How typhoid fever triggers severe neurological symptoms

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"About 15% of patients with typhoid fever develop serious neurological complications, including delirium and seizures, that are collectively described as acute encephalopathy. Until now, however, scientists have not clearly understood the mechanisms behind these life-threatening neurological effects. 

A new ... provides critical insights into how typhoid fever leads to encephalopathy. Researchers found that typhoid toxin, a key virulence factor only produced by the bacterium Salmonella Typhi, does not directly damage brain cells, as previously thought. Instead, it targets the endothelial cells lining the blood-brain barrier (BBB), causing significant barrier disruption and subsequent brain pathology.  ...

mice engineered to protect endothelial cells from toxin binding showed no neurological symptoms. ..."

From the abstract:

"Typhoid fever, primarily caused by Salmonella Typhi, can result in severe life-threatening complications such as encephalopathy. Here we elucidate the mechanisms by which typhoid toxin, a unique virulence factor of S. Typhi, mediates the neuropathology associated with typhoid fever.

Utilizing mice engineered to have specific tissues protected from toxin action and an in vitro model of the blood–brain barrier (BBB), we demonstrate that, rather than direct action on neuronal or glial cells, typhoid toxin causes neuropathology by disrupting the BBB.

Intravenous tracer studies confirmed significant BBB permeability changes following toxin exposure, an effect we found to be mediated by typhoid toxin’s CdtB catalytic subunit. We demonstrate that corticosteroids are effective at mitigating BBB disruption in vivo, supporting their use for managing typhoid fever neurological complications. Our data reveal mechanistic insight into how typhoid toxin causes encephalopathy and suggest targeted therapeutic interventions to alleviate the severe neurological manifestations of typhoid fever."

How typhoid fever triggers severe neurological symptoms | Yale News "Yale researchers have discovered how typhoid fever triggers neurological symptoms, offering new insight into treatment options."

Typhoid toxin causes neuropathology by disrupting the blood–brain barrier (no public access)