System Tuberculosis Research Articles

Clinical and diagnostic features of central nervous system tuberculosis in Indian children - a descriptive study.

Children with tuberculous meningitis (TBM) present with diagnostic challenges as they often have atypical clinical features. To describe the baseline characteristic features of children diagnosed with central nervous system (CNS) TB (TBM and tuberculoma). Retrospective descriptive study. Children less than 12 years presenting with neurological signs and symptoms were assessed for a therapeutic TBM trial eligibility. The results of their clinical, laboratory, neuroimaging, cerebrospinal fluid evaluations were analysed for TBM diagnosis. Of 600 children evaluated, 61(10%) had CNS tuberculosis; TBM 47, tuberculoma 14. 20(33%) had definite TBM. Mean age of children with TBM was 5 ± 3.4 years. Of 47, 13(28%), 21(45%) and 13(28%) had grade I, II, and III disease respectively. Abnormalities suggestive of TBM in MRI and computed tomography brain were observed in 76% (26/34) and 77% (24/31) respectively. Abnormal cerebrospinal fluid white blood cell count, protein and glucose were observed in 56% (24/43), 49% (22/45), 47% (21/45) respectively. Among 41 patients with TBM followed up until discharge, five died. Younger children with TBM have severe forms. Confirmatory results may not be available in all. A holistic approach to care including addressing complications of hydrocephalus and strokes is needed.

Effective cerebral tuberculosis treatment via nose-to-brain transport of anti-TB drugs using mucoadhesive nano-aggregates.

Central nervous system tuberculosis (CNS-TB) is a severe form of extra-pulmonary tuberculosis with high mortality and morbidity rates. The standard treatment regimen for CNS-TB parallels that of pulmonary TB, despite the challenge posed by the blood-brain barrier (BBB), which limits the efficacy of first-line anti-TB drugs (ATDs). Nose-to-brain (N2B) drug delivery offers a promising solution for achieving high ATD concentrations directly at infection sites in the brain while bypassing the BBB. This study aimed to develop chitosan nanoparticles encapsulating ATDs, specifically isoniazid (INH) and rifampicin (RIF). These nanoparticles were further processed into micro-sized chitosan nano-aggregates (NA) via spray drying. Both INH-NA and RIF-NA showed strong mucoadhesion and significantly higher permeation rates across RPMI 2650 cells compared to free ATDs. Intranasal administration of these NAs to TB-infected mice for four weeks resulted in a significant reduction of mycobacterial load by approximately ∼2.86 Log 10 CFU compared to the untreated group. This preclinical data highlights the efficacy of intranasal chitosan nano-aggregates in treating CNS-TB, demonstrating high therapeutic potential, and addressing brain inflammation challenges. To our knowledge, this study is the first to show nasal delivery of ATD nano-formulations for CNS-TB management.

Evaluation of Renal Functions in Patients with Genitourinary System Tuberculosis Involving the Kidney/Ureter: Single Center Experience

Evaluation of Renal Functions in Patients with Genitourinary System Tuberculosis Involving the Kidney/Ureter: Single Center Experience

Central Nervous System Tuberculosis in a Murine Model: Neurotropic Strains or a New Pathway of Infection?

Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB/c mice. In this present study, BALB/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb.

Pediatric and adult meningeal, parenchymal, and spinal tuberculosis: A neuroimaging review.

Neurotuberculosis is defined as a tuberculous infection of the meninges, brain parenchyma, vessels, cranial and spinal nerves, spinal cord, skull, and spine that can occur either in a localized or in a diffuse form. It is a heterogeneous disease characterized by many imaging appearances and it has been defined as "the great mimicker" due to similarities with many other conditions. The diagnosis of central nervous system (CNS)tuberculosis (TB) is based on clinical presentation, neuroimaging findings, laboratory and microbiological findings, and comprehensive evaluation of the response to anti-TB drug treatment. However, the absence of specific symptoms, the wide spectrum of neurological manifestations, the myriad of imaging findings, possible inconclusive laboratory results, and the paradoxical reaction to treatment make the diagnosis often challenging and difficult, potentially delaying adequate treatment with possible devastating short-term and long-term neurologic sequelae. Familiarity with the imaging characteristics helps in accurate diagnosis and may prevent or limit significantly morbidity and mortality. The goal of this review is to provide a comprehensive up-to-date overview of the conventional and advanced imaging features of CNS TB for radiologists, neuroradiologists, and pediatric radiologists. We discuss the most typical neurotuberculosis imaging findings and their differential diagnosis in children and adults with the goal to provide a global overview of this entity.

Longterm magnetic resonance imaging surveillance in central nervous system tuberculosis patients with anti-tuberculosis treatment success

Longterm magnetic resonance imaging surveillance in central nervous system tuberculosis patients with anti-tuberculosis treatment success

Central nervous system tuberculosis causing motor tractopathy-a case report

Central nervous system tuberculosis causing motor tractopathy-a case report

Central nervous system tuberculosis. Magnetic resonance imaging as the first line diagnostic tool

Central nervous system tuberculosis. Magnetic resonance imaging as the first line diagnostic tool

Effect of continuation of intensive phase on poor responders of antituberculosis treatment on morbidity and mortality in central nervous system tuberculosis (CNS-TB)

Effect of continuation of intensive phase on poor responders of antituberculosis treatment on morbidity and mortality in central nervous system tuberculosis (CNS-TB)

Central nervous system tuberculosis in patients with systemic rheumatic disease that were receiving immunosuppresive therapy

Central nervous system tuberculosis in patients with systemic rheumatic disease that were receiving immunosuppresive therapy

Matrix metalloproteinaze inchibitors system and experimental drug-resistant kidney tuberculosis treatment effectiveness

Matrix metalloproteinaze inchibitors system and experimental drug-resistant kidney tuberculosis treatment effectiveness

Central Nervous System Tuberculosis: Risk Factors for Mortality in a Propensity Score-Matched Case-Control Study.

Despite advancements in tuberculosis (TB) control and treatment in the United States (US), patients with central nervous system TB (CNS-TB) continue to experience significantly higher mortality rates than those without CNS-TB. This raises concerns regarding clinical management and the need for a deeper understanding of the risk factors contributing to these deaths. This study aimed to determine the predictors of mortality in patients with CNS-TB. We conducted a retrospective 1:2 propensity score-matched case-control study. Cases were TB patients diagnosed with TB of the meninges, brain, spinal cord, or peripheral nerves, as documented in the Florida Department of Health (FDOH) TB registry, between 2009 and 2021. Controls were TB patients without CNS-TB, also reported in the FDOH TB registry during the same timeframe. We employed conditional logistic regression models to investigate the factors contributing to mortality in cases compared with controls. We analyzed data from 116 cases and 232 matched controls. Patients with CNS-TB had a 5.69-fold higher risk of death than those without CNS-TB (adjusted odds ratio [aOR], 5.69 [95% confidence interval {CI}, 2.91-11.6]). Increased risk of death was associated with human immunodeficiency virus (HIV) coinfection (aOR, 1.93 [95% CI, .82-4.37]) and diabetes (aOR, 3.13 [95% CI, 1.28-7.47]). Miliary TB and non-HIV immunosuppression were significantly associated with being a case, while cavitary TB was less likely to be associated with being a case. Clinical management should prioritize screening and close monitoring of patients with HIV coinfection and diabetes to improve patient outcomes.

The role of TNF receptors as mediators of chronic vasculitis in possible milder forms of the CNS tuberculosis.

Central nervous system (CNS) tuberculosis (TB) is the most severe form of TB due to its high mortality and functional sequelae. There are several differential diagnoses for TB; and, it can also cause secondary conditions, such as vasculitis. 155 biopsies, corresponding to 155 different patients out of 5,386 registered biopsies from 2008-2013, met the criteria of unknown etiology vasculitis and evidence of cerebral vascular disease. These were analyzed to assess the presence of central nervous system TB. The selected cases were assessed with Suzaan Marais (SM) criteria for clinical tuberculosis. After that, Ziehl-Neelsen (ZN) staining and polymerase chain reaction (PCR) were performed to amplify a fragment of the insertion sequence IS6110 of M. tuberculosis. 21 patients met the criteria for definitive tuberculosis by ZN staining and PCR, and 2 met the criteria for possible tuberculosis. Tumor necrosis factor (TNF)-α, TNF-R1, and TNF-R2 were determined by immunohistochemistry in histological sections from formalin-fixed paraffin-embedded (FF-PE) tissues in the 23 selected patients. Granulomatous TB was present in almost half of the cases. TNF-R1 and TNF-R2 were expressed mainly in blood vessels, histiocytes, and macrophages. TNF-R2 expression was higher than the other markers, which suggests an anti-inflammatory response against M. tuberculosis. The histopathological presentation of TB is not always limited to granulomas, abscesses, or meningitis; there are also clinical presentations characterized only with chronic inflammation of nervous and vascular tissue.

Clinical features of the course of tuberculous meningitis in HIV-infected patients

Background. Central nervous system tuberculosis is one of the most severe forms of extrapulmonary tuberculosis, which is due to an unfavorable clinical course, a high incidence of neurological complications and deaths. Despite this, the problem of early diagnosis is still not solved.
 Aim. To study the clinical and laboratory-instrumental features of the early diagnosis of tuberculous meningitis in HIV-infected patients.
 Materials and methods. A retrospective analysis of 31 case histories of patients with tuberculous lesions of the meninges and central nervous system in the late stages of HIV infection who were treated at the Clinical Tuberculosis Dispensary of Krasnodar Territory in 20202022 was carried out. The data of clinical manifestations of the disease, the results of laboratory and instrumental methods of examination were analyzed. Statistical data processing was performed by Microsoft Office Excel 2021 with the calculation of averages, standard deviation.
 Results. Tuberculous lesions of the meninges and the central nervous system among HIV-infected people were more common in men of working age who were not previously registered in a tuberculosis dispensary. All HIV-infected patients had late stages of HIV infection with severe immunodeficiency: the content of CD4+ lymphocytes less than 100 cells was detected in 45.46%; from 100 to 200 cells/l of CD4+ lymphocytes were recorded in 36.36%, more than 200 cells/l in 18.18%. Also, in all the studied patients, the primary focus was established in the form of tuberculosis of the respiratory organs, represented in 56.52% of cases by disseminated pulmonary tuberculosis. More than 70% had generalized tuberculosis with damage to the kidneys, spleen, and peripheral lymph nodes. A feature of the manifestation of tuberculous meningitis in HIV-infected people can be considered a high frequency of acute increase in neurological symptoms. Of the cerebral manifestations, the most common were: headache, dizziness, photophobia. 13.04% of HIV-infected patients complained of nausea and vomiting. 91.30% showed signs of damage to the substance of the brain, represented by mono-, hemiparesis and damage to the cranial nerves, mainly IIIIV, VI, VII pairs. The composition of CSF in HIV-positive patients revealed the presence of mild pleocytosis (up to 100 cells/l) in 56.52% of cases. The nature of the change in the concentration of proteins, chlorides and glucose is nonspecific.
 Conclusions. The study revealed the features of medical and social characteristics, clinical and laboratory and instrumental picture of tuberculous meningitis in HIV-infected patients and without HIV infection.

FRI330 A Rare Case Of Hypogonadotropic Hypogonadism In A Patient With Disseminated Tberculosis And Tuberculoma Involving Tuberculum Sellae

Abstract Disclosure: J.S. Genkil: None. S. Ahsun: None. N. Mohan: None. C. Anastasopoulou: None. Introduction: Central nervous system (CNS) tuberculosis accounts for 1-10% of all tuberculosis (TB) infections and has been known to lead to irreversible consequences. CNS TB may present variably as meningeal tuberculosis, tuberculoma, tuberculous abscess, hydrocephalus, ventricular involvement or cerebritis. Tuberculomas involving the sellar region are amongst the rarest of presentations. We describe a unique case of hypogonadotropic hypogonadism with CNS tuberculoma. Case: A 46-year-old male with depression, alcohol use, tobacco smoking, and daily K2 spice use presented to the hospital with multiple days of upper extremity weakness, seizures, and slurred speech. Head CT was done that showed a soft tissue density with mild hypoattenuation on the right frontal region. MRI of the brain showed 3 round 4-5mm lesions with rim enhancement in the frontal lobes. Chest CT showed apical lung lesion. It was believed that patient had a malignant process with metastasis to the brain. During his course, it was discovered that he had TB exposure from his mother several months ago. Despite multiple negative AFB sputum samples, left lung biopsy confirmed TB diagnosis. He was subsequently diagnosed with tubercular meningitis with tuberculomas, one of them involving tuberculum sellae. The patient was started on antitubercular treatment with isoniazid, rifampin, pyrazinamide, streptomycin, and dexamethasone. Lab revealed normal thyroid studies, but very low total testosterone<20 ng/dl (Normal 220-872 ng/dl), with low FSH=2.6 IU/L (Normal 1-12 IU/L) and LH=0.8 IU/ml (Normal 0.6-12.1 IU/ml), with normal prolactin=7.9 ug/L (Normal 3.5-19.4 ug/L). To treat hypogonadotropic hypogonadism, the patient was started on weekly testosterone supplementation with testosterone cypionate 50 mg subcutaneous injections. Ultimately the patient was discharged to a full-time nursing facility and made significant clinical and functional improvement. Discussion: TB of the CNS is among the least common of extra pulmonary tuberculosis yet is associated with the most devastating manifestations making it a feared complication of TB. These lesions are associated with high rates of morbidity and mortality despite appropriate therapy so prompt diagnosis is key. CNS tuberculomas may present isolated or in combination with pulmonary TB. They are unique as they may masquerade as other intracranial space occupying lesions such as tumors or hematomas, further complicating diagnosis. In particular, sellar and suprasellar region tuberculomas are rare and can present with varied amount of hypopituitarism. In the patient’s case, he developed hypogonadotropic hypogonadism which was successfully treated with testosterone replacement. Hypogonadotropic hypogonadism can only be recognized if there is a high index of suspicion and can result in improvement of the quality of life with preservation of sexual function. Presentation: Friday, June 16, 2023

Diagnostic validity of MRI for central nervous system tuberculosis: protocol for a systematic review and meta-analysis

IntroductionCentral nervous system tuberculosis (CNSTB) is a severe condition, sometimes associated with a poor prognosis. Early diagnosis of CNSTB remains challenging, considering that conventional methods lack sensitivity or might lead...

A-257 Association Between Matrix Metalloproteinase-3 and its Post-Transcriptional Regulator miR-17-5p in the Pathogenesis of Tuberculous Meningitis Patients

Abstract Background Tuberculosis, a communicable disease caused by Mycobacterium tuberculosis is one of the top 10 causes of death worldwide. Tuberculous meningitis (TBM), an extra-pulmonary central nervous system tuberculosis is the most severe form with maximum mortality. To combat the complications of disease, host immune response gets activated which initially protects the host but later an exaggerated response leads to aggravation of the disease. This causes tremendous neuroinflammation which further increases the complications of the disease. Matrix metalloproteinase (MMPs) like MMP-9, 2 and 3 are known to cause damage to the blood brain barrier and have a role in the pathogenesis of disease particularly increasing the neuroinflammation. MMPs are regulated at post-transcriptional level by microRNAs (miRNA) that alter their levels by targeting various genes. Based on available literature we found miR-17-5p to be a key regulator of MMP3. In this study, we assessed the levels of MMP3 and its post-transcriptional regulator miR-17-5p in the cerebrospinal fluid (CSF) of TBM patients, healthy controls (HC) and non-infectious neuroinflammatory disease patients (NID). Methods In this study, 100 TBM patients were recruited based on the Lancet scoring system and CSF samples were collected. For NID control group, 25 patients with other non-infectious neuroinflammatory diseases like Guillain-Barre syndrome, multiple sclerosis were recruited. Twenty five HC CSF samples were collected from patients undergoing spinal anaesthesia for any lower limb surgery. The samples were stored at −80°C and processed when required for ELISA and quantitative real time PCR. Results We found a significant increase in levels of median MMP3 levels in the CSF of TBM patients compared to HC group (2.719 ng/ml vs 1.696 ng/ml). The MMP3 levels were also significantly elevated in the NID control group as compared to HC group (3.116 ng/ml vs 1.696 ng/ml). A stagewise comparison in TBM group showed an increase in levels of MMP3 with respect to HC but within stages results were comparable. The expression of MMP3 regulator miR-17-5p showed an upregulation in the CSF of TBM group as compared to NID and HC group. Conclusion An increase in levels of MMP3 was observed in both TBM and NID group which infers that MMP3 might have a role in neuroinflammation in neurological conditions. In our study groups we did not find any relation between miR-17-5p expression and MMP3 levels, indicating that there might be some other regulatory pathway altering the levels of MMP3 in neurological conditions. Hence, further studies can be done to highlight the explicit role of MMP3 in neuroinflammation which can then be targeted therapeutically to relieve the associated complications.

Predicting the Risk of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in HIV-Infected Patients with Central Nervous System Tuberculosis

Objective — to identify risk factors associated with the development of Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) in HIV-infected patients with central nervous system tuberculosis. The analysis assessed the relationship between the risk of develo­ping TB-IRIS with neurological manifestations and the following factors: 1) viral load before antiretroviral therapy (ART) initiation; 2) CD4+ lymphocyte of blood before ART initiation; 3) duration of antituberculosis therapy before starting ART; 4) presence of active tuberculosis at the time of ART initiation. Materials and methods. 112 cases of neurological TB-IRIS were analyzed. These patients were treated and observed during the 1 year in anti-tuberculosis facilities in Kyiv and Kyiv region in 2017—2021. All patients received ART in accordance with the HIV treatment protocols adopted in Ukraine. Treatment according to the standard of tuberculosis treatment adopted in Ukraine. The logistic regression model construction method was used to analyze. Statistical processing of the obtained data was carried out using free software — the EZR package (version 1.61; https://www.jichi.ac.jp/).The study was carried out as part of the applied research work 0121U107800 «Predicting the development of the incidence of tuberculosis in Ukraine in connection with the COVID-19 pandemic», funded by the Ministry of Health of Ukraine. Results and discussion. After calculations, two factor signs were identified, associated with the of deve­loping TB-IRIS with neurological manifestations: the baseline level of CD4+ lymphocytes in 1 μl of blood at the beginning of treatment and the presence of active tuberculosis at the time of ART initiation. Conclusions. It was found that the risk of developing TB-IRIS with neurological manifestations is significantly associated (p < 0.05) with the following factors: 1) the level of CD4+ lymphocytes in 1 μl at the beginning of treatment; 2) presence of active tuberculosis at the time of ART initiation.

Recent advances in microbiological and molecular biological detection techniques of tuberculous meningitis.

Tuberculous meningitis (TBM) is the most common type of central nervous system tuberculosis (TB) and has the highest mortality and disability rate. Early diagnosis is key to improving the prognosis and survival rate of patients. However, laboratory diagnosis of TBM is often difficult due to its paucibacillary nature and sub optimal sensitivity of conventional microbiology and molecular tools which often fails to detect the pathogen. The gold standard for TBM diagnosis is the presence of MTB in the CSF. The recognised methods for the identification of MTB are acid-fast bacilli (AFB) detected under CSF smear microscopy, MTB cultured in CSF, and MTB detected by polymerase chain reaction (PCR). Currently, many studies consider that all diagnostic techniques for TBM are not perfect, and no single technique is considered simple, fast, cheap, and efficient. A definite diagnosis of TBM is still difficult in current clinical practice. In this review, we summarise the current state of microbiological and molecular biological diagnostics for TBM, the latest advances in research, and discuss the advantages of these techniques, as well as the issues and challenges faced in terms of diagnostic effectiveness, laboratory infrastructure, testing costs, and clinical expertise, for clinicians to select appropriate testing methods.

Tuberculosis-immune reconstitution inflammatory syndrome in an immunocompetent patient

Tuberculosis-immune reconstitution inflammatory syndrome is commonly seen among patients with acquired immunodeficiency syndrome either as a paradoxical worsening of an already diagnosed disease or as an uncovering of a dormant infection. There is evidence of paradoxical worsening of central nervous system tuberculosis (CNS-TB) once the treatment is instituted even among immunocompetent patients leading to significant morbidity. We report a case of a previously well young woman with paradoxical worsening of CNS-TB after commencement of treatment. This case highlights an important possible clinical sequelae of CNS-TB, a practicing physician should be aware of.