RESUMO
Trypanosomes from animals are potential pathogens for humans. Several human cases infected by Trypanosoma lewisi, a parasite of rats, have been reported. The number of these infections is possibly underestimated. Some infections were self-cured, others required treatment with drugs used in human African trypanosomosis. An in vitro evaluation of these drugs and fexinidazole, a new oral drug candidate, has been performed against T. lewisi in comparison with T. brucei gambiense. All have comparable activities against the two parasites. Suramin was not effective. In vivo, drugs were tested in rats immunosuppressed by cyclophosphamide. The best efficacy was obtained for fexinidazole, and pentamidine (15 mg/kg): rats were cured in 7 and 10 days respectively. Rats receiving nifurtimox-eflornithine combination therapy (NECT) or pentamidine (4 mg/kg) were cured after 28 days, while melarsoprol was weakly active. The identification of efficient drugs with reduced toxicity will help in the management of new cases of atypical trypanosomosis.
Assuntos
Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêutico , Trypanosoma lewisi/efeitos dos fármacos , Tripanossomíase/tratamento farmacológico , Animais , Eflornitina/farmacologia , Eflornitina/uso terapêutico , Feminino , Humanos , Hospedeiro Imunocomprometido , Concentração Inibidora 50 , Melarsoprol/farmacologia , Melarsoprol/uso terapêutico , Camundongos , Nifurtimox/farmacologia , Nifurtimox/uso terapêutico , Nitroimidazóis/farmacologia , Nitroimidazóis/uso terapêutico , Parasitemia/tratamento farmacológico , Pentamidina/farmacologia , Pentamidina/uso terapêutico , Ratos , Ratos Wistar , Suramina/farmacologiaRESUMO
Arginase serum levels were increased in human African trypanosomiasis patients and returned to control values after treatment. Arginase hydrolyzes l-arginine to l-ornithine, which is essential for parasite growth. Moreover, l-arginine depletion impairs immune functions. Arginase may be considered as a biomarker for treatment efficacy.
Assuntos
Arginase/sangue , Biomarcadores/sangue , Monitoramento de Medicamentos/métodos , Tripanossomíase Africana/tratamento farmacológico , Feminino , Humanos , Masculino , Soro/química , Resultado do TratamentoRESUMO
In contrast to young rats, adult rats given i.p. Plasmodium berghei Anka (PbA) control the parasitaemia and repair their anaemia. Here, we investigated whether IgE and CD23/NO immune pathway could be implicated in this age-related resistance of adult rats to PbA. Eight-week-old rats displayed significantly higher levels of plasma total IgE (p=0.01) and soluble CD23 (p=0.003) during the peak of parasitaemia, compared to 4-week-old rats. IgE Fc-binding antibody or aminoguanidine administration to parasitized 8-week-old rats slightly delayed blood parasite clearance or exacerbated anaemia. These data suggest that IgE and CD23/NO could play an important role in the resistance of adult rats experiencing PbA primary intraerythrocytic development.
