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Tuberculous meningitis: a uniform case definition for use in

Tuberculous meningitis causes substantial mortality and morbidity in children and adults. More research is urgently Lancet Infect Dis 2010;
needed to better understand the pathogenesis of disease and to improve its clinical management and outcome. A 10: 803–12
major stumbling block is the absence of standardised diagnostic criteria. The different case definitions used in various Published Online
September 6, 2010
studies makes comparison of research findings difficult, prevents the best use of existing data, and limits the
DOI:10.1016/S1473-
management of disease. To address this problem, a 3-day tuberculous meningitis workshop took place in Cape Town, 3099(10)70138-9
South Africa, and was attended by 41 international participants experienced in the research or management of Department of Medicine,
tuberculous meningitis. During the meeting, diagnostic criteria were assessed and discussed, after which a writing GF Jooste Hospital, Manenberg,
committee was appointed to finalise a consensus case definition for tuberculous meningitis for use in future clinical South Africa (S Marais MBChB,
research. We present the consensus case definition together with the rationale behind the recommendations. This Prof R J Wilkinson FRCP); Clinical
Infectious Diseases Research
case definition is applicable irrespective of the patient’s age, HIV infection status, or the resources available in the Initiative, Institute of
research setting. Consistent use of the proposed case definition will aid comparison of studies, improve scientific Infectious Diseases and
communication, and ultimately improve care. Molecular Medicine, and
Department of Medicine,
University of Cape Town, South
Introduction Indonesia) attended the meeting. Participants included Africa (S Marais, R J Wilkinson);
Tuberculous meningitis is the most severe form of paediatric and adult neurologists, neurosurgeons, Imperial College, London, UK
tuberculosis and causes substantial morbidity and infectious diseases specialists, microbiologists, (G Thwaites PhD, R J Wilkinson);
Department of Paediatrics and
mortality in adults and children.1–10 The outcome of this immunologists, pharmacologists, and clinical trialists.
Child Health, Faculty of Health
disease is especially grave in patients with HIV.11–14 13 international tuberculous meningitis experts, all of Sciences, Stellenbosch
Clinicians face substantial challenges in the diagnosis and whom have published on the disease in international University, South Africa
management of tuberculous meningitis:15 disease peer-reviewed journals during the past 5 years, presented (J F Schoeman MD,
Prof P R Donald FRCP,
pathogenesis is poorly understood; rapid, sensitive, and their research findings. On the final day of the meeting,
Prof B J Marais PhD);
affordable diagnostic tests are not available; and the best the existing diagnostic criteria were assessed and a Department of Infectious
management has not been established by randomised consensus case definition for tuberculous meningitis Diseases, Cambridge University
controlled trials. Further research is urgently needed, but was developed. A writing committee of nine members Hospitals NHS Foundation
Trust, Cambridge, UK
the low frequency with which a definitive diagnosis is was appointed to review the existing data and develop the
(M E Török PhD); Department of
established and the absence of a uniform clinical case final consensus statement. Neurology, Sanjay Gandhi Post
definition are major obstacles. Detection of acid-fast bacilli Graduate Institute of Medical
(AFB) and culture isolation of Mycobacterium tuberculosis Standardised clinical case definition Sciences, Lucknow, India
(Prof U K Misra MD);
from cerebrospinal fluid (CSF) have been reported with In the past 5 years, studies have used various case definitions Department of Neurology, All
high frequency in some studies16,17 but are the exception in for tuberculous meningitis (panel 1).1,3,4,8,10,11,17,18,20–24 In most India Institute of Medical
most.1,7,18,19 Diagnosis usually relies on clinical evidence, definitions, patients are given a definite, probable, or Sciences, New Delhi, India
which combines supportive clinical, laboratory, and possible tuberculous meningitis status depending on (Prof K Prasad FRCP); and
National Institute for Medical
radiological findings. Standardised diagnostic criteria for clinical, laboratory, and radiological findings. Definite Research, Mill Hill, London, UK
tuberculous meningitis have not been established, and tuberculous meningitis cases usually include patients with (R J Wilkinson)
most reports have used different case definitions. This AFB on CSF microscopy or M tuberculosis cultured from Correspondence to:
absence of standardisation makes comparison of research CSF or another CNS source. However, some studies also Dr Suzaan Marais, Department of
findings difficult, prevents the best use of the existing included patients with M tuberculosis identified from Medicine, GF Jooste Hospital,
Manenberg, 7764, South Africa
data, and limits progress in management. To address specimens such as gastric aspirates, urine, or sputum,11,24 suzaanmarais@[Link]
these issues, an international tuberculous meningitis or with M tuberculosis identified by PCR8,25–27 or IgM ELISA.8
workshop took place in Cape Town, South Africa, in May, Criteria for probable or possible tuberculous meningitis
2009, to establish a consensus case definition for cases differ greatly between studies, especially between
tuberculous meningitis for use in future clinical research. studies done in children and adults. Some studies do not
We present the consensus case definition, which should distinguish between patients with confirmed and suspected
be uniformly applicable, irrespective of the patient’s age or tuberculous meningitis.4,7
HIV infection status or the resources available in the We propose that patients with suspected tuberculous
research setting. meningitis should be allocated to one of four diagnostic
The organisers of the meeting invited leading categories depending on the strength of clinical,
tuberculous meningitis researchers and clinicians with laboratory, or radiological findings. The proposed
experience managing patients with tuberculous categories are definite, probable, possible, and not
meningitis. 41 participants from seven countries (South tuberculous meningitis (figure 1). A patient suspected to
Africa, the UK, Vietnam, India, the USA, Malawi, and have tuberculous meningitis should be regarded as

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