Search Results (68)

Background and Objectives: The role of adenosine deaminase (ADA) in pulmonary tuberculosis (PTB) remains insufficiently defined in advanced forms of disease. Likewise, the systemic immune inflammatory index (SII) has not been validated in severe PTB. This 6-year prospective observational study aims to evaluate biomarker signatures of serum ADA and SII. Materials and Methods: According to the PTB case definition, 232 adult patients were divided into group 1, with a positive bacteriologic exam (n = 168), and group 2, without bacteriological confirmation (n = 64). ADA serum levels were compared by age, gender, nutritional status, morphologic and bacteriological pattern of PTB lesions, survival status, along with serum levels of other inflammatory biomarkers. All patients with comorbidities, interfering with the level of ADA, were excluded to avoid bias. Results: A total cohort of 208 PTB adults, aged 54.37 ± 14.365 years, included 156 males. The overall mortality was 11.53%. Death occurred after a mean interval of 1.63 ± 3.228 months after PTB diagnosis. ADA serum mean levels were 32.94 ± 9.146 IU/L, significantly higher in G1 (p = 0.002), in patients with delayed diagnosis of PTB (p = 0.000), with lung cavitation (p = 0.003), and death as a poor outcome (p ˂ 0.02). SII had a mean value of 1752.226 ± 2704.150, significantly increased in bacteriologically confirmed PTB cases (p = 0.018), delayed diagnosis (p = 0.002), cavitary advanced pulmonary tuberculosis (APT) (p = 0.002), and deceased (p = 0.003). Both an ADA cut-off elevated risk value of over 30 IU/L and SII of over 902 were fulfilled by 73 patients, with 2.10 higher risk of advanced PTB (p = 0.006) and 4.49 higher risk of mortality (p = 0.000). Conclusions: Serum ADA and SII are recommended as predictors of advanced and severe pulmonary TB. These findings indicate that ADA and SII, when elevated together, delineate a high-risk PTB phenotype with greater disease severity and early mortality. The combination offers a pragmatic, biomarker-based approach to risk stratification in PTB. Full article

Background: Differentiating nontuberculous mycobacterial pulmonary disease (NTM-PD) from pulmonary tuberculosis (PTB) remains challenging due to overlapping clinical features, particularly in resource-limited settings where diagnostic errors are frequent. This retrospective case–control study (January 2023–June 2024) aimed to identify key clinical predictors and develop a diagnostic model to distinguish NTM-PD from PTB. Methods: Patients initially presumed to have PTB (meeting clinical–radiological criteria but lacking bacteriological confirmation at admission) at a tertiary tuberculosis hospital were enrolled. Final diagnoses of NTM-PD (n = 105) and PTB (n = 105) were confirmed by mycobacterial culture identification. Clinical, laboratory, and radiological data were compared using univariate analysis. Variables showing significant differences (p < 0.05) were entered into multivariable logistic regression. Diagnostic performance was evaluated via receiver operating characteristic (ROC) curve analysis. Results: Female sex (odds ratio [OR] = 2.51, 95% confidence interval [CI] 1.12–5.60), hemoptysis (OR = 2.20, 1.05–4.62), bronchiectasis (OR = 5.92, 2.56–13.71), and emphysema/pulmonary bullae (OR = 2.69, 1.16–6.24) emerged as independent predictors of NTM-PD, while systemic symptoms favored PTB (OR = 0.45, 0.20–0.99). The model demonstrated 91.4% specificity and 68.6% sensitivity with an area under the curve [AUC] of 0.871. Conclusions: This high-specificity model helps prioritize NTM-PD confirmation in females with hemoptysis and structural lung changes (computed tomography evidence of bronchiectasis and/or emphysema) while maintaining PTB suspicion when systemic symptoms (fever, night sweats, weight loss) dominate. The approach may reduce misguided antitubercular therapy in resource-limited settings awaiting culture results. Full article

Background: Tuberculosis and COVID-19 co-infection poses significant clinical challenges, with pulmonary TB (PTB) and extrapulmonary TB (extraPTB) potentially influencing disease progression and outcomes differently. This study aims to compare the clinical manifestations, inflammatory markers, and outcomes between PTB and extraPTB patients with SARS-CoV-2 co-infection. Methods: A retrospective, cross-sectional study was conducted on 55 hospitalized adults with TB-COVID-19 co-infection from March 2020 to March 2022. Patients were divided into PTB (n = 32) and extraPTB (n = 23) groups. Demographic, clinical, laboratory, and imaging data were collected and analyzed using statistical models, including ANCOVA, LASSO regression, and Random Forest classification, to identify key predictors of hospitalization duration and mortality. Results: PTB patients had significantly lower BMI, worse oxygenation status, and greater lung involvement on CT compared to extraPTB patients. CRP was elevated in PTB, while IL-6 levels were higher in extraPTB. Hospitalization duration was primarily influenced by inflammatory and coagulation markers (IL-6, D-dimer, neutrophil count, systemic inflammatory index), while higher BMI was associated with shorter stays. Mortality risk was strongly correlated with oxygenation impairment (worst SpO₂, SpO₂ at diagnosis), inflammatory burden (CRP, LDH), and CT severity score, rather than TB localization. Conclusions: TB localization did not independently affect hospitalization duration or mortality risk. Instead, severe lung involvement, systemic inflammation, and hypoxemia were the strongest predictors of poor outcomes. These findings emphasize the importance of early risk stratification based on respiratory and inflammatory markers to optimize patient management. Further research is needed to clarify the long-term impact of TB-COVID-19 co-infection, particularly in extraPTB cases. Full article

Background/Objectives: Before the Coronavirus disease 2019 (COVID-19) era, the global prevalence of pulmonary arterial hypertension (PAH) was between 0.4 and 1.4 per 100,000 people. The long-term effects of protracted COVID-19 associated with pulmonary vascular disease (PVD) risk factors may increase this prevalence. According to preliminary data, the exact prevalence of early estimates places the prevalence of PVD in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 22%, although its predictive value remains unknown. PVD caused by COVID-19 co-infections is understudied and underreported, and its future impact is unclear. However, due to COVID-19/co-infection pathophysiological effects on pulmonary vascularization, PVD mortality and morbidity may impose a genuine concern—both now and in the near future. Based on reported studies, this literature review focused on the potential link between COVID-19, parasitic co-infection, and PVD. This review article also highlights hypothetical pathophysiological mechanisms between COVID-19 and parasitic co-infection that could trigger PVD. Methods: We conducted a systematic literature review (SLR) searching peer-reviewed articles, including link between COVID-19, parasitic co-infection, and PVD. Results: This review hypothesized that multiple pathways associated with pathogens such as underlying schistosomiasis, human immunodeficiency virus (HIV), pulmonary tuberculosis (PTB), pulmonary aspergillosis, Wuchereria bancrofti, Clonorchis sinensis, paracoccidioidomycosis, human herpesvirus 8, and scrub typhus coupled with acute or long COVID-19, may increase the burden of PVD and worsen its mortality in the future. Conclusions: Further experimental studies are also needed to determine pathophysiological pathways between PVD and a history of COVID-19/co-infections. Full article

Tuberculosis (TB) treatment monitoring is an essential tool for effective TB treatment management. Identifying parameters that predict adverse TB treatment outcomes could significantly improve clinical management. The association of hematological parameters with poor TB treatment outcomes is not well defined. To study the relationship of hematological parameters with TB treatment outcomes, we examined data from pulmonary tuberculosis (PTB) patients with successful (controls) and unsuccessful (cases) treatment outcomes. We enrolled 68 cases and 133 controls through a nested 1:2 case–control study, matching for age, sex, body mass index, diabetes status, alcohol and smoking. Hematological profiling showed significant difference in the absolute counts of white blood cells, lymphocytes, neutrophils and monocytes between cases and controls. In addition, increased neutrophil to lymphocyte ratio (NL) ratio and monocyte to lymphocyte (ML) ratio were present in cases in comparison to controls. Similarly, decreased hematocrit and red blood cell counts were detected in cases when compared with controls. Univariate and multivariate analysis demonstrated a significant association of absolute counts of WBC, neutrophils, monocytes, NL and ML ratios with poor treatment outcomes. The altered baseline hematological parameters are clearly associated with the poor TB treatment outcomes, showing potential for clinical prediction to enhance management of at-risk cases. Full article

Background and Objectives: Coinfection with SARS-CoV-2 and extrapulmonary tuberculosis (extraPTB) presents unique clinical challenges due to dual inflammatory responses and potential differences in patient profiles compared to those with SARS-CoV-2 infection alone. This study uniquely contributes to the underexplored interaction between extraPTB and SARS-CoV-2, focusing on systemic inflammation as a critical determinant of outcomes. Materials and Methods: This retrospective, cross-sectional study included 123 patients aged 19–91 years, hospitalized at Victor Babeș Hospital in Timișoara from March 2020 to March 2022. We compared 23 extraPTB and SARS-CoV-2 coinfected patients with 100 age-matched SARS-CoV-2-only patients. Clinical records were examined for demographic, clinical, and laboratory data. Results: The coinfected group was younger, with 65% under 40 years, and presented significantly higher IL-6, PCT, and transaminase levels. Coexisting COPD and type 2 diabetes were independent predictors of coinfection. A higher SpO2 at diagnosis was positively associated with coinfection likelihood (OR = 5.37), while CT scores indicated less pulmonary involvement in coinfected patients. Non-fatal outcomes were more frequent in the coinfection group (95.7% sensitivity), and only one coinfected patient had a fatal outcome versus 17 in the SARS-CoV-2-only group. Low SpO2 and elevated IL-6 were significant predictors of mortality, with severe symptoms tripling fatality odds. Conclusions: Coinfection with extraPTB and SARS-CoV-2 is associated with younger age, heightened systemic inflammation, and longer hospital stays but does not significantly increase mortality risk compared to SARS-CoV-2 alone. These findings underscore the importance of monitoring systemic inflammatory markers and developing tailored management strategies to improve long-term care outcomes for coinfected patients, especially in resource-limited settings. Full article

Observational studies indicate that variations in peripheral blood mononuclear cell (PBMC) subsets are associated with an increased risk of pulmonary tuberculosis (PTB) and coronavirus disease 2019 (COVID-19), but causal validation is lacking. Here, we combined single-cell expression quantitative trait locus (sc-eQTL) and two-sample mendelian randomization (MR) analyses to elucidate the causal relationship between PBMC subsets and the occurrence of PTB and COVID-19 and verified by RT-qPCR. We observed an increase in the CD4⁺ Effective Memory T Cell (CD4⁺ T_EM) cluster in both PTB and COVID-19 patients according to the single-cell transcriptional landscape of PBMC. Through MR analysis using an inverse variance weighted (IVW) method, we found strong evidence of positive correlations between CD4⁺ T_EM cell markers (GBP2, TRAV1-2, and ODF2L) and PTB, and between markers (LAG3 and SLFN5) and COVID-19, especially highlighted by lead eQTL-SNPs of GBP2 (rs2256752, p = 4.76321 × 10⁻¹⁵) and LAG3 (rs67706382, p = 6.16× 10⁻¹⁶). Similar results were observed in validation sets, and no pleiotropy was detected in sensitivity analyses including weighted median (WM), MR-Egger, MR-pleiotropy residual sum and outlier, and leave-one-out analyses (all p > 0.05). We visualized the colocalization of marker-eQTLs and markers of PTB and COVID-19 genome-wide association study (GWAS) associations. Based on CellChat analyses, monocytes communicated predominantly with CD4⁺ T_EM cells positively expressing PTB markers (GBP2, TRAV1-2, and ODF2L) and COVID-19 markers (LAG3 and SLFN5) in both PTB and COVID-19. Our data suggest a causal effect between two key CD4⁺ T_EM cell markers (GBP2 and LAG3) and the risk for PTB and COVID-19 infection. Our findings provide novel insights into the biological mechanism for PTB and COVID-19 infection, but future single-cell studies are necessary to further enhance understanding of this find. Full article

Stool samples have been reported to be useful for the diagnosis of pulmonary tuberculosis (PTB), especially in patients who are unable to produce sputum. However, contamination limits the usefulness of stool specimens in mycobacterial culture. In this study, a novel decontamination method of power ultrasound (PU) was evaluated for mycobacterial isolation from suspected PTB cases. Stool samples (n = 650) were collected, and each sample was divided into approximately three equal groups. In addition to an AFB smear (Auramine O method), the stool samples were treated using different decontamination methods (NaOH-NALC vs. PU methods). The sensitivity (calculated against CRS) and contamination rates between the two methods were compared using McNemar’s test. Of the 650 samples, 32 (4.92%) stool samples treated with the NaOH-NALC method were culture-positive, including Mycobacterium tuberculosis (M.TB; n = 21, 3.23%) and nontuberculous mycobacteria (NTM; n = 11, 1.69%). Sixty-one (9.38%) stool samples treated with the PU method were culture-positive, including M.TB (n = 37, 5.69%) and NTM (n = 24, 3.69%). Statistical analysis showed that a significant difference was found in the isolation rate of M.TB and NTM between the two methods (p < 0.05). Additionally, compared with the NALC-NaOH method (19.07%), stool samples treated with the PU method (13.23%) had a significantly lower contamination rate (p < 0.05). In conclusion, our findings suggest that the utilization of the PU method as a novel decontamination technique could significantly enhance the isolation rates of both NTM and M.TB when stool specimens are employed for culture. Compared to the NaOH-NALC method, this approach proves to be more effective in facilitating stool mycobacterial culture. Full article

Background: Guizhou Province in Southwest China has experimented with a centralized hospitalization (CH) treatment for active and severe cases of pulmonary tuberculosis (PTB). The objective of this study was to compare treatment outcomes of patients with tuberculosis (TB) receiving care in a CH setting with those receiving home-based (HB) care. In addition, this study aimed to assess the probability of their household contacts contracting tuberculosis infection. Method: A retrospective review of medical records was undertaken for patients with TB who completed their treatment in four counties in Guizhou, China, spanning from January 2022 to August 2023. In addition, a cross-sectional survey was conducted on the tuberculin skin test (TST) among household contacts of new patients with TB who had completed their treatment. Results: In the retrospective study, 94.8% had successful CH treatment, and 93.1% had successful HB treatment (p value = 0.70). In the prospective study, 559 and 448 household contacts of patients receiving CH treatment had 16 positive and 89 negative TST results, whereas those with HB treatment showed 26 positive and 74 negative TST results. Regarding a logistic regression analysis, the CH group was nearly two times more likely to test negative on the TST, 1.95 (95% CI: 0.98, 3.92). After adjusting for confounding variables, the odds ratio increased significantly to 4.42 (95% CI: 1.22, 16.04). Conclusions: CH for treatment of TB did not show superior success rates, but it may reduce the risk of transmitting tuberculosis infection to household contacts compared to home treatment. Full article

Background and Objectives: The concurrent occurrence of tuberculosis and COVID-19 coinfection poses significant clinical complexities, warranting a nuanced approach to diagnosis, management, and patient care. Materials and Methods: A retrospective, cross-sectional study was conducted on two groups: one comprising 32 patients with pulmonary TB (PTB) and COVID-19 co-infection, and one including 100 patients with COVID-19 alone. Data was collected from medical records, including patient history, clinical parameters, laboratory, imaging results, and patient outcome. Results: A lower BMI emerges as a significant marker suggesting underlying PTB in patients with SARS-CoV-2 co-infection. Type 2 diabetes mellitus increases the risk of death in PTB-SARS-CoV-2 co-infection. Co-infected patients show lymphocytopenia and higher neutrophil levels, CRP, transaminases, and D-dimer levels. Elevated CRP and ALT levels are linked to increased co-infection likelihood. Certain parameters like SpO2, CRP, ALT, AST, and D-dimer effectively differentiate between co-infected and COVID-19 patients. Platelet-to-lymphocyte ratio is notably higher in co-infected individuals. Lesion severity on imaging is significantly associated with co-infection, highlighting imaging’s diagnostic importance. Longer hospital stays are linked to co-infection but not significantly to death risk. Conclusions: Certain clinical and biological factors may serve as potential indicators of PTB co-infection in patients with SARS-CoV-2. Full article

Chronic immune activation in tuberculosis (TB) associated with human immunodeficiency virus (HIV) infection (HIV/TB) modifies their clinical course. We prospectively measured osteopontin (OPN), full-length galectin-9 (FL-Gal9), and total-Gal9 (T-Gal9) levels in 32 patients with HIV/TB coinfection treated with anti-tuberculosis and antiretroviral therapies over 6–18 months to determine the amelioration of inflammatory conditions in response to the therapies. We observed a significant time-dependent decrease in FL-Gal9 in both pulmonary TB (PTB, n = 20) and extrapulmonary TB (EPTB, n = 12) patients. The levels of T-Gal9, OPN, and CRP decreased significantly after treatment in only PTB patients. We calculated the inflammatory score (INS) indicating immunologic recovery based on the decline in OPN, FL-Gal9, T-Gal9, and CRP levels. Baseline levels of T-Gal9 and OPN positively correlated with INS in all TB and only PTB patients, respectively, indicating that their levels predict better recovery. In contrast, FL-Gal9 levels at the second visit negatively correlated with INS in EPTB patients. The decrease rate in OPN levels at the second visit also correlated positively with INS in PTB patients. Women showed a higher INS and lower levels of FL-Gal9 than men. The patients with moderate grade severity on chest X-ray had higher CD4 cell numbers than those with limited grade severity. Monitoring these markers will help to predict and assess the response to therapy as well as to devise strategies to reduce the complications caused by chronic immune activation in patients with HIV/TB coinfection. Full article

It is unclear how the immune system controls the transition from latent tuberculosis (TB) infection (LTBI) to active pulmonary infection (PTB). Here, we applied mass spectrometry cytometry time-of-flight (CyTOF) analysis of peripheral blood mononuclear cells to compare the immunological landscapes in patients with high tuberculous bacillary load PTB infections and LTBI. A total of 32 subjects (PTB [n = 12], LTBI [n = 17], healthy volunteers [n = 3]) were included. Participants with active PTBs were phlebotomized before administering antituberculosis treatment, whereas participants with LTBI progressed to PTB at the time of household screening. In the present study, CyTOF analysis identified significantly higher percentages of mucosal-associated invariant natural killer T (MAIT NKT) cells in subjects with LTBI than in those with active PTB and healthy controls. Moreover, 6 of 17 (35%) subjects with LTBI progressed to active PTB (LTBI progression) and had higher proportions of MAIT NKT cells and early NKT cells than those without progression (LTBI non-progression). Subjects with LTBI progression also showed a tendency toward low B cell levels relative to other subject groups. In conclusion, MAIT NKT cells were substantially more prevalent in subjects with LTBI, particularly those with progression to active PTB. Full article

Background: Tuberculosis (TB) is a global health burden caused by Mycobacterium tuberculosis (Mtb) infection. Fibronectin (Fn) facilitates Mtb attachment to host cells. We studied the Fn levels in smear-positive TB patients to assess its correlation with disease severity based on sputum smears and chest X-rays. Methods: Newly detected consecutive sputum AFB-positive pulmonary TB patients (n = 78) and healthy control subjects (n = 11) were included. The mycobacterial load in the sputum smear was assessed by IUATLD classification, ranging from 0 to 3. The severity of pulmonary involvement was assessed radiologically in terms of both the number of zones involved (0–6) and as localized (up to 2 zones), moderate (3–4 zones), or extensive (5–6 zones). The serum human fibronectin levels were measured by using a commercially available enzyme-linked immunosorbent assay (ELISA) kit (Catalogue No: CK-bio-11486, Shanghai Coon Koon Biotech Co., Ltd., Shanghai, China). Results: The PTB patients showed lower Fn levels (102.4 ± 26.7) compared with the controls (108.8 ± 6.8), but they were not statistically significant. Higher AFB smear grades had lower Fn levels. The chest X-ray zones involved were inversely correlated with Fn levels. The Fn levels, adjusted for age and gender, decreased with increased mycobacterial load and the number of chest radiograph zones affected. A Fn level <109.39 g/mL predicted greater TB severity (sensitivity of 67.57% and specificity of 90.38%), while a level <99.32 pg/mL predicted severity based on the chest radiology (sensitivity of 84.21% and specificity of 100%). Conclusions: The Fn levels are lower in tuberculosis patients and are negatively correlated with severity based on sputum mycobacterial load and chest radiographs. The Fn levels may serve as a potential biomarker for assessing TB severity, which could have implications for early diagnosis and treatment monitoring. Full article

Tuberculosis preventive treatment (TPT) is an important intervention in preventing infection and reducing TB incidence among household contacts (HHCs). A mixed-methods study was conducted to assess the “Test and Treat” model of TPT care cascade among HHCs aged ≥5 years of pulmonary tuberculosis (PTB) patients (bacteriologically/clinically confirmed) being provided TPT care under Project Axshya Plus implemented in Maharashtra (India). A quantitative phase cohort study based on record review and qualitative interviews to understand the challenges and solutions in the TPT care cascade were used. Of the total 4181 index patients, 14,172 HHCs were screened, of whom 36 (0.3%) HHCs were diagnosed with tuberculosis. Among 14,133 eligible HHCs, 10,777 (76.3%) underwent an IGRA test. Of them, 2468 (22.9%) tested positive for IGRA and were suggested for chest X-ray. Of the eligible 2353 HHCs, 2159 (91.7%) were started on TPT, of whom 1958 (90.6%) completed the treatment. The median time between treatment initiation of index PTB patient and (a) HHC screening was 31 days; (b) TPT initiation was 64 days. The challenges in and suggested solutions for improving the TPT care cascade linked to subthemes were tuberculosis infection testing, chest X-ray, human resources, awareness and engagement, accessibility to healthcare facilities, TPT drugs, follow-up, and assessment. A systematic monitoring and time-based evaluation of TPT cascade care delivery followed by prompt corrective actions/interventions could be a crucial strategy for its effective implementation and for the prevention of tuberculosis. Full article

Hospitalized patients with a high suspicion of pulmonary tuberculosis (HS-PTB) are isolated until a definite diagnosis can be determined. If doubt remains after negative sputum samples, bronchoscopy with bronchoalveolar lavage (BAL) is often sought. Still, evidence of the added value of BAL in this patient population is scarce. To address this issue, we included consecutive HS-PTB patients with negative sputum samples who underwent BAL between 2017 and 2018. Chest X-rays (CXR) and CT scans were evaluated by a chest radiologist blind to the final diagnosis. Independent predictors for PTB were assessed by multivariate regression, using all positive PTB patients between 2017 and 2019 (by sputum or BAL) as a control group (n = 41). Overall, 42 HS-PTB patients were included (mean age 51 ± 9, 36% female). BAL was a viable diagnostic for PTB in three (7%) cases and for other clinically relevant pathogens in six (14%). Independent predictors for PTB were ≥2 sub-acute symptoms (adjusted OR 3.18, 95% CI 1.04–9.8), CXR upper-lobe consolidation (AOR 8.70, 95% CI 2.5–29), and centrilobular nodules in chest CT (AOR 3.96, 95% CI 1.20–13.0, p = 0.02). In conclusion, bronchoscopy with BAL in hospitalized patients with HS-PTB had a 7% added diagnostic value after negative sputum samples. Our findings highlight specific predictors for PTB diagnosis that could be used in future controlled studies to personalize the diagnostic evaluation. Full article