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PubMed2001

Managing parasiticide resistance.

Resistance to antiparasitic drugs is all too common in parasites of veterinary interest. The fact that resistance has arisen in so many different species of parasite and hosts against so many different drugs and in so many geographic areas suggests that the resistances may have common features. Such features may be useful in generating ideas for resistance management. Although describing the nature and presence of resistance remains an important objective, there is now a pressing need to develop improved methods of detection of resistance and to devise schemes for integrated parasite management (IPM). Multidisciplinary teams of researchers and extension workers are exploring new ways to deal with the problem of resistance.

Animals↗
PubMed2001

Parasiticidal effects of peroxynitrite on ovine liver flukes in vitro.

Peroxynitrite (ONOO-) is a cytotoxic anion, produced by interaction between nitric oxide and superoxide in vivo in some inflammatory cells. This study investigated its effects on Fasciola hepatica and Dicrocoelium dendriticum isolated from ovine livers and kept in bile at room temperature. Peroxynitrite was synthesized using a quenched flow reactor and assayed spectrophotometrically. It was applied at different concentrations (10(-3.5) to 10(-2.3 M)) to the flukes kept in bile. The viability of the peroxynitrite-treated flukes was compared with a control group (n=5-7 per group). Control F. hepatica and D. dendriticum lived for 226+/-11and 208+/-14min, respectively. Life times were decreased by peroxynitrite at all concentrations used (P<0.001). At the highest concentration of peroxynitrite, F. hepatica and D. dendriticum lived only for 6.1+/-0.4 and 4.1+/-4.1+/-0.2min, respectively. Correlation between peroxynitrite concentration and parasite viability was significant in the case of F. hepatica (r= -0.842; P= 0.0035). A single application of peroxynitrite can decrease the life span of ovine liver flukes. A failure in the activation of hepatic macrophages in infected animals may lead to a decreased production of free radicals and, thus, peroxynitrite. Such a failure is likely to deprive the body of a defence tool against multicellular parasites.

Animals↗
PubMed1992

Parasiticidal effect of chemotherapy in alveolar hydatid disease: review of experience with mebendazole and albendazole in Alaskan Eskimos.

Evidence that the larval stage of Echinococcus multilocularis in humans is killed by chemotherapy is presented in a review of our 17-year experience with treatment of alveolar hydatid disease in Alaska. The efficacy of chemotherapy was assessed with use of an in vivo assay of parasite viability by means of inoculation of voles, immunohistochemical tests, and histopathologic findings. Of 14 tests performed for nine patients, 12 in vivo assays (86%) were negative after chemotherapy, while only two (17%) of 12 vole tests for seven untreated patients were negative. Regression of arrest of growth of metastatic and primary hepatic lesions, together with their partial-to-complete calcification and prolonged survival times has been observed among patients treated with the benzimidazole compounds. For six who received appropriate chemotherapy, treatment has been discontinued for an average of 4.6 years (range, 3-7 years) without an increase lesion size or other evidence of reactivation.

Adult↗
PubMed1998

Interleukin-12 enhances in vivo parasiticidal effect of benznidazole during acute experimental infection with a naturally drug-resistant strain of Trypanosoma cruzi.

The roles of gamma interferon (IFN-gamma) and interleukin-12 (IL-12) in mediating and/or enhancing the in vivo trypanosomicidal activity of the nitroheterocyclic derivative benznidazole (Bz) were evaluated during early stages of experimental Chagas' disease. Our results show that treatment of Trypanosoma cruzi-infected mice with anti-cytokine monoclonal antibodies (MAbs) had no apparent effect when the optimal dose of Bz (100 mg/kg of body weight) was used. In contrast, treatment with anti-IL-12 or anti-IFN-gamma MAbs enhanced the parasitemia and accelerated the mortality of mice treated with a suboptimal dose of Bz (25 mg/kg). Simultaneous treatment with a suboptimal dose of Bz and recombinant IL-12 (rIL-12) enhanced the efficacy of drug treatment in terms of parasitemia and mouse survival. Interestingly, we found that drug-resistant T. cruzi strains were found to be poor inducers of IL-12 both in vitro and in vivo compared to strains of T. cruzi which are susceptible or partially resistant to Bz treatment. These results suggest that early activation of the cellular compartment of the immune system by IL-12 may favor in vivo Bz activity against T. cruzi. In order to test this hypothesis mice infected with the drug-resistant Colombiana strain of T. cruzi were treated with 100 mg of Bz per kg plus different concentrations of rIL-12. By using the results of PCR and serological and parasitological methods as the criteria of a cure, our results indicate that a higher percentage of mice treated with Bz combined with rIL-12 than mice treated with Bz alone are cured.

Acute Disease↗
PubMed1999

Immunization of mice with a TolA-like surface protein of Trypanosoma cruzi generates CD4(+) T-cell-dependent parasiticidal activity.

The gene family encoding a trypomastigote-specific protein restricted to the part of the flagellum in contact with the cell body of the trypomastigote form of Trypanosoma cruzi has been isolated, characterized, and expressed in a baculovirus expression system. The gene family contains three tandemly repeated members that have 97 to 100% sequence identity. The predicted protein encoded by the gene family has both significant amino acid sequence identity and other physical and biological features in common with the TolA proteins of Escherichia coli and Pseudomonas aeruginosa. Based on these similarities, we have designated this gene family tolT. Immunization of mice with recombinant TolT generates a population of CD4(+) T lymphocytes that recognize T. cruzi-infected macrophages, resulting in the production of gamma interferon (IFN-gamma), which leads to NO production and a 50 to 60% reduction in parasite numbers compared to that seen with infected macrophages incubated with naive T cells. This population of T cells also produces both IFN-gamma and interleukin 2 (IL-2) but not IL-4 or IL-5 when incubated with spleen cells stimulated with TolT antigen, indicating that they are of the T-helper 1 type. T cells from mice chronically infected with T. cruzi also produce significant levels of IFN-gamma when cocultured with macrophages and either TolT protein or paraflagellar rod protein, indicating that both of these flagellar proteins produce positive T-cell responses in mice chronically infected with T. cruzi.

Animals↗
PubMed2004

The parasiticidal effect of electricity on Leishmania major, both in vitro and in vivo.

The effects of low electrical potentials on Leishmania major (MRHO/IR/75/ER) were investigated both in culture (in terms of promastigote viability) and in experimentally infected BALB/c and NMRI mice (in terms of the cure of pre-existing skin lesions). Exposure to direct-current potentials of 3, 6, 9 and 12 V (at 0.2-10.7 mA) killed all promastigotes in <15, <10, <10 and <10 min, respectively. When electrodes were used to pass similar direct currents across skin lesions on the tails of infected mice, all but the lowest voltage (3 V) caused unwanted ulceration. At 3 V, however, 3 weeks of electrotherapy, for 10 min twice weekly, initially appeared to cure all the lesions and the therapy was then halted. If given no electrotherapy, the BALB/c mice showed much greater Leishmania-attributable morbidity and mortality than the NMRI mice, and it was only in the treated BALB/c mice that relapses were observed, about 3 weeks after electrotherapy had ceased. The possible clinical use of electrotherapy in the treatment of human cutaneous leishmaniasis is discussed.

Animals↗
PubMed2006

Toxicity of four veterinary parasiticides on larvae of the dung beetle Aphodius constans in the laboratory.

The environmental risk assessment of veterinary pharmaceuticals for dung beetles is strongly hampered because no standardized test method is available so far. Therefore, a test with the temperate dung beetle species Aphodius constans was developed. The survival of beetle larvae was determined after exposure to four veterinary parasitical pharmaceuticals (ivermectin, moxidectin, dicyclanil, and praziquantel) representing different treatment regimes, modes of action, and effect levels. The test was performed in the laboratory (three week duration) with fresh dung, as well as formulated (dried, ground, and rewetted) dung as test substrate (i.e., at least one range-finding test, two definitive test runs per pharmaceutical). Ivermectin was the most toxic substance (median lethal concentration [LC50] = 0.88-0.98 mg of active substance per kilogram of dung dry weight [mg a.s./kg dung (dry wt)] followed by dicyclanil (LC50 = 1.5-6.0 mg a.s./kg dung [dry wt]) and moxidectin (LC50 = 4.0-5.4 mg a.s./kg dung [dry wt]), whereas praziquantel showed very low toxicity (LC50 > 1,000 mg a.s./kg dung [dry wt]). The toxicity in fresh and formulated dung differed by a factor of between 1.1 and 4. The comparison with literature data on toxic effects of these substances on dung beetles in the laboratory or in the field is difficult because no results for praziquantel and dicyclanil have been published so far. With the use of data from ivermectin and moxidectin, the test results are on the same order of magnitude as those known from other studies. On the basis of the experiments reported here, it is recommended that this test be standardized in an international ring test so that it can be incorporated into the risk assessment process as described in the respective international guidelines for the registration of veterinary pharmaceuticals.

Animal Diseases↗