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Aim: To comprehensively evaluate the association and impact of nutritional status and immune function on the severity of pulmonary tuberculosis (PTB). Methods: This descriptive cross-sectional study involved 952 participants who were diagnosed with active PTB. Severe PTB involves three or more lung field infections based on chest radiography. Nutritional status was evaluated using various indicators, including body mass index (BMI), the nutritional risk screening score (NRS-2002), total protein (TP), prealbumin (PA), transferrin (TRF), and serum albumin (ALB) levels and the prognostic nutritional index (PNI). Immune dysfunction was defined as a CD4+ count <500 cells/µl or a CD4+/CD8+ ratio <1. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were also calculated. Multivariate logistic and generalized linear regression were used to assess the associations between nutritional status, immune function, the severity of PTB, and the number of infected lung fields, adjusting for age, sex, and diabetes. Mediation analysis was conducted to evaluate the extent to which immune function mediated the impact of nutritional status on the severity of PTB. Sensitivity analysis was performed to enhance the robustness of the results. Results: Compared to those in the general PTB group, patients in the severe PTB group tended to be older men with diabetes. Higher nutritional risk, higher proportion of immune dysfunction and lower lymphocyte counts were observed in the severe group. BMI and the PNI were found to be protective factors, while PLR was identified as a risk factor for disease severity. Immune dysfunction and the PLR are mediators of the relationship between nutritional status and PTB severity. When BMI, the PNI, and the PLR were combined with traditional clinical indicators, these parameters showed promising diagnostic value, and the AUC reached 0.701 (95% CI: 0.668-0.734). Conclusion: The findings suggest that nutritional status is significantly associated with the severity of PTB, and immune function mediates the effects of nutritional status on the severity of PTB. Maintaining adequate BMI, PNI levels, and immune function or reducing PLR levels helps reduce the risk of severe PTB. [ABSTRACT FROM AUTHOR]

Abstract Pulmonary tuberculosis (TB) can result in irreversible damage and lead to tuberculous destructive lung (TDL), a severe chronic lung disease that is associated with a high mortality rate. Additionally, pulmonary hypertension (PH) is a hemodynamic disorder that can be caused by lung diseases. The objective of this study is to investigate the risk factors associated with PH in active TB patients diagnosed with TDL. We conducted a retrospective review of the medical records of 237 patients who were diagnosed with TDL, active pulmonary tuberculosis, and underwent echocardiography at the Third People’ Hospital of Shenzhen from January 1, 2016, to June 30, 2023. Univariate and multivariate logistic regression analyses were performed to identify factors that correlated with the development of pulmonary hypertension. Univariate and multivariate logistic regression analyses revealed that several factors were associated with an increased risk of pulmonary hypertension (PH) in individuals with tuberculosis destroyed lung (TDL). These factors included age (OR = 1.055), dyspnea (OR = 10.728), D-dimer (OR = 1.27), PaCO2 (OR = 1.040), number of destroyed lung lobes (OR = 5.584), bronchiectasis (OR = 3.205), and chronic pleuritis (OR = 2.841). When age, D-dimer, PaCO2, and number of destroyed lung lobes were combined, the predictive value for PH in patients with TDL was found to be 80.6% (95% CI 0.739–0.873),with a sensitivity of 76.6% and specificity of 73.2%. Advanced age, elevated D-dimer levels, hypercapnia, and severe lung damage were strongly correlated with the onset of PH in individuals with active pulmonary tuberculosis (PTB) and TDL. Furthermore, a model incorporating age, D-dimer, PaCO2, and the number of destroyed lung lobes might be valuable in predicting the occurrence of PH in patients with active PTB and TDL.

Pulmonary tuberculosis (TB) can result in irreversible damage and lead to tuberculous destructive lung (TDL), a severe chronic lung disease that is associated with a high mortality rate. Additionally, pulmonary hypertension (PH) is a hemodynamic disorder that can be caused by lung diseases. The objective of this study is to investigate the risk factors associated with PH in active TB patients diagnosed with TDL. We conducted a retrospective review of the medical records of 237 patients who were diagnosed with TDL, active pulmonary tuberculosis, and underwent echocardiography at the Third People’ Hospital of Shenzhen from January 1, 2016, to June 30, 2023. Univariate and multivariate logistic regression analyses were performed to identify factors that correlated with the development of pulmonary hypertension. Univariate and multivariate logistic regression analyses revealed that several factors were associated with an increased risk of pulmonary hypertension (PH) in individuals with tuberculosis destroyed lung (TDL). These factors included age (OR = 1.055), dyspnea (OR = 10.728), D-dimer (OR = 1.27), PaCO2 (OR = 1.040), number of destroyed lung lobes (OR = 5.584), bronchiectasis (OR = 3.205), and chronic pleuritis (OR = 2.841). When age, D-dimer, PaCO2, and number of destroyed lung lobes were combined, the predictive value for PH in patients with TDL was found to be 80.6% (95% CI 0.739–0.873),with a sensitivity of 76.6% and specificity of 73.2%. Advanced age, elevated D-dimer levels, hypercapnia, and severe lung damage were strongly correlated with the onset of PH in individuals with active pulmonary tuberculosis (PTB) and TDL. Furthermore, a model incorporating age, D-dimer, PaCO2, and the number of destroyed lung lobes might be valuable in predicting the occurrence of PH in patients with active PTB and TDL. [ABSTRACT FROM AUTHOR]

Background: One of the main infectious causes of morbidity and mortality worldwide is Mycobacterium tuberculosis. The Toll-like receptor (TLR) genes’ polymorphisms and mutations have been linked to an increased risk of infection in general. Objectives: This study aimed to investigate the association among TLR9 (rs148805533 Del/Ins), gene polymorphism, and pulmonary tuberculosis (PTB). Materials and Methods: Blood and sputum samples were collected from 70 patients with PTB and 30 healthy as a control group. Patients were diagnosed clinically by the specialized physician, in addition to use the acid-fast smear and culture on Lowenstein–Jensen. In addition, the molecular diagnostics technique was used by Gene Xpert device. The genotyping was carried out by using allele specific-polymerase chain reaction technique, and the TLR9 concentration was estimated by enzyme-linked immunosorbent assay (ELISA) technique. Results: The results of TLR9 polymorphism showed that the Ins/Ins allele, Del/Ins allele, and Del/Del allele genotypes frequencies at the site of (rs148805533) polymorphisms were significantly higher in PTB patients than the control groups (P = 0.05). The Ins/Ins allele genotype was the most frequent in PTB patients. In addition, the insertion allele was the most frequent in PTB patients and control groups. Conclusion: Our results indicated that in a sample of the local Iraqi population, the TLR9 (rs148805533) gene polymorphism may be a significant genetic determinant for PTB susceptibility.

Tuberculosis is an infectious airborne disease caused by Mycobacterium tuberculosis. Pulmonary tuberculosis is the ninth most frequent complication of diabetes mellitus. The co-existence of TB and DM in patient causes severe TB symptoms, modify radiological findings, slower response to treatment outcomes and prognosis. IFN-γ is the key cytokine which play role in the protective immune response against mycobacterium infection. The main function of IFN-γ is macrophage activation which is able to exert its microbicidal functions. Estimation and comparison of pre and post treatment serum IFN-γ among pulmonary tuberculosis among diabetic and non-diabetic patients. The study was conducted in the Departments of Biochemistry and Pulmonary Medicine, FMHS, SGT University, Budhera, Gurugram and District TB Centre, Gurugram, Haryana, India. In this study, 100 newly diagnosed PTB patients without diabetes mellitus and 100 newly diagnosed PTB patients with diabetes mellitus (PTB-DM) above 15 years of age were included after obtaining written consent. 5 mL venous blood was collected from patients of pre and post anti-tubercular treatment. The level of IFN-γ was measured by ELISA method. The circulating level of IFN-γ in PTB patients was significantly decreased in post-treatment (25.53 ± 6.12 pg/mL) compared to pre-treatment (58.76 ± 16.02 pg/mL) with t-value 32.03 and p-value <0.001. The circulating level of IFN-γ in PTB-DM patients was significantly decreased in post treatment (29.11 ± 7.41 pg/mL) compared to pre-treatment (44.14 ± 10.85 pg/mL) with t-value 31.35 and p-value <0.001. In the present study, level of IFN-γ in pre-treatment PTB patients (58.76 ± 16.02 pg/mL) was significantly raised compared to PTB-DM patients (44.14 ± 10.85 pg/mL) with t-value 7.55 and p-value <0.001. However, level of IFN-γ in post-treatment PTB patients (25.53 ± 6.12 pg/mL) was significantly low compared to PTB-DM patients (29.11 ± 7.41 pg/mL) with t-value 3.71 and p-value <0.001. The decreased level of IFN-γ in post-treatment compared to pre-treatment in both PTB and PTB-DM patients had shown efficacy of anti-tubercular treatment. However, the post treatment level of IFN-γ was high in PTB-DM patients compared to PTB patients which verified that effect of ATT was low in PTB-DM. [ABSTRACT FROM AUTHOR]

Objective: Solitary and solid pulmonary tuberculosis (PTB) and non-small cell lung cancer (NSCLC) can present overlapping imaging features, causing diagnostic dilemmas. Hence, this study aimed to identify positron emission tomography (PET) morphological features derived from fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) images for a better differential diagnosis. Methods: Clinical records and 18F-FDG PET/CT images of 175 patients confirmed with PTB and 311 patients with NSCLC were retrospectively reviewed. Parameters including patient demographics, PET-derived morphological features and metabolic parameters, and CT-derived morphological features were investigated. Logistic regression analysis was performed to assess the independent predictive factors associated with PTB. Results: PTB presented with more heterogeneous glucometabolism than NSCLC in PET imaging (50% vs 17%, P < 0.05), especially in lesions with a maximum diameter < 30 mm (39% vs. 5%, P < 0.05). NSCLC usually showed centric hypometabolism, whereas PTB more frequently presented with an eccentric metabolic pattern, mainly including piebald, half-side, lesser curvature, and greater curvature shapes. Multivariate logistic regression identified that glucometabolic heterogeneity, eccentric hypometabolism, smaller lesion size, calcification, satellite lesions, and higher CT value of the hypometabolic area were independently diagnostic factors for PTB. Conclusions: Morphological features derived from 18F-FDG PET images helped distinguish solitary and solid PTB from NSCLC. [ABSTRACT FROM AUTHOR]

Introduction: Patients with pulmonary tuberculosis (PTB) disease and positive sputum cultures are the main source of infection. Culture conversion time is inconsistent and defining the length of respiratory isolation is challenging. The objective of this study is to develop a score to predict the length of isolation period. Methods: A retrospective study was carried out to evaluated risk factors associated with persistent positive sputum cultures after 4 weeks of treatment in 229 patients with PTB. A multivariable logistic regression model was used to determinate predictors for positive culture and a scoring system was created based on the coefficients of the final model. Results: Sputum culture was persistently positive in 40.6%. Fever at consultation (1.87, 95% CI:1.02–3.41), smoking (2.44, 95% CI:1.36–4.37), >2 affected lung lobes (1.95, 95% CI:1.08–3.54), and neutrophil-to-lymphocyte ratio > 3.5 (2.22, 95% CI:1.24–3.99), were significantly associated with delayed culture conversion. Therefore, we assembled a severity score that achieved an area under the curve of 0.71 (95% CI:0.64–0.78). Conclusions: In patients with smear positive PTB, a score with clinical, radiological and analytical parameters can be used as a supplemental tool to assist clinical decisions in isolation period.

IntroductionChitinase, Indoleamine 2,3-dioxygenesae-1 (IDO-1) and heme oxygenase-1 (HO-1) are candidate diagnostic biomarkers for tuberculosis (TB). Whether these immune markers could also serve as predictive biomarkers of unfavorable treatment outcomes in pulmonary TB (PTB) is not known.MethodsA cohort of newly diagnosed, sputum culture-positive adults with drug-sensitive PTB were recruited. Plasma chitinase protein, IDO protein and HO-1 levels measured before treatment initiation were compared between 68 cases with unfavorable outcomes (treatment failure, death, or recurrence) and 108 control individuals who had recurrence-free cure.ResultsPlasma chitinase and IDO protein levels but not HO-1 levels were lower in cases compared to controls. The low chitinase and IDO protein levels were associated with increased risk of unfavourable outcomes in unadjusted and adjusted analyses. Receiver operating characteristic analysis revealed that chitinase and IDO proteins exhibited high sensitivity and specificity in differentiating cases vs controls as well as in differentiating treatment failure vs controls and recurrence vs controls, respectively. Classification and regression trees (CART) were used to determine threshold values for these two immune markers.DiscussionOur study revealed a plasma chitinase and IDO protein signature that may be used as a tool for predicting adverse treatment outcomes in PTB.

Background: Tuberculosis (TB) is an infectious disease which has long threatened human health, and new molecular diagnostic markers for its diagnosis are urgently needed. The study was designed to analyze the expression of hydroxyproline (HYP) in different specimens of pulmonary TB (PTB) and assess its auxiliary diagnostic value alone or in combination with the TB infection T lymphocyte spot assay (TSPOT.TB)., Methods: According to the inclusion criteria, 43 healthy controls (HCs) and 39 patients with nontuberculous general respiratory diseases were included as the respiratory control (RC) group, while 42 patients with newly treated TB were included as the PTB group. The expression of HYP in serum, urine, and bronchoalveolar lavage fluid (BALF) was detected with a HYP detection kit. Correlation analysis was used to detect the correlation of HYP and clinical indicators. Receiver operating characteristic (ROC) curve analysis was used to determine the sensitivity and specificity of HYP in diagnosing TB, both when used alone and in combination with TSPOT.TB., Results: The expression of HYP in serum of patients with TB was significantly increased as compared to that in controls (P=0.03), but there was no significant difference in the expression of HYP in urine (P>0.05). Compared with the general pneumonia control group, the expression of HYP in BALF of the PTB group was significantly increased (P<0.001). HYP expression in serum was positively correlated with C-reactive protein (CRP) level (r=0.4661, P=0.002), neutrophil (r=0.3338, P=0.03) and monocyte count (r=0.3462, P=0.02), and was negatively correlated with serum albumin expression (r=-0.3575, P=0.02). The expression of HYP in urine was positively correlated with neutrophil count (r=0.3508, P=0.02), neutrophil percentage (r=0.3804, P=0.047), and monocyte count (r=0.3263, P=0.04) but was negatively correlated with serum albumin expression (r=-0.4031, P=0.008). The expression of HYP in BALF was positively correlated with CRP (r=0.3652, P=0.02) but not with other indexes (P>0.05). ROC curve analysis indicated that the sensitivity, specificity, and area under the curve (AUC) of blood HYP were 66.67%, 72.09%, and 0.6481, respectively, while those of its combined diagnosis with TSPOT.TB were 78.57%, 96.77%, and 0.8690, respectively. The sensitivity, specificity, and AUC of HYP in BALF were 67.74%, 64.29%, and 0.7435, respectively, while those of its combined diagnosis with TSPOT.TB were 78.59%, 93.55%, and 0.8606, respectively., Conclusions: The expression of HYP in the serum and BALF of patients with PTB was higher than that of control group, and the expression of HYP was correlated with some clinical indicators. HYP demonstrated good sensitivity and specificity for the primary screening of PTB and higher sensitivity and specificity in the diagnosis of HYP when combined with TSPOT.TB. It may thus have certain value for auxiliary diagnosis in clinic., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1585/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Leptospirosis is a zoonotic infection caused by the pathogenic Leptospira. Leptospirosis is transmitted mainly through contact with contaminated rivers, lakes, or animals carrying Leptospira. Human leptospirosis has a wide range of non-specific clinical manifestations ranging from fever, hypotension, and myalgia to multi-organ dysfunction, which severely hampers the timely clinical diagnosis and treatment of leptospirosis. Therefore, there is an urgent clinical need for an efficient strategy/method that can be used for the accurate diagnosis of leptospirosis, especially in critically ill patients. Here, we report a case of a 75-year-old male patient with clinical presentation of fever, cough, and diarrhea. Initial laboratory tests and a computed tomography (CT) scan of the chest suggested only tuberculosis. The patient was finally diagnosed with pulmonary tuberculosis (PTB) combined with leptospirosis by sputum Xpert MTB RIF, epidemiological investigations, and delayed serological testing. Furthermore, through metagenomic next-generation sequencing (mNGS) of clinical samples of cerebrospinal fluid (CSF), urine, plasma and sputum, the causative pathogens were identified as Mycobacterium tuberculosis complex and Leptospira spp. With specific treatment for both leptospirosis and tuberculosis, and associated supportive care (e.g., hemodialysis), the patient showed a good prognosis. This case report suggests that mNGS can generate a useful complement to conventional pathogenic diagnostic methods through more detailed etiological screening (i.e., at the level of species or species complex).

Background: Multidrug-resistant pulmonary tuberculosis (MDR-PTB) has become a major cause of high morbidity and mortality related to TB. Conventional drug regimens are ineffective for the treatment of MDR-PTB patients with cavities. This study aimed to evaluate the clinical efficacy and safety of one-way endobronchial valves (EBVs) for the treatment of cavities in MDR-PTB patients. Methods: MDR-PTB patients with positive sputum cultures, sputum smears, and cavities were treated with EBVs in the drainage bronchus of the pulmonary cavity between November 2013 and March 2018. The participants comprised those who had failed previous anti-tuberculosis therapy, as determined by drug susceptibility testing. Results: Thirty-five MDR-PTB patients were included, three of whom were lost during follow-up. The size of the lung cavity was reduced in all of the patients after EBV implantation, including the three lost to follow-up. In the remaining 32 patients, the sputum culture conversion (SCC) rate reached 100%, and the cavity closure rate was 68.8%. There were no significant differences in the cavity closure rate between patients aged ≤40 and >40 years, between the upper and lower lobes, or between the use and non-use of linezolid groups (p > 0.05). Interestingly, the cavity closure rate was higher in women than in men (p = 0.005). Moreover, the cavity closure rate correlated with the time to SCC (correlation coefficient, 0.8933; p < 0.0001). There were no severe adverse events in the patients treated with EBV implantation. Conclusion: EBV installation is effective and safe for the treatment of cavities in MDR-PTB patients. The efficacy of EBV treatment may not be affected by age, disease course, or the location of the lung lobe in the cavity. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis is a major public health problem worldwide. It can present in an acute form especially in endemic settings, which might lead to missed and delayed diagnosis, prolonged hospital stays, and increased mortality in children. South Sudan has a high prevalence of tuberculosis in the adult population. However, there is no published data on paediatric tuberculosis. We aimed to determine the prevalence and factors associated with pulmonary tuberculosis in children admitted with pneumonia in Al Sabah Children’s Hospital, South Sudan. Method: This was a cross sectional study of 404 children aged 2 to 59 months admitted with severe pneumonia from June-October 2018 at Al Sabah Children’s Hospital. We excluded children on anti-TB treatment. Data were collected using a pretested questionnaire which captured socio-demographic characteristics, clinical history, physical examination, and laboratory investigations. Sputum examination for Mycobacterium tuberculosis was performed for all participants using X-pert MTB/RIF. Additional investigations included Chest X-ray and blood count. Results: We recruited 404 children, out of which 78 (19.3%) had pulmonary tuberculosis. Of these, 13 (16.7%) were bacteriologically confirmed while 65 (83.3%) were clinically diagnosed. The factors significantly associated with pulmonary tuberculosis were age above two years [AOR 2.32 (95% CI 1.04-5.17)] p value 0.039, positive HIV Status [AOR 24.2 (95% CI 2.88-202.62)] p value 0.003, severe acute malnutrition [AOR 15.67 (95% CI 6.68-36.73)] p value

BackgroundMost existing studies have only investigated the delayed effect of meteorological factors on pulmonary tuberculosis (PTB). However, the effect of extreme climate and the interaction between meteorological factors on PTB has been rarely investigated.MethodsNewly diagonsed PTB cases and meteorological factors in Urumqi in each week between 2013 and 2019 were collected. The lag-exposure-response relationship between meteorological factors and PTB was analyzed using the distributed lag non-linear model (DLNM). The generalized additive model (GAM) was used to visualize the interaction between meteorological factors. Stratified analysis was used to explore the impact of meteorological factors on PTB in different stratification and RERI, AP and SI were used to quantitatively evaluate the interaction between meteorological factors.ResultsA total of 16,793 newly diagnosed PTB cases were documented in Urumqi, China from 2013 to 2019. The median (interquartile range) temperature, relative humidity, wind speed, and PTB cases were measured as 11.3°C (−5.0–20.5), 57.7% (50.7–64.2), 4.1m/s (3.4–4.7), and 47 (37–56), respectively. The effects of temperature, relative humidity and wind speed on PTB were non-linear, which were found with the “N”-shaped, “L”-shaped, “N”-shaped distribution, respectively. With the median meteorological factor as a reference, extreme low temperature was found to have a protective effect on PTB. However, extreme high temperature, extreme high relative humidity, and extreme high wind speed were found to increase the risk of PTB and peaked at 31.8°C, 83.2%, and 7.6 m/s respectively. According to the existing monitoring data, no obvious interaction between meteorological factors was found, but low temperature and low humidity (RR = 1.149, 95%CI: 1.003–1.315), low temperature and low wind speed (RR = 1.273, 95%CI: 1.146–1.415) were more likely to cause the high incidence of PTB.ConclusionTemperature, relative humidity and wind speed were found to play vital roles in PTB incidence with delayed and non-linear effects. Extreme high temperature, extreme high relative humidity, and extreme high wind speed could increase the risk of PTB. Moreover, low temperature and low humidity, low temperature and low wind speed may increase the incidence of PTB.

This case study describes a unique scenario in which allergic bronchopulmonary aspergillosis (ABPA) was identified following treatment for pulmonary tuberculosis (PTB). ABPA is a complex pulmonary disorder that is often overlooked due to its nonspecific clinical presentation, especially in individuals concurrently diagnosed with tuberculosis (TB). Despite initial TB diagnosis and treatment, a 28-year-old male continued to experience respiratory symptoms, prompting further investigation that revealed underlying ABPA. This case underscores the importance of emphasizing the critical role of maintaining a high level of suspicion for ABPA in TB patients with persistent symptoms, highlighting the need for timely recognition and management to minimize further lung damage and improve patient outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Manishaa et al.)

Aim: To comprehensively evaluate the association and impact of nutritional status and immune function on the severity of pulmonary tuberculosis (PTB)., Methods: This descriptive cross-sectional study involved 952 participants who were diagnosed with active PTB. Severe PTB involves three or more lung field infections based on chest radiography. Nutritional status was evaluated using various indicators, including body mass index (BMI), the nutritional risk screening score (NRS-2002), total protein (TP), prealbumin (PA), transferrin (TRF), and serum albumin (ALB) levels and the prognostic nutritional index (PNI). Immune dysfunction was defined as a CD4 + count <500 cells/µl or a CD4 + /CD8 + ratio <1. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were also calculated. Multivariate logistic and generalized linear regression were used to assess the associations between nutritional status, immune function, the severity of PTB, and the number of infected lung fields, adjusting for age, sex, and diabetes. Mediation analysis was conducted to evaluate the extent to which immune function mediated the impact of nutritional status on the severity of PTB. Sensitivity analysis was performed to enhance the robustness of the results., Results: Compared to those in the general PTB group, patients in the severe PTB group tended to be older men with diabetes. Higher nutritional risk, higher proportion of immune dysfunction and lower lymphocyte counts were observed in the severe group. BMI and the PNI were found to be protective factors, while PLR was identified as a risk factor for disease severity. Immune dysfunction and the PLR are mediators of the relationship between nutritional status and PTB severity. When BMI, the PNI, and the PLR were combined with traditional clinical indicators, these parameters showed promising diagnostic value, and the AUC reached 0.701 (95% CI: 0.668-0.734)., Conclusion: The findings suggest that nutritional status is significantly associated with the severity of PTB, and immune function mediates the effects of nutritional status on the severity of PTB. Maintaining adequate BMI, PNI levels, and immune function or reducing PLR levels helps reduce the risk of severe PTB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lu, Xu, Li, Wang, Xie, Huang, Li and Fan.)

Introduction: Nontuberculous mycobacteria (NTM) and pulmonary tuberculosis (PTB) are difficult to distinguish in initial acid‐fast bacilli (AFB) smear‐positive patients. Objectives: Establish a predictive model to identify more effectively NTM infections in initial AFB patients. Methods: Consecutive AFB smear‐positive patients in the Respiratory Department of Shanghai Pulmonary Hospital from January 2019 to February 2020 were retrospectively analysed. A multivariate regression was used to determine the independent risk factors for NTM. A receiver operating characteristic (ROC) curve was used to determine the model's predictive discrimination. The model was validated internally by a calibration curve and externally for consecutive AFB smear‐positive patients from March to June 2020 in this institution. Results: Presenting with haemoptysis, bronchiectasis, a negative QuantiFERON tuberculosis (QFT) test and being female were characteristics significantly more common in patients with NTM (P ≤ 0.001), when compared with PTB. The involvement of right middle lobe, left lingual lobe and cystic change was more commonly seen on chest high‐resolution computed tomography (HRCT) in patients with NTM (P < 0.05), compared with PTB. Multivariate regression showed female, bronchiectasis, negative test for QFT and right middle lobe lesion were independent risk factors for NTM (P < 0.05). A ROC curve showed a sensitivity and specificity of 85.9% and 93.4%, respectively, and the area under the curve (AUC) was 0.963. Moreover, internal and external validation both confirmed the effectiveness of the model. Conclusions: The predictive model would be useful for early differential diagnosis of NTM in initial AFB smear‐positive patients. [ABSTRACT FROM AUTHOR]

Background: Multidrug-resistant pulmonary tuberculosis (MDR-PTB) has become a major cause of high morbidity and mortality related to TB. Conventional drug regimens are ineffective for the treatment of MDR-PTB patients with cavities. This study aimed to evaluate the clinical efficacy and safety of one-way endobronchial valves (EBVs) for the treatment of cavities in MDR-PTB patients. Methods: MDR-PTB patients with positive sputum cultures, sputum smears, and cavities were treated with EBVs in the drainage bronchus of the pulmonary cavity between November 2013 and March 2018. The participants comprised those who had failed previous anti-tuberculosis therapy, as determined by drug susceptibility testing. Results: Thirty-five MDR-PTB patients were included, three of whom were lost during follow-up. The size of the lung cavity was reduced in all of the patients after EBV implantation, including the three lost to follow-up. In the remaining 32 patients, the sputum culture conversion (SCC) rate reached 100%, and the cavity closure rate was 68.8%. There were no significant differences in the cavity closure rate between patients aged ≤40 and >40 years, between the upper and lower lobes, or between the use and non-use of linezolid groups (p > 0.05). Interestingly, the cavity closure rate was higher in women than in men (p = 0.005). Moreover, the cavity closure rate correlated with the time to SCC (correlation coefficient, 0.8933; p < 0.0001). There were no severe adverse events in the patients treated with EBV implantation. Conclusion: EBV installation is effective and safe for the treatment of cavities in MDR-PTB patients. The efficacy of EBV treatment may not be affected by age, disease course, or the location of the lung lobe in the cavity.

Emergomyces africanus (Es. africanus) is a novel thermally-dimorphic fungal pathogen, which belongs to the Ajellomycetaceae family. Several species have been described within the Emergomyces genus, namely Es. africanus, Es. canadensis, Es. pasteurianus, Es. orientalis and Es. europaneous, which were reported in Africa, Asia, Europe and North America. The first case in South Africa was reported in 2013. Only Es. africanus and Es. pasteurianus have been reported in South Africa thus far. The fungus causes disseminated emergomycosis mainly in immunocompromised patients, with a case fatality ratio of approximately 50%. [ABSTRACT FROM AUTHOR]

This audit report assessed the structure, processes and outcome of the pulmonary tuberculosis (PTB) management in adults conducted at eight government health clinics within the high TB burden Gombak district. All newly diagnosed PTB patients from November 2012 to November 2013 were identified from the tuberculosis registry. Patients less than 18 years old, were transferred out or extrapulmonary tuberculosis was excluded from the study. The assessment criteria for PTB were defined according to the latest Malaysian TB clinical practice guidelines (TB CPG) 2012. A total of 117 patients were included in this report and data were extracted and analysed using SPSS version 20.0. The mean age of patients was 40.4 ± 14.4 SD. Majority was men (63.2%). Out of 117 patients, 82.1% were Malaysian citizens and 17.9% were foreigners. Malays were the majority (65%) followed by 7.7% Chinese, 10.3% Indian and 17.1% others. The most common clinical feature was cough (88.0%) followed by loss of weight (58.1%), loss of appetite (57.3%), fever (56.4%), night sweat (30.8%) and haemoptysis (32.5%). Acid-fast bacilli (AFB) smear was positive in 94% of cases. Chest X-ray and human immunodeficiency virus (HIV) screening results were available for 89.1 and 82.1% cases respectively. The results for the sputum culture were available in 27.4% of patients and 54.7% were documented as done but pending results. The clinics have a successful directly observed therapy (DOT) program with 94.0% patients documented under DOT. Out of 53 patients on maintenance phase, 47.2% were identified as cured. Cure rate for those completed treatment was 100%. The defaulter rate was 17.1%. This audit demonstrated the attempt made by the clinics to adhere to the recommended guidelines. However, improvements are to be made in the documentation of medical records, tracing of investigation results and reduction of the number of defaulters.

Tuberculosis (TB) remains one of the major infectious diseases in the world with a high incidence rate. Drug-resistant tuberculosis (DR-TB) is a key and difficult challenge in the prevention and treatment of TB. Early, rapid, and accurate diagnosis of DR-TB is essential for selecting appropriate and personalized treatment and is an important means of reducing disease transmission and mortality. In recent years, imaging diagnosis of DR-TB has developed rapidly, but there is a lack of consistent understanding. To this end, the Infectious Disease Imaging Group, Infectious Disease Branch, Chinese Research Hospital Association; Infectious Diseases Group of Chinese Medical Association of Radiology; Digital Health Committee of China Association for the Promotion of Science and Technology Industrialization, and other organizations, formed a group of TB experts across China. The conglomerate then considered the Chinese and international diagnosis and treatment status of DR-TB, China's clinical practice, and evidence-based medicine on the methodological requirements of guidelines and standards. After repeated discussion, the expert consensus of imaging diagnosis of DR-PB was proposed. This consensus includes clinical diagnosis and classification of DR-TB, selection of etiology and imaging examination [mainly X-ray and computed tomography (CT)], imaging manifestations, diagnosis, and differential diagnosis. This expert consensus is expected to improve the understanding of the imaging changes of DR-TB, as a starting point for timely detection of suspected DR-TB patients, and can effectively improve the efficiency of clinical diagnosis and achieve the purpose of early diagnosis and treatment of DR-TB., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-1223/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: Children with primary immunodeficiency diseases (PIDs) are particularly vulnerable to infection of Mycobacterium tuberculosis (Mtb). Chest computed tomography (CT) is an important examination diagnosing pulmonary tuberculosis (PTB), and there are some differences between primary immunocompromised and immunocompetent cases with PTB. Therefore, this study aimed to use the radiomics analysis based on un-enhanced CT for identifying immunodeficiency status in children with PTB., Methods: This retrospective study enrolled a total of 173 patients with diagnosis of PTB and available immunodeficiency status. Based on their immunodeficiency status, the patients were divided into PIDs (n=72) and no-PIDs (n=101). The samplings were randomly divided into training and testing groups according to a ratio of 3:1. Regions of interest were obtained by segmenting lung lesions on un-enhanced CT images to extract radiomics features. The optimal radiomics features were identified after dimensionality reduction in the training group, and a logistic regression algorithm was used to establish radiomics model. The model was validated in the training and testing groups. Diagnostic efficiency of the model was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, precision, accuracy, F1 score, calibration curve, and decision curve., Results: The radiomics model was constructed using nine optimal features. In the training set, the model achieved an AUC of 0.837, sensitivity of 0.783, specificity of 0.780, and F1 score of 0.749. The cross-validation of the model in the training set showed an AUC of 0.774, sensitivity of 0.834, specificity of 0.720, and F1 score of 0.749. In the test set, the model achieved an AUC of 0.746, sensitivity of 0.722, specificity of 0.692, and F1 score of 0.823. Calibration curves indicated a strong predictive performance by the model, and decision curve analysis demonstrated its clinical utility., Conclusions: The CT-based radiomics model demonstrates good discriminative efficacy in identifying the presence of PIDs in children with PTB, and shows promise in accurately identifying the immunodeficiency status in this population., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-309/coif). F.W. is an employee of Shanghai United Imaging Intelligence Co., Ltd, a for-profit company, during the conduct of the study. The other authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

Abstract Objectives We aimed to analyze potential associations between vitamin D receptor (VDR) genetic variants and tuberculosis (TB) through a meta-analysis. Methods Systematic literature research of PubMed, Web of Science, Embase and CNKI was performed to identify eligible articles. Statistical analyses were conducted by using Review Manager. Results Totally 54 studies were enrolled for analyses. Pooled overall analyses suggested that VDR rs1544410 (dominant model: p = 0.02; allele model: p = 0.04), rs2228570 (recessive model: p = 0.01; allele model: p = 0.03) and rs731236 (recessive model: p = 0.02; allele model: p = 0.02) variants were significantly associated with TB. Further subgroup analyses by ethnicity revealed that rs1544410 variant was significantly associated with TB in South Asians (dominant and allele models) and Caucasians (dominant, recessive and allele models), rs2228570 variant was significantly associated with TB in East Asians (recessive model), and rs731236 variant was significantly associated with TB in South Asians (dominant, recessive and allele models). Conclusions Our meta-analysis suggested that VDR rs1544410, rs2228570 and rs731236 variants might serve as genetic biomarkers of TB in certain populations. Highlights • This is so far the most comprehensive evidence-based meta-analysis on VDR variants and TB. • VDR rs1544410, rs2228570 and rs731236 variants were all associated with TB in certain ethnicities. • Future investigations need to explore potential roles of other VDR variants in TB. [ABSTRACT FROM AUTHOR]

• NTM-PD and PTB can be differentiated by immunological and radiological traits. • Humoral and cellular immune function impaired in NTM-PD and PTB patients. • NTM-PD patients show lower TB-IGRA positivity rate. • Radiological analysis reveals significant differences between NTM-PD and PTB. • Diagnostic model for NTM-PD constructed using differential features, performs well. Although the incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is increasing annually, it is easily misdiagnosed as pulmonary tuberculosis (PTB). This study aimed to screen and identify the immunological and radiological characteristics that differentiate NTM-PD from PTB and to construct a discriminatory diagnostic model for NTM-PD, providing new tools for its differential diagnosis. Hospitalised patients diagnosed with NTM-PD or PTB between January 2019 and June 2023 were included in the study. Immunological and radiological characteristics were compared between the two groups. Based on the selected differential features, a logistic regression algorithm was used to construct a discriminatory diagnostic model for NTM-PD, and its diagnostic performance was preliminarily analysed. Patients with NTM-PD were significantly older than those with PTB and the tuberculosis-specific interferon-gamma release assay (TB-IGRA) positivity rate was significantly lower in the NTM-PD group. Moreover, the absolute counts of total T lymphocytes, CD4+ T lymphocytes, CD8+ T lymphocytes, NK cells, and B lymphocytes were significantly lower in patients with NTM-PD and PTB than in healthy controls. Additionally, patients with NTM-PD had a significantly lower absolute count of B lymphocytes than the PTB group. Radiological analysis revealed significant differences between patients with NTM-PD and PTB in terms of cavity wall thickness, bronchial dilation, lung consolidation, pulmonary nodule size, pulmonary emphysema, lung bullae, lymph node calcification, pleural effusion, mediastinal and hilar lymphadenopathy, and the tree-in-bud sign. Bronchial dilation was identified as the predominant risk factor of NTM-PD, whereas TB-IGRA positivity, lymph node calcification, pleural effusion, and mediastinal and hilar lymphadenopathies were protective factors. Based on this, we constructed a discriminatory diagnostic model for NTM-PD. Its receiver operating characteristic curve demonstrated good diagnostic performance, with an area under the curve of 0.938. At the maximum Youden index of 0.746, the sensitivity and specificity were 0.835 and 0.911, respectively. Patients with NTM-PD and PTB exhibited impaired humoral and cellular immune functions as well as significant differences in radiological features. The constructed NTM-PD diagnostic model demonstrated good diagnostic performance. This study provides a new tool for the differential diagnosis of NTM-PD. [ABSTRACT FROM AUTHOR]

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Background: CD4+CD25+FoxP3+ circulating regulatory T cells (Treg) play a fundamental role in the control of immune responses by down-regulating the function of effector CD4+ or CD8+ T cells. Active suppression by Treg might be important in controlling immune responses against Mycobacterium tuberculosis (Mtb). This study was conducted to evaluate the cellular immune response to Mtb, by evaluation of Treg cells in peripheral blood mononuclear cells (PBMCs) from patients with active pulmonary tuberculosis (PTB), patients with tuberculous pleurisy (TP) and healthy positive PPD persons as control, then evaluation after 6 months of anti-TB therapy, also evaluation of Treg cells in pleural fluid mononuclear cells (PFMCs) from patients with tuberculous pleurisy (TP). We compared the frequency of CD4+CD25+FoxP3+ circulating regulatory T cells (Treg) in 20 patients with active pulmonary TB (PTB), 15 tuberculous pleurisy (TP) and 20 control latent tuberculosis. Results: Treg frequencies in peripheral blood were significantly higher in patients with PTB and TP than in the control group (p

Background : To detect the predictors of treatment defaults in Pulmonary Tuberculosis (PTB) and Extra Pulmonary Tuberculosis (EPTB). Methods: In this cross sectional study 140 adults, with diagnosis of pulmonary tuberculosis (PTB) and extra pulmonary tuberculosis (EPTB), with treatment defaults, were included. The study protocol incorporated demographic, clinical characteristics of patients, structured questionnaire, physical examinations, radiological, laboratory investigations and relevant predictors for TB treatment defaults. The statistical analysis was performed using SPSS 20. Results: Mean age of study group was 42.3±20.3. Majority (67.1%) were male. Ninety four (67.1%) had PTB and 46 (32.9%) had EPTB. Factors identified to be associated with TB treatment default were male gender, distance from the health post, displacement, financial constraints, no body at home to bring medicine or take patients to hospital, routes closed in winters, subjective improvement of symptoms and travelling/shifting to other place. Conclusions: Treatment default is seen in pulmonary and extra pulmonary tuberculosis. Due to lack of uniform diagnostic and therapeutic strategy in EPTB treatment, most physicians treat on clinical symptoms for a prolonged duration of 12 to 24 months. [ABSTRACT FROM AUTHOR]

Conventionally, facultative intracellular pathogen, Mycobacterium tuberculosis (M.tb), the tuberculosis (TB) causing bacilli in human is cleared by cell-mediated immunity (CMI) with CD4+ T cells playing instrumental role in protective immunity, while antibody-mediated immunity (AMI) is considered non-protective. This longstanding convention has been challenged with recent evidences of increased susceptibility of hosts with compromised AMI and monoclonal antibodies conferring passive protection against TB and other intracellular pathogens. Therefore, novel approaches towards vaccine development include strategies aiming at induction of humoral response along with CMI. This necessitates the identification of mycobacterial proteins with properties of immunomodulation and strong immunogenicity. In this study, we determined the immunogenic potential of M.tb Zinc metalloprotease-1 (Zmp1), a secretory protein essential for intracellular survival and pathogenesis of M.tb. We observed that Zmp1 was secreted by in vitro grown M.tb under granuloma-like stress conditions (acidic, oxidative, iron deficiency and nutrient deprivation) and generated Th2 cytokine microenvironment upon exogenous treatment of Peripheral Blood Mononulear Cells (PBMCs) with recombinant Zmp1 (rZmp1). This was supported by recording specific and robust humoral response in TB patients in a cohort of 295. The anti-Zmp1 titers were significantly higher in TB patients (n=121) as against healthy control (n=62), household contacts (n=89) and non-specific infection controls (n=23). A significant observation of the study is the presence of equally high titers of anti-Zmp1 antibodies in a range of patients with high bacilli load (sputum bacilli load of 300+ per mL) to paucibacillary smear-negative pulmonary tuberculosis (PTB) cases. This clearly indicated the potential of Zmp1 to evoke an effective humoral response independent of mycobacterial load. Such mycobacterial proteins can be explored as antigen candidates for prime-boost vaccination strategies or extrapolated as markers for disease detection and progression.

Introduction: Patients with pulmonary tuberculosis (PTB) disease and positive sputum cultures are the main source of infection. Culture conversion time is inconsistent and defining the length of respiratory isolation is challenging. The objective of this study is to develop a score to predict the length of isolation period., Methods: A retrospective study was carried out to evaluated risk factors associated with persistent positive sputum cultures after 4 weeks of treatment in 229 patients with PTB. A multivariable logistic regression model was used to determinate predictors for positive culture and a scoring system was created based on the coefficients of the final model., Results: Sputum culture was persistently positive in 40.6%. Fever at consultation (1.87, 95% CI:1.02-3.41), smoking (2.44, 95% CI:1.36-4.37), >2 affected lung lobes (1.95, 95% CI:1.08-3.54), and neutrophil-to-lymphocyte ratio > 3.5 (2.22, 95% CI:1.24-3.99), were significantly associated with delayed culture conversion. Therefore, we assembled a severity score that achieved an area under the curve of 0.71 (95% CI:0.64-0.78)., Conclusions: In patients with smear positive PTB, a score with clinical, radiological and analytical parameters can be used as a supplemental tool to assist clinical decisions in isolation period., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Conventionally, facultative intracellular pathogen, Mycobacterium tuberculosis, the tuberculosis (TB) causing bacilli in human is cleared by cell-mediated immunity (CMI) with CD4+ T cells playing instrumental role in protective immunity, while antibodymediated immunity (AMI) is considered non-protective. This longstanding convention has been challenged with recent evidences of increased susceptibility of hosts with compromised AMI and monoclonal antibodies conferring passive protection against TB and other intracellular pathogens. Therefore, novel approaches toward vaccine development include strategies aiming at induction of humoral response along with CMI. This necessitates the identification of mycobacterial proteins with properties of immunomodulation and strong immunogenicity. In this study, we determined the immunogenic potential of M. tuberculosis Zinc metalloprotease-1 (Zmp1), a secretory protein essential for intracellular survival and pathogenesis of M. tuberculosis. We observed that Zmp1 was secreted by in vitro grown M. tuberculosis under granulomalike stress conditions (acidic, oxidative, iron deficiency, and nutrient deprivation) and generated Th2 cytokine microenvironment upon exogenous treatment of peripheral blood mononulear cells PBMCs with recombinant Zmp1 (rZmp1). This was supported by recording specific and robust humoral response in TB patients in a cohort of 295. The anti-Zmp1 titers were significantly higher in TB patients (n = 121) as against healthy control (n = 62), household contacts (n = 89) and non-specific infection controls (n = 23). A significant observation of the study is the presence of equally high titers of anti-Zmp1 antibodies in a range of patients with high bacilli load (sputum bacilli load of 300C per mL) to paucibacillary smear-negative pulmonary tuberculosis (PTB) cases. This clearly indicated the potential of Zmp1 to evoke an effective humoral response independent of mycobacterial load. Such mycobacterial proteins can be explored as antigen candidates for prime-boost vaccination strategies or extrapolated as markers for disease detection and progression. [ABSTRACT FROM AUTHOR]

Introduction: Chitinase, Indoleamine 2,3-dioxygenesae-1 (IDO-1) and heme oxygenase-1 (HO-1) are candidate diagnostic biomarkers for tuberculosis (TB). Whether these immune markers could also serve as predictive biomarkers of unfavorable treatment outcomes in pulmonary TB (PTB) is not known., Methods: A cohort of newly diagnosed, sputum culture-positive adults with drug-sensitive PTB were recruited. Plasma chitinase protein, IDO protein and HO-1 levels measured before treatment initiation were compared between 68 cases with unfavorable outcomes (treatment failure, death, or recurrence) and 108 control individuals who had recurrence-free cure., Results: Plasma chitinase and IDO protein levels but not HO-1 levels were lower in cases compared to controls. The low chitinase and IDO protein levels were associated with increased risk of unfavourable outcomes in unadjusted and adjusted analyses. Receiver operating characteristic analysis revealed that chitinase and IDO proteins exhibited high sensitivity and specificity in differentiating cases vs controls as well as in differentiating treatment failure vs controls and recurrence vs controls, respectively. Classification and regression trees (CART) were used to determine threshold values for these two immune markers., Discussion: Our study revealed a plasma chitinase and IDO protein signature that may be used as a tool for predicting adverse treatment outcomes in PTB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kumar, Nancy, Viswanathan, Sivakumar, Thiruvengadam, Ahamed, Hissar, Kornfeld and Babu.)

Objective: To find out the prevalence of concomitant active pulmonary Tuberculosis (TB) in patients of Chronic Obstructive Pulmonary Disease (COPD) using the gold standard liquid and solid culture media for the detection of acid fast bacillus. Methods: Eighty clinically and radiologically diagnosed cases of COPD of any severity, ≥40 years of age with no previous history of anti-tuberculous therapy were selected from department of Pulmonology, Jinnah Hospital, Lahore. Detailed demographic profile, clinical symptomatology and history of smoking were recorded. Sputum samples of these patients were subjected to ZiehlNeelsen (ZN) stain and culture on Lowenstein-Jensen (L.J) medium and Mycobacterium Growth Indicator Tube (MGIT) for the detection and isolation of Mycobacteriumtuberculosis (MTB). Results: Out of 80 COPD patients, 6 (7.5%) were culture positive for acid fast bacillus consistent with active tuberculous infection. The concomitance was more prevalent in elderly, male, smokers. MGIT was a more sensitive and a rapid technique to detect the presence of mycobacterium as compared to LJ culture media and ZN stain. Conclusion: The prevalence of active TB in COPD patients was 7.5%. Detection was improved when liquid culture media was employed for the detection of acid fast bacillus. Regular monitoring and screening of patients with COPD for PTB should be routinely carried out in susceptible cohort to avoid cross spreading of infection and appropriate management. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is a major health problem in most countries despite the availability of effective chemotherapy. The frequency and nature of anti-TB drugs induced adverse drug reactions (ADRs) have been matter of concern in many countries. In our programme patients take their medicines under the direct observation of a health care provider. It is therefore, important to monitor ADRs and increase awareness of health care providers about ADRs and their management. Objective: To get an over view of adverse drug reactions caused by first line anti-tuberculosis drugs used in the treatment of TB cases in directly observed therapy short course (DOTS). Study design, settings and duration: This descriptive observational study was carried out at chest clinic of Sir Ganga Ram Hospital, Lahore for a period of one year. Patients and Methods: Patient aged ≥15 years of age registered for treatment of tuberculosis in treatment category I at Model Chest Clinic, Sir Ganga Ram Hospital, Lahore were included in the study after obtaining consent. All patients were advised to visit health facility immediately if they had any feeling of drug reaction. Results: A total of 760 TB patients registered in treatment category I were included in the study. Out of 760 patients, 306 (40.2%) patients showed Adverse Drug Reactions (ADR) with anti TB drugs. Joint pain was the most common ADR, reported by 16.7% patients followed by skin itching in 11.5%, anorexia, nausea, abdominal pain in 7.63% and jaundice in 3.68% patients. Rash and visual impairment was reported by 0.26% each. Within gender, ADRs were mostly reported by females (41.9%) as compared to male patients (37.6%). Age wise majority (36%) of ADRs were reported by patients aged between 15-54 years as compared to those aged 55 years or above (4.2%). Most adverse effects settled themselves or with addition of some anti-allergic drugs for few days and in only 4.2% cases one or more ant TB drugs had to be discontinued. Conclusion: ADRs were observed in 40.2% TB patients but most reactions were of mild intensity and settled without any intervention. Only 4.2% reaction were severe enough to stop the drug and replace it with another drug. [ABSTRACT FROM AUTHOR]

This audit report assessed the structure, processes and outcome of the pulmonary tuberculosis (PTB) management in adults conducted at eight government health clinics within the high TB burden Gombak district. All newly diagnosed PTB patients from November 2012 to November 2013 were identified from the tuberculosis registry. Patients less than 18 years old, were transferred out or extrapulmonary tuberculosis was excluded from the study. The assessment criteria for PTB were defined according to the latest Malaysian TB clinical practice guidelines (TB CPG) 2012. A total of 117 patients were included in this report and data were extracted and analysed using SPSS version 20.0. The mean age of patients was 40.4 ± 14.4 SD. Majority was men (63.2%). Out of 117 patients, 82.1% were Malaysian citizens and 17.9% were foreigners. Malays were the majority (65%) followed by 7.7% Chinese, 10.3% Indian and 17.1% others. The most common clinical feature was cough (88.0%) followed by loss of weight (58.1%), loss of appetite (57.3%), fever (56.4%), night sweat (30.8%) and haemoptysis (32.5%). Acid-fast bacilli (AFB) smear was positive in 94% of cases. Chest X-ray and human immunodeficiency virus (HIV) screening results were available for 89.1 and 82.1% cases respectively. The results for the sputum culture were available in 27.4% of patients and 54.7% were documented as done but pending results. The clinics have a successful directly observed therapy (DOT) program with 94.0% patients documented under DOT. Out of 53 patients on maintenance phase, 47.2% were identified as cured. Cure rate for those completed treatment was 100%. The defaulter rate was 17.1%. This audit demonstrated the attempt made by the clinics to adhere to the recommended guidelines. However, improvements are to be made in the documentation of medical records, tracing of investigation results and reduction of the number of defaulters. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis (MTB) is the causative agent of pulmonary tuberculosis (PTB), a major health problem that leads to 1.5 million deaths annually. Host genetic factors play a significant role in disease resistance/susceptibility by altering immunity against MTB. Toll-like receptor (TLR) sensors such as TLR2, TLR4, TLR8, and TLR9 are known to play a pivotal role in PTB via modulating sensor expression and/or effector responses. Single-nucleotide polymorphism (SNP) rs187084 (T-1486C) of the TLR9 promoter is associated with various autoimmune disorders and cancers. A recent bioinformatic analysis predicted that the T-1486C SNP is involved in PTB, although its potential role is unclear. To investigate the role of T-1486C in PTB, we stimulated PBMCs with the H37Rv whole cell lysate. We found that the presence of the 'C' allele increases the transcriptional activity of the TLR9, which in turn induces high levels of Interferon gamma-induced protein 10 (IP-10), a biomarker for PTB. However, the expression of protective cytokines such as IFNγ and TNFα was observed significantly less with 'C' allele in comparison to 'T' allele. We further selected three different tribe populations showing differential susceptibility to PTB and performed genotypic analyses for the TLR9 promoter. We found a significantly lower minor allele frequency (MAF) of T-1486C in the Baiga tribe, wherein fewer PTB cases were reported, than that in the Gond and Korku tribes. Collectively, these data suggest that the minor 'C' allele at rs187084 locus may be associated with susceptibility to PTB, which may explain the relatively lower PTB rates observed in Baiga tribe members. [ABSTRACT FROM AUTHOR]

Background: Screening and identification of hematologic molecular indicators of pulmonary tuberculosis (PTB) is crucial for its diagnose and therapy. Therefore, our work aims to detect the diagnostic value of blood marker B and T lymphocyte attenuator (BTLA) in PTB, and provide a certain theoretical basis for the auxiliary diagnosis of PTB., Methods: Based on the inclusion criteria, 56 Patients with clinically confirmed pulmonary TB by clinical between January 2020 and December 2021 at our hospital were selected as the research objects of this study. Fifty-two matched healthy population at our hospital was used as the control group. Clinical characteristics were got from clinical laboratory. Real-time polymerase chain reaction (RT-PCR) was used to analyze changes in BTLA along with its ligand in peripheral blood. Changes in BTLA on the surface of different cells were analyzed by flow cytometry. The correlation test was used to determine the associations between BTLA and clinical indicators. Receiver operating characteristic (ROC) curve analysis was used to evaluate the auxiliary diagnostic value in PTB of BTLA expression from different sources., Results: Compared with the control, changes in peripheral blood BTLA in the PTB group were significantly increased (P=0.0187) rather than its ligand. Changes in BTLA on the surface of CD68 and antigen-presenting cell (APC) CD11c were significantly increased in the PTB group (P=0.0004, P<0.0001), while changes in BTLA on the surface of CD4 + T and CD8 + T cells were not significantly different (P=0.0792, P=0.8706). The expression of BTLA + CD11c + was negatively correlated with the expression of immunoglobulin A (IgA) (r=-0.2934, P=0.0282) and positively related to C-reactive protein (r=0.3277, P=0.0137). ROC curve analysis suggested that the area under the curve (AUC), sensitivity and specificity of BTLA RT-PCR detection were 0.6315, 53.57%, 57.69% while for BTLA + CD11c + detection were 0.8039, 88.46% and 73.21% and for BTLA + CD68 + detection were 0.6973, 60.71% and 61.54%., Conclusions: BTLA is highly expressed in peripheral blood and specific cell types of patients with PTB and is correlated with specific clinical indicators, which may be an important molecular marker for the auxiliary diagnosis of PTB., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-6060/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Highlights: [•] Nine studies involving 2195 cases and 2036 controls are included. [•] The associations between rs3751143 and both PTB and EPTB were separately analyzed. [•] Rs3751143 is associated with increased susceptibility to PTB and EPTB in Asians. [•] Population is one of the main sources of heterogeneity. [ABSTRACT FROM AUTHOR]

Summary: IFN-γ biased Th1 effector immune response is crucial for containment of Mycobacterium tuberculosis infection. Various T cell subsets with regulatory function dictate the generation of Th1 like cells. NKT cells are a specialized T cell subset known to be activated early in immune response and control T cell response via release of immunoregulatory cytokines like IFN-γ, IL-4 and IL-10. M. tuberculosis, with abundance of its cell wall lipids may potently activate NKT cells resulting in cytokine production and PD-1 expression. In this study, among 49 treatment naive active pulmonary tuberculosis patients, we found a higher percentage of PD1+ NKT cells correlating with sputum bacillary load. Furthermore, blocking PD-1 increased the number of IFN-γ producing NKT cells by inhibiting their apoptosis. Moreover, peripheral frequency of NKT cells declined with therapy suggesting their role in host T cell response. In this study, we concluded that PD-1 preferentially induces apoptosis of IFN-γ producing NKT cells while sparing NKT cells that produce IL-4. Such a polarized NKT cell function may impose a Th2 bias on the ensuing effector T cell response leading to inefficient clearance of M. tuberculosis. Inhibiting PD-1 may therefore alter the T cell response in favor of the host by rescuing type 1 NKT cells from apoptosis and boosting Th1 effector T cell functions against M. tuberculosis. [Copyright &y& Elsevier]

Abstract: In this study, we explored the local cytokine/chemokine profiles in patients with active pulmonary or pleural tuberculosis (TB) using multiplex protein analysis of bronchoalveolar lavage and pleural fluid samples. Despite increased pro-inflammation compared to the uninfected controls; there was no up-regulation of IFN-γ or the T cell chemoattractant CCL5 in the lung of patients with pulmonary TB. Instead, elevated levels of IL-4 and CCL4 were associated with high mycobacteria-specific IgG titres as well as SOCS3 (suppressors of cytokine signaling) mRNA and progression of moderate-to-severe disease. Contrary, IL-4, CCL4 and SOCS3 remained low in patients with extrapulmonary pleural TB, while IFN-γ, CCL5 and SOCS1 were up-regulated. Both SOCS molecules were induced in human macrophages infected with Mycobacterium tuberculosis in vitro. The Th2 immune response signature found in patients with progressive pulmonary TB could result from inappropriate cytokine/chemokine responses and excessive SOCS3 expression that may represent potential targets for clinical TB management. [Copyright &y& Elsevier]

Background: Sputum smear testing for acid fast bacilli is the gold standard for the diagnosis of tuberculosis. The role of culture in cases that are negative on sputum smear testing is being emphasized for early diagnosis of disease and prompt initiation of treatment. Objectives: To correlate the role of culture in diagnosing smear-negative pulmonary tuberculosis suspects. Study type, settings and duration: Descriptive study carried out in chest clinic of Sir Ganga Ram Hospital, Lahore in collaboration with Institute of Public Health Lahore from January 2012 to June 2012. Materials and Methods: Adults over 15 year of either gender having symptoms and X-ray findings consistent with pulmonary tuberculosis were selected. The sputa of sputum smear negative cases were inoculated on Löwenstein-Jensen medium culture medium to isolate the organism and correlate the culture positivity and negativity in smear negative cases. Results: A total of 88 sputa were negative for acid fast bacilli on smear which were subjected to culture on Löwenstein-Jensen medium. Of these 31(35%) grew acid fast bacilli and were thus confirmed positive by culture while rest 57 remained negative on culture. There was no significant difference in the symptoms and extent of lesions on X-ray between those who were culture positive or negative. Conclusion: Sputum culture should be done for the diagnosis or exclusion of smear negative clinically suspected and X-ray positive cases of pulmonary tuberculosis. Policy message: All clinically suspected and X-ray positive but sputum smear negative cases should undergo sputum culture for Mycobacterium tuberculosis on Löwenstein-Jensen medium. The facilities to culture the micro organism should be made available at district level by the tuberculosis control program. [ABSTRACT FROM AUTHOR]

Leptospirosis is a zoonotic infection caused by the pathogenic Leptospira . Leptospirosis is transmitted mainly through contact with contaminated rivers, lakes, or animals carrying Leptospira . Human leptospirosis has a wide range of non-specific clinical manifestations ranging from fever, hypotension, and myalgia to multi-organ dysfunction, which severely hampers the timely clinical diagnosis and treatment of leptospirosis. Therefore, there is an urgent clinical need for an efficient strategy/method that can be used for the accurate diagnosis of leptospirosis, especially in critically ill patients. Here, we report a case of a 75-year-old male patient with clinical presentation of fever, cough, and diarrhea. Initial laboratory tests and a computed tomography (CT) scan of the chest suggested only tuberculosis. The patient was finally diagnosed with pulmonary tuberculosis (PTB) combined with leptospirosis by sputum Xpert MTB RIF, epidemiological investigations, and delayed serological testing. Furthermore, through metagenomic next-generation sequencing (mNGS) of clinical samples of cerebrospinal fluid (CSF), urine, plasma and sputum, the causative pathogens were identified as Mycobacterium tuberculosis complex and Leptospira spp. With specific treatment for both leptospirosis and tuberculosis, and associated supportive care (e.g., hemodialysis), the patient showed a good prognosis. This case report suggests that mNGS can generate a useful complement to conventional pathogenic diagnostic methods through more detailed etiological screening (i.e., at the level of species or species complex)., Competing Interests: Authors WW, KW, YY, and RR are employed by MatriDx Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Wu, Wu, Ni, He, Zheng, Cheng, Yi, Ren and Jiang.)

Objectives: Tuberculosis is an infectious airborne disease caused by Mycobacterium tuberculosis . Pulmonary tuberculosis is the ninth most frequent complication of diabetes mellitus. The co-existence of TB and DM in patient causes severe TB symptoms, modify radiological findings, slower response to treatment outcomes and prognosis. IFN-γ is the key cytokine which play role in the protective immune response against mycobacterium infection. The main function of IFN-γ is macrophage activation which is able to exert its microbicidal functions. Estimation and comparison of pre and post treatment serum IFN-γ among pulmonary tuberculosis among diabetic and non-diabetic patients., Methods: The study was conducted in the Departments of Biochemistry and Pulmonary Medicine, FMHS, SGT University, Budhera, Gurugram and District TB Centre, Gurugram, Haryana, India. In this study, 100 newly diagnosed PTB patients without diabetes mellitus and 100 newly diagnosed PTB patients with diabetes mellitus (PTB-DM) above 15 years of age were included after obtaining written consent. 5 mL venous blood was collected from patients of pre and post anti-tubercular treatment. The level of IFN-γ was measured by ELISA method., Results: The circulating level of IFN-γ in PTB patients was significantly decreased in post-treatment (25.53 ± 6.12 pg/mL) compared to pre-treatment (58.76 ± 16.02 pg/mL) with t-value 32.03 and p-value <0.001. The circulating level of IFN-γ in PTB-DM patients was significantly decreased in post treatment (29.11 ± 7.41 pg/mL) compared to pre-treatment (44.14 ± 10.85 pg/mL) with t-value 31.35 and p-value <0.001. In the present study, level of IFN-γ in pre-treatment PTB patients (58.76 ± 16.02 pg/mL) was significantly raised compared to PTB-DM patients (44.14 ± 10.85 pg/mL) with t-value 7.55 and p-value <0.001. However, level of IFN-γ in post-treatment PTB patients (25.53 ± 6.12 pg/mL) was significantly low compared to PTB-DM patients (29.11 ± 7.41 pg/mL) with t-value 3.71 and p-value <0.001., Conclusions: The decreased level of IFN-γ in post-treatment compared to pre-treatment in both PTB and PTB-DM patients had shown efficacy of anti-tubercular treatment. However, the post treatment level of IFN-γ was high in PTB-DM patients compared to PTB patients which verified that effect of ATT was low in PTB-DM., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Highlights: [•] First attempt from north India to dissect IL-17 axis in human tuberculosis (TB). [•] No association of IL17A and IL17F gene variants in pulmonary and extra-pulmonary TB [•] Correlated the serum cytokine levels and genotypes [•] IL17 variants might not be a major influencing gene for tuberculosis in north Indians. [ABSTRACT FROM AUTHOR]

Summary: Background: India has a high tuberculosis (TB) burden. A significant percentage of TB patients are human immunodeficiency virus (HIV) positive. As the HIV epidemic is fueling the global TB epidemic, the prevalence of the virus in TB patients is a sensitive indicator of the spread of HIV into the general population in many regions. The aim of this study was to determine the prevalence of HIV–TB co-infection among a less studied population of Eastern India. Materials and methods: A cross-sectional record analysis study covering the period from 2000 to 2011 was conducted at Central Hospital of South Eastern Railway, Garden Reach, Kolkata, India. All tuberculosis patients consenting for HIV testing were included in the study after obtaining ethical clearance from the institution. The TB diagnosis was performed using clinical examination, sputum acid-fast bacillus (AFB) smear and chest radiography. HIV-positive cases were screened using an initial HIV tridot test, followed by repetitive tests using a Micro ELISA HIV Kit for HIV 1 and HIV 2 antigen. Results: Overall, 50 (12.3%) of the consenting 406 TB patients were HIV positive. Of these 406 patients, 44% had pulmonary TB, and 56% had extrapulmonary TB (EPTB). Coughing was the most common symptom (90%), followed by fever (78%). Pleural effusion (60.7%) was the most common form observed in the EPTB cases. Conclusions: The prevalence of HIV–TB co-infection was 12.3%. Consequently, all TB patients should be assessed for HIV risk factors and counseled to undergo HIV testing. Conversely, all HIV-positive cases should be screened for TB. [Copyright &y& Elsevier]

Background: Although the link between tuberculosis (TB) and biologics use is well established, the risk of TB among patients with psoriasis exposed to traditional systemic therapies remains elusive. Objectives: The aim is to investigate the association between traditional systemic therapies and TB among patients with psoriasis. Methods: We conducted a retrospective cohort study on the risk of active TB among patients with psoriasis and psoriatic arthritis, using the National Health Insurance Research Database of Taiwan, 1996 through 2008. Standardized incidence ratios of TB were analyzed in comparison with age- and gender-matched general population. Logistic regression was used in a nested case-control analysis to estimate the odds ratios of TB related to exposure to traditional systemic agents during the year before TB development. Results: Among the 81,266 patients in the psoriasis cohort, 497 new active TB cases were identified. The incidence rate of TB was 102 cases per 100,000 person-years among patients with psoriasis (standardized incidence ratio 1.22, 95% confidence interval 1.18-1.33). The risk of TB was higher in patients with severe disease (standardized incidence ratio 1.52, 95% confidence interval 1.46-1.74). To facilitate comparisons with the 497 active TB cases, a total of 1988 matched control subjects were selected for a nested case-control study. Patients taking systemic corticosteroids and nonsteroidal anti-inflammatory drugs were associated with higher incidence of TB, especially frequent users, after adjustment for multiple TB risk factors, drug exposures, hospital visits, and level of urbanization. Stratified analyses of current users and new users of these drugs revealed similar results. Finally, traditional systemic antipsoriatic treatment was not associated with TB on any of the analyses. Limitation: The National Health Insurance Research Database did not contain information regarding severity of psoriasis, smoking status, alcohol use, diet, laboratory parameters, chest radiograph, or history of recent contact with an individual with TB. Misclassification of disease cannot be ruled out in a registry-based database. The accessibility of health care may be associated with the level of urbanization, which could confound the effect of drugs in multivariate analyses. Conclusions: Severe psoriasis may be associated with an elevated TB risk. Traditional systemic therapies do not seem to be strongly associated with TB occurrence. [Copyright &y& Elsevier]

Background: Most existing studies have only investigated the delayed effect of meteorological factors on pulmonary tuberculosis (PTB). However, the effect of extreme climate and the interaction between meteorological factors on PTB has been rarely investigated., Methods: Newly diagonsed PTB cases and meteorological factors in Urumqi in each week between 2013 and 2019 were collected. The lag-exposure-response relationship between meteorological factors and PTB was analyzed using the distributed lag non-linear model (DLNM). The generalized additive model (GAM) was used to visualize the interaction between meteorological factors. Stratified analysis was used to explore the impact of meteorological factors on PTB in different stratification and RERI, AP and SI were used to quantitatively evaluate the interaction between meteorological factors., Results: A total of 16,793 newly diagnosed PTB cases were documented in Urumqi, China from 2013 to 2019. The median (interquartile range) temperature, relative humidity, wind speed, and PTB cases were measured as 11.3°C (-5.0-20.5), 57.7% (50.7-64.2), 4.1m/s (3.4-4.7), and 47 (37-56), respectively. The effects of temperature, relative humidity and wind speed on PTB were non-linear, which were found with the "N"-shaped, "L"-shaped, "N"-shaped distribution, respectively. With the median meteorological factor as a reference, extreme low temperature was found to have a protective effect on PTB. However, extreme high temperature, extreme high relative humidity, and extreme high wind speed were found to increase the risk of PTB and peaked at 31.8°C, 83.2%, and 7.6 m/s respectively. According to the existing monitoring data, no obvious interaction between meteorological factors was found, but low temperature and low humidity (RR = 1.149, 95%CI: 1.003-1.315), low temperature and low wind speed (RR = 1.273, 95%CI: 1.146-1.415) were more likely to cause the high incidence of PTB., Conclusion: Temperature, relative humidity and wind speed were found to play vital roles in PTB incidence with delayed and non-linear effects. Extreme high temperature, extreme high relative humidity, and extreme high wind speed could increase the risk of PTB. Moreover, low temperature and low humidity, low temperature and low wind speed may increase the incidence of PTB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nie, Lu, Wang, Yang, Sun, Zhang, Tian, Rifhat and Zhang.)

A quantitative, non-experimental, descriptive design was used to investigate the challenges of diagnosing pulmonary tuberculosis (PTB) in children under the age of five at 19 primary healthcare (PHC) clinics in the Ethekwini Health District in KwaZulu-Natal province of South Africa. A questionnaire was used to collect data from 38 respondents and descriptive statistics were used to analyse and summarise the data. The results showed PHC nurses did not have adequate knowledge to effectively diagnose PTB in children, and that PHC clinics were not adequately equipped to effectively diagnose PTB in children. Recommendations included regular in-service training programmes on the diagnosis and management of PTB in children, regular audits of tuberculosis records by clinic supervisors, supply of standard equipment for diagnosis of PTB in children, simplifying of protocols for diagnosis and management of PTB in children and the inclusion of the management of PTB in children in the curriculum of professional nurses' training. [ABSTRACT FROM AUTHOR]

To investigate the associations between single nucleotide polymorphism (SNP) of vitamin D receptor (VDR) gene and tuberculosis (TB) infection risk. 597 newly diagnosed pulmonary tuberculosis (PTB) patients from the Han population in Western China were randomly selected while 901 healthy subjects were divided into control group from September 2015 to September 2018. In the case-control study, 21 SNPs within the VDR gene were genotyped. Use SPSS 19.0 statistical software, SNP statistical software (Plink) and Pub-med network database to analyze the correlation between VDR SNP and PTB susceptibility. The 14 SNPs of VDR gene screened in the experiment were consistent with the frequency of PTB-related and minor alleles> 5% in HapMap Asian population. Three SNPs (rs58379944, rs11574012, rs12581281) were correlated with PTB by x 2 analysis. The rs58379944, rs11574012 alleles "G" and rs12581281 alleles "A" in genotype analysis were susceptible to tuberculosis. In the genotype analysis, allele "G" of rs58379944 and rs11574012 and allele "A" of rs12581281 provided protection against PTB infection. rs58379944, rs12581281 and rs11574012 allelic variants in VDR gene were found to be closely associated with PTB infection in the Han population in Western China. The protection it achieved may be one of the reasons for reducing the infection rate. • The first analysis between Vitamin D Receptor Gene Polymorphisms and PTB predisposition and its clinical traits in Western Chinese Han population. • The statistical analysis between candidate 3 SNPs (rs58379944, rs12581281, rs11574012) and phenotypes of PTB were conducted. • rs58379944, rs11574012 alleles "G" and rs12581281 alleles "A" in genotype analysis were susceptible to tuberculosis. • Polymorphisms of VDR can fight PTB infection and decrease the infection risk of Han population in Western China. [ABSTRACT FROM AUTHOR]