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Biomedical subjects

J A Mumford

Publications and source records attributed to J A Mumford.

At least 19 recordsLinked to original sources
PubMed2006

Use of DNA and recombinant canarypox viral (ALVAC) vectors for equine herpes virus vaccination.

In this study, experimental canarypox virus (ALVAC) and plasmid DNA recombinant vaccines expressing the gB, gC and gD glycoproteins of EHV-1 were assessed for their ability to protect conventional ponies against a respiratory challenge with EHV-1. In addition, potential means of enhancing serological responses in horses to ALVAC and DNA vaccination were explored. These included co-administration of the antigen with conventional adjuvants, complexation with DMRIE-DOPE and co-expression of the antigen along with equine GM-CSF. Groups of EHV primed ponies were vaccinated twice intra-muscularly with one dose of the appropriate test vaccine at an interval of 5 weeks. Two to 3 weeks after the second vaccination, ponies were infected intra-nasally with the virulent Ab4 strain of EHV-1 after which they were observed clinically and sampled for virological investigations. The results demonstrated that DNA and ALVAC vaccination markedly reduced virus excretion after challenge in terms of duration and magnitude, but failed to protect against cell-associated viremia. Noteworthy was the almost complete absence of virus excretion in the group of ponies vaccinated with ALVAC-EHV in the presence of Carbopol adjuvant or DNA plasmid formulated with aluminium phosphate. The administration of the DNA vaccine in the presence of GM-CSF and formulated in DMRIE-DOPE and of the ALVAC vaccine in the presence of Carbopol adjuvant significantly improved virus neutralising antibody responses to EHV-1. These findings indicate that DNA and ALVAC vaccination is a promising approach for the immunological control of EHV-1 infection, but that more research is needed to identify the immunodominant protective antigens of EHV-1 and their interaction with the equine immune system.

Adjuvants, Immunologic↗
PubMed2006

Description of the outbreak of equine influenza (H3N8) in the United Kingdom in 2003, during which recently vaccinated horses in Newmarket developed respiratory disease.

Between March and May 2003, equine influenza virus infection was confirmed as the cause of clinical respiratory disease among both vaccinated and unvaccinated horses of different breeds and types in at least 12 locations in the UK. In the largest outbreak, 21 thoroughbred training yards in Newmarket, with more than 1300 racehorses, were affected, with the horses showing signs of coughing and nasal discharge during a period of nine weeks. Many of the infected horses had been vaccinated during the previous three months with a vaccine that contained representatives from both the European (A/eq/Newmarket/2/93) and American (A/eq/Newmarket/1/93) H3NN8 influenza virus lineages. Antigenic and genetic characterisation of the viruses from Newmarket and elsewhere indicated that they were all closely related to representatives of a sublineage of American viruses, for example, Kentucky/5/02, the first time that this sublineage had been isolated in the uk. In the recently vaccinated racehorses in Newmarket the single radial haemolysis antibody levels in acute sera appeared to be adequate, and there did not appear to be significant antigenic differences between the infecting virus and A/eq/Newmarket/1/93, the representative of the American lineage virus present in the most widely used vaccine, to explain the vaccine failure. However, there was evidence for significantly fewer infections among two-year-old horses than older animals, despite their having similar high levels of antibody, consistent with a qualitative rather than a quantitative difference in the immunity conveyed by the vaccination.

Amino Acid Sequence↗
PubMed2006

Analysis of equid herpesvirus 1 strain variation reveals a point mutation of the DNA polymerase strongly associated with neuropathogenic versus nonneuropathogenic disease outbreaks.

Equid herpesvirus 1 (EHV-1) can cause a wide spectrum of diseases ranging from inapparent respiratory infection to the induction of abortion and, in extreme cases, neurological disease resulting in paralysis and ultimately death. It has been suggested that distinct strains of EHV-1 that differ in pathogenic capacity circulate in the field. In order to investigate this hypothesis, it was necessary to identify genetic markers that allow subgroups of related strains to be identified. We have determined all of the genetic differences between a neuropathogenic strain (Ab4) and a nonneuropathogenic strain (V592) of EHV-1 and developed PCR/sequencing procedures enabling differentiation of EHV-1 strains circulating in the field. The results indicate the occurrence of several major genetic subgroups of EHV-1 among isolates recovered from outbreaks over the course of 30 years, consistent with the proposal that distinct strains of EHV-1 circulate in the field. Moreover, there is evidence that certain strain groups are geographically restricted, being recovered predominantly from outbreaks occurring in either North America or Europe. Significantly, variation of a single amino acid of the DNA polymerase is strongly associated with neurological versus nonneurological disease outbreaks. Strikingly, this variant amino acid occurs at a highly conserved position for herpesvirus DNA polymerases, suggesting an important functional role.

Amino Acid Sequence↗
PubMed2005

Association between respiratory disease and bacterial and viral infections in British racehorses.

Respiratory disease is important in horses, particularly in young Thoroughbred racehorses, and inflammation that is detected in the trachea and bronchi (termed inflammatory airway disease [IAD]) is more significant in this population in terms of impact and frequency than other presentations of respiratory disease. IAD, which is characterized by neutrophilic inflammation, mild clinical signs, and accumulation of mucus in the trachea, may be multifactorial, possibly involving infections and environmental and immunological factors, and its etiology remains unclear. This 3-year longitudinal study of young Thoroughbred racehorses was undertaken to characterize the associations of IAD and nasal discharge with viral and bacterial infections. IAD was statistically associated with tracheal infection with Streptococcus pneumoniae (capsule type 3), Streptococcus zooepidemicus, Actinobacillus spp., and Mycoplasma equirhinis and equine herpesvirus 1 and 4 infections, after adjustment for variation between training yards, seasons, and age groups. The association with S. pneumoniae and S. zooepidemicus was independent of prior viral infection and, critically, was dependent on the numbers of organisms isolated. S. pneumoniae was significant only in horses that were 2 years old or younger. The prevalence and incidence of IAD, S. zooepidemicus, and S. pneumoniae decreased in parallel with age, consistent with increased disease resistance, perhaps by the acquisition of immunity. The study provided evidence for S. zooepidemicus and S. pneumoniae playing an important etiological role in the pathogenesis of IAD in young horses.

Animals↗
PubMed2005

Inflammatory airway disease, nasal discharge and respiratory infections in young British racehorses.

REASONS FOR PERFORMING STUDY: Respiratory disease is important in young Thoroughbred racehorses, but the variation in the rates of occurrence between different ages and training groups has not been characterised. OBJECTIVES: To determine the rates of respiratory disease, particularly inflammatory airway disease (IAD), as well as evidence of infection, and their variation between age and group. METHODS: Horses were examined monthly in 7 British flat training yards over a 3 year period. IAD was defined as increased mucus in the trachea with increased proportions of neutrophils in tracheal wash samples. Frequencies of disease outcomes were estimated from the data. RESULTS: The prevalence of IAD was 13.8% and the incidence was 8.9 cases/100 horses/month. Rates varied with training and age groups, decreasing in older animals. The prevalence of nasal discharge (ND) was 4.1%. Rates of bacterial isolation were more common than viral infections. The incidence and prevalence of several bacterial species decreased with age. CONCLUSIONS: IAD and ND were common in young racehorses, varying significantly between training groups and decreasing with age, consistent with infection playing a role in aetiology. POTENTIAL RELEVANCE: The high prevalence of IAD in 2-year-old horses in Britain suggests that routine endoscopic examination may be helpful in providing early diagnosis and appropriate therapy. The transmission of bacteria and viruses within and between groups of young animals and the role of infection, stable environment and factors inherent to each horse, including their genetic make-up, in the multifactorial aetiology of the disease all merit further study.

Age Factors↗
PubMed2004

The effects of strain heterology on the epidemiology of equine influenza in a vaccinated population.

We assess the effects of strain heterology (strains that are immunologically similar but not identical) on equine influenza in a vaccinated population. Using data relating to individual animals, for both homologous and heterologous vaccinees, we estimate distributions for the latent and infectious periods, quantify the risk of becoming infected in terms of the quantity of cross-reactive antibodies to a key surface protein of the virus (haemagglutinin) and estimate the probability of excreting virus (i.e. becoming infectious) given that infection has occurred. The data suggest that the infectious period, the risk of becoming infected (for a given vaccine-induced level of cross-reactive antibodies) and the probability of excreting virus are increased for heterologously vaccinated animals when compared with homologously vaccinated animals. The data are used to parameterize a modified susceptible, exposed, infectious and recovered/resistant (SEIR) model, which shows that these relatively small differences combine to have a large effect at the population level, where populations of heterologous vaccinees face a significantly increased risk of an epidemic occurring.

Animals↗
PubMed2003

Optimising vaccination strategies in equine influenza.

A stochastic model of equine influenza (EI) is constructed to assess the risk of an outbreak in a Thoroughbred population at a typical flat race training yard. The model is parameterised using data from equine challenge experiments conducted by the Animal Health Trust (relating to the latent and infectious period of animals) and also published data on previous epidemics (to estimate the transmission rate for equine influenza). Using 89 ponies, an empirical relationship between pre-challenge antibody and the probability of becoming infectious is established using logistic regression. Changes in antibody level over time are quantified using published and unpublished studies comprising 618 ponies and horses. A plausible Thoroughbred population is examined over the course of a year and the model is used to assess the risk of an outbreak of EI in the yard under the current minimum vaccination policy in the UK. The model is adapted to consider an alternative vaccination programme where the frequency of vaccination in older horses (2-year-olds and upwards) is increased. Model results show that this practical alternative would offer a significant increase in protection. Spread of infection between yards is also considered to ascertain the risk of secondary outbreaks.

Age Factors↗
PubMed2003

In vitro characterisation of high and low virulence isolates of equine herpesvirus-1 and -4.

Basic in vitro characteristics of high and low virulence isolates of equine herpesviruses-1 and -4 were investigated with particular reference made to the Ab4 and V592 isolates of EHV-1 as both have distinct endotheliotropism and clinical outcomes in pony challenge studies. Additionally, some EHV-4 isolates that showed variations in clinical outcome were included in some experiments. The aim of the study was to identify an in vitro characteristic that would differentiate strains of known virulence. Such a system could then be applied to vaccine and virulence studies as an effective screening tool. Viral growth kinetics in a variety of cell culture systems, plaque size, ability to replicate in fetal endothelium in organ culture, and sensitivity to acyclovir were compared. No reliable marker system that differentiated between higher and lower virulence isolates of EHV-1 and EHV-4 was identified.

Animals↗
PubMed2003

Radiological versus histological diagnosis in UIP and NSIP: survival implications.

BACKGROUND: High resolution computed tomography (HRCT) has an important diagnostic role in idiopathic interstitial pneumonia (IIP). We hypothesised that the HRCT appearance would have an impact on survival in patients with IIP. METHODS: HRCT scans from patients with histological usual interstitial pneumonia (UIP; n=73) or histological non-specific interstitial pneumonia (NSIP; n=23) were characterised as definite UIP, probable UIP, indeterminate, probable NSIP, or definite NSIP. Cox regression analysis examined the relationships between histopathological and radiological diagnoses and mortality, controlling for patient age, sex, and smoking status. RESULTS: All 27 patients with definite or probable UIP on HRCT had histological UIP; 18 of 44 patients with probable or definite NSIP on HRCT had histological NSIP. Patients with HRCT diagnosed definite or probable UIP had a shorter survival than those with indeterminate CT (hazards ratio (HR) 2.43, 95% CI 1.06 to 5.58; median survival 2.08 v 5.76 years) or HRCT diagnosed definite or probable NSIP (HR 3.47, 95% CI 1.58 to 7.63; median survival 2.08 v 5.81 years). Patients with histological UIP with no HRCT diagnosis of probable or definite UIP fared better than patients with histological UIP and an HRCT diagnosis of definite or probable UIP (HR 0.49, 95% CI 0.25 to 0.98; median survival 5.76 v 2.08 years) and worse than those with a histological diagnosis of NSIP (HR 5.42, 95% CI 1.25 to 23.5; median survival 5.76 v >9 years). CONCLUSIONS: Patients with a typical HRCT appearance of UIP experience the highest mortality. A surgical lung biopsy is indicated for patients without an HRCT appearance of UIP to differentiate between histological UIP and NSIP.

Algorithms↗
PubMed2003

Comparison of hamster and pony challenge models for evaluation of effect of antigenic drift on cross protection afforded by equine influenza vaccines.

REASONS FOR PERFORMING STUDY: Vaccination and challenge studies in ponies are the most relevant experimental system for predicting whether strains included in equine influenza vaccines are relevant, but they are difficult to perform. OBJECTIVES: In order to investigate the feasibility of using a small animal model, results of a cross-protection study in hamsters were compared with those from a previous pony challenge experiment. METHODS: Animals were immunised with inactivated vaccines containing one of 4 strains of equine influenza A H3N8 subtype virus isolated over a 26 year period (1963 to 1989), then challenged with a 1989 strain. RESULTS: Although there was no significant difference in titres of excreted virus between groups of vaccinated ponies, hamsters immunised with heterologous strains had significantly higher virus titres in the lung than hamsters vaccinated with the homologous strain. In both ponies and hamsters, the number of animals excreting virus was greater the earlier the isolation date of the vaccine strain, although this was only significant in the hamster study. CONCLUSIONS: Despite differences, the overall conclusion of both the pony and hamster models was that heterologous vaccines may be less effective than homologous vaccines at preventing virus excretion. POTENTIAL RELEVANCE: Further validation is required, but the hamster model shows potential for preliminary assessment of the effects of antigenic drift on vaccine efficacy.

Animals↗
PubMed2002

Modelling equine influenza 1: a stochastic model of within-yard epidemics.

This paper demonstrates that a simple stochastic model can capture the features of an epidemic of equine influenza in unvaccinated horses. When the model is modified to consider vaccinated horses, we find that vaccination dramatically reduces the incidence and size of epidemics. Although occasional larger outbreaks can still occur, these are exceptional. We then look at the effects of vaccination on a yard of horses, and in particular at the relationship between pre-challenge antibody level and quantity of virus shed when challenged with the virus. While on average, a high antibody level implies that less virus will be shed during the infectious period, we identify a high degree of heterogeneity in the response of horses with similar pre-challenge antibody levels. We develop a modified model that incorporates some heterogeneity in levels of infectivity, and compare this with the simpler model.

Animals↗
PubMed2001

Clinical and virological evaluation of the efficacy of an inactivated EHV1 and EHV4 whole virus vaccine (Duvaxyn EHV1,4). Vaccination/challenge experiments in foals and pregnant mares.

Pregnant mares and young foals were vaccinated with Duvaxyn EHV1,4, an inactivated and adjuvanted vaccine containing both the EHV-1 and 4 antigens. SN and CF antibody titres were induced two weeks after first vaccination. Antibody levels were boosted after second vaccination, however they never reached the levels induced after virus challenge. Young foals were challenged with virulent EHV-1 and EHV-4 field viruses. Pregnant mares were challenged with the highly abortigenic EHV-1 strain Ab4. Vaccinated animals showed a clear reduction in clinical signs and virus excretion compared to unvaccinated control animals. Log transformed antibody levels could be correlated to duration of virus excretion. The incidence of EHV-1 induced abortions was drastically reduced in vaccinated mares. Therefore, although vaccinated animals are not fully protected against disease, Duvaxyn EHV1,4 clearly reduces clinical symptoms, the duration of virus shedding and the quantity of virus shed. It can be concluded that vaccination of foals and pregnant mares with Duvaxyn EHV1,4 significantly reduces the risk of abortions and outbreaks of respiratory disease caused by circulating field viruses.

Abortion, Veterinary↗
PubMed2001

Preliminary evaluation of diagnostic tests using horses experimentally infected with trypanosoma evansi.

Seven surra negative horses were intravenously inoculated with 3 x 10(6)Trypanosoma evansi parasites derived from a camel. One horse was maintained as an uninfected negative control. Three antigen and three antibody detection tests were evaluated for diagnosis of infection in horses. The microhaematocrit centrifugation test (MHCT) was the most sensitive, first detecting parasites between one and three days (x 2.4) post infection (p.i.). The antigen (ag)-ELISA detected antigen between three and ten days (x 6.6) p.i. The latex agglutination test (LAT) first gave positive results on day 3 (x 3.0) p.i. Following the treatment of horses with trypanocidal drugs, the MCHT and the mouse inoculation test (MIT) became negative. Antigen levels using LAT declined and reached pre-infection levels in five out of six horses during the period of observation (92-279 days). Antigen levels using the ag-ELISA declined as well but did not reach pre-infection levels in any of the six horses.Three antibody detection techniques, ab-ELISA, card agglutination test (CATT), and immunofluorescent antibody test (IFAT) detected antibodies in the blood of all seven infected horses but not in the uninfected control. However, the ab-ELISA did not discriminate clearly between sera from infected and uninfected horses because unacceptably high ELISA background readings were detected in 15% of the surra negative horses shipped to the UAE from the UK. The ELISA antibody increased above pre-infection levels in the six horses experimentally infected, but not in one horse. In this horse the ELISA antibody level exceeded the cut-off level only after the reoccurrence of the T. evansi infection. The IFAT detected antibodies 15.7 days p.i. in all infected horses.

Animals↗
PubMed2001

Evaluation of a prototype sub-unit vaccine against equine arteritis virus comprising the entire ectodomain of the virus large envelope glycoprotein (G(L)): induction of virus-neutralizing antibody and assessment of protection in ponies.

An Escherichia coli-expressed recombinant protein (6hisG(L)ecto) comprising the entire ectodomain (aa 18-122) of equine arteritis virus (EAV) glycoprotein G(L), the immunodominant viral antigen, induced higher neutralizing antibody titres than other G(L)-derived polypeptides when compared in an immunization study in ponies. The potential of the recombinant G(L) ectodomain to act as a sub-unit vaccine against EAV was evaluated further in three groups of four ponies vaccinated with doses of 35, 70 or 140 microg of protein. All vaccinated animals developed a virus-neutralizing antibody (VNAb) response with peak titres 1-2 weeks after the administration of a booster on week 5 (VNAb titres of 1.8-3.1), 13 (VNAb titres of 1.4-2.9) or 53 (VNAb titres of 1.2-2.3). Vaccinated and unvaccinated control ponies were infected with EAV at different times post-vaccination to obtain information about the degree of protection relative to the levels of pre-challenge VNAb. Vaccination conferred varying levels of protection, as indicated by reduced or absent pyrexia, viraemia and virus excretion from the nasopharynx. The degree of protection correlated well with the levels of pre-challenge VNAb and, in particular, with levels of virus excretion. These results provide the first evidence that a sub-unit vaccine protects horses against EAV. The use of the sub-unit vaccine in combination with a differential diagnostic test based on other EAV antigens would enable serological discrimination between naturally infected and vaccinated equines.

Amino Acid Sequence↗