Improving host-directed therapy for tuberculous meningitis by linking clinical and multi-omics data

Crevel, Reinout van; Ávila-Pacheco, Julián; Thuong, Nguyen T T; Ganiem, Ahmad Rizal; Imran, Darma; Hamers, Raph L; Alisjahbana, Bachti; Dian, Sofiati; Estiasari, Riwanti; Tram, Trinh Thi Bich; Vinh, Dao Nguyen; Hoang, Hai; Donovan, Joseph; Ardiansyah, Edwin; Koeken, Valerie A C M; Kumar, Vinod; Netea, Mihai G.; Laarhoven, Arjan van; Clish, Clary B.; Thwaites, Guy

doi:10.1016/j.tube.2021.102085

Cited by 7 publications

(4 citation statements)

References 18 publications

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“…As part of the ULTIMATE project 21 , we sequenced DNA from 239 tuberculous meningitis patients. The genomic DNA sample was fragmented randomly by Covaris technology, resulting in fragments of 350bp after selecting the appropriate size range.…”

Section: Star Methodsmentioning

confidence: 99%

Sequencing whole genomes of the West Javanese population in Indonesia reveals novel variants and improves imputation accuracy

Ardiansyah,

Riza,

Dian

et al. 2024

Preprint

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SummaryExisting genotype imputation reference panels are mainly derived from European populations, limiting their accuracy in non-European populations. To improve imputation accuracy for Indonesians, the world’s fourth most populous country, we combined Whole Genome Sequencing (WGS) data from 227 West Javanese individuals with East Asian data from the 1000 Genomes Project. This created three reference panels: EAS 1KGP3 (EASp), Indonesian (INDp), and a combined panel (EASp+INDp). We also used ten West-Javanese samples with WGS and SNP-typing data for benchmarking. We identified 1.8 million novel single nucleotide variants (SNVs) in the West Javanese population, which, while similar to the East Asians, are distinct from the Central Indonesian Flores population. Adding INDp to the EASp reference panel improved imputation accuracy (R2) from 0.85 to 0.90, and concordance from 87.88% to 91.13%. These findings underscore the importance of including Indonesian genetic data in reference panels, advocating for broader WGS of diverse Indonesian populations to enhance genomic studies.

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Section: Star Methodsmentioning

confidence: 99%

Sequencing whole genomes of the West Javanese population in Indonesia reveals novel variants and improves imputation accuracy

Ardiansyah,

Riza,

Dian

et al. 2024

Preprint

Self Cite

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“…Whether tryptophan metabolism plays such a critical role in SCTB is undetermined. [ 93 , 94 ] Finally, whether adjunctive agents such as tumor necrosis factor alpha-blockers such as infliximab and thalidomide and other immunomodulatory strategies can further improve outcomes of patients who worsen despite antimycobacterial therapy and steroids needs to be studied. The role of aspirin and antifibrinolytics in the management of TBRM also should be studied in randomized trials.…”

Section: T Reatment Of S Pinal ...mentioning

confidence: 99%

Tuberculosis of the spinal cord

Manesh

Garg

Radhakrishnan

et al. 2023

Ann Indian Acad Neurol

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Tuberculosis involving the spinal cord is associated with high mortality and disabling long-term sequelae. Although tuberculous radiculomyelitis is the most frequent complication, pleomorphic clinical manifestations exist. Diagnosis can be challenging among patients with isolated spinal cord tuberculosis due to diverse clinical and radiological presentations. The principles of management of tuberculosis of the spinal cord are primarily derived from, and dependent upon, trials on tuberculous meningitis (TBM). Although facilitating mycobacterial killing and controlling host inflammatory response within the nervous system remain the primary objectives, several unique features require attention. The paradoxical worsening is more frequent, often with devastating outcomes. The role of anti-inflammatory agents such as steroids in adhesive tuberculous radiculomyelitis remains unclear. Surgical interventions may benefit a small proportion of patients with spinal cord tuberculosis. Currently, the evidence base in the management of spinal cord tuberculosis is limited to uncontrolled small-scale data. Despite the gargantuan burden of tuberculosis, particularly in lower and middle-income countries, large-scale cohesive data are surprisingly sparse. In this review, we highlight the varied clinical and radiological presentations, performance of various diagnostic modalities, summarize data on the efficacy of treatment options, and propose a way forward to improve outcomes in these patients.

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“…Host-directed therapies may act as adjunct treatment options for bacterial, viral, and parasitic infectious diseases. It includes commonly used drugs for communicable diseases with good safety profiles, immunomodulatory agents, biologics (e.g., monoclonal antibodies), nutritional products, and cellular therapy using the patient's own immune or bone marrow mesenchymal stromal cells [55] .…”

Section: Strategies To Deal With Challengementioning

confidence: 99%