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Biomedical subjects

Susan Dawson

Publications and source records attributed to Susan Dawson.

9 recordsLinked to original sources
PubMed2006

Evolutionary mechanisms of persistence and diversification of a calicivirus within endemically infected natural host populations.

In order to understand the evolutionary mechanisms of persistence and diversification within the Caliciviridae, we have been exploiting endemic infection of feline calicivirus within five geographically distinct household groups of cats. By sequencing immunodominant and variable regions of the capsid gene, we identified the relative contribution of the different evolutionary processes employed by the virus to ensure its long-term survival in the host population. Such strategies included progressive evolution of a given variant of a strain through mutation accumulation within an individual, sequential reinfection with either a variant of the same strain or with a different strain, and mixed infection. Recombination between different strains in this study has been reported in detail elsewhere (K. P. Coyne et al., J. Gen. Virol. 87:921-926, 2006). Here, we provide evidence to suggest that true long-term persistent infection in individuals is relatively rare, with the majority of apparent viral carriers undergoing a combination of progressive evolution and cyclical reinfection. Progressive evolution at the individual level and variant reinfection at both the individual and population levels were associated with positive selection. Two measures of evolution rate were determined; for a virus progressively evolving within an individual (1.32 x 10(-2) to 2.64 x 10(-2) substitutions per nucleotide per year, i.e., no transmission) and for a strain circulating within a population (3.84 x 10(-2) to 4.56 x 10(-2) substitutions per nucleotide per year, i.e., including transmission). Reiteration of both progressive evolution and variant reinfection appeared to lead to a gradual increase in the diversity of a given strain of virus, both in the individual and in the population, until eventually new strains emerged.

Animals↗
PubMed2006

Long-term analysis of feline calicivirus prevalence and viral shedding patterns in naturally infected colonies of domestic cats.

Feline calicivirus (FCV) is a highly infectious respiratory pathogen of domestic cats. The prevalence of FCV in the general cat population is high, particularly in multi-cat households, largely because many clinically recovered cats remain persistently infected carriers. In order to assess how FCV circulates in such groups and to assess the contribution that each individual animal makes to the epidemiology of the disease, we have carried out the first detailed analysis of long-term shedding patterns of FCV in individual cats within naturally infected colonies. The prevalence of FCV in each of the groups on individual sampling occasions ranged from 0% to 91%, with averages for the individual colonies ranging from 6% to 75%. Within each of the colonies, one to three distinct strains of FCV were identified. Individual cats showed a spectrum of FCV shedding patterns over the sampling period which broadly grouped into three categories: those that shed virus relatively consistently, those that shed virus intermittently, and those that appeared never to shed virus. This is the first report identifying non-shedder cats that appear resistant to FCV infection over long periods of time, despite being continually exposed to virus. Such resistance appeared to be age related, which may have been immune-mediated, although by analogy with other caliciviruses, factors such as host genetic resistance may play a role. Given that a proportion of the population appears to be resistant to infection, clearly the cohort of cats that consistently shed virus are likely to provide an important mechanism whereby infection can be maintained in small populations.

Animals↗
PubMed2006

The challenge for the next generation of feline calicivirus vaccines.

Feline calicivirus (FCV) has been shown to evolve within individual cats and in the environment of colonies. This evolution and the diversity it creates has important clinical implications, not only for the disease in cats, but also for attempts to control disease by vaccination. Generally speaking, existing vaccines appear to be very effective at controlling the majority of clinical disease. However, some concerns remain including a failure to induce sterilising immunity, occasional vaccine breakdowns, and for live vaccines, occasional vaccine-induced disease. Key areas for future vaccine development include monitoring and broadening the cross-reactivity of vaccine immunity to field viruses, especially the recently evolved highly virulent strains, and attempting to reduce/eliminate field virus shedding by vaccinated cats.

Animals↗
PubMed2006

Duration of immunity (DOI)--The regulatory issues.

This paper discusses the efficacy of cat and dog vaccines, with respect to duration of immunity and regulatory issues. The European Union (EU) regulatory requirements are described: briefly, efficacy claims, which include duration of immunity, have to be specific for the product and supported by controlled laboratory and field trials. As a result, the duration of immunity shown has typically been a minimum, because of the cost and welfare implications of keeping animals for long periods of time in isolation. In contrast, in the US, duration of immunity has not traditionally been required for each individual product, only for rabies vaccines and some other vaccines for which no other products are available. The consequence of this is that in the US, various scientific authorities have produced guidelines appropriate for individual diseases. Undoubtedly this will continue, although the regulatory authorities also appear to be moving towards a position where lack of information may be indicated on the product label, and studies are required to support extended duration of immunity claims. The advantages and disadvantages of laboratory challenge studies versus field trials are discussed, and the use of alternatives such as surrogate markers of protection. The approaches used for small animal vaccines are compared to those used, for example, in human medicine. The main issue for small animals is that unlike in some other species, the aim generally is to maximise protection in the individual, rather than induce protection at the population level. The drawbacks of the present EU system are summarised, and the ways in which the situation is currently being approached and improved are presented.

Animal Welfare↗
PubMed2005

Methicillin-resistant staphylococci in companion animals.

We determined the molecular characteristics of methicillin-resistant staphylococci from animals and staff at a small animal and equine hospital. Methicillin-resistant Staphylococcus aureus (MRSA) identical to human EMRSA-15 was found in dogs and hospital staff. In contrast, 5 distinct MRSA strains were isolated from horses but not from hospital staff.

Animals↗
PubMed2003

High genetic diversity of the immunodominant region of the feline calicivirus capsid gene in endemically infected cat colonies.

Feline calicivirus (FCV) is an important pathogen of domestic cats. In this study, we have determined the genetic diversity of FCV within four geographically separate colonies of endemically infected cats by sequencing the immunodominant and variable region E of the capsid gene. Comparison of isolates between colonies and between unrelated published sequences gave nucleotide distance values of 26-35% and 22-40%, respectively and suggested each colony was infected with a distinct virus strain. Comparison of isolates within individual endemically infected colonies showed nucleotide distance variability of 0-16%. This was greater than distances previously reported for epidemiologically related isolates from cases of acute disease (0-5%) and was consistent with the evolution of FCV from a single distinct ancestor sequence in each colony. The pattern of nucleotide substitutions generating the observed intra-colony diversity was associated with strong evidence for positive selection acting on immunodominant regions of the FCV capsid protein. We suggest that endemically infected colonies of cats may be important generators of genetic diversity for FCV and that this may ultimately lead to the generation of new strains.

Amino Acid Sequence↗
PubMed2002

Distribution of fim3 and flaA TTGE sequence types amongst isolates of Bordetella bronchiseptica from different host animals.

Isolates of Bordetella bronchiseptica associated with different animal hosts were analysed by fim3 and flaA genotyping by temporal temperature gradient gel electrophoresis (TTGE). All the isolates from cats (n = 138), dogs (n = 42) and pigs (n = 13) could be assigned to one of two fim3 and one of three flaA TTGE sequence types, respectively. Two avian isolates and a marmoset isolate exhibited novel fim3 sequence types. Dominant but different TTGE sequence types were apparent in isolates from dogs and pigs for both fim3 (87.5% and 100%, respectively, of isolates were the dominant type) and flaA (95% and 92%, respectively, of isolates were the dominant type). There was a wider distribution of TTGE sequence types amongst cat isolates. As both fimbriae and flagella have been implicated in adherence of bordetellae to host cells, sequence variations in fimbrial proteins and FlaA may have a role to play in host preferences.

Amino Acid Sequence↗