Sleep-Wake Dysregulation in Human African Trypanosomiasis: From Neuroinvasion to Neuronal Dysfunction

Area of Science:

• Neuroscience
• Tropical Medicine
• Sleep Medicine

Background:

• Human African trypanosomiasis (HAT), or sleeping sickness, is a neglected tropical disease characterized by central nervous system (CNS) invasion.
• Sleep and circadian rhythm abnormalities are prominent features of HAT, but the underlying mechanisms linking neuroinvasion, neuroinflammation, and sleep dysfunction remain unclear.

Purpose of the Study:

• To review current knowledge on sleep and circadian disturbances in HAT.
• To propose an integrated framework for Trypanosome-Associated Sleep Disorder (TASD) by examining parasite neuroinvasion, neuroinflammation, and CNS effects.
• To identify knowledge gaps and future research priorities.

Main Methods:

• A narrative review of literature identified through major biomedical databases.
• Searched terms included HAT, sleeping sickness, sleep disorders, circadian rhythms, neuroinflammation, and CNS invasion.
• Synthesized information on CNS invasion pathways, inflammatory responses, and disruption of circadian regulatory networks.

Main Results:

• Evidence links excessive daytime sleepiness, fragmented sleep, circadian misalignment, and neuropsychiatric symptoms to inflammatory cytokines, altered neurotransmitters, the kynurenine pathway, clock gene dysregulation, and suprachiasmatic nucleus disruption.
• Trypanosome-Associated Sleep Disorder (TASD) is presented as a syndrome-like phenotype of CNS involvement.
• A three-stage model of sleep-wake dysfunction in HAT is proposed.

Conclusions:

• Sleep pathology in HAT arises from a complex interplay of neuroinvasion, neuroinflammation, and disruption of circadian regulatory networks.
• A unified mechanistic framework is proposed to understand TASD.
• Further research is needed on biomarkers, disease staging, and neuronal damage for improved clinical management.