Biological Markers for Tuberculosis Meningitis May Help Provide Better Treatment Response

Tuberculosis meningitis is an infection that affects the brain and spinal cord and can lead to disability or even death. Because of the potential devastating effects of the infection, ways to assess the severity of the condition are imperative to determine how best to treat those who are infected. Recently, researchers from the Francis Crick Institute, Imperial College London, and the University of Cape Town have found a biological fingerprint for tuberculosis meningitis in children, that provides clues on “the severity of the condition, help[ing] to decide the best course of treatment, and clues for novel treatments,” according to a recent press release.

Mycobacterium tuberculosis, which normally attacks the lungs, can also infect the brain and spinal cord. Symptoms of infection “include headache, decreased level of consciousness, and neck stiffness,” as a result of swelling and lack of blood flow. A vaccine, bacille Calmette-Guerin (BCG), is available to prevent tuberculosis meningitis in countries with a high prevalence of tuberculosis, but children still become infected. In fact, according to the press release, “several thousand young children die of tuberculosis meningitis every year, and many more are left severely disabled.”

For their research, funded by Wellcome and published in Clinical Infectious Diseases, the scientists compared, “the blood and spinal cord fluid of 44 children with tuberculosis meningitis and 20 patients with other spinal cord disorders.” The median age of the children with tuberculosis meningitis was 3.3 years [0.3—13.1 years] and the ages for the patients with other spinal disorders included 2.8 years [0.8–8 years] for the 11 patients with fatty filum (abnormal filum terminale of the spinal cord), and 3.7 years [1.3-11.8 years] for the 9 pulmonary tuberculosis controls.

Through their comparison “the team identified a set of biological markers elevated in tuberculosis meningitis. The most common markers indicate damage of neurons and neuron-supporting cells, and their presence in the bloodstream and spinal cord can help to determine disease progression.”

Those children who “developed severe disabilities or died from tuberculosis meningitis had the highest levels of these biological markers, and the levels increased over time.” Specifically, the results showed that, “neuromarkers and inflammatory markers were elevated in cerebrospinal fluid on admission and for up to 3 weeks, but not in serum. Initial and highest concentrations in week 1 of S100B and neuron-specific enolase (NSE) were associated with poor outcome, as were highest concentration overall and an increasing profile over time in S100B, NSE and glial fibrillary acidic protein. Combined neuromarker concentrations increased over time in patients who died, whereas inflammatory markers decreased.”

Robert Wilkinson, Group Leader at the Crick and Imperial College London, and Director of the Wellcome Centre for Infectious Diseases Research in Africa at the University of Cape Town is quoted in the press release as stating, “This is the first time that anyone has found a set of biological markers for tuberculosis meningitis.” The researchers posit that studying these biological markers of “ongoing neuronal injury” will provide better indication of disease severity than markers that indicate an immune response.