3%) were on disease-modifying anti-rheumatic drugs (DMARDs) and 26 (66.7%) were on corticosteroids during IGRA testing. A total of eight patients (20.5%) received anti-TB medications. In the positive IGRA group, the mean age was 55.7 years and the female-to-male ratio was 3:1. The most common rheumatologic condition was rheumatoid arthritis (n = 69, 56%). Sixty-five (52.8%) patients were on conventional DMARDs, 43 (34.9%) were on corticosteroids during IGRA testing, and 74 (60%) received anti-TB medications. Two cases (1.6%) of active TB infections were detected among patients with positive IGRA tests, both of whom were receiving anti-tumor necrosis factor alpha inhibitor treatment in combination with methotrexate. No cases of active TB infection were observed in the indeterminate IGRA group. Conclusion Long-term data on the risk of TB activation in positive and indeterminate IGRA results for rheumatological conditions are low. It is recommended to reassess the choice of using anti-TNF-α, with a positive IGRA result if no other feasible alternatives can be offered. Our findings stress the importance of age, underlying diseases, and immunosuppressive treatments in interpreting IGRA results and guiding patient management. A large multicenter study is needed to understand the differences and outcomes of such patients in TB endemic and nonendemic geographical areas.

DdPCR provides a sensitive test compared with GeneXpert MTB/RIF and mNGS for suspected Mycobacterium tuberculosis infection.

The Metagenomics next-generation sequencing (mNGS) and GeneXpert MTB/RIF assay (Xpert) exhibited a sensitivity for tuberculosis (TB) diagnostic performance. Research that directly compared the clinical performance of ddPCR analysis, mNGS, and Xpert in mycobacterium tuberculosis complex (MTB) infection has not been conducted. The study aimed to evaluate the diagnostic performance of ddPCR compared to mNGS and Xpert for the detection of MTB in multiple types of clinical samples. The final clinical diagnosis was used as the reference standard. Out of 236 patients with suspected active TB infection, 217 underwent synchronous testing for tuberculosis using ddPCR, Xpert, and mNGS on direct clinical samples. During follow-up, 100 out of 217 participants were diagnosed with MTB infection. Compared to the clinical final diagnosis, ddPCR produced the highest sensitivity of 99% compared with mNGS (86%) and Xpert (64%) for all active MTB cases. Twenty-two Xpert-negative samples were positive in mNGS tests, which confirmed the clinical diagnosis results from ddPCR and clinical manifestation, radiologic findings. Thirteen mNGS-negative samples were positive in ddPCR assays, which confirmed the clinical final diagnosis.ddPCR provides a higher sensitive compared to Xpert and mNGS for MTB diagnosis, as defined by the high concordance between ddPCR assay and clinical final diagnosis.