Murine cysticercosis model: influence of the infection time and the time of treatment on the cysticidal efficacy of albendazole and praziquantel.

In the search of new alternatives for neurocysticercosis treatment, Taenia crassiceps ORF strain cysticerci have been used instead of T. solium for in vitro studies. Up to date, the main criteria for the use of the murine cysticercosis model for drug efficacy evaluation have not been assessed. The aim of the present study was to evaluate the influence of two of the main variables related to the in vivo efficacy: the length of drug treatment and the starting time of treatment after experimental infection, using albendazole (ABZ) and praziquantel (PZQ) as test drugs. Additionally, the relationship between the number of cysts and the parasite weight was assessed. For the study, female BALB/c mice were experimentally infected with T. crassiceps cysts. Three different post-infection periods (10, 20 and 30 days) and three different lengths of treatment with ABZ or PZQ (10, 20 and 30 days) were selected. The efficacy of each treatment was evaluated by comparison with a control group. Our results show that for in vivo efficacy studies, the best time to start the drug treatment is 10 days post-infection and that a minimum of 20 days of treatment is required when ABZ or PZQ are used as positive control. Moreover, in this model the parasite weight can be used as a rapid tool to measure the in vivo drug activity.

Historic of therapeutic efficacy of albendazol sulphoxide administered in different routes, dosages and treatment schemes, against Taenia saginata cysticercus in cattle experimentally infected.

The present study aimed to notify the history of albendazole sulphoxide (ALB-SO) and albendazole (ALBZ) efficacy against Taenia saginata cysticercus (Cysticercus bovis) parasitizing experimentally infected bovines. A total of 11 efficacy trials were performed between the years of 2002 and 2010. In order to perform these trials, animals were individually inoculated with 2×10(4) eggs of T. saginata in each study's day zero (D0). For every trial, a positive control group (untreated infected animals) and a negative control group (animals that were neither infected nor treated) were used. ALB-SO or ALB were administered in the different dosages, in different days of treatments. In a last study with this formulation, this active principle was administered orally, mixed with the mineral supplement, on the 60th DPI, in a dosage of 30mg/kg. In all trials, on the 100th DPI, all animals were euthanized and submitted to the sequenced slicing of 26 anatomical segments (fragments of approximately five millimeters) for the survey of T. saginata cysticercus. With the obtained results it is possible to verify that in the first trials, conducted in 2002, ALB-SO reached, independently of dosage and treatment scheme, efficacies superior to 98% (arithmetic means). The trials conducted in 2005 (2.5mg/kg on the 30th, 60th, and 90th DPI) obtained values of efficacy all inferior to 60%. In 2008, the trials with 2.5 and 7.7mg/kg demonstrated efficacy values inferior to 40%, for both dosages and treatment schemes (30th/60th/90th DPI and 60th DPI). When this formulation was administered orally on the dosage of 30mg/kg on the 60th DPI, the efficacy against T. saginata cysticercus reached 88.28%. ALB administered orally showed efficacy values of 0.0%, 29.88% and 28.64% in the dosages of 5, 10 and 15mg/kg, respectively, using the treatment schemes described above for each dosage. Based on the results of these trials, conducted in an eight year period (2002-2010) using the sequenced slicing method for evaluating the efficacy of the aforementioned formulations against T. saginata cysticercus, it is possible to observe that, amongst the few molecules used in the chemotherapic treatment against T. saginata larvae, ALB-SO, administered in varied routes, dosages and treatment schemes, the studies conducted in 2008, 2009, and 2010, have a low therapeutic efficacy against C. bovis in Brazil, while ALBZ had insignificant efficacy values against T. saginata larvae parasitizing experimentally infected bovines. However, future studies using molecular biology will be necessary to assess whether the difference on the efficacy of the ALB-SO can be related to strain or another specific factor.

Treatment with dehydroepiandrosterone in vivo and in vitro inhibits reproduction, growth and viability of Taenia crassiceps metacestodes.

The aim of this work was to explore the effect of dehydroepiandrosterone (DHEA) on the establishment, growth and reproduction of the metacestode stage of the tapeworm Taenia crassiceps, both in vivo and in vitro. Administration of DHEA prior to infection in mice of both sexes reduced the parasite load by 50% compared with untreated mice. This protective effect was not associated with the immune response, since there was no effect of DHEA treatment on mRNA levels of IL-2, IFN-gamma, IL-4 or IL-10. DHEA treatment of infected mice increased androgen receptor expression in splenocytes of both sexes. Moreover, in vitro treatment of T. crassiceps with DHEA reduced reproduction, motility and viability in a dose- and time-dependent fashion. Results indicate that DHEA has strong negative direct modulatory effects on murine cysticercosis. We suggest the use of hormonal-analogues for protective purposes as a therapeutic approach to prevent murine cysticercosis.

Gonadectomy and progesterone treatment induce protection in murine cysticercosis.

The effects of progesterone on castrated mice of both sexes infected with Taenia crassiceps cysticerci were studied. Gonadectomy and treatment with progesterone before infection decreased parasite loads by 100% compared with intact uninfected mice. mRNA levels of IFN-gamma and IL-2 (typically associated to Th1-like profiles) were markedly decreased in infected gonadectomized (Gx) mice, whereas progesterone treatment of infected Gx mice did not affected its expression. mRNA levels of IL-4, and IL-10 (typically associated with Th2-like profiles) were reduced by gonadectomy, whereas restitution with progesterone did not affected this pattern in infected Gx progesterone-treated mice. Infection markedly induced expression of progesterone receptor isoform A in splenocytes of Gx mice (5-fold), whereas isoform B had no changes. Progesterone metabolism to dehydroepiandrosterone (DHEA) in Gx animals was increased 3-fold only in infected progesterone-treated uninfecteds of both sexes, but was not detectable in infected Gx progesterone-treated mice. Conversely, DHEA levels increased 100-fold in infected Gx progesterone-treated mice. However, androgen receptor expression in splenocytes of male mice showed a reduction by gonadectomy, and by infection, whereas in females AR expression showed no changes in the different mouse groups. These results suggest that progesterone, through its metabolism to DHEA, negatively affects the establishment, growth, and reproduction of Taenia crassiceps, by a mechanism that does not implicate a classic genomic pathway involving a nuclear androgen receptor.

Evaluation of the efficacy of albendazole against the larvae of Taenia solium in experimentally infected pigs, and kinetics of the immune response.

Cysticercosis, a disease of economic and public health importance, is caused by Cysticercus cellulosae, the metacestode stage of Taenia solium. Experimental induction of cysticercosis was achieved in young pigs by feeding an optimum dose of 20,000 T. solium (Indian strain) eggs after immunosuppression, to assess the effect of albendazole and development of the immune response to cysticercus antigens before and after treatment. Histopathological studies revealed the presence of cysticerei in liver, lungs and muscles. Treatment with albendazole at 15 mg kg-1 body weight daily for 30 days starting from day 0 or 15 days post-infection resulted in 100% cure rates. Increases in antibody titre to crude soluble extract and a Sephadek G-200 purified antigenic fraction of Cysticercus cellulosae were found on days 25, 40 and 55 post-infection in untreated pigs and those in which treatment started on day 15 post-infection, whereas no increase in antibody response was observed in pigs in which treatment started on day 0.

Etipatogenia de la Neurocisticercosis

La miastenia gravis es la enfemedad parasitaria más frecuente del sistema nervioso central. La cisticercosis ocurre cuando el hombre se transforma en el huésped intermediario en el ciclo biológico de la taenia solium, al ingerir sus huevecillos a partir de alimentos contaminados. Estos huevecillos se transforman en oncosferas en el tracto intestinal, las oncosferas entran a la circulación y son transportadas a los tejidos del huésped, donde se desarrollan las larvas (cisticercos). El cisticerco está compuesto de dos partes principales, La membrana vesicular y el escólex, el cual tiene una estructura similar que la taenia adulta, es decir, cuerpo, cuello y cabeza armada con ventosas y ganchos. Como resultados de un complejo ataque inmunológico del huésped, los cisticercos entran en un proceso de degeneración que termina con la muerte del parásito; este proceso incluye cuatro estadios desnominados: vesicular, coloidal, nodular y calcificado, por otra parte, el tejido cerebral adyacente también presenta cambios que incluyen: edema cerebral, gliosis, infiltrado inflamatorio y degeneración neuronal, ademas la pared de los vasos sanguineos vecinos suele ser invadida por este infiltrado inflamatorio, condicionadose un proceso de endarteritis con engrosamiento de la adventicia, fibrosis de la media e hiperplasia del endotelio. Existen casos en que la respuesta inmune se desarrolla lentamente y los parásitos permanecen viables durante muchos años; los mecanismos por los que los cisticercosis evaden la vigilancia inmunológica del huesped incluirán: variación antigiénica, mimetismo e inmunosupresión . por otra parte, algunos pacientes presentan un estado de hipersensibilidad en el cual los cisticercos son rechazados inmediatamente después de su entrada al sistema nervioso; en estos casos, el tejido cerebral adyacente también suele ser afectado. Entre los extremos de tolerancia inmune e hipersensibilidad, se encuentra una amplia gama de respuesta inflamatoria inducidad por esta interacción huesped-parásito. Probablemente, el sexo del huesped y el complejo HLA juegen un rol importante en el susceptibilidad o la resistencia a la enfermedad.

Cysticercosis vaccine: cross protecting immunity with T. solium antigens against experimental murine T. crassiceps cysticercosis.

Vaccination of mice with an antigen extract from Taenia solium cysticerci induced protection against challenge with T. crassiceps cysticerci as successfully as did antigen extracts from T. crassiceps. Vaccination was more effective in male than in female mice and in the resistant strain (BALB/B) more so than in the susceptible strain (BALB/c). While only the resistant strain was completely protected by vaccination, the parasite load of the susceptible strain was significantly reduced by vaccination. Cross immunity between the human and murine parasites establishes murine T. crassiceps cysticercosis as a convenient laboratory model in which to test promising T. solium antigens aimed at vaccine development against T. solium cysticercosis. Further, results point to strong interactions of the immune system with sexual and histocompatibility factors in the host's dealing with cysticercosis.