British Infection Society GuidelinesBritish Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children
Introduction
Central nervous system (CNS) tuberculosis occurs in approximately 1% of all patients with active tuberculosis. It results from the haematogenous dissemination of Mycobacterium tuberculosis from primary pulmonary infection and the formation of small subpial and subependymal foci (Rich foci) in the brain and spinal cord.1 In some individuals foci rupture and release bacteria into the subarachnoid space causing meningitis. In others, foci enlarge to form tuberculomas without meningitis.
The timing and frequency of these events in relation to primary pulmonary infection is dependent upon age and immune status. In children, dissemination usually occurs early and the risk of CNS tuberculosis is highest in the first year following infection1; in high tuberculosis prevalence countries CNS tuberculosis predominantly effects very young children (<3years). In low tuberculosis prevalence countries such as the UK, most cases are in adults, often immigrants from areas of high tuberculosis prevalence.2 Immune-suppressed adults, especially those with HIV infection, are more likely to suffer disseminated disease with CNS involvement.3 Other risk factors include alcoholism, diabetes mellitus, malignancy, corticosteroid treatment, and agents that block the action of tumour necrosis factor.4
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Methods and evidence-based rating system
The methods used to formulate these guidelines are based on those recommended by the grades of recommendation, assessment, development, and evaluation (GRADE) working group.5 The writing committee was selected to represent the range of specialists involved with the management of CNS tuberculosis: respiratory physicians, infectious disease physicians, neurologists, clinical microbiologists, HIV physicians, and paediatricians. The committee formulated the guidelines around a series of important
Tuberculous meningitis
The diagnosis of TBM in older children and adults is frequently obscured by days to weeks of non-specific symptoms (Table 2),6, 7, 8, 9, 10, 11, 12 such as headache, fever, vomiting, and anorexia. Failure to thrive, loss of weight, irritability, poor appetite, sleep disturbance, vomiting and abdominal pain are often seen in young children.13 A history of recent tuberculosis contact is common in children (50–90%) as are atypical neurological presentations. Seizures, both febrile and non-febrile,
What is the best anti-tuberculosis drug regimen?
Chemotherapy for CNS tuberculosis follows the model of short course chemotherapy for pulmonary tuberculosis – an intensive phase of treatment, followed by a continuation phase. But unlike pulmonary tuberculosis, the optimal drug regimen and duration of each phase are not clearly established. Isoniazid and rifampicin are the key components of the regimen. Isoniazid penetrates the CSF freely104, 105 and has potent early bactericidal activity.106 Rifampicin penetrates the CSF less well (maximum
Empirical treatment: when to start, when to stop?
Many patients with CNS tuberculosis require empirical therapy; inevitably, some will receive unnecessary treatment. A recent study, performed in Ecuador, reported that a substantial decrease in the threshold to treat TBM produced only a modest increase in the numbers treated.150 However, the relationship between treatment threshold and the numbers treated is unlikely to be the same in the UK.
There are no published studies that help determine when empirical therapy should be stopped.
Conflict of interest
None
Acknowledgments
We are indebted to the many individuals who provided critical review of these guidelines. In particular, we would like to thank the British Thoracic Society, the British HIV Association, the Association of British neurologists, the British Paediatric and Immunity Group and the members of the British Infection Society for their comments and suggestions. We thank Dr Kumar Das for neuroradiological advice.
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Cited by (0)
- h
Tel.: +44 20 7594 3094. Organisations represented: none.
- i
Organisations represented: British HIV Association (BHIVA).
- j
Tel.: +44 20 74059200. Organisations represented: none.
- k
Organisations represented: none.
- l
Tel.: +44 0151 706 4703. Organisations represented: Association of British Neurologists.
- m
Tel.: +44 121 434 2357.Organisations represented: British Infection Society and British Thoracic Society.