Taking a new look at tuberculous meningitis

Using Bayesian statistics to reanalyse clinical data highlights a link between survival and the genetic makeup of tuberculous meningitis patients.
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Brain from a fatal case of tuberculous meningitis. The protective layers (or leptomeninges) which wrap the brainstem and cerebellum (bottom third) are markedly thickened by a fluid build-up linked to the inflammatory process. Image credit: Adapted from Yale Rosen (CC BY-SA 2.0)

Tuberculous meningitis is a serious infection of the lining of the brain, which affects over 100,000 people a year. Without treatment, it is always fatal: even with proper antibiotics, about a quarter of patients do not survive and many will have permanent brain damage. Overactive inflammation is thought to contribute to this process. Corticosteroid drugs, which dampen the inflammatory process, are therefore often used during treatment. However, they merely reduce mortality by 30%, suggesting that only some people benefit from them.

Two recent studies have linked the genetic makeup of individuals who have tuberculous meningitis to how they respond to corticosteroids. There were, in particular, differences in the LTA4H gene that codes for an inflammation-causing protein. According to these results, only individuals carrying high-inflammation versions of the LTA4H gene would benefit from the treatment. Yet a third study did not find any effect of the genetic background of patients.

All three papers used frequentist statistics to draw their conclusions, only examining the percentage of people who survived in each group. Yet, this type of analysis can miss important details. It also does not work well when the number of patients is small, or when the effectiveness of a drug varies during the course of an illness.

Another method, called Bayesian statistics, can perform better under these limitations. In particular, it takes into account the probability of an event based on prior knowledge – for instance, that the risk of dying varies smoothly with time.

Here, Whitworth et al. used Bayesian statistics to reanalyse the data from these studies, demonstrating that death rates were correlated with the type of LTA4H gene carried by patients. In particular, corticosteroid treatment worked best for people with the high inflammation versions of the gene. However, regardless of genetic background, corticosteroids were not effective if patients were extremely sick before being treated.

The work by Whitworth et al. demonstrates the importance of using Bayesian statistics to examine the effectiveness of medical treatments. It could help to design better protocols for tuberculous meningitis treatment, tailored to the genetic makeup of patients.