In addition to parasite spread, the severity of disease observed in cases of human African trypanosomiasis (HAT), or sleeping sickness, is associated with increased levels of inflammatory mediators, including tumor necrosis factor (TNF)-␣ and nitric oxide derivatives. In the present study, quercetin (3,3,4,5,7-pentahydroxyflavone), a potent immunomodulating flavonoid, was shown to directly induce the death of Trypanosoma brucei gambiense, the causative agent of HAT, without affecting normal human cell viability. Quercetin directly promoted T. b. gambiense death by apoptosis as shown by Annexin V binding. In addition to microbicidal activity, quercetin induced dose-dependent decreases in the levels of TNF-␣ and nitric oxide produced by activated human macrophages. These results highlight the potential use of quercetin as an antimicrobial and anti-inflammatory agent for the treatment of African trypanomiasis.Human African trypanosomiasis (HAT), or sleeping sickness, is provoked by the inoculation of Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense into humans by a tse-tse fly. HAT is considered a reemerging disease, mainly due to the deterioration of health facilities in endemic areas. Blood monocytes and tissue macrophages play a key role in the control of parasite numbers, and an increased number of activated hematopoietic cells are observed during trypanosomiasis (33). Trypanosome-derived products were also shown to activate the generation by macrophages of various proinflammatory mediators including tumor necrosis factor alpha (TNF-␣), nitric oxide (NO), and interleukin-1 (IL-1) (7,19,28). TNF-␣ and NO fulfill important functions in host-parasite interactions as they control infections by various pathogens, including T. b. gambiense (6,21,32). In addition, chronic secretion of macrophage-derived mediators is in part responsible for the pathogenic aspects of HAT (18,20,25,27). Accordingly, a correlation can be made between high levels in serum of TNF-␣ and disease severity in HAT (25), and successful treatment with melarsoprol significantly reduced the circulating concentration of this cytokine in HAT patients (27).Only a few drugs are available to treat HAT, and some of them are effective only during the first phase of disease or are difficult to administer because of their high toxicity. These facts led us to investigate the effects of nutrition-derived flavonoids on in vitro interactions between T. b. gambiense and human leukocytes. Flavonoids are produced in plants in response to environmental stress such as adverse weather or attacks by insects, animals, or pathogens (37). For humans, the main flavonoid dietary sources are fruits, beverages, vegetables, dry legumes, and cereals. Recently, various purified polyphenolic compounds were defined as strong free-radical scavenging agents that display antitumoral, antimicrobial, and anti-inflammatory activities (3).Quercetin and its derivatives are among the most common polyphenolic flavonoids present in plants such as onions, ginkgo biloba, and tea ...

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Soluble intercellular adhesion molecule-1 (sICAM-1) level was measured in sera from 41 patients with Schistosoma mansoni schistosomiasis and compared with the sICAM-1 level in 41 healthy subjects. A significant increase in serum sICAM-1 was observed in patients with schistosomiasis compared with control subjects. As they were inhabitants of the French Antilles, the patients were, however, not settled in a malaria endemic zone, allowing this cause of sICAM-1 enhancement to be eliminated. No correlation was found between the level of sICAM-1 and the schistosomiasis serological titre. Such results favour the hypothesis of an activation of vascular endothelial cells due to egg deposition.

In the course of previous works, we described an IgM monoclonal antibody directed to a carbohydrate epitope located on the gut epithelium surface of the Schistosoma mansoni adult worm. We provided evidence that this epitope was present in all stages of the parasite and was particularly abundant in eggs. The current work was performed in order to specify the epitope localisation, at each stage, by immunohistochemical techniques. The epitope appears to be located on the peripheral membranes of the adult worm, while it is produced by the alive miracidium in the eggs located in the tissues and subsequently spred out inside the periovular granuloma. Moreover, in adult worms, the observed structure presents itself as a soluble form in organic solvents; on the other hand, in eggs, the epitope was essentially found made of an hydrosoluble substance. These datas can explain why, in experimentally infected mice, the epitope is mainly determined in urines at the sixth week of infestation, when eggs are settled down in the tissues. Besides, the inhibition of the monoclonal antibody fixation by a pentose which contains the Lewis X antigen, pointed out that the carbohydrate structure recognised by the monoclonal antibody could be the Lewis X antigen or a very closed structure.