Sleeping sickness and the central nervous system

Chronic African trypanosomiasis is associated with progressive behavioural deficits, for which there is a complex underlying central nervous system (CNS) pathology. This has been extensively studied in man and a range of experimental animals. An initial meningitis, which can occur quite early in the infection, is followed by a breakdown of the choroid plexus, movement of the parasite into certain localized brain areas, and subsequent encephalitis. The encephalitis consists of a chronic, widespread inflammation with perivascular infiltrations of B-cells, plasma cells, inactivated T-cells and macrophages. The blood-brain barrier is damaged and a vasogenic oedema ensues. Astrocytes and microglia become reactive and the cytokine/mediator network is perturbed. The alterations in some of these signalling substances, e.g. the prostaglandins, may induce some of the behavioural changes, e.g. the hypersomnia. The immunopathology in the CNS may be brought about by elevated levels of active substances in the cerebrospinal fluid, caused by parasite infection.