When given to sheep as a single oral dose at 0.1 mg/kg, the Bia component of the avermectins caused a reduction of >95% in the numbers of Haemonchus contortus, Ostertagia circumcincta (including inhibited L4 larvae), Tricho- Fermentation-derived natural products which are attributed with anthelmintic activity have been described in the literature. Hygromycin B, which has been used in treating domestic animals in practice, was described in 1958 (8). It was shown to have some effect upon adult swine ascarids when fed to infected pigs (7) but found ineffective against the migrating larvae of Ascaris suum (6). The principal utility of hygromycin B appears directed against members of the nematode order Ascaroidea. In this paper we report the anthelmintic activity of a natural product, the B18 component of the avermectins (3, 9), an a-L-oleandrosyl-a-L-oleandroside macrocyclic lactone, against nematode parasites of cattle, sheep, dogs, and chickens.MATERIALS AND METHODS Sheep. Sheep raised under "parasite-free" conditions (i.e., management conditions designed to ensure minimal exposure to helminth infection) and weighing between 14 and 25 kg at the time of treatment were experimentally infected with third-stage infective larvae of six nematode species, passaged in the laboratory as pure isolates, according to the following: day 0, 360 Oesophagostomum columbianum; day 16, 7,500 Ostertagia circumcincta and 7,500 Trichostrongylus colubriformis; day 18, 7,500 Trichostrongylus axei and 7,500 Cooperia oncophora; day 21, 2,000 Haemonchus contortus. The isolates of T. colubriformis and H. contortus used to infect sheep were tolerant to benzimidazole anthelmintic treatment, requiring more than the recommended use level of various benzimidazoles for high-order efficacy. Numbers of larvae were estimated by counting multiple samples of larval suspensions in tap water, and each animal was infected per os with 5 ml of larval suspension containing the desired number.On day 35, when the infections were patent, 15 infected sheep were randomly allotted to five treatment groups of three sheep each. The groups were randomly allotted to infected control (no treatment, two groups) or treatment with avermectin B,I at 0.

Dichelobacter nodosus is the essential causative agent of footrot in sheep. The major D. nodosus-encoded virulence factors that have been implicated in the disease are type IV fimbriae and extracellular proteases. To examine the role of the fimbriae in virulence, allelic exchange was used to insertionally inactivate the fimA gene, which encodes the fimbrial subunit protein, from the virulent type G D. nodosus strain VCS1703A. Detailed analysis of two independently derived fimA mutants revealed that they no longer produced the fimbrial subunit protein or intact fimbriae and did not exhibit twitching motility. In addition, these mutants were no longer capable of undergoing natural transformation and did not secrete wild-type levels of extracellular proteases. These effects were not due to polar effects on the downstream fimB gene because insertionally inactivated fimB mutants were not defective in any of these phenotypic tests. Virulence testing of the mutants in a sheep pen trial conducted under controlled environmental conditions showed that the fimA mutants were avirulent, providing evidence that the fimA gene is an essential D. nodosus virulence gene. These studies represent the first time that molecular genetics has been used to determine the role of virulence genes in this slow growing anaerobic bacterium.

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One thousand two hundred and sixty seven isolates of Bacteroides nodosus from 292 sheep in 58 flocks were examined. Of these, 1260 could be classified by slide agglutination into 8 serogroups designated A to H. Up to 6 serogroups were detected in individual flocks, with up to 4 serogroups being detected in a single foot. Of the 292 sheep examined, 38 (13%) carried mixed serogroup infections. Determination of the range of serological types infecting a flock frequently required the examination of a number of isolates from each of a number of sheep. Cross-tube agglutination tests carried out on 44 isolates and their antiserums indicated that members of some serogroups could be divisible into subgroups or serotypes. These results suggested that 16 or more serotypes of B. nodosus might exist. The nature of the antigens responsible for both slide and tube agglutination reactions needs to be determined.