Veterinary pharmacovigilance. Part 5. Causality and expectedness

In the European Union and elsewhere there is a requirement to ascribe causality to adverse drug reactions which occur in treated animals. In the EU, the ABON system of causality assessment is used but the assignment of causality assigned is not always self evident, and it may be complicated for a variety of reasons. In this paper, the approaches to causality assessment, based on a number of key criteria which examine the administration of the drug in relation to the sequence of ensuing events and the presence of biological plausibility are examined, along with the utility of using algorithms to facilitate this process. Unexpected adverse drug reactions usually require expedited reporting, depending on national or regional regulatory requirements. Again, deciding on what might constitute an expected (or unexpected) adverse reaction, particularly when a product may be intended for use in a number of species, and when within any one species a number of breeds may be treated, is not necessarily a straightforward issue. However, an approach to facilitate the decision- making process, based on a similar approach used in the pharmacovigilance of human medicinal products is discussed.     

Variable and strain dependent colonisation of chickens by Escherichia coli O157

The prevalence of enterohaemorrhagic Escherichia coli (EHEC) O157 in poultry is considered minimal compared with other species, especially ruminants. However, deliberate inoculation studies have shown that poultry are readily and persistently infected by this organism but that the mechanism of colonisation is independent of intimin, a recognised factor in host-EHEC interactions in mammalian species, and may be dependent upon flagella. Few strains of EHEC O157 have been tested in poultry and here 1-day-old and 6-week-old chicks were inoculated with seven non-toxigenic E. coli O157 strains in separate experiments. Persistence was measured semi-quantitatively by bacteriological assessment of E. coli O157 cultured from cloacal swabs (shedding score). In the 1-day-old chick model that was monitored for 43 days, all seven strains established well after inoculation. In the 6-week-old chicken model, one strain established and gave consistently high shedding for the duration of the experiment (156 days). Whereas of the remaining six strains, two persisted for 113 days, two persisted for 43 days, one persisted for 22 days and one strain was never detected.     

Prevalence of leptospira species among farmed and domestic animals in Greece

A total of 1527 serum samples from pigs, goats, sheep, cattle and dogs in Greece were examined by the microscopic agglutination test and 11-8 per cent of them had antibodies against one or more Leptospira serovars at titres of 1/100 or more. The predominant serovar affecting farm animal species was Bratislava, and Copenhageni was common among dogs and the second most important serovar when all animals were considered together. Another prevalent serovar was Australis, but antibodies to Pomona were detected only in goats and cattle.     

Interaction with avian cells and colonisation of specific pathogen free chicks by Shiga-toxin negative Escherichia coli O157:H7 (NCTC 12900)

The prevalence of Escherichia coli O157:H7 infection in birds is low but several deliberate inoculation studies show that poultry are readily and persistently infected by this organism indicating a possible threat to public health. The mechanisms of colonisation of poultry are not understood and the aim is to establish models to study the interaction of E. coli O157:H7, at the cellular and whole animal levels. A non-toxigenic E. coli O157:H7 (NCTC 12900) was used in adherence assays with an avian epithelial cell line (Div-1) and used to inoculate 1-day-old SPF chicks. In vitro, NCTC 12900 induced micro-colonies associated with cytoskeletal arrangements and pedestal formation with intimate bacterial attachment. In the 1-day-old SPF chick, a dose of 1 x 10(5) cfu resulted in rapid and extensive colonisation of the gastrointestinal tract and transient colonisation of the liver and spleen. The number of E. coli O157:H7 organisms attained approximately 10(8) cfu/ml caecal homogenate 24h after inoculation and approximately 10(7) cfu/ml caecal homogenate was still present at day 92. Faecal shedding persisted for 169 days, ceasing 9 days after the birds came into lay and 6% of eggs were contaminated on the eggshell. Histological analysis of tissue samples from birds dosed with 1x10(7) cfu gave evidence for E. coli O157:H7 NCTC 12900 induced micro-colonies on the caecal mucosa, although evidence for attaching effacing lesions was equivocal. These models may be suitable to study those factors of E. coli O157:H7 that mediate persistent colonisation in avian species.     

The effect of nitrogen source and concentration,medium pH and buffering on in vitro shoot growth and rooting in Eucalyptus marginata

This work examined the effect of nitrogen source and medium buffering on the micropropagation of Eucalyptus marginata Donn ex Sm. The number of shoots was increased when media contained 2-(N-morpholino) ethanesulfonic acid (MES) but this increase was minor and only applied to one of the two clones tested. Highest root production was obtained when the medium contained 7.5 mM nitrogen in a ratio of 2NO₃⁻:1NH₄⁺ and was buffered with 10 mM MES. In the rooting medium the pH was influenced most significantly by the nitrogen source, and then whether the medium was buffered. The media pH remained relatively constant when nitrate was the sole nitrogen source and this was assisted by the addition of 10 mM MES. Lower concentrations (<10 mM) of MES were less effective in buffering media over a four-week culture period in both shoot multiplication and rooting medium.     

Heterozygosity for genes influencing a quantitative trait

Choosing families to sample for a quantitative trait locus mapping experiment is a critical component of experimental design because only heterozygous families contribute information to the analysis. Additive genetic variance of a paternal half-sib family can be partitioned into two parts: a variance component of maternal source that is constant across different families and a variance component of paternal source that is defined as an index of heterozygosity of a sire. This index is shown to be an upper limit of variance among marker genotypes of a half-sib family and can be used to identify highly heterozygous sires, thus improving the power of detecting QTL in detection studies. Simulated progeny phenotypic data were used to estimate sire's heterozygosity index via an ANOVA method, and accuracy of the estimation was evaluated with the correlation coefficient between the true and estimated index summarized both as the correlation and by the correct ranking of results as measured by the ratio of the true average heterozygosity index of experimentally selected parents to average heterozygosity of all sires. Positive but small correlation can be achieved in the estimation of a sire's heterozygosity when based on the daughters' phenotypic data, and accuracy was improved when progeny-tested sons were used to estimate their grandsire's heterozygosity index, depending on the genetic model of a trait and the size and structure of families.     

A laboratory study of an inactivated bivalent iron restricted Salmonella enterica serovars Enteritidis and Typhimurium dual vaccine against Typhimurium challenge in chickens

A commercial inactivated iron restricted Salmonella Typhimurium and Salmonella Enteritidis vaccine was used to vaccinate chicks at 1 day and again at 4 weeks of age, with challenge by a high and a low dose of S. Typhimurium given either orally or by contact with seeder birds inoculated orally with a high dose of S. Typhimurium. In all three challenge regimes, the shedding of challenge strain was reduced significantly (p < 0.05) in vaccinated birds compared with unvaccinated controls. Vaccination reduced colonisation of internal organs after challenge by contact seeder birds. However, no effect of vaccination upon colonisation of internal organs after either high or low oral challenge was apparent. In conclusion, the data indicate that the vaccine should be a useful tool in the control of S. Typhimurium infection in chickens.     

Recurrent ossifying epulis in a dog

A seven-year-old neutered/male Siberian Husky-cross dog was referred for evaluation of a gingival mass. Two years previously, the referring veterinarian had resected an ossifying epulis from the same area between the maxillary left first and second premolars. The neoplasm recurred 4-months after the original surgery. En bloc resection provided tumor-free margins. An oral examination 12-months following surgery indicated no gross signs of recurrence.