Levamisole vaccine combinations. 1. Heightened antibody response.

Levamisole was combined with a clostridial vaccine and experiments conducted in sheep to determine the effect on anthelminitic and vaccine efficacy. Vaccine potency was assessed in separate experiments in 200 sheep (divided into 5 groups). The individuals in each group were injected with one of the following 5 different preparations: levamisole combined with anaerobic vaccine at pH of either 3.5 or 6.0, vaccine alone at a pH of either 3.5 of 6.0, and levamisole alone. The combined levamisole/vaccine preparations had been stored for not less than 6 months prior to testing. A statistically-significant heightened antibody response to 5 antigenic components in the vaccine was obtained when the pH of the vaccine was reduced to 3.5 and the vaccine was given in combination with levamisole. This trend was present in the antibody response of the sheep when a pooled sample of the individual serums was tested at 6 weeks, 8 weeks and 14 weeks (8 weeks after the second injection). From the analysis of the individual serums at week 8 (2 weeks after the 2nd injection) there was evidence that the distribution curve of the titres had shifted to the right suggesting that the zero or poor responders in the population had improved immunocompetence, with the better responders also improving proportionately. The immunogenicity of the blackleg component was tested in sheep, 9 weeks and 32 weeks after the second injection and gave complete protection to a lethal challenge of Clostridium chauvoei. This combination offers not only increased ease of administration by providing a single anthelmintic and anaerobic vaccines injectable preparation (probably treatment with either or both is the two most common and important veterinary procedures undertaken by farmers, but in addition, the antibody titre of the treated animals is significantly increased. Part 2 of this paper establishes that the anthelmintic efficacy of the levamisole/vaccine combination was not impaired and that tissue reactions at the site of injection were acceptable.

Hydatid disease in Australia.

Human hydatidosis is caused by infection with the cystic stage of the hydatid tapeworm of dogs, Echinococcus granulosus. Although the disease is entirely preventable, the prevalence of hydatidosis in Australia has not decreased since the first surveys were taken in the early part of this century. Principal reasons for this appear to be a general lack of knowledge of the life history, epidemiology and control methods for E. granulosus, coupled with ineffective community based eradication campaigns. The purpose of this paper is to briefly discuss the important facts relevant to control and eventual eradication of hydatid disease.

The anthelmintic efficacy of fenbendazole against thiabendazole-resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep.

The anthelmintic efficacy of fenbendazole (methyl 5-(phenylthio)-2-benzimidazole carbamate) was tested in sheep against standardised strains of Hcaemonchus contortus and Trichostrongylus colubriformis, known to be resistant to thiabendazole (LD90 for thiabendazole against H ontortus was 200 mg/kg bodyweight and against T colubriformis was 150 mg/kg). Fenbendazole at dose rates of 5, 10 and 20 mg/kg per os reduced total worm counts in H contortus infected sheep by 66, 90 and 100 per cent respectively, with similar reductions recorded for worm egg outputs. For the thiabendazole resistant strain of T colubriformis, fenbendazole reduced total worm counts in infected sheep by 4, 44 (40-48), 79 (75-83), 96 and 100 per cent at dose rates of 5, 10, 20, 40 and 80 mg/kg per os. Significant suppression of worm-egg production by thiabendazole resistant T colubriformis was obtained with fenbendazole at dose levels of 5 mg/kg and above. The implications of these results are discussed in the light of the increasing occurrence of strains of trichostrongylid nematodes resistant to currently available benzimidazole anthelmintics.

The specificity of nematode allergens in the diagnosis of human visceral larva migrans.

Extracts of nematodes have been used as skin test antigens in the diagnosis of nematode infections for many years. Ascaris lumbricoides and Toxocara canis are two nematodes commonly involved in human parasitism, the latter being associated with the clinical condition of Visceral Larva Migrans. In vitro and in vivo experiments reported in this paper confirm experimentally, as well as clinically, the existence of cross-reacting antigens between T. canis and Ascaris spp., and probably between T. canis and other nematodes. These cross-reactions compromise the usefulness of skin tests in the diagnosis of such parasitic infections.

Studies on immune responses to parasite antigens in mice. I. Ascaris suum larvae numbers and antiphosphorylcholine responses in infected mice of various strains and in hypothymic nu/nu mice.

In terms of day 7 lung larvae numbers, mice vary markedly in their suscepibility to a first infection with the nematode worms, Ascaris suum, and the highly susceptible strain, C57Bl, is resistant to second infection. Time course studies suggested that the period of residence in the liver or migration to, or into, the lungs are stages of the life cycle in which natural or acquired resistance of the host is expressed. The traits, susceptibility and resistance to first infection, were under polygenic control and no linkage of susceptibility to the major histocompatibility complex of C57Bl mice (H-2b) was observed. Acquired resistance (to second infection) has not been dissected because of our inability to show adoptive transfer of resistance to naive recipeints. Studies in hypothymic BALB/c. nu/nu mice indicate that natural resistance (to first infection) is not affected by a lack of T cells. The T cell dependence of acquired resistance in C57Bl mice remains in doubt although in the relatively resistant strain BALB/c, hypothymic nu/nu mice after second infection contain as many larvae in their lungs and liver as are present after first infection. An eosinophilia is observed in infected intact mice but not in infected T cell-deficient mice. Partially T cell-dependent serum antibodies and plaque-forming cells to phosphorylcholine (PC) were present in mice infected with A. suum but no evidence was obtained that this anti-PC antibody response was in any way protective for the host. The cell membrane-acitive properties of PC and related molecules suggest that PC-containing parasite antigens may be tolerogens for certain of the B cells with specificity for parasite antigens. A state of partial tolerance involving high affinity antibody production may be one means whereby parasites survive in natural or unnatural hosts.

Studies on immune responses to parasite antigens in mice. III. Nippostrongylus brasiliensis infections in hypothymic nu/nu mice.

Normal mice of several strains reject the nematode worm Nippostronglyus brasiliensis from the intestine within 14 days (and most often within 10 days) of injection of high numbers of infective third stage larvae (L3). Previously-infected mice are markedly resistant to a second infection. Hypothymic, nu/nu ('nude') mice continue to harbor worms long after intact mice have rejected the worm burden and an inoculum of T cells at the time of, or several days after L3 injection, leads to worm elimination within 14 days in nu/nu mice. As yet no evidence is available to indicate whether or not T cells with specificity for parasite antigens are required in a reconstitutive inoculum in nu/nu mice. Pretreatment of normal mice with cyclophosphamide, at doses reported to lead to temporary B cell hypofunction, does not result in delayed rejection of worms but the participation of B cell products (antibodies) cannot be discounted on the basis of this result. The nu/nu mouse - N. brasiliensis system will be useful in the search for, and characterization of, parasite antigens which gain access to the lymphoid organs and circulation of parasitized mice and in the analysis of T cell subtypes (both functional and surface Thy and Ly alloantigenic subtypes) involved in worm elimination.

The anthelmintic efficacy of fenbendazole against a mixed nematode infection in sheep.

Fenbendazole (methyl-5-(phenylthio)-2-benzimidazole carbamate) at dose rates of 5 mg/kg and above was 100 per cent effective in eliminating a naturally acquired Dictyocaulus filaria infection in sheep. The drug was 100 per cent effective in eliminating concurrent infections of adult Trichostrongylus axei, Haemonchus contortus, Haemonchus placei, Ostertagia circumcincta, Ostertagia ostertagii, Cooperia oncophora, Cooperia mcmasterii, Nematodirus spathiger, Neumatodirus filcollis, Oesophagostomum venulosum and Chabertia ovina. Fenbendazole was 93 per cent and 97 per cent effective at doses of 5 and 10 mg/kg respectively in removing infection with adult T colubriformis, and post-treatment worm-egg production was completely suppressed in surviving female worms. No adverse side-effects were observed in treated sheep at either of the two dose rates used.