Advances in the Management of Tuberculosis Meningitis

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About this Research Topic

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Background

Tuberculosis (TB), a bacterial infectious disease, remains the most frequent and important infectious disease, causing significant morbidity and death in humans worldwide. About a fourth of the world's population has been estimated to be infected with Mycobacterium tuberculosis (Mtb), the etiologic agent of TB. The World Health Organization estimates that eight to ten million new cases of TB occur annually worldwide, and the incidence of TB is currently increasing due to the ongoing COVID-19 pandemic. In this context, TB is among the leading causes of death from a single infectious agent, with approximately 1.6 million deaths in 2021.

Although TB primarily affects the pulmonary system, extra-pulmonary TB (EPTB) has become more common among individuals with underlying health conditions, including immunosuppression, such as those with HIV infection or receiving therapy for cancer. Central nervous system TB is a part of EPTB and includes TB meningitis (TBM), intracranial tuberculomas, and spinal tuberculous arachnoiditis.

TBM, the most severe among EPTB, is associated with the highest level of morbidity and mortality among various forms of EPTB. TBM, a medical emergency and common among EPTB, is thought to occur mainly through the hematogenous dissemination of Mtb from the lungs (secondary to pulmonary TB) or other infected organs. Delay in treating TBM results in either death or substantial permanent neurological morbidity. However, due to its broad, non-specific clinical spectrum of symptoms, TBM remains challenging to diagnose and treat. Clinical features of TBM include cerebral infarcts and mass lesions, fever for more than 7 days, headache and neck stiffness. Stroke occurs in 45% of patients with TBM both in the early and later stages, mainly in the basal ganglia region, and predicts poor outcomes at 3 months. Thus, the improved clinical outcome of TBM requires early and accurate diagnosis and an effective treatment strategy. The anti-TB drug regimen used for TBM treatment, which is the same as for the treatment of pulmonary TB (i.e., a combination of Isoniazid [INH], Rifampicin [RIF], Ethambutol [EMB] and Pyrazinamide [PZA]), is ineffective due to variable and incomplete drug penetration across the blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barriers. Adjunctive corticosteroid therapy dampens inflammation and improves overall survival among TBM patients. The combination therapy of standard anti-TB drugs, along with dexamethasone, has been shown to prolong survival and reduce mortality among HIV-negative TBM cases. However, corticosteroid treatment poses risks for immune suppression; no significant difference was noted in the severity of vasculitis among TBM cases treated with adjunctive corticosteroids combined with standard antibiotic therapy compared to the antibiotics alone-treated patients. Moreover, an adjunctive corticosteroid with antibiotic treatment did not affect the elevated levels of inflammatory cytokines, such as TNF-a, in the CSF of the TBM cases. Furthermore, despite the successful completion of antibiotic treatment, patients with TBM suffer from permanent neurologic damage. Together, these scientific observations highlight the urgent need for additional research to understand the pathophysiology of TBM and to develop better diagnostic tools and treatment modalities.

This comprehensive Research Topic invites cutting-edge research findings and reviews on:

• The recent advances in the understanding of the host immune responses against TBM.
• Pathogenesis in TBM.
• Novel therapies for TBM.
• Prevention of TBM.
• Novel diagnosis for TBM.
• COVID-related disruptions in managing TBM.

This subject area includes clinical studies as well as in vitro and in vivo models of TBM that explore host-Mtb interactions and evaluation of novel diagnostic, therapeutic and vaccine approaches. Studies investigating the molecular, cellular, immunological and metabolic aspects of TBM with or without co-morbid conditions such as diabetes, HIV infection and cancer will also be considered suitable for this Research Topic.

Keywords: Tuberculosis, Mycobacterium Tuberculosis, EPTB, TB, TBM, Meningitis

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