Funder
NIAID/National Institutes of Health (US)
Principal Investigators
Dr Darma Imran (IBIS)
Professor Reinout van Crevel (ULTIMATE)
Dr Riwanti Estiasari (ULTIMATE)
Associate Professor Raph Hamers (IBIS and ULTIMATE)
Duration
December 2018 (IBIS)/April 2019 (ULTIMATE) – March 2023
Status
Patient recruitment in IBIS is currently ongoing. Laboratory analysis in ULTIMATE is currently ongoing. Results are expected in 2023 and 2024.
Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis with an estimated global burden of more than 100,000 cases per year. HIV is the most important risk factor for developing and dying from TBM, with mortality approaching 50%.
Intracerebral inflammation has long been recognized as an important determinant of TBM outcome, and anti-inflammatory treatment with adjunctive corticosteroids are usually given with anti-tuberculosis drugs, although clinical trials have only proven their survival benefit in HIV-negative patients, with no apparent reduction in long-term neurological disability and uncertain effect in HIV-infected patients.
Furthermore, adjunctive corticosteroids seem beneficial in some patients, but ineffective or even harmful in others, maybe as a result of the highly variable inflammation and immunopathology in TBM. Therefore, there is a clear need to optimize host-directed therapy in TBM. However, its development is hampered by lack of knowledge concerning the biological pathways involved in the host immune responses and the immunopathology, and uncertainty as to how corticosteroids reduce TBM mortality.
The IBIS study is an observational cohort study in adults with suspected CNS infection (meningitis, encephalitis, brain abscess, myelitis) to define clinical presentation, etiology, management and outcome of patients with central nervous system infections in Indonesia. IBIS serves as a platform for clinical trials and a specimen repository for future studies.
IBIS is the utilized as part of the NIH-funded ULTIMATE (Using tryptophan metabolism and response to corticosteroids to define new targets for TB meningitis) project, which uses state-of-the-art omics technology and computational biology in the USA and the Netherlands to address key knowledge gaps in TBM pathogenesis, ULTIMATE’s primary objective is to identify metabolic or other biomarkers predicting the effect of corticosteroids on TBM outcome and prioritize causal pathways for new host-directed therapies.
