Efficacy of doramectin against experimental infections by some nematode parasites in cattle in New Zealand

A study was undertaken to determine the efficacy of the novel avermectin, doramectin, against experimental larval and adult infections of three species of nematode parasite important to cattle production in New Zealand. Eighteen worm-free dairy bull beef calves were randomly allocated on live weight to three similar treatment groups. Each calf was given 30,000 Ostertagia ostertagi, 20,000 Cooperia spp. and 10,000 Trichostrongylus axei infective larvae as a single dose. One group was treated with doramectin 6 days after infection while the remaining groups received saline or doramectin 27 days after infection. Given as a single subcutaneous injection behind the ear, doramectin at 200 microg/kg removed 99.9-100% of adult and larval stages of O. ostertagi, Cooperia spp. and T. axei when compared to infections established in untreated controls (p<0.001). No adverse reactions were observed following treatment in the doramectin-treated animals. No injection site lesions were found by palpation following treatment or by injection site examination at necropsy.     

Prevention of blowfly strike on coarse and fine woolled sheep with the insect growth regulator dicyclanil

OBJECTIVE: To assess a ready-to-use formulation of dicyclanil to prevent blowfly strike on coarse and fine woolled sheep under New Zealand conditions. DESIGN: Randomized clinical field trials. PROCEDURE: In a first field trial, coarse wooled sheep treated with a ready-to-use, 5% dicyclanil formulation were compared with untreated control sheep for up to 21 weeks. In a second field trial, fine woolled sheep, treated with the same dicyclanil formulation, were compared with untreated sheep for up to 19 weeks. Efficacy was assessed by calculating the aggregated cumulative strike rate. RESULTS: For trial 1 (coarse woolled sheep) the aggregated cumulative strike rate at the end of the trial at week 21 after treatment reached 3.9% and 19.1% for treated and untreated sheep, respectively. For the treated animals the aggregated cumulative strike rate reached the 1% and 2% benchmarks between weeks 11 and 12. For trial 2 (fine woolled sheep) the aggregated cumulative strike rate at the end of the trial at week 19 reached 0.6% and 7.5% for treated and untreated sheep, respectively. Wool length at the time of application did not substantially influence the efficacy of dicyclanil. CONCLUSION: Under New Zealand field conditions, a ready-to-use 5% spray-on formulation of dicyclanil protected coarse woolled sheep for at least 12 weeks and fine woolled sheep for at least 19 weeks.     

Safety of temperature sensitive mutant Mycoplasma gallisepticum vaccine

A temperature sensitive (ts) vaccine strain designated ts-11 was selected after exposure of a low passage culture of the immunogenic Australian field isolate (strain 80083) of Mycoplasma gallisepticum to 100 mg/ml of N-methyl-N-nitro-N-nitrosoguanidine. Viable counts (assayed as colour changing units (CCU)/25 microliters) of a thawed stock culture of ts-11 were typically log10 3 to log10 5 higher when incubated at 33 degrees C (the permissive temperature) than duplicate viable counts incubated at 39.5 degrees C (the restrictive temperature). Doses of approximately 2 x 10(7) CCU of ts-11 caused no gross lesions or loss of egg production when inoculated into the air sacs of susceptible chickens and no clinical or pathological signs of sinusitis when inoculated into the infraorbital sinuses of susceptible turkey poults, whereas the parent strain 80083 was demonstrably pathogenic. However, 1 of 10 poults inoculated intra-abdominally with approximately 2 x 10(7) CCU of ts-11 did show signs of mild airsacculitis. Eight-week-old pullets were vaccinated by eye drop with up to 1.4 x 10(7) CCU of ts-11 and simultaneously subjected to several stressful management practices, without apparent ill effects. Administration by coarse aerosol of 5 ml of ts-11 vaccine/25 day-old broilers, with or without 25 doses of infectious bronchitis virus vaccine caused no obvious signs of respiratory disease. The non virulent ts phenotype was maintained after 3 passages of strain ts-11 in chickens. Chickens vaccinated 3 weeks previously with ts-11 or with strain 80083 were placed in contact with susceptible chickens for a period of 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunogenicity of a temperature sensitive mutant Mycoplasma gaffisepticum vaccine

The immunogenicity of the ts-11 vaccine strain of Mycoplasma gallisepticum was assessed following eye drop or coarse aerosol administration in chickens of various ages. Protection was evalualted following intra-abdominal (IA) or fine droplet aerosol administration of virulent M. gallisepticum, usually the Ap3AS strain and was measured mainly by the scoring of gross air sac lesions or by egg production. Vaccination of chickens with ts-11 did not elicit a substantial serum antibody response as measured by rapid serum agglutination test, or ELISA. Protection was never demonstrated when no M. gallisepticum serum antibody response was detected in a vaccinated group of chickens. Failure to protect occurred usually, although not invariably, following aerosol administration of the vaccine. Vaccination by eye drop usually, although not invariably provided protection against challenge. In one experiment, chickens vaccinated by eye drop at 8-weeks were as susceptible as non vaccinated controls when challenged by IA inoculation at 13-weeks-of-age. Yet other birds from the same vaccinated group were resistant when challenged in an identical way at 23-weeks. No measurable increase in M. gallisepticum specific serum antibody concentrations occurred in the intervening period. Equally surprising was the response of another group of birds in the same experiment that had been vaccinated with a higher dose of ts-11. An antibody response was detected in this group, but they were susceptible to challenge at 23-weeks. Interestingly, a drop in egg production commenced 4 weeks after challenge, 2 weeks later than that observed in a non vaccinated group challenged at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Akabane disease in sheep

Perinatal lamb mortality, associated with malformations of the CNS due to Akabane viral infection, occurred in 4 of 9 flocks of ewes lambing on 3 farms between 26 May and 14 November, 1976. Cases were restricted to ewes conceiving prior to the second week of March and lambing between 26 May and 19 July. As judged by seroconversion in sentinel flocks on 2 of the farms, field infection with Akabane virus occurred mainly between mid-February and mid-April. Malformations of the CNS occurred in 42.5%, 51.2%, 100% and 31.0% of the dead lambs examined in the affected flocks respectively. Prevalence in the 4 affected flocks, expressed as the proportion of ewes lambing which delivered at least one malformed foetus, was 6.1%, 8.4%, 88.9% and 5.7% respectively. Lamb mortality due to malformations of the CNS was 7.1%, 5.5%, 92.3% and 5.7% of lambs born. Age-specific prevalence was calculated for 3 of the 4 flocks and 2-year-old ewes accounted for 71.4% and 76.9% of total cases respectively in 2 flocks, whereas in one flock malformations occurred at equivalent frequencies throughout several older age groups. Birthweights of affected lambs were usually significantly lighter than those of unaffected lambs of similar sex and birth-type, and their mean duration of gestation was slightly, and significantly, prolonged. Micrencephaly (88.1% of cases) and hydrocephalus (68.7% of cases) were the outstanding pathological features of the malformations with hydranencephaly, microgyria, porencephaly and attenuation of the spinal cord occurring at much lower frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preserving new anthelmintics: a simple method for estimating faecal egg count reduction test (FECRT) confidence limits when efficacy and/or nematode aggregation is high

As it has been 30 years since a new anthelmintic class was released, it is appropriate to review management practices aimed at slowing the development of anthelmintic resistance to all drug classes. Recommendations to delay anthelmintic resistance, provide refugia and the use of a simulation model were reviewed to find optimum treatment strategies that maintain nematode control. Simulated Australian conditions indicated that a common successful low-risk treatment program was a rapid rotation between a "triple-combination" product (benzimidazole+levamisole+abamectin) and a new high-efficacy drug (monepantel). Where Haemonchus contortus was a threat, moxidectin was required at critical times because of its persistent activity against this parasite. Leaving up to 4% of adult sheep untreated provided sufficient "refugia" for non-selected worms to reduce the risk of selecting for anthelmintic resistance without compromising nematode control. For a new anthelmintic, efficacy estimated by faecal egg count reduction (FECR) is likely to be at or close to 100%, however using current methods the 95% confidence limits (CL) for 100% are incorrectly determined as 100%. The fewer eggs counted pre-treatment, the more likely an estimate of 100% will occur, particularly if the true efficacy is >90%. A novel way to determine the lower-CL (LCL) for 100% efficacy is to reframe FECR as a binomial proportion, i.e. define: n and x as the total number of eggs counted (rather than eggs per gram of faeces) for all pre-treatment and post-treatment animals, respectively; p the proportion of resistant eggs is p = x/n and percent efficacy is 100 ×(1-p) (assuming equal treatment group sizes and detection levels, pre- and post-treatment). The LCL is approximated from the cumulative inverse beta distribution by: 95%LCL=100 ×(1-(BETAINV(0.975, x+1, n-x+1))). This method is simpler than the current method, independent of the number of animals tested, and demonstrates that for 100% efficacy at least 37 eggs (not eggs per gram) need to be counted pre-treatment before the LCL can exceed 90%. When nematode aggregation is high, this method can be usefully applied to efficacy estimates lower than 100%, and in this case the 95% upper-CL (UCL) can be estimated by: 95% UCL = 100 ×(1((BETAINV(0.025, x+1, n-x+1))), with the LCL approximated as described above. A simulation study to estimate the precision and accuracy of this method found that the more conservative 99%CL was optimum; in this case 0.975 and 0.025 are replaced by 0.995 and 0.005 to estimate the LCL and UCL, respectively.     

Managing anthelmintic resistance: Modelling strategic use of a new anthelmintic class to slow the development of resistance to existing classes

AIM: To test the hypothesis that a single strategic treatment with a new class of anthelmintic could slow the development of resistance to existing classes of anthelmintic.

METHODS: An existing model was used to simulate nematode parasite dynamics and the development of anthelmintic resistance. Variations on a five-drench preventive programme of treatments for lambs, in which either zero, the first, third or fifth treatment was substituted with a different class of drug, were compared for the time to reach treatment failure (defined as efficacy <95%). The sensitivity to variations in the death rate of adult worms, that varied from 1 to 5%, and the dominance of resistance genes were also assessed.

RESULTS: Replacing one of the five treatments with a different class of anthelmintic almost always slowed the development of resistance, and was never worse than using the same drug for all treatments. Further, there were large differences in the relative time to treatment failure depending on which treatment was substituted. Changing the first treatment always had the least benefit, whereas changing the fifth treatment always had the greatest. This pattern was independent of the daily death rate of adult worms, and was not influenced by the dominance of resistance under treatment.

CONCLUSIONS: The results indicated that strategic substitution of a single treatment with a new class of anthelmintic, at the end of a series of preventive treatments to lambs using an existing class, could slow the further development of resistance to the latter. This strategic use of a new anthelmintic class has the potential to greatly extend the life of existing anthelmintics if these are still effective.