Six months therapy for tuberculous meningitis

Sophie Jullien1, Hannah Ryan1, Manish Modi2, Rohit Bhatia3

1. Liverpool School of Tropical Medicine, Department of Clinical Sciences, Liverpool, UK
2. Postgraduate Institute of Medical Education and Research, Department of Neurology, Chandigarh 160 012, India
3. All India Institute of Medical Sciences, Department of Neurology, New Delhi, India

Jullien S, Ryan H, Modi M, Bhatia R. Six months therapy for tuberculous meningitis. Cochrane Database of Systematic Reviews 2016, Issue 9. Art. No.: CD012091. DOI: 10.1002/14651858.CD012091.pub2.

To access the full-text article, please click here: DOI: 10.1002/14651858.CD012091.pub2

What is tuberculous meningitis and why is the duration of treatment important?

Tuberculous meningitis (TBM) is a severe form of tuberculosis, which affects the membranes that cover the brain and spine. It is associated with high rates of death and disability. While there are standardized international recommendations for treating people with pulmonary tuberculosis (tuberculosis of the lungs) for six months with antituberculous therapy, there is a wide range of differing recommendations and practices for treating people with TBM worldwide. Some specialists recommend nine months, 12 months, or even longer treatment for TBM in order to prevent relapse of the disease. Longer regimens have potential disadvantages: they are associated with poor adherence to treatment, which could contribute to increased relapse and development of drug resistance; and increased costs to patients and healthcare systems.

What the evidence shows

This Cochrane review assessed the effects of six months regimens for treating people with TBM, compared with longer regimens. Cochrane researchers examined the available evidence up to 31 March 2016. They did not find any trial that directly compared people with TBM treated for six months with people with TBM treated for longer. They included seven studies with 458 participants that evaluated six months of treatment, and 12 studies with 1423 participants that evaluated longer treatment. Although the treatment regimens in the included studies varied, most participants received standard first-line antituberculous drugs, and were followed up for more than a year after the end of treatment. The studies included adults and children with TBM, but few participants were HIV-positive.

Relapse was an uncommon event across both groups of studies, with only one death attributed to relapse in each group. Most deaths occurred during the first six months of treatment in both groups of studies, which showed that treatment duration did not have a direct impact on the risk of death in these studies. There was a higher death rate in participants treated for longer than six months, and this probably reflects the differences between the participants in the two groups of studies. Few participants defaulted from treatment, and adherence was not clearly documented.

They found no evidence of high relapse rates in people treated for six months, and relapse was uncommon in all patients irrespective of regimen. There may be differences between the participants treated for six months and longer than six months that could have led to bias (confounding factors), so further research would help determine if shorter regimens are safe. Most of the data were in patients without HIV, and so these inferences do not apply to patients who are HIV-positive.