Understanding How Typhoid Fever Can Cause Severe Neurological Symptoms

Typhoid fever, caused by the bacteria Salmonella Typhi, remains a significant health concern worldwide, especially in regions with inadequate sanitation. While it is primarily known for high fever, weakness, and gastrointestinal issues, approximately 15% of patients experience serious neurological complications such as delirium, seizures, and altered mental states—collectively termed as acute encephalopathy. Despite the severity of these symptoms, the underlying mechanisms have long been poorly understood.

Recent research from Yale University has shed new light on how typhoid fever leads to such neurological effects. The study, published in Nature Microbiology, reveals that the typhoid toxin produced by Salmonella Typhi does not directly damage brain cells as previously suspected. Instead, the toxin targets the endothelial cells that form the blood-brain barrier (BBB), a critical structure that shields the brain from harmful substances in the bloodstream.

The disruption of the BBB caused by the toxin leads to inflammation, swelling (edema), and consequently, neurological dysfunction. The research demonstrated that protecting the endothelial cells from toxin binding prevented neurological symptoms in mouse models, emphasizing the importance of vascular damage over direct neuronal injury.

Furthermore, the study found that the damage to the BBB could be mitigated using corticosteroids like dexamethasone, which reduce inflammation and help maintain barrier integrity. This finding highlights a potential therapeutic approach for managing severe neurological symptoms in typhoid fever.

Understanding that the vascular system and the BBB play a central role shifts the focus of future treatments and preventative strategies. It underscores the importance of managing inflammation and protecting blood vessel health to prevent or lessen neurological complications.

Typhoid fever affects about 12 million people annually, resulting in around 200,000 deaths, predominantly in low-income countries. The research underscores the need for improved treatment options and vaccines to combat this infectious disease and its severe complications.

This discovery not only advances scientific knowledge but also opens new avenues for clinical interventions aimed at safeguarding the brain in typhoid infections.

Source: https://medicalxpress.com/news/2025-05-typhoid-fever-triggers-severe-neurological.html