Megazol combined with suramin improves a new diagnosis index of the early meningo‐encephalitic phase of experimental African trypanosomiasis

Abstract

SummaryIn human African trypanosomiasis (HAT), the parasites invade the central nervous system (CNS), leading to the development of meningo-encephalitis and an irreversible demyelinating process, which kills the patient unless specific treatment is undertaken. Among the experimental trypanocides, the nitroimidazole derivative megazol alone at optimal doses does not cure late-stage disease tested in mouse models, however the combination of suramin and megazol is able to cure infected mice without CNS involvement. We recently developed an experimental model of HAT with a sharp decrease in both the food intake and the body weight which may constitute an effective index of the early meningo-encephalitic phase. Using this model, we tested this hypothesis by the exclusive effectiveness of a megazol and suramin combination treatment to eliminate CNS trypanosomes. Sprague-Dawley rats were infected with Trypanosoma brucei brucei AnTat 1.1E. Food intake and body weight were measured daily from the day of infection to death. Haematocrite was measured twice a week. Treatment consisted of 20 mg suramin per kg body weight administered intraperitoneally (i.p.) alone, or three daily doses (80 mg/kg) of megazol given per os, or suramin (20 mg/kg, i.p.) followed 24 h later by three daily doses (80 mg/kg) of megazol given per os. Treatment was followed by an increase in daily body weight and food intake similar to those of the control animals, 2 weeks after treatment. The anaemia developed after infection is also cleared as shown by the haematocrite measurements. The rats treated with megazol alone died about 29 days after treatment and those treated with suramin, after about 26 days. Seven months later, no signs of relapse were seen in 10 of 12 rats treated with the therapeutic combination, indicating that this chemotherapy regimen was curative. The results support our previous finding, i.e. the decrease in body weight may constitute a diagnosis index of the early meningo-encephalitic phase.

Cerebral and Peripheral Changes Occurring in Nitric Oxide (NO) Synthesis in a Rat Model of Sleeping Sickness: Identification of Brain iNOS Expressing Cells

“…We also demonstrated that trypanosomes can be present in the CSF in the absence of clinical symptoms [19]. We found that staining of trypanosomes in the brain was evidenced at D16, confirming previous observations done in the Sprague Dawley rat model [20]. Trypanosomes were observed around the ventricular cavities in areas where the BBB is most permeable, i.e., at the level of circumventricular organs, median eminence and subfornical organ of the hypothalamus [21].…”

Structure of Severe Fever with Thrombocytopenia Syndrome Virus Nucleocapsid Protein in Complex with Suramin Reveals Therapeutic Potential

“…Among the resulting ligands, Suramin showed highest affinity for SFTSV-N. Suramin is a drug used for the treatment of trypanosomiasis and helminthiasis (37,38). Recently, its potential as an antineoplastic agent in the treatment of cancers and as an antiviral agent is being evaluated (39)(40)(41).…”

Pathogenicity of bloodstream and cerebrospinal fluid forms of <i>Trypanosoma brucei rhodesiense</i> in Swiss White Mice

“…brucei at 13-dpi [23]. It has been suggested that the onset of weight loss could be associated with the initiation of second stage trypanosomosis in mice [24]. It is noted that body weight loss and anorexia are controlled by the hypothalamus, and as such the effect could be caused by entry of parasites into the brain [25].…”