Tuberculous Meningitis Research Articles

Masks of cancers in the practice of an infectious disease doctor

The purpose of this work is to remind doctors of practical medicine about the importance of differential diagnosis with cancers in general pediatric practice and to increase the vigilance of clinicians regarding the similarity of manifestations of oncology and infectious diseases on the example of specific clinical cases. We conducted an empirical, descriptive study of 4 clinical cases of cancers in children. We selected them among 21 patients who were diagnosed with cancer during the inpatient treatment at the Kyiv City Children’s Infectious Disease Hospital in 2014–2019. The first clinical case describes a brain neoplasm that was initially thought to be acute VZV encephalitis in an 11-year-old child. The second is a case of acute leukemia in a 3-year-old child who was hospitalized with suspected meningococcal infection. In the third case, we presented a 7-year-old patient who was admitted with infectious mononucleosis and as a result, was diagnosed with hemophagocytic syndrome, immunodeficiency and Duncan disease. The latest case demonstrates the combination of tuberculous meningitis and cerebral astrocytoma in a 15-year-old patient, which was initially mistaken for viral encephalitis. Conclusions. Awareness of cancers is important in the diagnosis of infectious nosologies. Dynamic monitoring and the use of a wide range of laboratory and instrumental methods allows to prevent diagnostic errors and to seek treatment in a timely manner.

Spontaneous nosocomial Proteus mirabilis meningitis in a Human Immunodeficiency Virus (HIV)-infected adult patient: a case report

BackgroundGram-negative bacillary meningitis remains a rare occurrence, even in patients with human immunodeficiency virus. Current literature only describes anecdotal cases of spontaneous nosocomial Proteus mirabilis meningitis. This report describes the clinical manifestations and management of a patient with healthcare-associated spontaneous Gram-negative bacillary meningitis in a patient with advanced human immunodeficiency virus disease.Case presentationA 23-year-old Congolese female was hospitalized in a human immunodeficiency virus specialized center for ongoing weight loss, chronic abdominal pain, and vomiting 9 months after initiation of treatment for tuberculosis meningitis. Hospitalization was complicated by healthcare-associated Gram-negative bacillary meningitis on day 18. Blood and cerebrospinal fluid cultures confirmed Proteus mirabilis. Antibiotic susceptibility testing showed extended spectrum beta-lactamase resistant to common antibiotics, and sensitive to meropenem. Despite initiation of high-dose meropenem by intravenous infusion (2 g every 8 hours), the patient did not improve, and died after 4 days of meropenem treatment. Gram-negative bacillary meningitis remains rare and is associated with an unfavorable prognosis.ConclusionsThis case report highlights the importance of microbiological identification of pathogens in resource-limited settings. As Gram-negative bacillary meningitis does not present with pleocytosis in patients with advanced human immunodeficiency virus, a negative lumbar puncture cannot exclude this diagnosis. Access to clinical bacteriology in resource-limited settings is essential to enable correct antibiotic treatment and avoid overuse of antibiotics to which there is already resistance. It further plays an essential role in public health by identifying antibiotic susceptibilities. Infection prevention and control measures must be reinforced in order to protect patients from such avoidable healthcare-associated infections.

A case report about a child with drug-resistant tuberculous meningitis

BackgroundHematogenous disseminated tuberculosis predisposes to concurrent tuberculous meningitis (TBM), the most devastating and disabling form of tuberculosis. However, children often have atypical clinical symptoms, difficulty in specimen collection, low specimen content, and an increasing incidence of drug-resistant tuberculosis. Thus, the accurate diagnosis and timely treatment of childhood tuberculosis face monumental challenges.Case presentationThe 14-year-old female presented to the hospital with intermittent fever, headache, and blurred vision. Her cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis, an elevated protein level, and a decreased chloride level. And her CSF tested positive for TB-RNA. Xpert MTB/RIF detected Mycobacterium tuberculosis in her CSF, but the rifampin resistance test was unknown. Subsequently, her CSF culture was positive for Mycobacterium tuberculosis. The drug sensitivity test (DST) revealed resistance to isoniazid, rifampin, and fluoroquinolones. A computed tomography (CT) of the chest showed diffuse miliary nodules in both lungs. Intracranial enhanced magnetic resonance imaging (MRI) showed “multiple intensified images of the brain parenchyma, cisterns, and part of the meninges.” The final diagnosis is miliary pulmonary tuberculosis and pre-extensive drug-resistant TBM. After 19 months of an oral, individualized antituberculosis treatment, she recovered with no significant neurological sequelae.ConclusionFor patients with miliary pulmonary tuberculosis, especially children, even if there are no typical clinical symptoms, it is necessary to know whether there is TBM and other conditions. Always look for the relevant aetiological basis to clarify whether it is drug-resistant tuberculosis. Only a rapid and accurate diagnosis and timely and effective treatment can improve the prognosis and reduce mortality and disability rates.

Exploration of the Risk Factors of Anemia in Patients with Tuberculous Meningitis in South China.

Central nervous system (CNS) infection has a high incidence and mortality worldwide. Tuberculous meningitis (TBM) accounts for approximately 5-6% of all extrapulmonary tuberculosis (TB), and is considered an extremely lethal form of CNS TB, which has become an important threat to human health. Anemia is a common symptom of TB, and its prevalence is generally higher in patients with TBM than in other meningitis patients and healthy individuals. Anemia can increase a person's susceptibility to common infectious diseases, including TB, by compromising the immune system. Information regarding anemia during the hospitalization of TBM is still scarce in China. This study aimed to describe in detail the prevalence of anemia in patients with TBM in Southern China and its association with the clinical forms of TB, as well as other characteristics of these patients. We conducted a retrospective analysis of patients diagnosed with TBM at two tertiary hospitals in southern China. The demographic characteristics, clinical characteristics, and laboratory results of 114 patients with TBM were collected. Multivariate logistic regression analysis was performed to explore the risk factors for anemia in patients with TBM. Electronic medical record data of adult patients diagnosed with TBM from January 2004 to December 2019 were reviewed. Among 134 patients with TBM, 20 were excluded and 114 were analyzed, of whom 33 had anemic, the prevalence rate of anemia was 28.9%. Among patients with anemia, 51.5% had hypochromic microcytic anemia, 33.3% had normochromic normocytic anemia, and 15.2% had macrocytic anemia. Fever duration, TBM grade III and ESR were found to be independent predictors of anemia. Anemia was highly prevalent in patients with TBM, mainly hypochromic microcytic anemia. Besides, Fever duration, TBM grade III and ESR are predictors of anemia in patients with TBM.

Incidence and Risk Factors of Cranial Nerve Palsy in Patients with Tuberculous Meningitis: A Retrospective Evaluation.

Tuberculous meningitis (TBM) is a common form of central nervous system (CNS) tuberculosis (TB). Cranial nerve palsy is a serious complication of TBM. Literature regarding this subject is still limited in China. This study evaluated the incidence of cranial nerve palsy in patients with TBM in South China, its association with the clinical forms of TB, and other patient characteristics. A retrospective chart review of patients with a diagnosis of TBM between January 2004 and December 2019 was conducted, and the demographic characteristics, clinical characteristics, and laboratory results of 114 patients were collected and followed up for 3 months. A multivariate logistic regression analysis model was used to explore the risk factors of cranial nerve palsy in patients with TBM. A total of 114 patients were enrolled in this study. Cranial nerve palsy was observed in approximately 38 (33.3%) of TBM patients. Among them, 13 (28.3%) had optic nerve palsy, 24 (52.2%) had oculomotor nerve palsy, 5 (10.9%) had abducens nerve palsy, 2 (4.3%) had auditory nerve palsy, 1 (2.2%) had glossopharyngeal nerve palsy, and 1 (2.2%) had vagus nerve palsy. Using logistic regression analysis, focal neurological deficit, extracranial TB and cerebrospinal fluid (CSF) total white cell count (WCC) were shown to be risk factors for cranial nerve palsy. The prevalence rate of cranial nerve palsy was 33.3% in patients with TBM. Focal neurological deficits, extracranial TB and CSF total WCC are important predictors of cranial nerve palsy in patients with TBM.

Cerebrospinal Fluid Adenosine Deaminase for the Diagnosis of Tuberculous Meningitis

Background: A consensus on the diagnostic utility of cerebrospinal fluid adenosine deaminase (ADA) for tuberculous meningitis (TBM) is lacking. Methods: Patients aged ≥12years admitted with CNS infections were enrolled prospectively. ADA was measured with spectrophotometry. Results: We enrolled 251 TBM and 131 other CNS infections. The optimal cutoff of ADA was calculated at 5.5 U/l against microbiological reference standard with area under curve 0.743, sensitivity 80.7%, specificity 60.3%, positive likelihood ratio 2.03 and negative likelihood ratio 3.12. The widely used cutoff value 10 U/l had specificity 82% and sensitivity 50%. The discriminating power was higher for TBM versus viral meningoencephalitis than bacterial or cryptococcal meningitis. Conclusion: Cerebrospinal fluid ADA has a low-to-modest diagnostic utility.

SG-APSIC1042: Cutaneous cryptococcosis in patient with advanced HIV disease: Is it possible to give antifungal monotherapy?

Objectives:Cryptococcus infection is one of the major human immunodeficiency virus (HIV)–related opportunistic infections, and the CD4 count falls below 100 per µL. Primary treatment for HIV-associated cutaneous cryptococcosis is amphotericin B (AmB) plus flucytosine. Methods: We present the case of a man with advanced HIV disease who developed whole-body cutaneous lesions yet improved with high-dose fluconazole alone. Results: A 33-year-old Asian man with a medical history of pulmonary tuberculosis and cryptococcal meningitis with complete treatment, injection drug use, and HIV infection with default of antiretroviral treatments (ART) 3 years earlier, presented to the emergency department with fever, oral thrush, and 30-pound weight loss over 6 weeks. He also had plaques, multiple hard papulonodules with central ulceration, and macular skin lesions all over his body of varying size. Blood cultures were negative for bacteria growth, but fungal microscopy of the blood culture showed unspecific hypha. Histopathology examination of the skin biopsy showed a classic “soap bubble” appearance, which is associated with Cryptococcus infection. Laboratory values revealed anemia (8.6 g/dL), leukopenia (2.9 ×109/L), lymphopenia (58/µL), and thrombocytopenia (145 ×109/L). The CD4 cell count was 18/µL, and the serum viral load was 638.665 copies/mL. Lumbar puncture could not be performed due to patient refusal. Treatment with high-dose fluconazole (1,200 mg) for 3 months was initiated and is planned to continue with consolidation and maintenance dose. ART was administered 4 weeks after starting antifungal therapy. His fever resolved and slow regression of the skin lesions occurred after treatment was given. Conclusions: Cutaneous cryptococcosis was assessed by biopsy of the cutaneous lesion, which is essential to confirming the diagnosis. In the case of cryptococcosis, skin infection may indicate a further progression of advanced HIV disease. In HIV-infected patients with Cryptococcus findings in any part of the body, a lumbar puncture should be considered to rule out central nervous system infection. Although neither AmB nor flucytosine was given due to unavailability in this area, the patient improved. In resource-limited settings, high-dose fluconazole alone may be useful as an alternative treatment, although it is also very challenging.

Mortality and sequelae of tuberculous meningitis in a high-resource setting: A cohort study, 1990–2017

IntroductionTuberculous meningitis (TBM), the most serious form of tuberculosis, results in high mortality and long-term disability in low-resource countries. We investigated temporal trends in mortality and sequelae in a high-resource low-incidence country. MethodsWe performed a retrospective cohort study of all adult patients with TBM at two third-level teaching hospitals in Barcelona (Spain), between January 1990 and December 2017, assessing temporal trends in mortality and sequelae after 12 months over four consecutive 7-year time windows. Rates observed across the four periods were adjusted for covariates. ResultsOf the 135 cases included, all but one started tuberculosis (TB) treatment and 120 (89.6%) received rifampicin, isoniazid, and pyrazinamide, with or without ethambutol. The probability of being alive at month 12 was 81.8%, with no differences among the four periods: in comparison with the 1990–1996 period, the adjusted hazard ratios and 95% confidence intervals (CI) were 2.55 (0.71–9.25), 0.70 (0.13–3.85), and 1.29 (0.28–5.91) for the 1997–2003, 2004–2010, and 2011–2017 periods respectively. Sequelae were present in 28.3% at month 12, with no differences across the four periods in the adjusted analysis: in comparison with the 1990–1996 period, the odds ratios and 95% CIs were 0.80 (0.09–7.22); 1.94 (0.21–17.96), and 2.42 (0.25–23.07) for the 1997–2003, 2004–2010, and 2011–2017 periods respectively. ConclusionThis study shows that TBM still causes high mortality and disability even in a high-resource low-incidence TB setting and without improvement over time.

Missed Opportunities in the Diagnosis of Tuberculosis Meningitis.

Tuberculosis meningitis (TBM) has high mortality and morbidity. Diagnostic delays can impact TBM outcomes. We aimed to estimate the number of potentially missed opportunities (MOs) to diagnose TBM and determine its impact on 90-day mortality. This is a retrospective cohort of adult patients with a central nervous system (CNS) TB International Classification of Diseases, Ninth/Tenth Revision (ICD-9/10) diagnosis code (013*, A17*) identified in the Healthcare Cost and Utilization Project, State Inpatient and State Emergency Department (ED) Databases from 8 states. Missed opportunity was defined as composite of ICD-9/10 diagnosis/procedure codes that included CNS signs/symptoms, systemic illness, or non-CNS TB diagnosis during a hospital/ED visit 180 days before the index TBM admission. Demographics, comorbidities, admission characteristics, mortality, and admission costs were compared between those with and without a MO, and 90-day in-hospital mortality, using univariate and multivariable analyses. Of 893 patients with TBM, median age at diagnosis was 50 years (interquartile range, 37-64), 61.3% were male, and 35.2% had Medicaid as primary payer. Overall, 407 (45.6%) had a prior hospital or ED visit with an MO code. In-hospital 90-day mortality was not different between those with and without an MO, regardless of the MO coded during an ED visit (13.7% vs 15.2%, P = .73) or a hospitalization (28.2% vs 30.9%, P = .74). Independent risk of 90-day in-hospital mortality was associated with older age, hyponatremia (relative risk [RR], 1.62; 95% confidence interval [CI], 1.1-2.4; P = .01), septicemia (RR, 1.6; 95% CI, 1.03-2.45; P = .03), and mechanical ventilation (RR, 3.4; 95% CI, 2.25-5.3; P < .001) during the index admission. Approximately half the patients coded for TBM had a hospital or ED visit in the previous 6 months meeting the MO definition. We found no association between having an MO for TBM and 90-day in-hospital mortality.

Research progress on specific and non-specific immune effects of BCG and the possibility of BCG protection against COVID-19.

Bacille Calmette-Guérin (BCG) is the only approved vaccine for tuberculosis (TB) prevention worldwide. BCG has an excellent protective effect on miliary tuberculosis and tuberculous meningitis in children or infants. Interestingly, a growing number of studies have shown that BCG vaccination can induce nonspecific and specific immunity to fight against other respiratory disease pathogens, including SARS-CoV-2. The continuous emergence of variants of SARS-CoV-2 makes the protective efficiency of COVID-19-specific vaccines an unprecedented challenge. Therefore, it has been hypothesized that BCG-induced trained immunity might protect against COVID-19 infection. This study comprehensively described BCG-induced nonspecific and specific immunity and the mechanism of trained immunity. In addition, this study also reviewed the research on BCG revaccination to prevent TB, the impact of BCG on other non-tuberculous diseases, and the clinical trials of BCG to prevent COVID-19 infection. These data will provide new evidence to confirm the hypotheses mentioned above.

Isolated 3rd Nerve Palsy Presenting in a Background of Multiple Cerebellar Tuberculoma with Tubercular Meningitis

Isolated 3rd Nerve Palsy Presenting in a Background of Multiple Cerebellar Tuberculoma with Tubercular Meningitis

A study of risk factors for tuberculous meningitis among patients with tuberculosis in China: An analysis of data between 2012 and 2019.

The present study aimed to explore the risk factors for tuberculous meningitis (TBM) among patients with tuberculosis (TB). This retrospective study was conducted on patients with TB who were hospitalized in Beijing Chest Hospital between January 2012 and December 2019. Demographic and clinical data of patients with TB were extracted from electronic medical records using a standardized data collection system. Logistic regression was used to analyze the risk factors associated with TBM. Of the total number of 22,988 cases enrolled, 3.1% were cases of TBM, which included 127 definite and 581 probable TBM, respectively. Multivariate analysis showed that definite TBM was significantly associated with patients aged < 30 years [adjusted odds ratio (aOR) = 3.015, 95% confidence interval (CI): (1.451-6.266)], who were farmers [aOR = 1.490, 95%CI: (1.020-2.177)], with miliary pulmonary TB [aOR = 105.842, 95%CI: (71.704-156.235)], and with malnutrition [aOR = 2.466, 95%CI: (1.110-5.479)]. Additionally, probable TBM was significantly associated with patients aged < 30 years [aOR = 2.174, 95% CI: (1.450-3.261)], aged 30-59 years [aOR = 1.670, 95% CI: (1.222-2.282)], who were farmers [aOR = 1.482, 95%CI: (1.203-1.825)], with miliary pulmonary TB [aOR = 108.696, 95%CI: (87.122-135.613)], and with a digestive system TB [aOR = 2.906, 95%CI: (1.762-4.793)]. An age of < 30 years, being a farmer, and having miliary pulmonary TB were risk factors for TBM among patients with TB. Further screening of patients with TB with aforementioned characteristics could facilitate clinicians to identify patients with TBM at an early stage.

Intracranial giant tuberculoma: A 7-year institutional experience and literature review

BackgroundIntracranial tuberculomas are infrequent with a lower morbidity and mortality compared to tubercular meningitis. Giant intracranial tuberculomas are rarer but important differentials for intracranial space-occupying lesions causing focal neurological deficits depending on anatomical location and size. MethodsHistopathologically confirmed giant intracranial tuberculomas selected based on institutional size criteria (<12 Years-old: ≥25 mm; 12–18 Years-old: ≥35 mm; ≥18 Years-old: ≥40 mm) were retrospectively reviewed and analyzed for clinical features, radiology, surgical management, and outcomes in patients admitted from 2015 to 2022. ResultsTen patients were included (Males:Females = 3:7; Age: 8–68 Years, Average: 30.1 Years). Mean duration of symptoms was 2.84 months. Two patients demonstrated active systemic tuberculosis. Previous tubercular infections included pulmonary involvement in four, meningeal in three, and a cerebellar tuberculoma in one patient. Cerebrospinal fluid analysis in five patients demonstrated no tubercle bacilli. Seven lesions were supratentorial and three infratentorial. Giant tuberculomas demonstrated profound T2 hypointensity, sub-marginal T2 hyperintense crescents, and significant perilesional vasogenic edema. Craniotomy and excision were mainstay except in one case treated only with ventriculoperitoneal shunting. Three additional patients underwent ventriculoperitoneal shunting for hydrocephalus. One patient died from aspiration pneumonia and sepsis following a postoperative seizure. Anti-Tubercular Therapy (ATT) was advised for 18 months. Follow up ranged from 4 to 18 months. One patient was medically managed for ATT-induced hepatitis, hepatic encephalopathy, and coincidental paradoxical reaction. Remainder of patients showed complete resolution of symptomatology and absence of new symptoms till latest follow up. ConclusionClinical course of giant tuberculomas differ from non-giant variants in characteristic radiology, more intensive ATT, and possibility for partial debulking/excision.

Comparison of Protein B Polymerase Chain Reaction (PCR) With IS6110 PCR for Diagnosis of Tuberculous Meningitis Patients.

Purpose Tuberculous meningitis (TBM) is a diagnostic challenge. With the conventional staining and culture techniques being too insensitive and time-consuming, and the commercial detection systems being costly, polymerase chain reaction (PCR) seems lucrative for routine laboratories. The purpose of this study was to evaluate the diagnostic potential of protein b antigen polymerase chain reaction (Pab PCR) for TBM, in comparison to IS6110. Another purpose was to compute a cut-off at which adenosine deaminase (ADA) could diagnose TBM. Material and methods This is a prospective case-control study to measure the diagnostic accuracy of PCR, BACTEC culture, Lowenstein-Jensen (LJ) culture, ADA, and acid-fast bacilli (AFB) smear tests in TBM. CSF from 50 TBM patients (10 confirmed, 40 clinically suspected) and 40 controls was subjected to Pab PCR and IS6110 PCR, and performance was compared against culture and composite reference standards. Results The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of Pab PCR in diagnosing TBM were 82%, 100%, 100%, and 81.63%, respectively, and that of IS6110 PCR were 74%, 100%, 100%, and 75.47%, respectively. Both PCRs outperformed culture (p<0.001). Though performance of both PCRs was comparable (p=0.335) with excellent agreement (k=0.86), Pab PCR detected four additional cases, one culture-positive and three culture-negative clinically suspected. ADA of 6.5 IU/L was able to differentiate between TBM and non-TBM with 86% sensitivity and 63% specificity. Conclusions Molecular tools such as PCR have the potential to increase the clinician's ability to diagnose tuberculous meningitis. Pab PCR is a rapid and reliable method for diagnosing TBM in routine microbiology laboratories.

A rare rapidly progressive presentation of tuberculous meningitis

Tubercular Meningitis (TBM) usually presents as a sub-acute to chronic illness, with duration of symptoms ranging from weeks to months before clinical presentation. The course of disease is divided into 3 clinical stages- the stage of prodrome, phase of neurological symptoms and paretic stage, which usually progresses gradually over a period.Here we report an unusual case of TB meningitis in young female, which progressed rapidly over a period of 7-10 days from symptom onset, without any prodromal features or previous evidence of Koch’s, to reach a non-salvageable stage despite all the available diagnostic and therapeutic modalities.

Factors Associated with Morbidity and Mortality Among Sexually Active Asian Adolescents and Young Adults with Perinatally Acquired HIV.

We assessed morbidity and mortality among Thai and Vietnamese adolescents and young adults with perinatally acquired human immunodeficiency virus (PHIV) compared with matched HIV-negative peers, 12-24 years of age. Data on serious adverse events (SAEs) were prospectively collected between 2013 and 2018 according to U.S. NIH Division of AIDS criteria. Of 288 youth, 142 had PHIV and 146 were HIV negative. At enrollment, the overall median age was 19 (interquartile range [IQR] 17-20) years, 67% were female, and 95% were Thai. Almost all PHIV youth (99%) were receiving antiretroviral therapy; 50% self-reported adherence ≥95%. Median CD4 was 579 (IQR 404-800) cells/mm3, and 24% had HIV-RNA ≥1,000 copies/mL. During follow-up, 31 (22%) PHIV youth and 9 (6%) HIV-negative youth had at least one SAE. The overall crude SAE rate was 4.66 (3.42-6.35) per 100 person-years (PY); 7.22 (5.08-10.26) per 100 PY among youth with PHIV and 2.10 (1.09-4.03) per 100 PY in HIV-negative youth (p < .001). All seven deaths that occurred were among those with PHIV and primarily due to opportunistic infections (e.g., pneumocystis pneumonia, tuberculous meningitis). In multivariate analyses, having PHIV, being <20 years of age, and having anogenital high-risk human papillomavirus (HPV) infection with types 16 and/or 18 increased risk of SAEs. Among PHIV youth, CD4 count <350 cells/mm3, HIV-RNA ≥1,000 copies/mL, advanced WHO stages, and having anogenital HPV 16 and/or 18 infection predicted higher incidence of SAEs; no prior use of alcohol was protective. These data emphasize the need for tailored interventions for adolescents with PHIV to prevent long-term morbidity and mortality.

Successful treatment of tuberculous meningitis in an Indian female under hemodialysis therapy.

Hemodialysis is a well-known risk factor for severe infection by putting patients under an immunocompromised state. Such patients are prone to opportunistic pathogen and present with atypical manifestations during infection. Tuberculous meningitis is a central nervous system infection of Mycobacterium tuberculosis, accounting for the highest mortality of all forms of tuberculosis. In fact, the mortality rate of tuberculous meningitis in hemodialysis patients is extremely poor because early clinical diagnosis is difficult. Here, we report a case of tuberculous meningitis in a 61-year-old Indian hemodialysis patient, who presented with fever of unknown origin and was successfully treated with empiric treatment with standard four-drug regimen against tuberculosis. Comprehensive screening of the origin of fever revealed only the positive results of interferon-gamma release assay, which led us to initiate an empiric therapy for tuberculosis, before making a definitive diagnosis by cerebrospinal fluid nested PCR. Soon after the initiation of the treatment, the fever immediately abated. Although the patient experienced a single episode of paradoxical worsening and severe liver injury, she recovered well without any complications. This report provides a clinical course of the disease in a hemodialysis patient, highlighting the importance of early clinical diagnosis and rapid initiation of empirical tuberculosis treatment.

A Case Report of concurrent SARS-CoV-2 infection and multi-drug-resistant tuberculous meningitis

Abstract Infrequently documented, drug-resistant tuberculous meningitis presents diagnostic and treatment challenges, particularly during SARS-CoV-2 coinfection. Timely identification is crucial to prevent severe complications, yet the optimal treatment course remains uncertain, marked by elevated morbidity and mortality rates. Standard guidelines recommend at least four potent secondline anti-TB drugs. Amid a pandemic, it’s vital not to solely focus on COVID-19 but to explore various aspects. This case outlines a 20-year-old with multi-drug-resistant tuberculous meningitis and SARS-CoV-2, in contact with an MDR pulmonary tuberculosis case. Diagnosis involved molecular and bacteriological cerebrospinal fluid examinations. GeneXpert MTB/RIF revealed rifampicin resistance, and subsequent testing indicated TB resistance to multiple drugs. Tuberculous meningitis, a predominant manifestation, demands careful attention for accurate diagnosis and strategic management. The judicious selection and duration of efficacious drugs are pivotal in treating MDR tuberculous meningitis.

Potential of Neuroinflammation-Modulating Strategies in Tuberculous Meningitis: Targeting Microglia.

Tuberculous meningitis (TBM) is the most severe complication of tuberculosis (TB) and is associated with high rates of disability and mortality. Mycobacterium tuberculosis (M. tb), the infectious agent of TB, disseminates from the respiratory epithelium, breaks through the blood-brain barrier, and establishes a primary infection in the meninges. Microglia are the core of the immune network in the central nervous system (CNS) and interact with glial cells and neurons to fight against harmful pathogens and maintain homeostasis in the brain through pleiotropic functions. However, M. tb directly infects microglia and resides in them as the primary host for bacillus infections. Largely, microglial activation slows disease progression. The non-productive inflammatory response that initiates the secretion of pro-inflammatory cytokines and chemokines may be neurotoxic and aggravate tissue injuries based on damages caused by M. tb. Host-directed therapy (HDT) is an emerging strategy for modulating host immune responses against diverse diseases. Recent studies have shown that HDT can control neuroinflammation in TBM and act as an adjunct therapy to antibiotic treatment. In this review, we discuss the diverse roles of microglia in TBM and potential host-directed TB therapies that target microglia to treat TBM. We also discuss the limitations of applying each HDT and suggest a course of action for the near future.

Non-communicating hydrocephalus a complication of tuberculous meningitis

This paper explores the topic of non-communicating hydrocephalus as a complication of Tuberculous meningitis (TBM). It covers various aspects related to TBM and its associated complications, including clinical presentation, diagnostic procedures, management strategies, and patient care. The importance of early diagnosis, initiation of antituberculous therapy, and surgical interventions such as endoscopic septum pellucidotomy and external ventricular drain placement are discussed in relation to managing hydrocephalus in TBM patients. The significance of close monitoring, supportive care, adherence to medication, and infection control measures is emphasized. Additionally, the paper highlights the need for patient education, family support, and addressing financial concerns in the holistic care of individuals with TBM. Overall, this paper provides valuable insights into the understanding and management of non-communicating hydrocephalus as a complication of Tuberculous meningitis.