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.

The peritrophic membrane of the female sandfly Phlebotomus papatasi.

The ultrastructure of the peritrophic membrane of the female sandfly Phlebotomus papatasi has been studied at various times after blood meals. The membrane begins to form within four hours of the blood meal with the secretion by the entire midgut epithelium of an electron-dense amorphous material. Subsequently, the membrane is stabilized and strengthened by the production of a layer of irregular chitinous microfibres, the whole membrane then forming a complete and resilient sac apparently unaffected by boiling 9 M potassium hydroxide. The membrane appears redundant 48 hours after the blood meal and fragments, possibly as a result of chitinase activity. The membrane's main functions are probably the prevention of clogging of the microvillous brush border by the blood meal and the confinement of large proteins, particularly serum trypsin inhibitors, to the endoperitrophic space while allowing sandfly proteases access to the blood meal periphery. Blood is not required to stimulate membrane production. Saline taken by blood feeding into the midgut also stimulates membrane formation. Phlebotomus papatasi females may lack an efficient anticoagulant, at least in the midgut, as blood meals frequently include fibrin clots.