Standardized approaches for clinical sampling and endpoint ascertainment in tuberculous meningitis studies

Arjan van Laarhoven, Ursula K. Rohlwink, Felicia C. Chow, Sean Wasserman, Sofiati Dian, Rachel P.J. Lai, Lidya Chaidir, Raph L. Hamers, Robert J. Wilkinson, David R. Boulware, Fiona V. Cresswell

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, has poorly understood immunopathology and high mortality and morbidity despite antituberculous therapy. This calls for accelerated clinical and basic science research in this field. As TBM disproportionally affects poorer communities, studies are often performed in resource-limited environments, creating challenges for data collection and harmonisation. Comparison of TBM studies has been hampered by variation in sampling strategies, study design and choice of study endpoints. Based on literature review and expert consensus, this paper provides firstly, practical recommendations to enable thorough diagnostic, pathophysiological and pharmacokinetic studies using clinical samples, and facilitates better data aggregation and comparisons across populations and settings. Secondly, we discuss clinically relevant study endpoints, including neuroimaging, functional outcome, and cause of death, with suggestions of how these could be applied in different designs for future TBM studies.

Original languageEnglish (US)
Article number204
JournalWellcome Open Research
StatePublished - 2019

Bibliographical note

Funding Information:
Grant information: This work was supported by the Wellcome Trust through grants to RJW [104803, 203135], a Wellcome Clinical PhD Fellowship to FVC [210772], support to the Francis Crick Institute [FC00110218] and funding for RLH. FCC is also supported by Fogarty International Center of the National Institutes of Health [R21TW011035]. RJW is also funded by Meningitis Now and the Francis Crick Institute, which receives funding from Cancer Research UK [FC00110218], the UK Medical Research Council [FC00110218], and the Wellcome Trust [FC00110218]. RPJL is funded by UK Medical Research Council [MR/R008922/1]. SW is supported by the European & Developing Countries Clinical Trials Partnership [CDF1018], Wellcome Trust [203135/Z/16/Z], and National Institutes of Health [K43TW011421] (PI, Wasserman).

Publisher Copyright:
© 2019 Rohlwink UK et al.


  • Endpoints
  • Imaging
  • Immunology
  • Metabolomics
  • Microbiology
  • Outcome
  • Proteomics
  • Sampling
  • Tuberculous meningitis


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