Pulmonary Tuberculosis Infection Research Articles

The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication.

Severity of COVID-19 is affected by multiple factors; however, it is not understood how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure affects the control of viral replication. Here, we demonstrate that immune events in the mouse lung closely preceding SARS-CoV-2 infection affect viral control and identify innate immune pathways that limit viral replication. Pulmonary inflammatory stimuli including resolved, antecedent respiratory infections with Staphylococcus aureus or influenza, ongoing pulmonary Mycobacterium tuberculosis infection, ovalbumin/alum-induced asthma, or airway administration of TLR ligands and recombinant cytokines all establish an antiviral state in the lung that restricts SARS-CoV-2 replication. In addition to antiviral type I interferons, TNFα and IL-1 potently precondition the lung for enhanced viral control. Our work shows that SARS-CoV-2 may benefit from an immunologically quiescent lung microenvironment and suggests that heterogeneity in pulmonary inflammation preceding SARS-CoV-2 exposure may contribute to variability in disease outcomes.

An item bank to measure health-related quality of life among young children (0-5-years-old) affected by respiratory illnesses – expert stakeholders and end-users from the Western Cape, South Africa

BackgroundHealth-related quality of life (HRQoL) is a crucial patient-centred outcome for developing policy. However, there is a lack of appropriate HRQoL measures for young children (0-5-years), who are particularly vulnerable to respiratory illnesses like pulmonary tuberculosis (PTB) and other respiratory infections, especially in low- and middle-income countries (LMICs). We aimed to develop a disease-specific HRQoL item bank for young children with acute and chronic respiratory illnesses.MethodsAn exploratory sequential design with three phases was used to develop a HRQoL item bank. The content validity of the item bank was evaluated by local and international experts specialising in HRQoL and child health. The group included paediatric pulmonologists, researchers with expertise in respiratory illnesses, and experts in scale development. Cognitive interviews with 37 caregivers of children with TB, pneumonia, adenovirus respiratory infection, other lower respiratory tract infections, reactive airway disease, and protracted bronchitis in Cape Town, South Africa, and consultations with 22 stakeholders were conducted for final revisions. The item bank was progressively refined at each phase of the study.FindingsThe Delphi experts recommended dividing the item bank into two age groups (0-2-years and 3-5-years) and using a 5-point Likert scale. Overall, 41 items (42%) met the predetermined > 70% threshold for inclusion in the item bank. Cognitive interviews confirmed that the domains were relevant. Minor modifications were made to five items in cohort 1 (0-2-years) and seven in cohort 2 (3-5-years), with 8 items (13%) and 14 items (22%) excluded. Phase 3 consultations emphasised the importance of including all seven domains and expanding the items to cover early childhood development, play, social interactions, and care routines. The final item bank includes versions for both age groups and incorporates these refinements.ConclusionAn item bank was developed as a first step to develop a comprehensive disease-specific HRQoL tool for young children with respiratory illnesses in an LMIC. Input from caregivers and content experts was crucial in creating two HRQoL item banks tailored to the developmental differences between 0 and 2 and 3-5-year age groups. Their contributions ensured the tool effectively captures age-appropriate aspects of HRQoL. Future studies should focus on assessing the validity and reliability of these item banks.

CD4+ Effective Memory T Cell Markers GBP2 and LAG3 Are Risk Factors for PTB and COVID-19 Infection: A Study Integrating Single-Cell Expression Quantitative Trait Locus and Mendelian Randomization Analyses.

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+ TEM) 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+ TEM 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+ TEM 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+ TEM 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.

Clinical profiles and related factors in tuberculosis patients with positive sputum smear mycobacterium tuberculosis tests

The aim of this study was to explore the related factors linked to the development and infectivity of tuberculosis. This was achieved by comparing the clinical characteristics of patients with pulmonary tuberculosis (TB) who tested positive in smear Mycobacterium tuberculosis tests with this who tested negative in smear mycobacterium tests but positive in sputum Gene Xpert tests. We gathered clinical data of 1612 recently hospitalized patients diagnosed with pulmonary tuberculosis who tested positive either in sputum Gene-Xpert test or sputum smear Mycobacterium tuberculosis tests. The data was collected from January 1, 2018 to August 5, 2023, at Sichuan Provincial People's Hospital. We conducted separately analyzes and comparisons of the clinical characteristics between the two groups of patients, aiming to discussed the related factors influencing the development and infectivity of tuberculosis. In comparison to the GeneXpert positive group, the sputum smear positive group exhibited a higher proportion of elderly patients (aged 75–89) and individuals classified as underweight (BMI < 18.5 kg/m2). Furthermore, this group was more prone to experiencing symptoms such as weight loss, coughing and sputum production, hemoptysis, shortness of breath, and difficulty breathing. Moreover, they are also more likely to develop extrapulmonary tuberculosis, such as tuberculous meningitis, tuberculous pleurisy, and tuberculous peritonitis. These clinical features, when present, not only increase the likelihood of a positive result in sputum smear tests but also suggest a high infectivity of pulmonary tuberculosis. Elderly individuals (aged 75 to 89) who are underweight (BMI < 18.5 kg/m2), display symptom of cough, expectoration, hemoptysis and dyspnea-particularly cough and expectoration-and those with extra pulmonary tuberculosis serve as indicators of highly infectious pulmonary tuberculosis patients. These patients may present with more severe condition, carrying a higher bacteria, and being more prone to bacterial elimination. Identification of these patients is crucial, and prompt actions such as timely and rapid isolation measures, cutting off transmission routes, and early empirical treatment of tuberculosis are essential to control the development of the disease.

Prediction Models for HIV Infection in Infants: Analysis of Scoring Systems on Maternal, Infants, and Mode of Delivery Risk Factors.

Diagnosis for HIV in infants is hard to determine, particularly in limited- resource areas. A delay in the diagnosis of HIV-infected infants will lead to high morbidity and mortality. The purpose of this project is to construct a model of an HIV-positive infant and develop a useful and practical scoring system to estimate the likelihood of mother-to-child transmission that can be applied in the field. A cross-sectional study on 100 subjects through medical records of infants born to HIV-infected mothers was conducted at four hospitals and one community health center. Several models of risk prediction scores of HIV-infected infants were then made. Furthermore, the performed validation was performed on 20 subjects of infants born to mothers with HIV in three hospitals by comparing the scoring system and the result of the PCR RNA examination performed at the age of 6 weeks old. The risk of HIV-infected infants was higher in mothers who did not receive ARV through PMTCT programs (OR 33.6; 95% CI 4.0 to 282.2), pulmonary TB infection (OR 5.1; IK95% 1.6 to 16.0) and vaginal delivery (OR 9.2; IK95 2.2 to 38.0%). Two models can predict the occurrence of infected HIV infants effectively. Model 1 consists of maternal age, maternal ARVs, lung TB infection, gestational age, mode of delivery, and sex of the infants with sensitivity and specificity of 78.9% and 70.8% (AUC=0.817 [95% CI 0.709 to 0.926]) and likelihood ratio score of 4. Model 2 consists of ARVs to the mother, pulmonary TB infection, and mode of delivery with sensitivity and specificity of 73.7% and 86.1%; AUC value of 0.812 (95% CI 0.687 to 0.938) and likelihood ratio of 5. External Validation gave similar results to the Model 2 scoring system with PCR RNA. The prediction score of HIV-infected infants in Model 2 can be used in newborns of HIV-positive mothers as an effective and practical risk screening tool for HIV-infected infants before the gold standard examination by PCR.

Risk of lung diseases in patients with previous carbon monoxide poisoning: a nationwide population-based cohort study in the Republic of Korea

Introduction Carbon monoxide poisoning is associated with severe damage to various organs. In this study, we aimed to determine if previous carbon monoxide poisoning was associated with an increased risk of lung diseases. Methods The study population was derived from the National Health Insurance Service database of Korea between 1 January 2002 and 31 December 2021. Adults with carbon monoxide poisoning, with at least one visit to medical facilities between 2002 and 2021, were included. For comparison, an equal number of matched controls with the same index date were selected from the database. Results A total of 28,618 patients with carbon monoxide poisoning and 28,618 matched controls were included in this study. Approximately 42.8 per cent of the patient and control groups were female, with a mean age of 51.3 years. In patients with carbon monoxide poisoning, there was a significant increase in the risk of lung cancer (adjusted hazard ratio, 1.84; 95 per cent confidence interval, 1.42–2.39; P < 0.001), chronic obstructive pulmonary disease (adjusted hazard ratio, 1.60; 95 per cent confidence interval, 1.36–1.89; P < 0.001), pulmonary tuberculosis (adjusted hazard ratio, 1.46; 95 per cent confidence interval, 1.13–1.88; P = 0.003), and non-tuberculous mycobacterial infection (adjusted hazard ratio, 1.54; 95 per cent confidence interval, 1.01–2.36; P = 0.047). Discussion In this retrospective cohort study, previous carbon monoxide poisoning was associated with an increased risk of lung cancer, chronic obstructive pulmonary disease, pulmonary tuberculosis, and non-tuberculous mycobacterial infection. Further studies are needed to confirm such an association in other populations and the risk of lung diseases due to the toxic effect of carbon monoxide from different sources. Conclusions Previous carbon monoxide poisoning was associated with an increased risk of lung diseases, but the relative importance of the causes and sources of exposure was not known. The long-term management of survivors of acute carbon monoxide poisoning should include monitoring for lung cancer, chronic obstructive pulmonary disease, pulmonary tuberculosis, and non-tuberculous mycobacterial infection.

Metastatic Poorly Differentiated Lung Cancer Shrouded in Pulmonary Tuberculosis – Lessons to Learn!

Tuberculosis (TB) remains an important cause of morbidity and mortality in many countries including India. It is a major public health concern particularly for India, as it has the highest burden of TB cases with two deaths occurring due to TB every 3 min. The incidence of lung cancer is reportedly higher in patients with pulmonary TB than in the general population. However, a diagnosis of bronchogenic carcinoma superimposed on pulmonary TB is difficult to establish due to masking of the signs, symptoms, and radiologic findings by the preexisting disease. On the other hand, the presence of underlying lung malignancy has been correlated with an increased risk of developing TB and even associated with poorer outcomes. Here, we share an interesting case where metastatic lung carcinoma was suspected and diagnosed, due to a good and careful follow-up in a young patient with active pulmonary TB infection.

Predictors of Fatal Outcome in Newly Diagnosed Tuberculosis/HIV Co-Infection with Chronic Alcoholism (Clinical Case)

Our own case of tuberculosis/HIV co-infection’s diagnosis in chronic alcoholism and analysis of the fatal outcome predictors are presented. The patient abused alcohol for a long time in the presented case, he was hospitalised with acute psychosis in a psychoneurological dispensary, where pulmonary tuberculosis and HIV infection were diagnosed for the first time during additional examination. The patient was admitted to the department in serious condition after prolonged alcohol intoxication. The patient’s condition stabilized after detoxification therapy. Antimycobacterial therapy according to the scheme of an individual treatment regimen, antiretroviral therapy, treatment of hepatitis B and C, detoxification therapy, prophylaxis with Biseptol and Fluconazole and symptomatic therapy were prescribed. After 20 days immune reconstitution inflammatory syndrome developed. It was manifested with meningitis and cryptococci were detected in the cerebrospinal fluid 17 days later. Prescribed treatment of cryptococcal meningoencephalitis with fluconazole in high doses intravenously had a significant positive effect, which made it possible to reduce the dose of the drug to the maintenance level. The treatment was not stopped, but sterility of the liquor was not achieved. After 98 days the patient entered a coma and after 113 days he died from the progression of multiple organ failure and cryptococcal meningitis. It should be noted that the patient was diagnosed with tuberculosis with multiple drug resistance for the first time, the treatment of which had positive dynamics, despite the progression of multiple organ failure and the presence of cryptococcal meningoencephalitis. Therefore, although tuberculosis was not the direct cause of the patient’s death, the disease itself deepened the severity of the general condition. Considering the presented clinical case, it was established that predictors of the fatal outcome of newly diagnosed tuberculosis/HIV co-infection in chronic alcoholism are: antisocial lifestyle; concomitant diseases (tuberculosis, chronic viral hepatitis B and C); cryptococcal meningoencephalitis; fever, altered mental status, cryptococci in the cerebrospinal fluid; the number of CD4+ lymphocytes is less than 200/μL; lack of early screening for CrAg; early initiation of antiretroviral therapy before the diagnosis of cryptococcal meningoencephalitis, which provokes immune reconstitution inflammatory syndrome, against the background of which cryptococcal infection progresses; monotherapy of cryptococcal meningoencephalitis with Fluconazole. Knowledge and practice gaps among medical practitioners contribute to the high fatality rate of cryptococcal meningoencephalitis in tuberculosis/HIV co-infection in chronic alcoholism.

Tuberkulosis Paru Terkonfirmasi Bakteriologis dengan Komplikasi Pneumotoraks

This study aims to identify epidemiological characteristics, analyze risk factors, evaluate clinical management, and assess long-term outcomes in patients with bacteriologically confirmed pulmonary tuberculosis and pneumothorax complications. Simple studies can be performed to evaluate the effectiveness of bacteriological confirmed pulmonary tuberculosis management approaches with pneumothorax complications. This study will involve retrospective analysis of medical data from patients who have been diagnosed with bacteriological confirmed pulmonary tuberculosis and have pneumothorax complications in a health facility. The data to be collected includes information about patient characteristics, such as age, sex, smoking history, BCG immunization status, and history of comorbidities such as HIV/AIDS or diabetes. The results of the study above that the patient had pulmonary tuberculosis infection that had been confirmed through bacteriological tests, and also experienced complications in the form of pneumothorax, which is a buildup of air in the pleural cavity that results in pressure on the lungs. This condition requires careful medical attention and proper management to effectively address both issues and optimize the patient's recovery.

Prevalence of pulmonary tuberculosis and HIV infections and risk factors associated to tuberculosis in detained persons in Antananarivo, Madagascar

The incidence rate of tuberculosis in prisons is estimated to be 8 times greater than that in the general population in Madagascar. Our objectives were to estimate the prevalence of pulmonary tuberculosis and HIV infection among prisoners and to identify risk factors associated with tuberculosis. We conducted a cross-sectional study at the central prison of Antananarivo from March to July 2021. Individual male and female inmates aged ≥ 13 years who had lived in the prison for at least three months prior to the study period were included as participants. Acid-fast bacilli detection by microscopy and/or culture, an intradermal tuberculin test, a chest X-ray, and a rapid diagnostic orientation test for HIV were performed. Among 748 participants, 4 (0.5%) were confirmed to have pulmonary tuberculosis. Overall, 14 (1.9%) patients had “confirmed” or “probable” tuberculosis [0.90–2.84, 95% CI]. The proportion of participants with latent tuberculosis infection was 69.6% (517/743) based on a positive tuberculin test without clinical symptoms or radiography images indicating tuberculosis. Out of 745 HIV screening tests, three showed reactive results (0.4%). Age (OR = 4.4, 95% CI [1.4–14.0]) and prior tuberculosis treatment (or episodes) were found to be associated with confirmed and probable tuberculosis.

Prevalence and Factors Associated with Pulmonary Tuberculosis Infection among HIV/AIDS Patients Attending an ART Clinic: A Study at Fort Portal Regional Referral Hospital

Among the over 33 million individuals living with HIV/AIDS, one-third also contracted tuberculosis, making it a significant co-infection. Tuberculosis emerged as the primary cause of illness and death within the HIV/AIDS community, responsible for approximately 30% of all fatalities among those affected. While curable when accurately diagnosed and promptly treated, addressing tuberculosis in HIV/AIDS patients required special attention due to the intricacies involved in diagnosing and treating both conditions concurrently. Employing a quantitative cross-sectional design, the study aimed to ascertain PTB prevalence and its socio-demographic and behavioral determinants among HIV/AIDS patients attending the ART clinic. Eighty-seven participants were selected via simple random sampling, with questionnaires serving as the primary data collection tool. The findings revealed a significant association between age over 45 years and the occurrence of pulmonary TB, with an odds ratio of 0.71 (0.45–3.77) and a p-value of 0.035. Additionally, male gender exhibited a notable association with PTB among HIV patients, with an odds ratio of 0.48 (0.15-8.14) and a p-value of 0.001. Furthermore, the study indicated a correlation between PTB occurrence and HIV patients, with an odds ratio of 0.35 (0.001-3.79) and a p-value of 0.024. The study's conclusion highlighted that approximately 18.4% of HIV-positive patients had experienced pulmonary tuberculosis. Recommendations included promoting good adherence to ART and TB prophylaxis among HIV patients to bolster immunity against TB. Encouraging HIV patients to steer clear of behaviors that heighten TB risk, such as smoking and excessive alcohol consumption, was also advised. Additionally, the government was urged to enhance support and supplies for individuals living with HIV and tuberculosis, aiming to prevent disease progression through tertiary interventions. Keywords: HIV/AIDS patients; Tuberculosis; PTB among HIV patients, Smoking and alcohol drinking, ART clinic.

Evaluation of cytokine profiles related to Mycobacterium tuberculosis latent antigens using a whole-blood assay in the Philippines.

There is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens. Patients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, including mycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay. A total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p < 0.001) and the community exposure group (p < 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p < 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP-10-specific IFN-γ levels among the groups. The patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS.

A Model for the Propagation and Control of Pulmonary Tuberculosis Disease in Kenya

Pulmonary tuberculosis is among the leading infectious diseases causing mortality worldwide. Therefore, scaling up intervention strategies to reduce the spread of infections in the population is imperative. In this paper, a population-based compartmental approach has been employed to formulate a mathematical model of pulmonary tuberculosis that incorporates an asymptomatic infectious population. The model includes asymptomatic infectious individuals since they spread infections incessantly to susceptible populations without being noticed, thus contributing to the high rate of infection transmission. Qualitative and numerical analyses were performed to determine the impact of various intervention strategies on controlling infection transmission in the population. Sensitivity and numerical results indicate that increasing screening of latently infected and asymptomatic infectious individuals reduces infection transmission to the susceptible population. Numerical results demonstrate that the combination of vaccination, screening, and treatment of all forms of pulmonary tuberculosis is the most effective intervention in decreasing infection transmission. Furthermore, a combination of screening and treatment of all forms of pulmonary tuberculosis proves more effective than a combination of vaccination and treatment of symptomatic infectious individuals alone. Treating the symptomatic infectious population alone is identified as the least effective intervention for curtailing infection transmission in the susceptible population. These study findings will guide healthcare officials in making decisions regarding the screening of latently infected and asymptomatic infectious pulmonary tuberculosis patients, thereby aiding in the fight against epidemics of this disease.

Prevalence of Nosocomial Venous Thromboembolic Complications in New Tuberculosis Patients and Relapses: Data from the Moscow City Registry (A Multicenter Study)

The objective: to evaluate VTEC in new tuberculosis patients and relapses, to determine main factors influencing its development (according to data of the patients admitted to Moscow tuberculosis hospitals)Subjects and Methods. Based on the data of epidemiological tuberculosis monitoring system of Moscow, treatment outcomes of 4609 tuberculosis patients admitted to tuberculosis hospitals from 2020 to 2022 were retrospectively analyzed. The incidence of VTEC was estimated.Results. Totally 214/4609 cases of VTEC were identified (4.6%; 95% CI 4.1-5.3%), among which the incidence of DVT made 3.5% (95% CI 3.0-4.1%), SVP 1.5% (95% CI 1.2-1.9%), and PATE 0.6% (95% CI 0.4-0.8%). The most significant risk factors of thrombotic complications in tuberculosis patients were identified, those factors included HIV infection (RR 3.8; 95% CI 2.7-4.5) and fibrous cavernous form of pulmonary tuberculosis (RR 9.1; 95% CI 4.7-17.6). The overall prevalence of VTEC in tuberculosis hospitals was 3 or more times higher than in general clinics (according to the published data).Conclusion. The data obtained indicate that patients hospitalized for pulmonary tuberculosis face a high risk of VTEC development that requires prediction and prevention.

An Overview of The Total Leukocyte Count in Pulmonary Tuberculosis Patients at RSUD Gambiran Kediri City

The leukocyte count examination in tuberculosis infection serves to monitor the inflammation caused by Mycobacterium tuberculosis. An increasing leukocyte count can lead to complications such as pleuritis. The purpose of this study was to determine the total leukocyte count of pulmonary tuberculosis patients at RSUD Gambiran, Kediri City, based on gender and age. This research was a descriptive retrospective study. Data analysis was conducted using Microsoft Excel and presented in the form of tables and diagrams. The results of this study showed that pulmonary tuberculosis infection was more prevalent in males, with 26 individuals (62%) affected. In terms of age groups, the highest infection rate was in the 21-60 years age range, with 30 individuals (71%) affected. As for leukocyte count elevation (leukocytosis), it was more commonly observed in males with a count of 14.57 µL. In terms of age groups, leukocytosis was frequently observed in the 21-60 years age range, with a count of 48.66 µL. Out of the 42 samples, 19 individuals had a normal leukocyte count, while the remaining 23 individuals experienced leukocytosis. From the results of the study, it can be concluded that not all pulmonary tuberculosis patients experience leukocytosis; some patients maintain a normal leukocyte count.

Particulate matter deposition and its impact on tuberculosis severity: A cross-sectional study in Taipei

The objective of this study was to examine the association between the lung lobe-deposited dose of inhaled fine particulate matter (PM2.5) and chest X-ray abnormalities in different lung lobes of pulmonary tuberculosis (TB), multidrug-resistant tuberculosis (MDR-TB), and non-tuberculosis mycobacteria infections (NTM). A cross-sectional study was conducted between 2014 and 2022, comprising 1073 patients who were recruited from chest department clinic in a tertial refer hospital in Taipei City, Taiwan. Ambient 1-, 7-, and 30-day PM2.5 exposure and the deposition of PM2.5 in different lung lobes were estimated in each subject. The β coefficient for PM2.5 and deposited PM2.5 in lungs with the outcome variables (pulmonary TB, MDR-TB, and NTM infection) was derived through regression analysis and adjusted for age, gender, BMI, smoking status, and family income. We observed that a 1 μg/m3 increase in ambient PM2.5 was associated with an increase of MDR-TB infections of 0.004 times (95%CI: 0.001–0.007). A 1 μg/m3 increase in 1-day and 7-day PM2.5 deposition in left upper lobe and left lower lobe was associated with an increase in chest X-ray abnormalities of 9.19 % and 1.18 % (95%CI: 0.87–17.51 and 95%CI: 0.08–2.28), and 4.52 % and 5.20 % (95%CI: 0.66–8.38 and 95%CI: 0.51–9.89) in left lung of TB patients, respectively. A 1 μg/m3 increase in 30-day PM2.5 deposition in alveolar region was associated with an increase in percent abnormality of 2.50 % (95%CI: 0.65–4.35) in left upper lobe and 3.33 % (95%CI: 0.65–6.01) in right middle lobe, while in total lung was 0.63 % (95%CI: 0.01–1.27) in right upper lobe and 0.37 % (95%CI, 0.06–0.81) in right lung of MDR-TB patients. Inhaled PM2.5 deposition in lungs was associated with an exacerbation of the radiographic severity of pulmonary TB, particularly in pulmonary MDR-TB patients in upper and middle lobes. Particulate air pollution may potentially exacerbate the radiographic severity and treatment resistance in individuals with pulmonary TB.

Triggering Receptor Expressed on Myeloid Cells 2 Mediates the Involvement of M2-Type Macrophages in Pulmonary Tuberculosis Infection.

Macrophage play a significant work in the development of tuberculosis. This study aims to investigate the relationship between TREM2 and macrophage polarization, as well as the related cytokines. This study involved 43 pulmonary tuberculosis patients and 37 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of M1/M2 macrophage-related cytokines IL-10 and IL-12 in the peripheral blood of pulmonary tuberculosis patients. The relative mRNA expression levels of TREM2, IL-10 and IL-12 were detected using quantitative real-time PCR (qRT-PCR). Additionally, Spearman rank correlation analysis was used to preliminarily assess the correlation between TREM2 and M1 / M2 macrophages. Hematoxylin-eosin (HE) staining was performed to observe the pathological manifestations of pulmonary tuberculosis lesions. Immunohistochemical (IHC) staining was used to observe the localization of the macrophage-specific molecule CD68, the M1 specific molecule iNOS, the M2 specific molecule CD163, and TREM2. The lesions of pulmonary tuberculosis patients showed Langhans multinucleated macrophages and tuberculous granulomas. The ELISA results indicated that the expression levels of IL-10 and IL-12 were significantly increased in peripheral blood of pulmonary tuberculosis patients. Additionally, the relative mRNA expression levels of TREM2, IL-10 and IL-12 were also significantly higher in the pulmonary tuberculosis group. Furthermore, a positive correlation was observed between TREM2 and IL-10, which are secreted by M2 macrophages. IHC revealed significant positivity of TREM2 and macrophage-related markers in tuberculous granuloma. Specifically, TREM2 and M2 macrophage marker CD163 were significantly expressed in the cytoplasm and membrane of Langhans multinucleated macrophages. The role of macrophage polarization in pulmonary tuberculosis is significant, and further investigation is needed to understand relationship between TREM2 and M2 macrophages.

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

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

Immunopathology of Pulmonary Mycobacterium tuberculosis Infection in a Humanized Mouse Model.

Despite the availability of antibiotic therapy, tuberculosis (TB) is prevailing as a leading killer among human infectious diseases, which highlights the need for better intervention strategies to control TB. Several animal model systems, including mice, guinea pigs, rabbits, and non-human primates have been developed and explored to understand TB pathogenesis. Although each of these models contributes to our current understanding of host-Mycobacterium tuberculosis (Mtb) interactions, none of these models fully recapitulate the pathological spectrum of clinical TB seen in human patients. Recently, humanized mouse models are being developed to improvise the limitations associated with the standard mouse model of TB, including lack of necrotic caseation of granulomas, a pathological hallmark of TB in humans. However, the spatial immunopathology of pulmonary TB in humanized mice is not fully understood. In this study, using a novel humanized mouse model, we evaluated the spatial immunopathology of pulmonary Mtb infection with a low-dose inoculum. Humanized NOD/LtSscidIL2Rγ null mice containing human fetal liver, thymus, and hematopoietic CD34+ cells and treated with human cytokines were aerosol challenged to implant <50 pathogenic Mtb (low dose) in the lungs. At 2 and 4 weeks post infection, the tissue bacterial load, disease pathology, and spatial immunohistology were determined in the lungs, liver, spleen, and adipose tissue using bacteriological, histopathological, and immunohistochemical techniques. The results indicate that implantation of <50 bacteria can establish a progressive disease in the lungs that transmits to other tissues over time. The disease pathology in organs correspondingly increased with the bacterial load. A distinct spatial distribution of T cells, macrophages, and natural killer cells were noted in the lung granulomas. The kinetics of spatial immune cell distribution were consistent with the disease pathology in the lungs. Thus, the novel humanized model recapitulates several key features of human pulmonary TB granulomatous response and can be a useful preclinical tool to evaluate potential anti-TB drugs and vaccines.

Hyperglycemia modulates M1/M2 macrophage polarization in chronic diabetic patients with pulmonary tuberculosis infection

Increased susceptibility to bacterial infections like tuberculosis (TB) is one of the complications of type 2 diabetes, however the underlying mechanisms remains poorly characterized. To explore how chronic hyperglycemia in diabetes affects progression of active TB, we examined mRNA expression of M1 (proinflammatory) and M2 (anti-inflammatory) cytokines/markers, in monocyte-derived macrophages obtained from patients with PTB + DM (pulmonary TB + diabetes mellitus type 2), patients with DM alone, patients with PTB alone, and healthy individuals (controls). Our findings indicate a dysregulated cytokine response in patients with both PTB and DM, characterized by decreased expression levels of interferon-gamma (IFN-γ) and inducible nitric oxide synthase (iNOS), along with increased expression levels of interleukin-1 beta (IL-1β) and CD206. Furthermore, we observed a positive correlation of IL-1β and CD206 expression with levels of glycosylated hemoglobin (HbA1c) in both PTB + DM and DM groups, while IFN-γ showed a positive correlation with HbA1c levels, specifically in the PTB + DM group. Additionally, M1 cytokines/markers, IL-1β and iNOS were found to be significantly associated with the extent of sputum positivity in both PTB and PTB + DM groups, suggesting it to be a function of increased bacterial load and hence severity of infection. Our data demonstrates that tuberculosis in individuals with PTB + DM is characterized by altered M1/M2 cytokine responses, indicating that chronic inflammation associated with type 2 diabetes may contribute to increased immune pathology and inadequate control of tuberculosis infection.