Tuberculous meningitis (TBM) causes a high burden of morbidity and mortality, disproportionately affecting developing countries. HIV-associated TB immune reconstitution inflammatory syndrome (TB-IRIS) affecting the central nervous system (CNS) is associated with particularly high mortality. The challenge of treating TBM lies not only in targeting the mycobacterium but also managing the ensuing inflammation. An optimal treatment strategy would effectively eradicate the pathogen and moderate the inflammatory response.

There are no specific diagnostic tests for CNS TB paradoxical reaction (CNS TB-PR) or CNS TB-IRIS and distinguishing clinical deterioration due to paradoxical reactions from therapeutic failure may be difficult. Evidence to inform treatment recommendations for CNS TB-PR is lacking and there are no consensus guidelines. Corticosteroids are the most widely used. Other host-directed strategies have been proposed, such as TNF inhibition. An improved understanding of the pathophysiology of CNS TB-PR is important for early diagnosis and treatment to improve outcomes.

The goal of this research topic is to promote research that improves understanding of the clinical presentation, risk factors, diagnosis, and treatment of CNS TB-PR and to elucidate mechanisms of immunopathology to identify potential treatment targets and preventative strategies. More specifically:

• To better understand the clinical features of paradoxical reaction, and how to differentiate it from deterioration due to mycobacterial treatment failure.
• To determine the pathophysiology and pathology of paradoxical reaction
• To inform management of paradoxical reactions

We aim to collect original research studies, reviews, and mini-reviews with immunological profiling, genetics, and omics data, covering:

• Clinical studies associated with immunological profiling, genetics, and omics data.
• Studies of pathology and central nervous system imaging
• Case reports of rare presentations of CNS TB and CNS TB-PR
• Studies of CNS TB-IRIS

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Frontiers in Immunology

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