Extrapulmonary Tuberculosis Infection Research Articles

Clinco-demographic Aspects of Pulmonary and Extrapulmonary Tuberculosis Among Pediatric Patients Admitted to Benghazi Children Hospital, Benghazi 2023

In Benghazi Children’s Hospital, the infectious department has been a critical topic in the past few years for the frequent admission of tuberculosis cases, which has not been investigated in a descriptive research paper for some time; therefore, our study focused on the clinical features and demographic characteristics of pulmonary and extrapulmonary tuberculosis infection in pediatric patients at our hospital between 2020 and 2023, when accessibility to healthcare facilities was limited because of the C OVID-19 pandemic quarantine. Of the 54 patients included in our case series descriptive study, 38(70.4%) had both pulmonary and extrapulmonary tuberculosis, 13(24.1%) had pulmonary tuberculosis, and 3(5.6%) had extrapulmonary tuberculosis, with the most frequent age interval affected being 0-4 years, the majority were female 33(61.1%), and the most frequent extrapulmonary tuberculosis was abdominal, which was detected in 25(60.97%) of the patients. Of the 45 samples obtained for GeneXpert assessment, 33(73%) were positive, and for the 19 tuberculin skin tests conducted, 12(63.2%) were positive, and only four patients died during the admission as a result of tuberculosis infection morbid consequences, while the rest were discharged to the follow-up infectious clinic.

Risk Factors for Extrapulmonary Tuberculosis Among US Veterans, 1990-2022.

To determine factors that put US veterans with active tuberculosis at risk for extrapulmonary tuberculosis (EPTB) compared with pulmonary tuberculosis. We included veterans with laboratory-confirmed tuberculosis from 1990-2022 in our retrospective cohort study. Multivariable logistic regression was used to estimate the association of demographic and clinical risk factors with EPTB. Of 7493 veterans aged 20-100 years (median, 58 years) with laboratory-confirmed tuberculosis, 1397 (19%) had EPTB. The most common EPTB infection among veterans was pleural (31.4%), while meningitis carried the highest mortality risk at 90 days. Factors independently associated with EPTB among veterans were non-Hispanic black race/ethnicity, diabetes mellitus, human immunodeficiency virus infection, severe kidney disease, and all-cause mortality within 90 days after tuberculosis diagnosis. Our study demonstrated several risk factors for EPTB among US veterans. Healthcare providers should be educated regarding patient populations at risk for EPTB, especially given the challenges in diagnosing this disease and the importance of instituting early treatment to prevent severe illness and death.

Analysis of the prevalence characteristics and risk factors of pulmonary tuberculosis combined with extrapulmonary tuberculosis in elderly patients

To analyze the clinical features, epidemiological characteristics, risk factors, and complication characteristics of pulmonary tuberculosis (PTB) combined with extrapulmonary tuberculosis (EPTB) in elderly patients (aged > 60 years). Clinical data were collected from pathogen positive elderly patients with PTB hospitalized in a teaching hospital in Zhejiang from 2017 to 2023. We retrospectively analyzed the risk factors for complications of EPTB in elderly patients with PTB by univariate and multivariate logistic regression models. We also described the characteristics of complications in PTB with EPTB. A total of 781 PTB elderly patients were enrolled, of whom 86 (11.01%) had complicated EPTB. The most commonly invasive sites for EPTB were thoracic spine (17.53%), cervical lymph nodes (13.40%), and meninges (12.37%). 60 < aged < 80 years (OR = 2.876, 95%CI 1.290–6.412; P = 0.010), anaemia (OR = 2.212, 95%CI 1.135–3.967; P = 0.018) and osteoporosis (OR = 4.925, 95%CI 1.501–16.160; P = 0.009) were the independent risk factors for PTB with EPTB infection. PTB with EPTB had a higher proportion of multiple serous cavity effusion (19.8% vs. 12.2%) and longer hospitalisation (17 vs. 15, P = 0.004). 60 < aged < 80 years, anaemia and osteoporosis were found to be independent risk factors for PTB with EPTB in elderly patients. We compared the epidemiological and clinical characteristics of PTB with EPTB. These results are important for improving the diagnosis of EPTB, reducing complications, and improving prognosis.

Disseminated tuberculosis complicated by intramuscular abscesses, meningoencephalitis, and hemophagocytic lymphohistiocytosis: a case report

BackgroundAs disseminated extrapulmonary tuberculosis infection can involve multiple systems and result in atypical clinical manifestations that mimic other diseases, the diagnosis may be difficult, especially in elderly patients. Delaying treatment can adversely affect the prognosis. And to achieve better prognosis, early detection and diagnosis are necessary, as well as early initiation of comprehensive treatment.Case presentationWe present the case of a 78-year-old man with disseminated tuberculosis who developed the uncommon complication of urinary retention due to a psoas abscess, meningoencephalitis, and the rare secondary hemophagocytic lymphohistiocytosis syndrome. The patient achieved a favorable outcome following targeted therapy with antitubercular medications.ConclusionsThis case highlights that disseminated extrapulmonary tuberculosis infection can present with a variety of manifestations, and may exhibit many rare and complex clinical presentations. Prompt and accurate diagnosis and treatment play a crucial role in improving prognosis for the patients with persistent fever.

Uncommon presentation of gastrointestinal tuberculosis-A case series

Tuberculosis (TB) is a common disease in underdeveloped countries. Of all tuberculosis cases worldwide, 28% were reported from India. The most prevalent site of infection is the lungs (pulmonary TB), whereas extrapulmonary tuberculosis (EPTB) is less common. The most common form of EPTB in India is Lymph Node TB, which accounts for around 35% of total EPTB cases. Splenic tuberculosis incidence is 8 % whereas tuberculosis of pancreas and gall bladder is extremely rare. Pancreatic and gallbladder tuberculosis (GT) is extremely rare and presents with non-specific features. The clinical manifestations of EPTB are variable, imitate other diseases, and are usually confused with other diseases. Thus, it is crucial to be cautious and highly suspicious of EPTB infection in endemic areas. Probability of developing EPTB in immunocompromised patients is higher than in immunocompetent patients. The burden of EPTB in HIV patients ranges from 15 to 20% of all TB cases in HIV-negative patients, while in HIV-positive people, it accounts for around 40–50% of new TB cases. Histopathological examination (HPE) and positive Acid-Fast Bacilli (AFB) smears are used to make the diagnosis. ATT is given to such patients for 6 months. Due to such a diverse presentation of TB, here, we report a case series of extrapulmonary TB occurring in the abdomen in, pancreas, gallbladder, and spleen.

Obstructive Jaundice Secondary to Hepatic Hilar Tuberculosis Without Pulmonary Involvement.

Tuberculosis (TB) can affect the biliary system, mimicking cholangiocarcinoma without pulmonary involvement.Early recognition of biliary TB and treatment can prevent permanent complications and invasive intervention requirements.Using standard anti-tuberculous medications has shown high efficiency in treating and eradicating mycobacterial infection in such locations.

A physiologically-based pharmacokinetic model for tuberculosis drug disposition at extrapulmonary sites.

Tuberculosis (TB) is a leading cause of mortality attributed to an infectious agent. TB primarily targets the lungs, but in about 16% cases can affect other organs as well, giving rise to extrapulmonary TB (EPTB). However, an optimal regimen for EPTB treatment is not defined. Although the recommended treatment for most forms of EPTB is the same as pulmonary TB, the pharmacokinetics of EPTB therapy are not as well studied. To address this gap, we formulate a whole-body physiologically-based pharmacokinetic (PBPK) model for EPTB that for the first time includes the ability to simulate drug concentrations in the pleura and lymph node, the most commonly affected sites of EPTB. Using this model, we estimate the time-dependent concentrations, at potential EPTB infection sites, of the following four first-line anti-TB drugs: rifampicin, ethambutol, isoniazid, and pyrazinamide. We use reported plasma concentration kinetics data to estimate model parameters for each drug and validate our model using reported concentration data not used for model formulation or parameter estimation. Model predictions match the validation data, and reported pharmacokinetic parameters (maximum plasma concentration, time to reach maximum concentration) for the drugs. The model also predicts ethambutol, isoniazid, and pyrazinamide concentrations in the pleura that match reported experimental values from an independent study. For each drug, the predicted drug concentrations at EPTB sites are compared with their critical concentration. Simulations suggest that although rifampicin and isoniazid concentrations are greater than critical concentration values at most EPTB sites, the concentrations of ethambutol and pyrazinamide are lower than their critical concentrations at most EPTB sites.

Postrenal transplant tuberculosis of the ankle joint

Tuberculosis (TB) is one of the common infections after renal transplantation in developing countries. Patients who receive kidney grafts are at an increased risk for the development of mycobacterial disease than the general population, because of uremia and the immunosuppressants used in the posttransplant period, all of which interfere with T-cell function. Extrapulmonary TB is more common in renal allograft recipients and may present with dissemination or atypical features. Although extrapulmonary TB occurs frequently, isolated ankle joint TB is a rare form of extrapulmonary TB infection. We report here a renal allograft recipient with ankle joint TB presenting 6 months after transplantation with persistent pain in the left ankle joint associated with swelling and mild restriction of joint movement. He was diagnosed to be having an osteomyelitis of the talus bone extending to the navicular and anterior part of the calcaneus. He underwent open debridement and CB-NAAT of the tissue, which showed mycobacterium TB and rifampicin resistance was not detected. He was started on antituberculous treatment. This report highlights the need for a high index of suspicion for diagnosing TB early among renal transplant recipients and diagnostic difficulties of the TB disease due to insidious and nonspecific clinical presentation. Also, the treatment has to be monitored closely due to drug interaction between immunosuppressants and anti-TB drugs.

Burden of Mycobacterium tuberculosis and Associated Factors among Presumptive Extra pulmonary Tuberculosis Patients from Selected Health Facilities, Addis Ababa, Ethiopia

BackgroundExtra pulmonary tuberculosis (EPTB) accounts for a significant proportion of tuberculosis (TB), a devastating disease of public health concern. The complexity of the cases, the involvement of many organs, resource constraints, and concerns regarding drug resistance make disease diagnosis and treatment difficult. This study aimed to determine the burden of tuberculosis and associated factors among presumptive EPTB patients in selected hospitals in Addis Ababa. Material and methodsA cross-sectional study was conducted from February to August 2022 in selected public hospitals in Addis Ababa. Those who attended the hospitals and were presumptively diagnosed as EPTB patient were included in the study. Sociodemographic and clinical data were collected using a semistructured questionnaire. The GeneXpert MTB/RIF assay, Mycobacterium Growth Indicator Tube (MGIT) culture, and solid culture using Löwenstein–Jensen (LJ) medium were used. The data were entered and analyzed using SPSS version 23, and a p-value ≤ 0.05 was considered as statistically significant. ResultsFrom a total of 308 participants enrolled in this study, the measured burdens of extrapulmonary tuberculosis using the Xpert MTB/RIF assay, liquid culture, and solid culture were 54 (17.5%), 45 (14.6%), and 39 (12.7%), respectively. In this study, sex, contact history with known TB cases, having a purulent type of aspirate, and being HIV positive had statistically significant associations with EPTB. ConclusionsThe burden of extrapulmonary tuberculosis among presumptive extrapulmonary tuberculosis cases was found to be significant. Sex, contact history with a known TB case, having apurulent type of aspirate, and being HIV positive were found to be associated with extrapulmonary tuberculosis infection. Strict adherence to the national tuberculosis diagnosis and treatment guidelines is important, while the true burden of the disease should be ascertained using standard diagnostic tests for better prevention and control interventions.

Extrapulmonary tuberculosis presentation in the form of a chest wall abscess with no pulmonary involvement in the UK: a case report

The presentation of an extrapulmonary manifestation of tuberculous (TB) infection to a tertiary care facility in the UK is a rare event given its low prevalence. This case report focuses on an atypical presentation of an extrapulmonary tuberculosis (EPTB) infection in the form of a chest wall abscess. This was recognized and managed appropriately. This case however elucidates vital learning as migration from around the globe would contribute to an increasing number of TB/EPTB infections. The wide array and indolent nature of their presentation creates diagnostic and treatment challenges. Appreciation for the epidemiology, risk factors, effective and prompt treatment with follow up protocols would help develop pathways for better care. Within the UK, despite it being a low-risk country for TB, there is need for increased awareness, education with established management pathways and governance for TB and EPTB infections.

An Overview of Extra Pulmonary Tuberculosis in Smear Negative Cases and their Analysis

Mycobacterium tuberculosis (MTB), a bacterium which causes the tuberculosis disease, is one of the most trounce disease in the country. It mainly affects the lungs and other parts of the body. Currently smear-positive cases are further confirmed through chest radiography for PTB. These cases are further subjected for short course chemotherapy (SCC), followed by first line primary drugs, a scheme undertaken by National Tuberculosis Programme to overcome PTB infection. However, the identification of infection through smear-negative results are challenging as the cases may become positive over the time and progresses to cause the Extra Pulmonary Tuberculosis (EPTB). Such infections are asymptomatic and referred to as latent infection, where, MTBremains stable for many years at a specific site and later activates. Worldwide about 10-25% of latent infections progress to an active disease and if undiagnosed, the mortality rate may reach up to 50%. Twenty five percent of EPTB infection differs from organ to organ of the body. However, in such cases, diagnosis may be elusive and is usually delayed. The proper identification of infection that strongly focuses on the infection of either i.e., TB or EPTB is the need of the hour. The diagnosis of EPTB will be elusive, necessitating a high index of suspicion over TB or EPTB. However, smear-negative cases may be positive for EPTB infection, where the suspects are to be further subjected for molecular methods of EPTB detection and confirmation.

Case Report Tuberculous Spondylitis in Elderly with Polyneuropathy

Background Tuberculous (TB) spondylitis or Pott’s Disease is a manifestation of extrapulmonary tuberculosis infection caused by the hematogenous and lymphomatous spread of Mycobacterium Tuberculosis, causing infection in the vertebral bones. Approximately 10% of extrapulmonary TB cases are TB spondylitis. Pulmonary and extrapulmonary tuberculosis cases are considerable cases in developing countries. Indonesia is a country with the third-highest prevalence of TB in the world after China and India.Objective The aim of this study was to report a case of TB spondylitis in a 66 years old woman with polyneuropathy at Bethesda Hospital Yogyakarta.Case description A 66 years old female patient presented with complaints of pain and difficulty in moving the left lower limb 3 months ago. The patient had a history of hypertension 5 years ago, while the family history was not specific. The patient was generally in pain with full awareness and cooperation. Vital sign examination showed blood pressure 140/80 mmHg, pulse 82 beats per minute, and respiratory rate of 22 breaths per minute. The lumbosacral-MRI examination was performed without contrast material and L2-L5 TB Spondylitis, with L2-L3 Disc protrusion, was found.Conclusion Tuberculous spondylitis (TB) may cause paradiscal inflammation, edema, and progressive bone destruction due to lysis of anterior bone tissue and secondary ischemia which will lead to collapse. Pain, difficulty moving, and local swelling are the most common complaints. Abnormalities in the curvature, misalignment of the vertebrae, deformity and bone destruction might be found in MRI radiological imaging. Treatment of TB spondylitis prioritizes administering of anti-TB drugs combined with immobilization using a girdle. The prognosis for TB spondylitis varies depending on the clinical manifestations.

Comparative diagnostic value of GeneXpert MTB/RIF, PCR targeting IS6110 and culture for the diagnosis of spinal tuberculosis

Introduction Spinal tuberculosis is an extra-pulmonary tuberculosis infection caused by Mycobacterium tuberculosis (MTB) which affects the vertebrae. Culture test is the «gold standard» diagnostic method, but it takes a long time. PCR is a method of a shorter time than the culture test, so it can be an alternative diagnostic method for MTB. Materials and Methods This study is a cross-sectional study. The data were analyzed with diagnostic tests on patients with suspected spinal tuberculosis who performed surgery in Hasan Sadikin Hospital in Bandung. Clinical examinations and diagnostic examinations were done in 40 patients and surgery was performed to obtain samples from the spinal cord and the infected tissue. GeneXpert, PCR targeting IS6110 and culture tests were performed. The research was conducted at the Department of Orthopaedics and Traumatology and the Clinical Pathology Laboratory of FK UNPAD/RSHS from September 2019 to September 2020. Results GeneXpert assay compared with culture tests as the standard diagnostic method showed sensitivity of 96.67 %; specificity of 90.00 %; positive predictive value 96.67 %; and a negative predictive value of 90.00 %, with an accuracy of 95.00 %. The PCR targeting IS6110 against culture showed that the sensitivity of MTB bacterial infection was 93.33 %, the specificity was 80.00 %, the positive predictive value was 93.33 %, the negative predictive value was 80.00 %, and the accuracy was 90.00 %. Conclusion This study concluded that the GeneXpert MTB/RIF RT-PCR assay has a high sensitivity, specificity, and accuracy compared to PCR targeting IS6110 in examining tissue samples in patients with spinal TB.

A 17-Year-old Boy With Nodular Lesions in the Thyroid and Lymphadenopathy.

A 17-Year-old Boy With Nodular Lesions in the Thyroid and Lymphadenopathy.

Rapid Detection and Quantification of Mycobacterium tuberculosis DNA in Paraffinized Samples by Droplet Digital PCR: A Preliminary Study.

Background: Rapid and reliable diagnosis of tuberculosis (TB) represents a diagnostic challenge in compartmentalized extrapulmonary TB infection because of the small number of mycobacteria (MTB) and the frequent lack of fresh samples to perform culture. Here, we estimate the performances of homemade droplet digital PCR (ddPCR)-based assays against culture in 89 biopsies, for those fresh and formalin-fixed and paraffin-embedded (FFPE) subsamples were available.Methods: MTB diagnosis in fresh subsamples was performed by culture. Fresh subsamples were also analyzed for acid-fast bacilli smear-microscopy (AFB) and Xpert® MTB/RIF (Xpert). MTB examination was repeated in blind in the 89 FFPE subsamples by in-house ddPCR assays targeting the IS6110 and rpoB. Analytical sensitivity of ddPCR assays was evaluated using serial dilution of H37Rv strain. Limit of detection (LOD) was calculated by probit analysis. Results were expressed in copies/106 cells.Results: IS6110 and rpoB ddPCR assays showed a good linear correlation between expected and observed values (R2: 0.9907 and 0.9743, respectively). Probit analyses predicted a LOD of 17 and 40 copies/106 cells of MTB DNA for IS6110 and rpoB, respectively. Of the 89 biopsies, 68 were culture positive and 21 were culture negative. Considering mycobacterial culture as reference method, IS6110 assay yielded positive results in 67/68 culture-positive samples with a median interquartile range (IQR) of 1,680 (550–8,444) copies/106 cells (sensitivity: 98.5%; accuracy: 98.9). These performances were superior to those reported by the rpoB assay in FFPE subsamples (sensitivity: 66.20%; accuracy: 74.1) and even superior to those reported by Xpert and AFB in fresh subsamples (sensitivity: 79.4 and 33.8%, respectively; accuracy: 84.3 and 49.4, respectively). When Xpert and AFB results were stratified according to mycobacterial load detected by rpoB and IS6110 ddPCR, bacterial load was lower in Xpert and AFB negative with respect to Xpert and AFB-positive samples (p = 0.003 and 0.01 for rpoB and p = 0.01 and 0.11 for IS6110), confirming the poor sensitivity of these methods in paucibacillary disease.Conclusion: ddPCR provides highly sensitive, accurate, and rapid MTB diagnosis in FFPE samples, as defined by the high concordance between IS6110 assay and culture results. This approach can be safely introduced in clinical routine to accelerate MTB diagnosis mainly when culture results remain unavailable.

Mycobacterium bovis Bacillus Calmette-Guérin-Infected Dendritic Cells Induce TNF-α-Dependent Cell Cluster Formation That Promotes Bacterial Dissemination through an In Vitro Model of the Blood-Brain Barrier.

CNS tuberculosis (CNSTB) is the most severe manifestation of extrapulmonary tuberculosis infection, but the mechanism of how mycobacteria cross the blood-brain barrier (BBB) is not well understood. In this study, we report a novel murine in vitro BBB model combining primary brain endothelial cells, Mycobacterium bovis bacillus Calmette-Guérin-infected dendritic cells (DCs), PBMCs, and bacterial Ag-specific CD4+ T cells. We show that mycobacterial infection limits DC mobility and also induces cellular cluster formation that has a similar composition to pulmonary mycobacterial granulomas. Within the clusters, infection from DCs disseminates to the recruited monocytes, promoting bacterial expansion. Mycobacterium-induced in vitro granulomas have been described previously, but this report shows that they can form on brain endothelial cell monolayers. Cellular cluster formation leads to cluster-associated damage of the endothelial cell monolayer defined by mitochondrial stress, disorganization of the tight junction proteins ZO-1 and claudin-5, upregulation of the adhesion molecules VCAM-1 and ICAM-1, and increased transmigration of bacteria-infected cells across the BBB. TNF-α inhibition reduces cluster formation on brain endothelial cells and mitigates cluster-associated damage. These data describe a model of bacterial dissemination across the BBB shedding light on a mechanism that might contribute to CNS tuberculosis infection and facilitate treatments.

Особенности патогенетических механизмов туберкулезного перитонита в эксперименте

The prevalence of tuberculous peritonitis that has been observed in the recent decades is the result of lymphohematogenous spread of Mycobacterium tuberculosis (MBT) from lungs and other extrapulmonary sources. It is still unclear why certain organs and anatomical regions get involved in the inflammatory process during generalization of the tuberculosis infection. Why do some cases develop into peritoneal tuberculosis and other into kidney tuberculosis? Thus study aimed to investigate the pathogenesis of tuberculous peritonitis in a reproducible biological model. Tuberculous peritonitis was modeled in 18 rabbits (10 in the test group, 8 in control) by intraperitoneal inoculation of the MBT suspension. In order to suppress peritoneal macrophages and major cytokines, test group rabbits were injected with the TNFα inhibitor and iron (III) hydroxide sucrose complex before being infected, while control group rabbits received no immunosuppressive drugs. Autopsy of the control group animals revealed changes characteristic of pulmonary tuberculosis in 37.5% of cases, with no damage to other organs and systems registered. Conversely, test group rabbits had the signs of tuberculous peritonitis in their abdominal cavities. The results of this study suggest that it is the local immunity of an anatomical area that largely determines whether a secondary focus of extrapulmonary tuberculosis infection will develop there or not. For the peritoneum, a smaller pool of peritoneal macrophages and weaker cytokine production is a necessary and sufficient condition to have tuberculous peritonitis developing therein.

Value of gamma interferon enzyme-linked immunospot assay in the diagnosis of peritoneal dialysis-associated tuberculous peritonitis

BackgroundTuberculous peritonitis is the most common form of extrapulmonary tuberculosis infection in peritoneal dialysis patients. However, diagnosing tuberculous peritonitis quickly and early has always been a challenge for nephrologists. Mycobacterium tuberculosis antigen-specific gamma interferon enzyme-linked immunospot (IFN-γ ELISPOT) assay has been widely used in the clinical diagnosis of tuberculous pleurisy and peritonitis, but its use has not been reported for uremia.MethodsThis study mainly verified the feasibility of using the M. tuberculosis antigen-specific IFN-γ ELISPOT assay in the diagnosis of continuous ambulatory peritoneal dialysis (CAPD) patients with tuberculous peritonitis. Taking M. tuberculosis culture as the gold standard, the IFN-γ ELISPOT assay was used to analyze peripheral blood and peritoneal dialysis fluid of patients, and the receiver operating characteristic (ROC) curves in patients with tuberculous peritonitis (TBP) or non-tuberculous peritonitis (NTBP) were analyzed.ResultsThe area under the receiver operating characteristic curve (AUC) was 0.927 (95% CI 0.816–1.000, P = 0.001) for the ELISPOT assay with peritoneal fluid mononuclear cells (PFMC), which was higher than that for the ELISPOT assay with peripheral blood mononuclear cells (PBMC) (0.825, 95% CI 0.6490–1.000, P = 0.011). The cutoff value for the diagnosis of TBP was 40 spot-forming cells (SFCs)/2 × 105 for the ELISPOT with PBMC, with a sensitivity of 55.6%, a specificity of 92.3%, and a diagnostic efficiency of 77.3%. The cutoff value for the diagnosis of TBP was 100 SFCs/2 × 105 for the ELISPOT on PFMC, with a sensitivity, specificity, and diagnostic efficiency 77.8%, 84.6%, and 81.8%, respectively. Parallel and serial testing algorithms appeared more accurate than single ELISPOT assays with PBMC, but ELISPOT assays with PFMC.ConclusionsThe IFN-γ release test can be used for the early diagnosis of CAPD-related TBP; compared with peripheral blood, peritoneal fluid may be a more effective and accurate medium to diagnose CAPD complicated with tuberculous peritonitis.

Increased risk of pulmonary and extrapulmonary tuberculosis infection in patients with polycystic kidney disease: a nationwide population-based study with propensity score-matching analysis

BackgroundPolycystic kidney disease (PKD) is a common renal disorder affecting approximately 1 in 1000 live births. Tuberculosis (TB) is an infectious disease worldwide. This study investigated the risk of TB infection in patients with PKD.MethodsA nationwide population-based cohort study was performed using Taiwan’s National Health Insurance Research Database. We used patients’ hospitalization files for the entire analysis during 2000–2012. As per diagnosis, we divided patients into PKD and non-PKD cohorts and the major outcome was TB infection.ResultsA total of 13,540 participants with 6770 patients in each cohort were enrolled. The PKD cohort had a higher risk of TB infection than did the non-PKD cohort after adjusting for age, sex, and comorbidities (adjusted hazard ratio (aHR) = 1.91, 95% confidence interval [CI] = 1.51–2.43). When classifying by sites of pulmonary TB (PTB) and extrapulmonary TB (EPTB), the PKD cohort demonstrated a significantly higher risk of EPTB (aHR = 2.44, 95% CI = 1.46–4.08) as well as a risk of PTB (aHR = 1.69, 95% CI = 1.29–2.22). When stratified by the presence or absence of a comorbidity, high TB infection risk was noted in the PKD patients without any comorbidity (HR = 2.69, 95% CI = 1.69–4.30).ConclusionsTaken together, our findings suggest that PKD is associated with a 1.91-fold increased risk of TB infection. Medical professionls should maintain a high index of suspicion in daily practice for patients with PKD, particularly those with EPTB infection.

BCG-Infected Dendritic Cells Induce TNF-alpha Dependent Cell Cluster Formation That Damage theBlood Brain Barrier

Abstract Central nervous system tuberculosis (CNSTB) is the most serious manifestation of extrapulmonary tuberculosis infections representing 5–10% of all cases. How Mycobacterium tuberculosis (Mtb) crosses the blood-brain barrier (BBB) and enters the CNS is not well understood. We applied a novel in vitro model of BBB model that consists of primary brain astrocytes and microvessel endothelial cells to test the mechanisms how mycobacterium-infected DCs interact with peripheral blood mononuclear cells (PBMC) and affect the BBB. We show that mycobacterium hinders DC migration, and infected DCs adhere to brain microvessel endothelial cells and induce PBMC cell cluster formations. Infected DC-induced cell clusters contain 24% CD11c+, 57%CD11b+, and 16% CD4+ cells. PBMC and infected DC clusters strongly adhered to the in vitro BBB and over time induced cluster associated damage (CAD). CAD correlated with mitochondrial disorganization and the degradation of tight junction proteins ZO-1 and claudin-5, and upregulation of cellular adhesion molecules VCAM-1 and ICAM-1 on endothelial cells. Anti-TNF-a inhibition reduced cell cluster formation as well as ICAM-1 expression on brain microvessel endothelial cells and mitigated CAD. This research leads to better knowledge in understanding how mycobacteria infected cells affect the BBB that could lead to better therapeutic treatments for mycobacterial infection of the CNS.