A clinical practice guideline for tuberculous meningitis

Joseph Donovan¹, Fiona V Cresswell², Elizabeth W Tucker³, Angharad G Davis⁴, Ursula K Rohlwink⁵, Julie Huynh⁶, Regan Solomons⁷, James A Seddon⁸, Nathan C Bahr⁹, Arjan van Laarhoven¹⁰, Suzanne T Anderson¹¹, Sanjay K Jain¹², Felicia C Chow¹³, Sophie Pattison¹⁴, James E Scriven¹⁵, Gabriela Singh⁵, Rob E Aarnoutse¹⁶, Jan-Willem C Alffenaar¹⁷, Sofiati Dian¹⁸, Abi Manesh¹⁹, Robin Basu Roy²⁰, Varinder Singh²¹, Ronald van Toorn⁷, Caryn M Upton²², Reinout van Crevel²³, Kelly E Dooley²⁴, Diana Gibb¹¹, David Meya²⁵, Robert J Wilkinson²⁶, Ewelina Rogozińska²⁷, Usha K Misra²⁸, Anthony Figaji⁵, Guy E Thwaites⁶

Affiliations

¹ Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: jdonovan@oucru.org.
² Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; Global Health and Infection, Brighton and Sussex Medical School, Brighton, UK; Medical Research Council Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Nakiwogo Road, Entebbe, Uganda.
³ Department of Anesthesiology and Critical Care Medicine, Division of Pediatric Anesthesiology and Critical Care Medicine, John Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, John Hopkins University School of Medicine, Baltimore, MD, USA; Center for Infection and Inflammation Imaging Research, John Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ The Francis Crick Institute, London, UK; Wellcome Discovery Research Platforms in Infection, Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa; Queen Mary and Barts Tuberculosis Centre, Queen Mary University London, London, UK.
⁵ Division of Neurosurgery, Department of Surgery, Neuroscience Institute, University of Cape Town, Observatory, South Africa.
⁶ Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK.
⁷ Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁸ Desmond Tutu TB Centre, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Department of Infectious Diseases, Imperial College London, London, UK.
⁹ Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
¹⁰ Department of Internal Medicine, Radboudumc, Nijmegen, Netherlands.
¹¹ MRC Clinical Trials Unit, University College London, London, UK.
¹² Center for Tuberculosis Research, John Hopkins University School of Medicine, Baltimore, MD, USA; Center for Infection and Inflammation Imaging Research, John Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, John Hopkins University School of Medicine, Baltimore, MD, USA.
¹³ Department of Neurology and Department of Infectious Diseases, University of California, San Francisco, CA, USA.
¹⁴ UCL Library Services, Library, Culture, Collections and Open Science (LCCOS), University College London, London, UK.
¹⁵ Department of Microbes, Infection & Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK.
¹⁶ Department of Pharmacy, Radboudumc, Nijmegen, Netherlands.
¹⁷ Institute for Infectious Diseases and Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Westmead Hospital, Department of Pharmacy, Westmead, NSW, Australia.
¹⁸ Department of Neurology and Research Center for Care and Control of Infectious Disease, Faculty of Medicine, Universitas Padjadjaran and Hasan Sadikin Hospital, Bandung, Indonesia.
¹⁹ Department of Infectious Diseases, Christian Medical College, Vellore, India.
²⁰ Queen Mary and Barts Tuberculosis Centre, Queen Mary University London, London, UK.
²¹ National Center for Excellence in Pediatric Tuberculosis, Department of Pediatrics, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, Bangla Sahib Marg, New Delhi, India.
²² TASK Clinical Research Centre, Cape Town, South Africa.
²³ Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK; Department of Internal Medicine, Radboudumc, Nijmegen, Netherlands.
²⁴ Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
²⁵ Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
²⁶ The Francis Crick Institute, London, UK; Wellcome Discovery Research Platforms in Infection, Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa; Department of Infectious Diseases, Imperial College London, London, UK.
²⁷ Meta-Analysis Group, University College London, London, UK.
²⁸ TS Misra Medical College, Apollo Medics Super Specialty Hospital and Vivekanand Polyclinic and Institute of Medical Sciences, Lucknow, India.

PMID: 40840485
PMCID: PMC12419961 (available on 2026-02-18)
DOI: 10.1016/S1473-3099(25)00364-0

Review

A clinical practice guideline for tuberculous meningitis

Joseph Donovan et al. Lancet Infect Dis. 2025.

. 2025 Aug 18:S1473-3099(25)00364-0.

doi: 10.1016/S1473-3099(25)00364-0. Online ahead of print.

Authors

Affiliations

¹ Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: jdonovan@oucru.org.
² Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; Global Health and Infection, Brighton and Sussex Medical School, Brighton, UK; Medical Research Council Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Nakiwogo Road, Entebbe, Uganda.
³ Department of Anesthesiology and Critical Care Medicine, Division of Pediatric Anesthesiology and Critical Care Medicine, John Hopkins University School of Medicine, Baltimore, MD, USA; Center for Tuberculosis Research, John Hopkins University School of Medicine, Baltimore, MD, USA; Center for Infection and Inflammation Imaging Research, John Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ The Francis Crick Institute, London, UK; Wellcome Discovery Research Platforms in Infection, Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa; Queen Mary and Barts Tuberculosis Centre, Queen Mary University London, London, UK.
⁵ Division of Neurosurgery, Department of Surgery, Neuroscience Institute, University of Cape Town, Observatory, South Africa.
⁶ Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK.
⁷ Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁸ Desmond Tutu TB Centre, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; Department of Infectious Diseases, Imperial College London, London, UK.
⁹ Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
¹⁰ Department of Internal Medicine, Radboudumc, Nijmegen, Netherlands.
¹¹ MRC Clinical Trials Unit, University College London, London, UK.
¹² Center for Tuberculosis Research, John Hopkins University School of Medicine, Baltimore, MD, USA; Center for Infection and Inflammation Imaging Research, John Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, John Hopkins University School of Medicine, Baltimore, MD, USA.
¹³ Department of Neurology and Department of Infectious Diseases, University of California, San Francisco, CA, USA.
¹⁴ UCL Library Services, Library, Culture, Collections and Open Science (LCCOS), University College London, London, UK.
¹⁵ Department of Microbes, Infection & Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham, Birmingham, UK.
¹⁶ Department of Pharmacy, Radboudumc, Nijmegen, Netherlands.
¹⁷ Institute for Infectious Diseases and Sydney Pharmacy School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Westmead Hospital, Department of Pharmacy, Westmead, NSW, Australia.
¹⁸ Department of Neurology and Research Center for Care and Control of Infectious Disease, Faculty of Medicine, Universitas Padjadjaran and Hasan Sadikin Hospital, Bandung, Indonesia.
¹⁹ Department of Infectious Diseases, Christian Medical College, Vellore, India.
²⁰ Queen Mary and Barts Tuberculosis Centre, Queen Mary University London, London, UK.
²¹ National Center for Excellence in Pediatric Tuberculosis, Department of Pediatrics, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, Bangla Sahib Marg, New Delhi, India.
²² TASK Clinical Research Centre, Cape Town, South Africa.
²³ Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, Oxford University, Oxford, UK; Department of Internal Medicine, Radboudumc, Nijmegen, Netherlands.
²⁴ Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
²⁵ Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
²⁶ The Francis Crick Institute, London, UK; Wellcome Discovery Research Platforms in Infection, Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa; Department of Infectious Diseases, Imperial College London, London, UK.
²⁷ Meta-Analysis Group, University College London, London, UK.
²⁸ TS Misra Medical College, Apollo Medics Super Specialty Hospital and Vivekanand Polyclinic and Institute of Medical Sciences, Lucknow, India.

PMID: 40840485
PMCID: PMC12419961 (available on 2026-02-18)
DOI: 10.1016/S1473-3099(25)00364-0

Abstract

Tuberculous meningitis is the most severe form of tuberculosis, causing death or disability in around half of those affected. There are no up-to-date international guidelines defining its optimal management. Therefore, the Tuberculous Meningitis International Research Consortium conducted a systematic review of available evidence to address key management questions and to develop practice guidance. The consortium includes representatives from India, Indonesia, South Africa, Uganda, Viet Nam, Australia, the Netherlands, the UK, and the USA. Questions were developed using the Population, Intervention, Comparator, Outcome (PICO) format for tuberculous meningitis diagnosis, anti-tuberculosis chemotherapy, adjunctive anti-inflammatory therapy, and neurocritical and neurosurgical care. A Grading of Recommendations, Assessment, Development and Evaluations approach was used to assess the certainty (or quality) of evidence and establish the direction and strength of recommendations for each PICO-based question. We provide evidence-based recommendations for the optimal treatment and diagnosis of tuberculous meningitis, alongside expert opinion. We expose substantial knowledge and evidence gaps, thereby highlighting current research priorities.

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Conflict of interest statement

Declaration of interests AGD was supported by a Wellcome clinical PhD fellowship (award number 175479) and a Crick clinical postdoctoral fellowship (via Meningitis Now) for the duration of this project. The funders had no influence on the content of the work. AF received grants from a Wellcome Trust Discovery Grant and South African NRF SARChI Chair Neurosciences, unrelated to this publication, and is the President-elect for the International Society for Pediatric Neurosurgery and is the President of the Society of Neurosurgeons of South Africa. AvL received funding from the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (R01AI145781 and R01AI165721). DM received funding from the UK Medical Research Council and US NIH. FCC received funding from the NIH (R21TW011035, T32NS131126, and R01NS126086) and received medicolegal consulting fees. FVC declares institutional grants from Wellcome and Janssen and Viiv; is on the data and safety monitoring board for the SaDAPT and DOLPHIN3 (NCT03249181) trials; and has a trial steering committee membership for the ILANA (NCT05294159) study. JES received an NIH R21 grant (1R21NS134516-01) for investigating cerebrovascular flow in tuberculous meningitis. NCB received funding from the NIH (NINDS K23 NS110470 and NIAID R01 AI170158). RBR declares funding from the National Institute for Health and Care Research (NIHR; academic clinical lectureship CL-2018-20-001), and is a named inventor for Prostanoid receptor modulators to treat non-tuberculous mycobacterial infections (WO2024/069179A1). RJW received institutional grants from Wellcome, Cancer Research UK, Medical Research Council, NIH, and NIHR; and support for attending meetings or travel from Wellcome (refunded to institution) and the Gates Foundation (refund of personal costs). RvC is on the data and safety monitoring board for two randomised controlled trials on tuberculous meningitis (no payments received). SKJ received an institutional grant from the US NIH. The other authors declare no competing interests.

References

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A clinical practice guideline for tuberculous meningitis

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A clinical practice guideline for tuberculous meningitis

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Conflict of interest statement

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