Immunopathological aspects of trypanosomal meningoencephalitis in vervet monkeys after relapse following BerenilR treatment

Abstract

Four quarantined vervet monkeys were treated with intramuscular BerenilR in patent CNS infection after experimental trypanosome inoculation with Typanosoma brucei rhodesiense or T. brucei brucei. All four animals relapsed in the post-therapeutic survival time of 37 to 209 days when they had fully developed me~ngoencepha~tis in histological sections with the presence of interstitial intracerebral trypanosomes, which were confirmed in two monkeys by electron microscopy. In both, sequential samples of the serum and cerebrospinal fluid were analysed for circulating immune complexes, immunoglobulins and albumin. From these results the intracerebral IgG synthesis and the impairment of the blood-brain-barrier were calculated, both being present in advanced infection. Circulating immune complexes were present in the serum, but could not be demonstrated in the cerebrospinal fluid. The monkey model therefore permits the study of various aspects of cerebral trypanosomiasis. BerenilR treatment is inefficient in patent CNS infection and leads to a protracted, less virulent disease course with terminal men~g~ncephalitis and intracerebral "persister" trypanosomes. This drug-induced trypanosome shift with me~ngoencepha~tis could be used for chemotherapeutic purposes to test new compounds in late stage disease.

Trypanosomiasis and the brain

“…2) (Hunter et al 1992 b). An increased neuroinflammatory reaction as a result of sub-curative drug treatment is not an idiosyncrasy of our model since this phenomenon has been reported by several researchers (Schmidt and Sayer, 1982 ;Poltera et al 1985) and could relate to the development of the PTRE found in human cases of HAT (Hunter et al 1992 a).…”

Delineating neuroinflammation, parasite CNS invasion, and blood-brain barrier dysfunction in an experimental murine model of human African trypanosomiasis

“…The neuroinflammatory changes were most apparent in the white matter of the cerebral hemispheres but also occurred in the circumventricular areas. The neuroinflammatory picture has also been described in rodent [9] , [16] , [27] , [29] , [39] , [40] , [41] , [42] , [43] and primate [7] , [44] , [45] , [46] models of trypanosome infection. Although these studies reported a similar response to that described in human cases the development of a meningoencephalitis, with inflammatory cells infiltrating the brain parenchyma, was only seen on a few occasions and was more commonly associated with treatment failures [7] , [45] , [47] .…”

Passage of parasites across the blood-brain barrier

“…To facilitate the spread of the parasite to its definite host, the cat, it has been suggested that persistent Toxoplasma infections in rodents may change the rodents’ behavior to show reduced avoidance of the predator cats 116 , 117 . It has also been suggested that African trypanosomes may hide in the brain, behind the BBB, between relapses in sub-optimally treated individuals 118 - 121 . In contrast to toxoplasmosis, there are no obvious changes in the behavior of the host caused be this parasite that could be associated with an increased rate of transmission.…”