Late stage infection in sleeping sickness.

Area of Science:

• Neuroscience
• Parasitology
• Infectious Diseases

Background:

• Trypanosomes cause sleeping sickness, a neurological disease.
• The mechanism of parasite entry into the brain remains unclear.
• Previous studies noted parasite presence in cerebrospinal fluid of late-stage patients.

Purpose of the Study:

• To elucidate the pathway of trypanosome invasion into the brain.
• To identify the initial site of parasite entry and their subsequent movement.
• To understand the parasite's interaction with brain structures and host defenses.

Main Methods:

• Analysis of electron micrographs from infected rodent brains.
• Time-course analysis of parasite location post-infection (over 20 days).
• Histological examination of brain tissue, choroid plexus, and associated spaces.

Main Results:

• Trypanosomes enter the brain via the choroid plexus, penetrating the epithelial layer to reach the ventricular system.
• No parasites were found within the brain parenchyma outside of blood vessels.
• Parasite survival in cerebrospinal fluid and choroid plexus stroma is limited; they enter the subarachnoid space to evade degradation.
• Brain infection is dependent on the formation of long, slender trypanosomes.

Conclusions:

• The choroid plexus is the primary entry point for trypanosomes into the brain.
• Trypanosomes do not extensively colonize the brain parenchyma but reside near the glia limitans.
• Parasites may re-populate blood vessels from these locations, disrupting sleep-wake cycles.